APRIL 2011, VOL 3, NO 2

AprIl 2011

www.InFErtIlItyrEpronEwS.CoM

Vol 3, no 2

Impact of Egg, Sperm, and Embryo Continuity of Care Focus of prEG Donor Conception on Families CLINIC PROFILE

The Role of Fertility Clinics

Interview with Carolyn E. Keating, BSN, RN-C, NP Registered Nurse Clinician, PREG, Greenville, SC

By Wendy Kramer Co-founder and Director of the Donor Sibling Registry

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Top row, left to right: Laura Kalatges; Lindsay Thomason, MSN, WHNP; John Nichols, MD; John Payne, MD; Faith Ripley, BS, CPC; Barbara Sims; Meredith Mason, MLT-ASCP. Bottom row: Rene Bridges, BSN; Kristi Fowler, MT-AAMA; Kelly Taylor, AAB; Jennifer Settle, BS.

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ith locations in South and North Carolina, Piedmont Reproductive Endocrinology Group (PREG) also garners patients from Georgia, Tennessee, and Virginia, thanks to its high success rates and personalized patient care.

The lotus flower in the clinic’s logo was chosen because “it is considered the ‘fertility flower’ as well as the feminine principle,” as is stated on PREG’s website (www.pregonline. com/preg_physicians_and_staff.php).

Evolving Feelings and Mixed Messages Our research shows that donors’ feelings can change over time, as can the feelings of parents and children in their approach to donor conception. Some parents feel more confident about it as their children grow older, and some gain confidence through better educating themselves. Some have been offered Continued on page 4

Fertility Care in the Midst of Healthcare reform: An Uncertain Future

Briefly describe the history of your infertility clinic

Sue Jasulaitis, RN, MS Clinical Research Manager, Fertility Centers of Illinois

PREG is the brain child of John Nichols, MD. After completing his fellowship in reproductive endocrinology at the University of Texas Southwestern Medical Center in 1995,

Implications of Hydrosalpinges for IVF outcomes John J. Rapisarda, MD Infertility and Obstetrics and Gynecology, Fertility Centers of Illinois

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an anonymous donor can have difficult consequences for families down the road.

Carolyn E. Keating, a registered nurse clinician at PREG, talked with Infertility & Reproductive News, sharing information on this fertility group and what makes it special.

Continued on page 5

ubal factor infertility is a common indication for treatment using in vitro fertilization (IVF).

Although individuals with proximal (isthmic) tubal occlusion have excellent success rates using IVF, it has been

n your role as an infertility clinician, you can have a profound effect on parents’ feelings about using donor conception, choosing an open versus an anonymous donor, their attitudes on disclosure, a child’s right to know the methodology of his/her conception, and a child’s curiosity and desire to search for biological relatives.

Infertility clinicians can help parents to realize that many donor offspring feel curious about their genetic, ancestral, and medical backgrounds, and that choosing

shown in numerous studies that distal disease leading to a dilated hydrosalpinx has a deleterious effect on IVF outcome.1 Exactly how the presence of a hydrosalpinx affects IVF success rates is not well understood, but it has been proposed Continued on page 8

The Publicationof of The Official Offical Publication

We thank Watson Pharmaceuticals, Inc., for their gold level support. ©2011 Novellus Healthcare Communications, LLC

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mid much controversy and debate, President Obama signed into law a new healthcare reform policy last year. This healthcare reform law, known as the Patient Protection and Affordable Care Act (ACA), consists of 2 components—the ACA and the Health Care and Education Reconciliation Act. Starting in 2010, this law provides numerous healthcare provisions that will be implemented over the next 4 years.

This complicated act will generate

many changes to the current healthcare delivery system, including improved access to basic healthcare coverage, insurance reforms, required employer coverage and tax reporting, funding for specific healthcare research, and overhauls for the subsidized college lending program.

This new bill has given many Americans new patient rights and benefits.

But how does this new law affect reproductive medicine? At present, the answers are few.

Continued on page 6

IN THIS ISS UE INFERTILITY UPDATES . . . . . . . . . . . . .

“Fertility rescue” offering hope to patients with cancer Role of nurses in guiding PGD The benefits of personal fertility monitors WOMEN’S HEALTH . . . . . . . . . . . . .

Heart disease a risk even for young women IOM calls for greater leadership role for nurses Carbamazepine exposure and spina bifida

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PHARMACY CORNER

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First FDA-approved conception kit COMPLIMENTARY CE

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Hypoactive sexual desire disorder Commentary: Female sexual health UROLOgY NEWS

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Shock-wave therapy for severe erectile dysfunction NUTRITION

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The benefits of choline during pregnancy

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Committed to Fertility Pharmacy Excellence 8ZZi\[`k\[ Zfek`el`e^ \[lZXk`fe gif^iXdj G\\i$kf$g\\i Zc`e`ZXc glYc`ZXk`fej Fe\$fe$fe\ elij\ Xe[ gXk`\ek ZfejlckXk`fej EXk`feXc Zfm\iX^\ n`k_ Z\ekiXc Xe[ i\kX`c ]lcÓ ccd\ek For medication delivery call:

Frisco, Texas: 800-424-9002 Fax: 800-874-9179 fertility.walgreens.com/clinicians

©2011 Walgreen Co. All rights reserved. SP13361-0111

From the Editor WWW.INFERTILITYREPRONEWS.COM

PUBLISHING STAFF

Publisher Jack Iannaccone jack@infertilitynurse.org 732-992-1537 Editorial Director Dalia Buffery dalia@novellushc.com 732-992-1889 Associate Editor Lara J. Reiman lara@novellushc.com 732-992-1892 Editorial Assistant Jessica A. Smith

welcome to Spring!

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s the cold weather recedes, we look forward to the exciting activities warm weather brings. For some, warm weather signifies the start of the outdoor grilling season. Don’t forget to submit your favorite recipes to our popular online forum.

For healthcare professionals, the approach of warm weather often means making plans to attend a variety of excellent educational conferences. As an ongoing feature, Infertility & Reproductive News provides a directory of upcoming meetings in reproductive health. Take advantage of past meeting coverage at www.infertilityrepronews.com,

Director, Client Services Russell Hennessy russell@novellushc.com 732-992-1888 Senior Production Manager Lynn Hamilton Quality Control Director Barbara Marino Business Manager Blanche Marchitto Editorial Contact: Telephone: 732-992-1892 Fax: 732-656-7938

MISSION STATEMENT Infertility & Reproductive News is the official publication of the American Academy of OB/GYN and Infertility Nurses. Infertility & Reproductive News provides practical, authoritative, cutting-edge information on the physiologic, medical, and psychological aspects of women’s health, focusing on the role of the infertility practitioner, including nurses, MDs, PhDs, NPs, and PAs, in patient care. Our journal offers a forum for nurses, nurse practitioners, physician assistants, physicians, administrators, researchers, and all others involved in infertility and women’s health to discuss the entire scope of current and emerging diagnostic and therapeutic options, as well as counseling and patient follow-up for women throughout their reproductive years and beyond. Infertility & Reproductive News promotes peer-to-peer collaboration among all infertility professionals toward the advancement of integrated services for optimal delivery of patient care and offers continuing education for all clinicians involved in these interrelated fields of women’s reproduction.

Infertility & Reproductive News, ISSN 2153-6562 (print); ISSN 2153-6546 (online), is published 6 times a year

by Novellus Healthcare Communications, LLC, 241 Forsgate Drive, Suite 205D, Monroe Twp, NJ 08831. Copyright ©2011 by Novellus Healthcare Communications, LLC. All rights reserved. Infertility & Reproductive News is a trademark of Novellus Healthcare Communications, LLC. No part of this publication may be reproduced or transmitted in any form or by any means now or hereafter known, electronic or mechanical, including photocopy, recording, or any informational storage and retrieval system, without written permission from the Publisher. Printed in the United States of America.

The ideas and opinions expressed in Infertility & Reproductive News do not necessarily reflect those of the Editorial Board, the Editors, or the Publisher.

Publication of an advertisement or other product mentioned in Infertility & Reproductive News should not be construed as an endorsement of the product or the manufacturer’s claims. Readers are encouraged to contact the manufacturers about any features or limitations of products mentioned. Neither the Editors nor the Publisher assume any responsibility for any injury and/or damage to persons or property arising out of or related to any use of the material mentioned in this publication.

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and link to highlights of upcoming meetings. This directory may provide the help you need to determine which conference best fits your educational needs.

We will continue to provide meeting updates and meeting coverage designed to keep you informed on the issues and trends affecting your practice. I look forward to meeting you in the coming months at several of these exciting meetings.

Sue Jasulaitis, RN, MS Editor-in-Chief

Editorial Board Sandra Fernandez, RPh, PharmD Pharmacist Mandell’s Clinical Pharmacy, NJ

Norah S. Nutter, MSN, WHNP-BC, IBCLC Women’s Health Nurse Practitioner Magnolia OB/GYN Myrtle Beach, SC

Margaret-Rose Agostino, DNP, MSW, RN-BC, IBCLC Assistant Professor Department of Nursing Delaware State University

Jennifer Iannaccone, RNC Nursing Manager, IVF Coordinator IVF New Jersey

Kutluk Oktay, MD, FACOG Director, Division of Reproductive Medicine & Infertility, Department of Obstetrics & Gynecology; Director, Institute for Fertility Preservation, NY

Barbara Alice, RN, APN-C, MSN Nursing Manager, IVF Coordinator South Jersey Fertility Center

Carolyn E. Keating, BSN, RNC, NP Piedmont Reproductive and Endocrinology Group Greenville, SC

Cyndi Gale Roller, PhD, RN, CNP, CNM Program Director, Women’s Health College of Nursing Kent State University, OH

Monica R. Benson, BSN, RNC Nurse Manager Third Party Reproduction, RMA New Jersey

Cheryl Kilbourne, RN Clinical Director Women and Children Services Waccmaw Hospital, SC

Patricia Rucinsky, RN, BSN Clinical Nurse Manager IRMS at Saint Barnabas, NJ

Melissa B. Brisman, Esq Owner Reproductive Possibilities, LLC Surrogate Fund Management, LLC

Juergen Liebermann, PhD, HCLD IVF Laboratory Director River North Fertility Centers of Illinois, Chicago

Christopher S. Sipe, MD OB/GYN & Reproductive Endocrinology Fertility Centers of Illinois, Chicago

Kit Devine, MSN, ARNP Advanced Nurse Practitioner Fertility & Endocrine Associates, Kentucky

Mary M. Macgregor, RNC IVF Nurse Coordinator Fertility Institute of New Orleans, LA

Dale C. Smith, RN, MPH, MSN NFP Nursing Supervisor DHEC Region 6 Conway, SC

Richard P. Dickey, MD, PhD Director, Reproductive Medicine Fertility Institute of New Orleans, LA

Donna Makris, RN, BSN, IBCLC Parent Education Coordinator OB/GYN, St. Peter’s Medical Center, NJ

Harvey J. Stern, MD, PhD Director, Reproductive Genetics Genetics & IVF Institute Fairfax, VA

Gina Paoletti-Falcone, RN, BSN Clinical Services Manager Freedom Fertility Pharmacy Byfield, MA

Jill Marchetti, RN Director, Egg Donor Program IVF New Jersey

Kriston Ward, RN, MS, NP-C Strong Fertility Center University of Rochester Medical Center, Rochester, NY

Donielle Farrington, RNC Clinical Nursing Manager Brunswick Hills OB/GYN, NJ

Debra Moynihan, WHNP-BC, MSN Women’s Health Nurse Practitioner Carolina OB/GYN, SC

Joan Zaccardi, MS, DrNP Administrative Practice Manager Urogynecology Arts of New Jersey

EDITOR-IN-CHIEF

Sue Jasulaitis, RN, MS Clinical Research Manager Fertility Centers of Illinois, Chicago

APRIL 2011 l VOLUME 3, NUMBER 2

3

Infertility Updates

Impact of Egg, Sperm, and Embryo Donor... adequate opportunities to think about the long-term impact that donor conception may have on their family and their child before they decided to conceive this way, and others do not.

However, some parents remain uncertain or even ashamed about having used donor conception to create their family, even though they love their children.

Some are confused and conflicted by mixed messages they receive from the infertility clinic or the sperm bank staff about using gamete donation. Some do not receive any counseling, and some counselors advocate telling the child the truth about their conception, whereas others may say, “it is the parenting that really counts.” These types of mixed messages can make important decisions seem very complicated for the parents. Parents need to be given the opportunity to make decisions based on the best welfare of the children to be born, not based on their own fears. the Burden of Genetic Secrets Families that are not encouraged to be open and honest with their families and children about donor conception may become so uncomfortable with their decision to keep the “secret” that it can ultimately become a wedge in the relationship between them and their children. Most parents who think that they are keeping the “secret” end up having very confused children, because many children eventually say that they always knew that something just “was not right.” Parents who disclose the truth to children at a young age can avoid many difficulties later on. Our research shows that many donor offspring who are told the truth later in life feel angry and betrayed.

Some parents hope that telling the truth will mean that their child will never have curiosity about their donor.

The truth is that even though children may know from an early age about the methodology of their conception, they still often feel the need to know about their half siblings and/or their donors.

Just like in adoption, some donor offspring are mildly curious about their genetic parents, and some have a burning desire to know about the missing half of their backgrounds.

It is an innate human desire to want to know where we come from. I have heard some parents describe their donor as “just a piece of genetic material” or “just a donated cell.” Parents should be very careful when speaking of a child’s donor in this way, because children may feel terribly guilty about wishing to know about and searching for their biological family. To a parent it may be just

4

Wendy Kramer

I urge you to initiate discussions at your clinic about how to incorporate into your practice the needs of people born through donor conception, before conception. The donors and the recipients need appropriate counseling and information so that they could make fully educated decisions. a “donated cell,” but to the child it is half of their genetic heritage and identity. Often, it is not knowing one’s biological parent and one’s biological roots that is the focus of most negative feelings, even for children who are told the truth about their conception, as can be seen from their comments: • “It makes me angry that I am denied the basic right of knowing who my father was and what ethnicity I am.”

• “I am angry and frustrated that I can’t get information about my heritage, genetics, looks, and medical history. I feel that half my identity has been stolen by the doctor, and that is unjust.”

We presented at the 2010 American Society for Reproductive Medicine meeting and at the 2011 British Fertility Society meeting the results of our survey of 759 donor offspring. The following responses were cited as reasons for searching for their donors (respondents could choose more than 1 answer): • To see what the donor looks like: 88% • To learn more about my ancestry: 69.2% • To learn more about myself: 67.6% • To learn more about my medical background: 60.7% • So that they can know who I am: 52% • To establish a relationship with the donor: 36.9%.

APRIL 2011 l VOLUME 3, NUMBER 2

Among donor offspring, 87% desire to connect with their half siblings, and of those who are not in contact with their donors, 83% wish to be. Furthermore, 73.5% recommend using a willing-to-be-known donor, urging future parents to consider the implications on the child: 1. “Consider every possible emotion that your child could go through. Emotionally, this can be a very difficult issue for donor children, even as adults. Make sure, if you decide to go through with it, that you have answers to the questions your child will ask. (That can be everything from medical history to marital status to family questions, job, interests...anything.) That’s the difficult part for me, sometimes. I don’t have any answers.”

2. “I would say please, please, please be honest with your child about their origins from day 1. It is the right and best thing to do. My parents never told anybody that they’d used a sperm donor, but the truth still came out eventually. I can’t tell you how big a shock it was to discover at the age of 25 that the man I think of as my dad isn’t my biological father.”

3. “I think that a donor who is willing to be known is extremely important.

At the very least, a donor-conceived child should have genetic and medical information available to them.”

Medical Implications Most donors are not adequately counseled about donor-conceived persons and their curiosities. Of 164 sperm donors and 155 egg donors surveyed, 80% and 63.3%, respectively, stated that they were not “adequately” counseled on the potential curiosities of

Some 23% of sperm donors and 34.2% of egg donors say that they or close family relatives have health concerns or genetic risk factors that they have learned of since donating. donor offspring. Many donors who visit the Donor Sibling Registry (DSR) are frustrated that their clinics did not alert them of the place where they could make mutual-consent contact (ie, DSR), because 23% of sperm donors and 34.2% of egg donors say that they or close family relatives have health concerns or genetic risk factors

Continued from page 1

The Donor Sibling Registry DSR was founded in 2000 to assist individuals conceived by sperm, egg, or embryo donation who are seeking to make mutually desired contact with others with whom they share genetic ties. With more than 30,350 current members, the DSR has helped to connect more than 8175 donor offspring with their half siblings and/or sperm or egg donors and has initiated national research in this area. For more information visit www.donorsiblingregistry.com. that they have learned of since donating that would be important for recipient families to know about.

A child should have the option to learn of new medical information relevant to his or her biological parent that was not available at the time of conception. At the DSR, we talk regularly with parents, donors, and donorconceived adults who are facing challenges as a result of being part of a “donor family.” the role of the Infertility Clinic One way to take the stigma out of donor conception is to change the culture of secrecy that has surrounded it for so long. Clinic staff could play a major role in setting the stage for an open and honest family dynamic.

Nonbiological parents need to know that telling the child does not mean losing the love of their child, and that it is normal for children to become curious about their genetic family. It is important for parents to know that a child’s need to reach out to the genetic family in no way negates the love and support they feel toward the family in which they grew up.

Although fertility clinics are busy with achieving pregnancy as their main goal, they will make a huge contribution to donor families if they prepare them from the start with the appropriate education and help them to understand the needs and rights of donorconceived persons.

I urge you to initiate discussions at your clinic about how to incorporate into your practice the needs of people born through donor conception, before conception. The donors and the recipients need appropriate counseling and information so that they could make fully educated decisions, and families need to know about the availability of DSR as a place where they can share and update medical information with one another and make mutual-consent contact, if desired. ■

Clinic Profile

Continuity of Care Focus of prEG...

Dr Nichols worked in a variety of academic healthcare settings. While caring for couples struggling with fertility issues, he came to realize that although large medical centers could provide a high level of reproductive technology, such institutions lacked the continuity of care and human connection found in the small office setting. He further understood that reproductive technology often came with an expensive price tag. Dr Nichols challenged himself to provide reproductive services that would combine the best of cutting-edge technology, meet the emotional needs of these couples, and be cost-effective.

In January 2002, PREG opened its doors in a small, 1000-square-foot space, with 5 employees committed to this vision. Today, 9 years later, 4 of the original 5 employees continue to work alongside Dr Nichols and his associate, John Payne, MD. These employees, along with 18 others covering 3 sites in 2 states, continue to provide high-tech, patient-centered care to clients from the entire southeast region of the United States.

What are some of the ways in which you support your patients?

We view the patient as an integral part of our team. Being part of the team, they must have access to the rest of the team (physicians and staff). We believe that patients deserve to have their concerns and ideas addressed, and have their needs respected, and, within reason, honored. How do we do this?

During business hours, the phone is answered by a real human being rather than by a computer advising clients to “listen carefully to the following options.” All employees are requested to answer the phone whenever possible and route the patient or patients to the person who can best provide for their needs, and do so in a timely manner.

We work with all patients who have a condition that will not wait, even if it is only the patient who is the one who views the situation as emergent. We strive to accommodate the patient’s request, whether it is driven by a medical, emotional, or social need. Still, some calls are triaged and routed to the voicemail of the employee who is best equipped to assist. Sincere attempts are made, however, to minimize this practice. Personal contact begins with being able to contact a real person. This is a core value of PREG. We try to truly listen to what the patient is saying. Although as healthcare providers we may have strong feelings about the course of treatment that a patient should pursue, we acknowledge that what may be medically right

in a given situation may not be the right course for a particular person or couple.

We recognize that emotion, finances, family, or even religion affect decisions.

We also recognize that fertility evaluation and treatments require large commitments of time, and that there is life for our patients aside from fertility treatments. Having said this, we try to accommodate appointments to the patient’s work or other life commitment schedules whenever possible. Like most centers, we have 24/7 physician on-call

Continued from page 1

The laboratory staff consists of 4 fulltime personnel. These skilled members of our team allow us to get truly “STAT” results and provide high-quality semen, as well as embryo services. They are also the “queens of quality control” at PREG, guiding us through the regulatory process to adhere to the highest standards of care.

As a relatively small, private facility, we are proud that we can offer a full range of assisted reproductive technology (ART) services while maintaining

Although our pregnancy rates are very good—more than 60% for IVF for patients aged <35 years, and close to 50% averaging all age categories— that still leaves families who do not get pregnant.

—Carolyn E. Keating, BSN, RN-C, NP

patients. Many profess “family values,” but PREG truly values family.

What is the greatest challenge faced at PREG? The greatest challenge by far is dealing with patients who fail to get pregnant. This particularly affects our IVF coordinator, Stephanie Biggerstaff, RN. IVF coordinators, by the nature of the job, develop very close bonds with couples going through ART cycles.

Although our pregnancy rates are very good—more than 60% for IVF for patients aged <35 years, and close to 50% averaging all age categories—that still leaves families who do not get pregnant. We all understand intellectually that “success” sometimes means helping families to be comfortable as a “family of 2 or even 1.” Yet when a patient fails to get pregnant, we still feel that somehow we have failed them. No one likes to fail those they care about, and employees at PREG truly do care about their patients.

What is the greatest reward? coverage, we start early, stay late, and cover weekends for all nonroutine appointments. We see approximately 1000 new patients each year.

What are your main services?

We have a fully accredited operating room, which allows us to perform procedures requiring intravenous sedation (ie, hysteroscopic resections, egg retrievals) or general anesthesia (ie, tubal reversals). This enables us to schedule procedures at the medically optimal time that is also convenient for patients and the staff. Having contractual agreements with local anesthesia groups gives us the flexibility to tailor anesthesia requirements to the needs of each patient. In vitro fertilization (IVF) retrievals are never done without anesthesia, except when requested by the patient.

Hysterosalpingograms are also done on site in our own radiology suite. Onsite operating room and radiology allow us to reduce the cost of many procedures by nearly 60% compared with not having these services. Conservation of resources is just as important to us as it is to the patient.

We have financial counselors who help patients to understand their benefits, as well as run interference for them, if needed, with their insurance carriers.

Our counselors also help the patients to identify potential funding to assist in treatment. We partner with complementary therapists for hypnosis, acupuncture, and massage therapy. We can also coordinate referrals to nutritionists, as well as psychologists and attorneys.

the feel of the close relationships fostered in family medicine practices. In addition to IVF, intracytoplasmic sperm injection, and preimplantation genetic diagnosis, we maintain an inhouse donor egg program. We also provide services for those requiring gestational carriers, as well as donor sperm.

We are excited about having recently begun an embryo adoption program using anonymously donated frozen embryos.

Positive pregnancy tests and the babies who come back to visit are the greatest rewards. It is a bit like winning the lottery every day—so we have been told, anyway. Each day starts with one or more chances to help families fulfill their dreams. When you are successful, knowing that you have contributed to helping create a family definitely generates endorphins. Having those patients refer friends and family is very affirming. It means that we have done our job well.

How are nurses supported in your organization?

What is coming up next at PREG?

Drs Nichols and Payne support nursing education. This is echoed by our practice administrator, Faith Ripley, and is reflected in PREG policies. Our nursing team leader, Kelli Cunningham, RN, MSN, has pulled together a team of 3 nurse practitioners, 2 registered nurses, and a medical assistant who has completed all core classes for her nursing degree. All reasonable requests for continuing education are honored and encouraged.

State-of-the-art technology is made available to all nursing staff, and management is constantly looking for ways to improve the care we provide to our patients.

Most important, PREG is supportive of the personal and family needs of staff members. To reduce stress, all members of the nursing team are cross-trained to cover several aspects of the practice. If a nurse at one site needs to be out for any reason, she knows that one of her colleagues will cover the needs of her

A new support group for patients with polycystic ovarian syndrome was launched in February 2011, and our electronic medical records system was implemented in March. This system will help with record keeping at our 3 separate sites. Our outreach coordinator, Nikki Hicks, has a nursing background, and she is busy combining her marketing, media, and medical passions into a social media outreach campaign to educate current patients and to reach out to potential new clients.

In response to this growth, we hope to add a third physician within the next 2 years. In keeping with the continuing education focus, PREG will cover the cost for all nurses to become certified as reproductive endocrinology and infertility nurses through the new program offered by the American Society for Reproductive Medicine.

Drs Nichols and Payne are both on the prowl for the next new technological breakthrough. ■

APRIL 2011 l VOLUME 3, NUMBER 2

5

Infertility Updates

Fertility Care in the Midst...

Fertility Coverage Questions Although the healthcare reform bill promises expanded healthcare coverage, the law does not address which specific diseases will be covered by or excluded from this expanded coverage.

Specifically, this legislation does not require or even address coverage for infertility care.1 Currently, 15 states in the country have laws requiring mandated insurance coverage for infertility diagnosis and treatment. So far, no information is available to determine how this new legislation will affect existing state infertility mandates, but there may be some hope on the horizon for infertility patients and for practices.

The state-based American Health Benefit Exchanges must be offered by all states by 2014. The ACA will provide state funds to establish and manage a health insurance exchange system.2 According to the Institute of Medicine (IOM), this will allow individuals and businesses to purchase health insurance directly through exchanges—competitive marketplaces where buyers can compare coverage.3 These exchanges will offer patients a choice of qualified health plans that meet certain standards of care, but will differ in coverage benefits provided. These plans also impose limits on patient costs (coinsurance).2 These qualified health plans will cover the general categories of ambulatory patient services, emergency services, hospitalization, maternity and newborn care, mental health and substance abuse services, prescription drugs, rehabilitative services and devices, laboratory services, preventive and wellness services, chronic disease management, and pediatric services.2 Uninsured individuals who elect not to purchase health insurance will be heavily taxed and penalized.

Although it remains speculation at this point, these qualified health plans could potentially provide coverage levels that mimic the current statemandated fertility coverage, therefore providing state-controlled insurance coverage for fertility care. Initially, these exchanges will be available only to individuals who either lack employer-provided coverage or to small businesses with fewer than 100 employees.

In 2017, states can open enrollment in these exchanges to larger employers.2 Also, an “essential health benefits package” will be drafted by 2014. This package will include a comprehensive list of services, but it will be limited to what a “typical employer plan” will provide. The IOM is currently launching a consensus study designed to make recommendations that will help to establish the criteria for an essential health

benefits package.3 The goal of the IOM will not be to define specific services included in the package, but to evaluate how insurers determine medical necessi-

Continued from page 1

10% of adjusted gross income for unreimbursed medical expenses.5 This will severely impact couples seeking to pay for their fertility care

This legislation does not require or even address coverage for infertility care. So far, no information is available to determine how this new legislation will affect existing state infertility mandates, but there may be some hope on the horizon for infertility patients and for practices.

ty and covered benefits. From there, the IOM will make recommendations aimed at balancing the healthcare needs of diverse segments of the population.3 Because this plan has not yet been drafted, the details are forthcoming. tax Implications Another known impact the new healthcare reform law will have on fertility services involves changes to healthcare tax incentives. These changes will place a cap on contributions to tax-deferred flexible-spending accounts. Starting in 2013, this legislation limits contributions to flexiblespending accounts to $2500.4 In addition, the legislation raises the threshold to itemized deductions from 7.5% to

through tax-free spending accounts, while allowing them to recoup even fewer tax credits for costly out-of-pocket medical expenses.

Fertility and other Specialty nurses Despite the new patient rights to healthcare coverage, access to covered fertility services continues to remain uncertain. And where does fertility/ reproductive endocrinology and infertility nursing stand in this controversy?

In a recent article, Laura Stokowski, RN, MS, highlighted new options and opportunities for nurses in the wake of the ACA.6 These new opportunities are geared toward transitioning nurses in the direction of roles in primary care and wellness. For nurse specialists, these

options are less than appealing.

Regardless of the specialty, nurses who gravitate toward specialty fields are driven by a passion for advanced nursing roles.

In most cases, working in specialty nursing fields requires additional education, clinical practice experience, or nursing internships. In these fields, most nurses have obtained advanced degrees and certifications. Many of these nurses sit on legislative and advisory boards designed to educate and create clinical practice standards, as well as shape patient care for new generations of specialty nurses. To these select nurses, the “opportunity” to transition to primary and wellness care is not a welcome one.

What does the future hold for nurses in these specialty fields? Again, at present, the answers are few. ■ references 1. RESOLVE: The National Infertility Association. Statement: healthcare reform. www.resolve.org/about/state ment-healthcare-reform.html. Accessed April 4, 2011.

2. Patient Protection and Affordable Care Act of 2009: Health Insurance Exchanges. Subtitle D— Available Coverage Choices for All Americans, Part I—Establishment of Qualified Health Plans. April 20, 2010. www.naic.org/documents/index_health_reform_ general_ppaca_ins_provs.pdf. Accessed April 4, 2011.

3. Institute of Medicine of the National Academies.

Meeting 1: determination of essential health benefits.

January 12-14, 2011. www.iom.edu/Activities/Health Services/EssentialHealthBenefits/2011-JAN-12.aspx.

Accessed April 4, 2011.

4. Stanger T. Healthcare flexible spending accounts face the scalpel. December 10, 2009. http://news.consumerreports.org/money/2009/12/save-flexible-spendingaccount-fsa-health-care-bill-senator-chuck-schumerhearing-aid.html. Accessed April 4, 2011.

5. The Patient Protection and Affordable Care Act. Title IX. Modification of itemized deduction for medical expenses. §9013a. January 5, 2010. http://docs.house.gov/ energycommerce/ppacacon.pdf. Accessed April 12, 2011.

6. Stokowski LA. Nurses and the Affordable Care Act: opportunities and options. A discussion with Mary Wakefield, RN, PhD. February 17, 2011. Medscape Today News. www.medscape.com/viewarticle/737413.

Accessed April 4, 2011.

“Fertility rescue” offering Hope to patients with Cancer Patients treated free at Sher Institutes for Reproductive Medicine

By Caroline Helwick

O

n a diagnosis of cancer, the patient’s foremost concern is becoming cancer-free. Putting the cancer treatment first, many young women—and their oncologists—neglect to consider a concern that will arise later: the ability to become pregnant.

Even if fertility issues are addressed at the time of a cancer diagnosis, the high cost of fertility preservation often becomes the next obstacle.

For young women who contact the Sher Institutes for Reproductive Medicine (SIRM), things could be different. At 9 SIRM centers across the country, patients with cancer can have their eggs frozen and stored, later

“Per egg, we have a 30% to 40% chance of taking home a baby, which is a very high success rate for live births. We now have the technology that allows us to offer this fertility program to cancer patients.”

—Al Peters, MD

fertilized with a partner’s sperm, and the embryos later transferred at no cost through a new program called “Fertility Rescue.”

The program arose with SIRM found-

er Geoffrey Sher, MD, who said that he feels a “moral obligation” to help young patients with cancer to have families.

SIRM is therefore offering patients with cancer a $10,000 egg freezing Continued on page 7

6

APRIL 2011 l VOLUME 3, NUMBER 2

Infertility Updates

“Fertility rescue” offering Hope... cycle for free. The expensive fertility drugs used for stimulation are donated by pharmaceutical companies. SIRM also asks its anesthesiologists to donate their time. oncologists often not proactive with patients Al Peters, MD, Medical Director of SIRM’s Greater Lehigh Valley, PA, and New Jersey centers, said that the institute is “committed to the reproductive needs of all patients but especially appreciates the very special needs of cancer patients.” Approximately 10% of patients with cancer are of reproductive age and can become infertile as a result of chemotherapy and radiotherapy.

But studies have shown that although oncologists are aware of the infertility risks, they do not do much about it. In a 2009 national survey of oncologists, 70% discussed the issue with patients, but only 25% referred patients to fertility specialists.

“There needs to be more awareness among physicians,” Dr Peters said.

SIRM is able to offer this service because of advances in technology— specifically vitrification or “fast freezing,” which allows eggs to be much more viable, he said.

“Five years ago, using older methods of egg freezing, the chance that an embryo would become a baby was just 4%. Now, per egg, we have a 30% to 40% chance of taking home a baby, which is a very high success rate for live births,” he said. “We now have the technology that allows us to offer this fertility program to cancer patients.”

SIrM’s Free program SIRM is offering 1 free IVF cycle, which includes the stimulation process, monitoring, egg harvest, freezing, and eventual transfer after fertilization with the partner’s sperm. Fertility Rescue is also open to men desiring sperm cryopreservation.

Oncologists are cooperative with this process, according to Dr Peters. He said

that most will accept a few weeks’ delay in starting chemotherapy. “We are increasing estrogen levels for just a short time, and for most women 1 cycle is sufficient,” he pointed out.

To date, just a handful of patients have taken advantage of the program, but SIRM is gearing up to accommodate 150 patients as word spreads. “We

Continued from page 6

will see how it goes from that point,” Dr Peters said. “We are hoping other fertility centers will see what we are doing and jump on board.”

Jennifer Giarcamelli, RN, nurse manager at the New Jersey center, joined SIRM after undergoing IVF herself. “I know that helping a woman achieve something as special as pregnancy is

very gratifying,” she said. “I am working with a cancer patient now who did not have this service available when she needed it, and she is using an egg donor.

But we have made leaps and bounds in what is possible for cancer patients.

Cancer patients think their dreams of having a family are gone, but this free program gives them an option.” ■

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OVA1 oa no ncologist. O VA1® is a age 18, 18, ovarian ovarian adnexal adnexal mass mass present present ffor or w hich ssurgery urger y iiss p lanned, a nd n ot y et rreferred eferred tto the malignancy present when physician’s clinical and evaluation does the llikelihood ikelihood tthat hat m alignancy is p r e s e nt w hen tthe he p hysician’s iindependent n d e p e n d e nt c linical a nd rradiological adiological e valuation d oes not not indicate indicate malignancy. malignancy.

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APRIL 2011 l VOLUME 3, NUMBER 2

7

Infertility Updates

Implications of Hydrosalpinges for IVF... that the draining tubal fluid is toxic to the developing embryo, or to the endometrium, by inhibiting the expression of substances that are important to implantation, or perhaps the fluid results in mechanical flushing of the embryo from the uterus.2,3 Although the mechanism is not well established, current data clearly demonstrate a significant adverse impact of a dilated hydrosalpinx on pregnancy outcome in individuals undergoing IVF. Two separate meta-analyses each concluded that the presence of a hydrosalpinx reduces implantation, pregnancy, and live birth rates by nearly 50%, and increases the rate of early pregnancy losses.4,5 treatment options Various treatment alternatives have been proposed, but the data are insufficient to reach a definitive conclusion about the optimal approach. One study demonstrated that antibiotic use in women with hydrosalpinges before and after embryo transfer resulted in outcomes that were equivalent to other groups of patients undergoing IVF.6 This finding has not been confirmed by follow-up studies. Others have advocated aspiration of the hydrosalpinx fluid at the time of oocyte retrieval.7,8 Data are conflicting regarding the effectiveness of this technique, because the fluid often reaccumulates within 2 days of the procedure. Several small case reports have recently documented successful pregnancies after hysteroscopic placement of a microinsert (Essure) to occlude the proximal fallopian tube.9-12 Further studies, with more patients, are needed before this procedure can be advocated.

The mainstay of successful treatment of dilated hydrosalpinges to improve IVF outcome is through laparoscopic surgery. Possible surgical alternatives include distal neosalpingostomy, proximal tubal occlusion with cautery (tubal ligation), and salpingectomy. Although neosalpingostomy will allow decompression and drainage of the hydro salpinx, one study involving approximately 30 patients reported a 70% recurrence of the hydrosalpinx postoperatively, and a very poor ongoing pregnancy rate.13 This method should probably be reserved for patients who are opposed to more definitive surgical procedures that will eliminate the possibility of conception through means other than IVF. Although there are more data to support the efficacy of salpingectomy over tubal ligation, several studies have shown similar outcomes for these 2 techniques.14-16

8

Proximal tubal occlusion has the advantage of being easier to perform than salpingectomy, especially in the

The mainstay of successful treatment of dilated hydrosalpinges to improve IVF outcome is through laparoscopic surgery. presence of extensive pelvic adhesions.

In addition, it is less likely to interfere with blood flow to the ovary, which could compromise the response to med-

Continued from page 1

ication. Concerns with this approach relate primarily to the potential for pain or infection that may result from leaving a dilated tube in place that is blocked proximally and distally. This has not been reported to be a significant complication of this procedure in published studies thus far.

Conclusion Women with hydrosalpinges represent a unique subgroup of patients undergoing assisted reproduction who may benefit from surgical intervention before IVF. Patient counseling is critical to identify couples who may wish to accept the risk of an approximately 50% lower pregnancy rate and a 2-fold greater rate of miscarriage in the hope of avoiding an invasive surgical procedure. ■ references 1. Practice Committee of American Society for Reproductive Medicine in collaboration with Society of Reproductive Surgeons. Salpingectomy for hydro salpinx prior to in vitro fertilization. Fertil Steril. 2008; 90(5 suppl):S66-S68.

2. Daftary GS, Kayisli U, Seli E, et al. Salpingectomy increases peri-implantation endometrial HOXA10 expression in women with hydrosalpinx. Fertil Steril.

2007;87:367-372.

3. Chanelles O, Sifer C, Hugues JN, et al. Hydrosalpinx and infertility: what about conservative surgical management? Fertil Steril. 2009;88(suppl):S125.

4. Zeyneloglu HB, Arici A, Olive DL. Adverse effects of hydrosalpinx on pregnancy rates after in vitro fertilization-embryo transfer. Fertil Steril. 1998;70:492-499.

5. Camus E, Poncelet C, Goffinet F, et al. Pregnancy rates after in-vitro fertilization in cases of tubal infertility with and without hydrosalpinx: a meta-analysis of published comparative studies. Hum Reprod. 1999;14: 1243-1249.

6. Hurst BS, Tucker KE, Awoniyi CA, Schlaff WD. Hydrosalpinx treated with extended doxycycline does not compromise the success of in vitro fertilization.

Fertil Steril. 2001;75:1017-1019.

7. Van Voorhis BJ, Sparks AE, Syrop CH, Stovall DW. Ultrasound-guided aspiration of hydrosalpinges is associated with improved pregnancy and implantation rates after in-vitro fertilization cycles. Hum Reprod. 1998;13: 736-739.

8. Hammadieh N, Coomarasamy A, Ola B, et al.

Ultrasound-guided hydrosalpinx aspiration during oocyte collection improves pregnancy outcome in IVF: a randomized controlled trial. Hum Reprod. 2008;23: 1113-1117.

9. Hitkari JA, Singh SS, Shapiro HM, Leyland N. Essure treatment of hydosalpinges. Fertil Steril. 2007;90: 1663-1666.

10. Mijatovic V, Veersema S, Emanuel MH, et al. Essure hysteroscopic tubal occlusion device for the treatment of hydrosalpinx prior to in vitro fertilization-embryo transfer in patients with a contraindication for laparoscopy. Fertil Steril. 2010;93:1338-1342.

11. Galen DI. Utilization of the Essure® micro-insert for the treatment of hydrosalpinx prior to in vitro fertilization. Fertil Steril. 2009;88(suppl 1):S16.

12. Nichols JE, West JR. Success of Essure® with micro inserts in the treatment of hydrosalpinx prior to in vitro fertilization (IVF)/frozen embryo transfer (FET) and pregnancy outcomes. Fertil Steril. 2010;(suppl):S245.

13. Bayrak A, Harp D, Saadat P, et al. Recurrence of hydrosalpinges after cuff neosalpingostomy in a poor prognosis population. Fertil Steril. 2003;(suppl 3):S82.

14. Kontoravdis A, Makrakis E, Pantos K, et al. Proximal tubal occlusion and salpingectomy result in similar improvement in in vitro fertilization outcome in patients with hydrosalpinx. Fertil Steril. 2006;86:1642-1649.

15. Surrey ES, Schoolcraft WB. Laparoscopic management of hydrosalpinges before in vitro fertilizationembryo transfer: salpingectomy versus proximal tubal occlusion. Fertil Steril. 2001;75:612-617.

16. Stadtmauer LA, Riehl RM, Toma SK, Talbert LM. Cauterization of hydrosalpinges before in vitro fertilization is an effective surgical treatment associated with improved pregnancy rates. Am J Obstet Gynecol.

2000;183:367-371.

nurses providing Front-line Guidance for preimplantation Genetic Diagnosis

By Rosemary Frei, MSc

N

urses play a vital role in helping patients to navigate through the process of preimplantation genetic diagnosis (PGD), say Patricia Hershberger, PhD, APN, and colleagues in a new article (Hershberger PE, et al. Nurs Womens Health. 2011;15:36-45).

The authors stress that nurses, advanced practice nurses, and other front-line healthcare providers “are critical in providing accurate information, education, and anticipatory guidance about PGD to high–genetic-risk couples. [They] can also assist couples by anticipating ethical concerns and supporting research surrounding PGD use.”

Commenting on this article, Michael Guarnaccia, MD, Medical Director, Center for Women’s Reproductive Care, and Director, PGD program, Columbia University Medical Center, New York City, said, “It is a very nice overview of contemporary PGD and PGS [preimplantation genetic selection], geared for nurses

APRIL 2011 l VOLUME 3, NUMBER 2

and ancillary medical personnel.”

In the 2 decades since PGD was first used successfully to diagnose known genetic disorders in couples at high risk for such disorders, it has gained widespread acceptance. This multistage process includes in vitro fertilization, cell biopsy, genetic analysis, and

Nurses and other front-line PGD clinicians are well positioned to provide detailed information and assistance to couples considering this procedure. embryo transfer. Its most common application is for the detection of single-gene disorders that appear in child-

hood, such as cystic fibrosis, sickle cell anemia, and fragile X syndrome.

Dr Hershberger and colleagues noted that an emerging application is to prevent genetic conditions that manifest in adulthood, such as Huntington’s disease and Alzheimer’s disease. Its other applications include identifying an unbalanced chromosomal complement in the embryo when a strong possibility of this occurring is suspected.

Nurses and other front-line PGD clinicians are well positioned to provide detailed information and assistance to couples considering this procedure, including discussing cost and the possibility that misdiagnosis or creation of non–mutation-free embryos may occur.

They also “may need to address the initial ethical, legal, and psychosocial concerns among high–genetic-risk couples surrounding PGD use,” the authors wrote. “Foremost, couples may contemplate…whether or not it is appropriate for parents to determine aspects of a future child’s genetic composition.” ■

Join the Academy at

www.obgyn-infertility-nurse.org Annual membership $39.95 includes more than $200 off future Annual Meeting registration for Full Members.

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Member Benefits Include: • A subscription to Infertility & Reproductive News, the official Academy publication providing practical, authoritative, cutting-edge information on the physiologic, medical, and psychological aspects of human reproduction, with a new focus on the role of infertility and reproductive nurses, together with physicians, and other fertility experts in patient care ($150 value).

WWW.THEOBG YNNURSE.CO M VOL 3, NO 1

CLINIC PRO FILE

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VOL 3, NO 1

By Caroline Helwi ck

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eart disease is not just a diseas e of older wome n; in fact, even care nurse practitioner and cofounder of pregnancy can Heartstrong, LLC place younger (www.heart-stron women at risk com). for g. tions. This 3-part heart-related condi- Latrel With her colleague Margi la, she has coauth e series will help nurses in the recogn guide includ ing Take Charg ored 3 books, ition and mana ment of the numb e: er 1 killer of Amer ge- Guide to a Healthier Heart A Woman’s women—heart ican (2008). diseas CLINIC PRO This information e.

So, You FILE 2010 Association was presented at the Facto Think You Know the Risk rs? of Wom en’s Health, Obstetric and Neon “Ther ASRM HIG an

by Carolyn Strim atal Nurses meeting in mortae has been alarm HLIG ing increa HTS se ike, RN, MSN, CCRN, wome lity from heart disease amon APN-C, of the Wom n, possibly becau g Interview with Left to right: se they are more Margaret M. Robinat St. Joseph’s Regio en’s Heart Center ‘comp Ali lex’ than Cathy McCab Nasseri, MD, PhD; Sheev nal Medical Cente Director, The son, RN e, Paters Valley Hospital r, Women have men,” Ms Strimike said. on, NJ. Ms Strim Director; Dehan RN; Carol Zollinger, RN; a Talebian, MD; Adrienne Fertility Cente Marciniak, RN, Margaret Post, ike hormo Chen, MD. is an nes r, Paramus, NJ acute cal roles By Wayne that play critiBSN; RN; Margaret M. Robinson, in heart Kuzna RN, healthr. Declin ing s the staff of the nfertility is aContinue Valley Hospital SPOTLIGHT d onhealth page 4 public Fertility Cente Could priority, ment you tell us abou declared Mauri r in Paramus, NJ of Infertility was zio Macaluso, t the history celebrates of the clinic?

MD, 2010 by DrPH, from the completed in 10-year anniversarythe milestones of a 135 national and Division of Repro The Valley Hospi ductive Healt international and helping to - experts, with h at the Cente tal ate 1000 babies the goal of Disease Control , Margaret M. Robin cre- was originally put togethFertility Center rs for preser and ving the ability promoting and RN, Director of as he laid the groun Prevention (CDC), conce of Americans Fertility and Embry son, satellite affiliate of New er in 2001 as a to ive naturally gy Services, took York University By Rosemary olo and the ability the 2010 meeti d for a symposium at Amer Frei, MSc time to talk with - (NYU) Fertility Cente of ican ng of the Amer OB/GYN Nurse r in New York the City. Betwe Society for Repro -NP/PA about ican to term women to carry a pregnancy en 2001 reven and the ting or plann ductiv ter and its servic and deliver a health 2006 cen- the monit es.

In 2002, “2 millio e Medicine. oring and saw patien we did all y child. has become easier ing pregnancy One particular n women in stable ts in New area of focus is Jersey, but our , thanks to a relationships the prepatients would vention of pelvic could not conce then have has cleverly designed set of beads inflam despit mator ive, e trying for y disease that by mean also recently Continued on page Macaluso, descri 12 months,” said Dr infect s of chlamydia screening, NAMS HIG 11 “app” on the iPhonbeen released as an an ious disease that bing the ration HLIGHTS e can affect fertilit making infertility ale for such CycleBeads (Phot for just $2.99. screening may y; a priorit lead to reduce A National Actio y. beads that a woma o) is a string of 32 of tubal scarrin n can use to count g and infertility, d rates Prevention, Detec n Plan for the the number of days although the impact of chlam tion, and Mana since her period Left to right: ydia screening Ali Nasseri, MD, ge and started to inferti let on her lity rates remains Cathy McCab PhD; Sheeva when e, Talebian, know to be determined.

By Wayne Kuzna very unlike MD; Adrienneshe is likely or Director; Dehan RN; Carol Zollinger, RN; and to Marcin MargaretlyPost, wheth conce r Chen, MD. iak, RN, BSN; ive. er pregnancy RN; Marga A “virtual” versio is likely. A Continued on page M. Robins woma SPO n calledret bout half of 4 also TLIG set the HT iCycleBeadson, RN, n can was launched program to send postm alerts in December. women are unabl enopausal the therapeutic s the staff of the Valley touch With the fertile when she is inside or outside Hospital of Could regim a button of her Fertilien window. imper ty is their osteoporosise to follow and if wome it shows Cente you, tell ative, r in Paramus, women us abou where n are celebr foundates treatment risk NJ, they regimens, accord to bethe histoWhen of are their? menstrual t the theinclinic in amilest ry high-ones group10-ye ing to findings for ar cycle 95% effectiused correctly, the beads are nonad of a present- or heren ed at the 2010 anniv ce,and The ersary chang ve.

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Infertility Updates

physicians Spreading the word about personal Fertility Monitors

By Rosemary Frei, MSc

“We’ve been using the Clearblue Easy Monitor since 1999 to help women monitor their menstrual cycles and the fertile phase…to help them achieve or avoid pregnancy.”

C

linicians should consider counseling couples about “user-friendly” fertility monitors to aid in conception or prevent pregnancy, several fertility experts suggest. Thomas Bouchard, MD, and Stephen Genuis, MD, discussed some of these devices in a new article (Bouchard TM, et al. CMAJ. 2011;183:73-76).

The Clearblue or Clearplan Easy Fertility Monitor and the Persona Monitor are available in North America, although the Persona Monitor is only available via the Internet (it is approved for use in Europe but not in North America).

The Persona Monitor on its own, and the Clearblue combined with a pregnancy-optimizing approach known as the Marquette Method, have each been shown in retrospective studies to have more than 93% effectiveness at pregnancy avoidance and pregnancy achievement. Randomized trials are under way to verify these data.

“I found [the monitors] to be a good option,” Dr Bouchard, resident, Department of Medicine, University of Cal-

—Richard Fehring, PhD, RN

gary, Canada, told Infertility & Reproductive News.

The Clearblue Easy Monitor produces a fertility reading of “low,” “high,” or “peak,” with “high” indicating an elevated urine estrone-3-glucuronide (E13-G) level and “peak,” a surge in luteinizing hormone (LH).

The Persona Monitor displays a green light during the user’s infertile phase, and a red light during the fertile phase, as well as an egg symbol, which indicates a surge in LH and imminent ovulation. The authors note that the Persona Monitor has a lower threshold for detection of E1-3-G, and therefore has a slightly larger window of possible fertility—something that can be partic-

ularly useful for women with short fertility phases.

The devices are particularly wellsuited to women with conditions such as a history of migraines, deep vein thrombosis, pulmonary embolism, or stroke who have contraindications to hormonal contraception. They also are good alternatives for those who are “disinclined toward artificial methods of contraception for philosophical or religious reasons,” write Drs Bouchard and Genuis.

They note that the Clearblue Easy Monitor may be less reliable in women with short fertile phases when used to avoid pregnancy. These women may benefit from the longer window

defined by the Persona Monitor, as well as by using the Marquette Method, they noted.

Another proponent of their use is Richard Fehring, PhD, RN, Professor, College of Nursing, Marquette University, Milwaukee, WI. Drs Bouchard and Genuis cited some of his studies, including a study describing the Marquette Method that Dr Fehring created for optimizing pregnancy that involves the Clearblue Easy Monitor; and one retrospective trial showing a 90.8% to 99% efficacy rate.

In a 2009 study, Dr Fehring and colleagues found a 2% pregnancy rate with completely correct use, and a 12% rate with typical use of the Marquette Method; its use with cervical mucus monitoring was found more effective than mucus monitoring alone (Fehring RJ, et al. J Reprod Med. 2009;54:165-170).

“We’ve been using the Clearblue Easy Monitor since 1999 to help women monitor their menstrual cycles and the fertile phase…to help them achieve or avoid pregnancy,” Dr Fehring said. ■

Women’s Health

women and Heart Disease across the lifespan, part II Even Young Women Are at Risk

By Caroline Helwick

A

lthough heart disease is perceived as a condition seen primarily in postmenopausal women, “premature” heart disease does occur. In young women, heart disease can be induced by illicit drugs or anorexia, and can be associated with pregnancy.

Risk factors for young women include diabetes, smoking, clotting disorders, and polycystic ovarian syndrome, said Carolyn Strimike, RN, MSN, CCRN, APN-C, Women’s Heart Center, St. Joseph’s Regional Medical Center, Paterson, NJ, at the 2010 meeting of the Association of Women’s Health, Obstetric and Neonatal Nurses.

Signs and symptoms associated with minor and major heart abnormalities can occur during pregnancy, and may be cause for concern. “Pregnancy may be arrhythmogenic in women with and without heart disease,” Ms Strimike noted. Palpitations, in most cases, are a result of sinus tachycardia and are related to circulatory adaptations in pregnancy. Supraventricular tachycardia (SVT) exacerbations are also common and can be treated with beta-blockers and digoxin. New-onset ventricular tachycardia also occurs. It is usually not

10

associated with structural heart disease, responds well to beta-blockers, and resolves postpartum.

Peripartum cardiomyopathy, or dilated cardiomyopathy (ie, enlargement of the heart muscle), can occur between the last month of pregnancy and 5

“Young women have worse outcomes than young men when they do have a heart attack....

We need to focus our attention on young women.”

—Carolyn Strimike, RN, MSN, CCRN, APN-C

months postpartum. Its cause is unknown, but several risk factors have been identified, including increased maternal age, multifetal pregnancy, gestational hypertension, multiparity, preeclampsia, and black race.

No treatment guidelines exist, but the standard of care during pregnancy is sodium and fluid restriction plus diuret-

APRIL 2011 l VOLUME 3, NUMBER 2

ics, hydralazine, nitroglycerin, and amlodipine. Postpartum, treatment consists of diuretics and angiotensinconverting enzyme inhibitors. Patients with SVT during pregnancy are at increased risk for its occurrence in subsequent pregnancies.

Preeclampsia does not predispose women to heart disease, but it increases the lifetime risk for chronic hypertension, diabetes, thromboembolism, and stroke.

Migraines that occur during pregnancy are associated with a doubling of risk for heart attack, a 15-fold risk for stroke, and an increased risk for hypertensive disorders.

In nonpregnant women, hormonal fluctuations may be the cause of palpitations, irregular heartbeat, and SVT. “Cyclical variation” in SVT has been demonstrated, because the incidence of such episodes is twice as high on day 28 of the menstrual cycle as on day 14.

This phenomenon has led many clinicians to misdiagnose SVT as “anxiety,” she said, suggesting that women with “panic attacks” that are not resolving with antianxiety agents be referred for a cardiac workup.

“We had one 22-year-old patient with ‘refractory panic attacks’ who underwent radiofrequency ablation and had no more episodes,” Ms Strimike reported.

Heart Attacks in pregnancy About 250 pregnant women in the United States have heart attacks during pregnancy, and this number is climbing with increasing maternal age. Heart attacks that occur 24 hours before or after delivery are more often fatal, although overall mortality rates have declined to about 10% (still high compared with 2% in nonpregnant women).

The majority of these heart attacks are a result of spontaneous coronary artery dissection or thrombus. More than 75% of cases of spontaneous coronary artery dissection occur in women.

Treatment options include stenting, beta-blockers, or nitroglycerin.

“It’s important to note that, unfortunately, young women have worse outcomes than young men when they do have a heart attack,” she emphasized.

“The higher mortality rate equalizes as you get older. We need to focus our attention on young women and be aggressive with our treatments.” ■

Womenâ&#x20AC;&#x2122;s Health

In Utero Carbamazepine Exposure linked to Spina Bifida risk Valporic Acid Poses Greater Risk

By Rosemary Frei, MSc

I

n utero exposure to the antiepileptic drug carbamazepine (Tegretol) puts babies at a â&#x2030;Ľ2.6 times increased risk for spina bifida, a recent European analysis published online showed (Jentink J, et al. BMJ. 2010;341:c6581. doi:10.1136/bmj.c6581).

This was a systematic review of 9 studies involving carbamazepine use during the first trimester of pregnancy.

The databases contained information on 3,881,592 children with congenital malformations born in 14 European countries.

Lead investigator Lolkje de Jong-van den Berg, PhD, PharmD, and colleagues identified 5 subgroups of children with conditions that appeared to have increased prevalence, including spina bifida, total anomalous pulmonary venous return, cleft lip (with or without cleft palate), diaphragmatic hernia, and hypospadias.

A case-control analysis using the European Surveillance of Congenital Anomalies Antiepileptic Study Database showed an increased risk associated with carbamazepine for only spina bifida, not for the other 4 conditions.

was found for the 4 other malformations associated with carbamazepine monotherapy or for all 5 malformations with monotherapy with any other antiepileptic agent, except valproic acid.

â&#x20AC;&#x153;Our study can help in the decisionmaking regarding whether carbamazepine should be the drug of choice in pregnancy,â&#x20AC;? Dr de Jong-van den Berg said. â&#x20AC;&#x153;However, the best option regard-

ing treatment can be chosen only on an individual basis by the woman and her neurologist before pregnancy, weighing the benefits of epilepsy control against the risk of teratogenicity.â&#x20AC;? â&#x2013;

Not all pre-natalâ&#x20AC;&#x2122;s are created equal!

â&#x20AC;&#x153;Our study can help in the decision-making regarding whether carbamazepine should be the drug of choice in pregnancy.â&#x20AC;? â&#x20AC;&#x201D;Lolkje de Jong-van den Berg, PhD, PharmD

In addition, the data showed that valproic acid was associated with a much greater risk for spina bifida than carbamazepine. â&#x20AC;&#x153;We found that carbamazepine is specifically related to an increased risk of spina bifida, but that it is relatively safe compared with valproic acid,â&#x20AC;? Dr de Jong-van den Berg told the OB/GYN Nurse-NP/PA. â&#x20AC;&#x153;But you have to keep in mind that the absolute risk of specific major malformations is still small,â&#x20AC;? she added.

In an accompanying editorial (BMJ. 2010;34:c6582), Irena Nulman, MD, Associate Professor of Pediatrics, University of Toronto, Ontario, wrote that this new analysis confirms reports from the 1980s on spina bifida in babies born to women who took carbamazepine during pregnancy.

Dr de Jong-van den Bergâ&#x20AC;&#x2122;s team found between a 2.6-fold and 4.2-fold increased probability of children being born with spina bifida when their mothers used carbamazepine during pregnancy. In contrast, no increased probability

Make the connection at www.neevoprenatal.com

Prenatal vitamins containing synthetic folic acid have limitations.

See if the benefits of NeevoDHAÂŽ are for you.

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APRIL 2011 l VOLUME 3, NUMBER 2

11

Women’s Health

which treatment Is Best for Heavy Menstrual Bleeding?

Levonorgestrel-Releasing Intrauterine System Gets Thumbs Up

By Rosemary Frei, MSc

T

he growing evidence about treatments for refractory heavy menstrual bleeding adds to the confusion surrounding which treatment may be best. Two recent studies have attempted to shed some clarity on this subject.

levonorgestrel-releasing Intrauterine System The first was a meta-analysis of 30 randomized controlled trials that evaluated different treatments for heavy menstrual bleeding (Middleton LJ, et al. BMJ. 2010;

341:c3929). In these trials, patient dissatisfaction was overall low with all the treatments, including first- and secondgeneration endometrial destruction, hysterectomy, and the levonorgestrel-releasing intrauterine system (LRIS [Mirena]).

Nature’s Active Folate for Prenatal Care NÉEVODHA® capsule Rx Description is a medical food for use only under medical supervision for the dietary management of impaired metabolic processes in women under a doctor’s care who face high to intermediate risk pregnancies and are unable to fully metabolize or absorb folic acid.

WARNING: Accidental overdose of iron-containing products is a leading cause of fatal poisoning in children under 6. Keep this product out of reach of children. In case of accidental overdose, call a doctor or poison control center immediately.

Precautions Folates, when administered as a single agent in doses above 0.1mg daily, may obscure pernicious anemia in that hematologic remission can occur while neurological manifestations remain progressive.

The product contains: Each Blue gelatin capsule contains: Dietary Ingredients: L-Methylfolate Calcium(as Metafolin®)* .............................................................................1.13mg** Calcium (tricalcium phosphate) ............................................................................................. 75mg Elemental Iron (ferrous fumarate) .......................................................................................... 27mg Vitamin C (ascorbic acid)....................................................................................................... 40mg Vitamin E (D-alpha-tocopherol) .................................................................................................30IU Vitamin B6 (pyridoxine as pyridoxine HCI) ............................................................................ 25mg Vitamin B9 (folic acid) ...................................................................................................... 400mcg Vitamin B12 (methylcobalamin) ................................................................................................. 1mg Docosahexaenoic Acid (DHA) ............................................................................................. 250mg*** *CAS# 151533-22-1 is the registry of the absolute stereochemistry of L-methylfolate calcium. **1.13mg L-Methylfolate (calculated as L-methyltetrahydrofolic acid) is the molar equivalent of 1.0mg folic acid. Metafolin® (L-Methylfolate) is a registered trademark of Merck KGaA, Darmstadt, Germany. ***Docosahexaenoic acid (DHA) from an algal source. *Metafolin (L-methylfoalte calcium) is a substantially diastereoisomerically pure source of L-methylfolate containing not more than 1% D-methylfolate which results in not more than 0.011 milligrams of D-methylfolate in NeevoDHA. Capsule Ingredients: DHA (docosahexaenoic acid from an algal source), gelatin, tricalcium phosphate, glycerine, beeswax, ferrous fumarate, ascorbic acid, lecithin, pyridoxine HCI, D alpha tocopherol, soybean oil, L-methylfoalte, titanium dioxide, methylcobalamin, folic acid, ethyl vanillin, FD&C blue #1, FD&C red #40, food grade white ink (ammonium hydroxide, isopropyl alcohol, N-butyl alcohol, propylene glycol, shellac glaze in SD-45, simethicone, titanium dioxide). CONTAINS SOY Indication and Usage NeevoDHA® capsules are for the specific dietary management of impaired metabolic processes in those women with distinct nutritional requirements for any of the following conditions: hyperhomocysteinemia during pregnancy 4,5,6,7; high risk recurrent pregnancy loss 5,7; impaired folic acid absorption 2,3; impaired metabolism due to 677C-T mutations in the methylenetetrahydrofolate reductase gene 8,10,11; and dysfunctional folic acid metabolism 11,12. NeevoDHA® should only be used under medical supervision.

Rationale for Distinct Nutritional Requirements Medical foods are intended for a patient who has a limited or impaired capacity to ingest, digest, absorb, or metabolize ordinary foodstuffs or certain nutrients, or who has other special medically determined nutrient requirements, the dietary management of which cannot be achieved by the modification of the normal diet alone.

NeevoDHA® contains folate in the form of L-methylfolate which is the biologically active folate isomer.

L-methylfolate is the body’s preferred form of folate because it is directly usable by the human organism for certain metabolic processes. There are well documented studies 2, 3, 6,8,12 which have established folic acid’s ineffectiveness regarding inherited disorders of folate transport and metabolism. These disorders limit and impair the capacity to ingest, digest, absorb or metabolize folic acid. Folic acid, the synthetic form of folate, must be metabolized in a four step process by the body to become the biologically active L-methylfolate. Unmetabolized levels of folic acid were found in 78% of plasma samples from women given >400 mcg of folic acid per day 1. Unmetabolized folic acid has a high affinity to bind to the cellular folate transport mechanism. This has been shown to reduce the transfer of the active metabolite L-methylfolate across the blood brain barrier 2,3.

D-methylfolate or 6(R)-5-methyltetrahydrofolate [6(R)-5-MTHF] is the other diastereoisomer of folate.

Studies administering doses of 2.5 mg per day or higher resulted in plasma protein binding of D-methylfolate higher than L-methylfolate causing a significantly higher renal clearance of L-methylfolate when compared to D-methylfolate.4 Further, D-methylfolate is found to be stored in tissues in the body, mainly in the liver. D-methylfolate is not metabolized by the body and has been hypothesized to inhibit regulatory enzymes related to folate and homocysteine metabolism and reduces the bioavailability of L-methylfolate.5 Hyperhomocysteinemia is an independent risk factor of vascular and endothelial dysfunction in maternal patients. Although hyperhomocysteinemia is not due to folate deficiencies alone, it can be indicative of dietary deficiencies of essential nutrients, increased catabolism, clearance and excretion of essential nutrients, hormonal influence on folate metabolism or an intrinsic metabolic disorder. Increased homocysteine levels can also increase the risk of recurrent early pregnancy loss as well as increase maternal complications. Disturbed homocysteine metabolism has also been shown to have a greater effect in women with early pregnancy losses 4,5,6,7. In the cell, 6(S)-5-MTHF (L-methylfolate) is used in the methylation of homocysteine.

The prevalence of the 677C-T mutations in the methylenetetrahydrofolate reductase gene in pregnant women was shown to be 53% 8. Studies show that enzyme activity necessary to convert folic acid to its active form (L-methylfolate) can be reduced by as much a 72% in patients with the 677C-T mutation in the methylenetetrahydrofolate reductase gene 9. In certain studies, women with the 677C-T mutation in the methylenetetrahydrofolate reductase gene (MTHFR) had significantly higher risk for recurrent pregnancy loss, congenital abnormalities and other adverse pregnancy outcomes 10,11. Other MTHFR gene variants (A1298C and MTHFD) that affect folic acid bioavailability have been associated with folate metabolism and the incidence of congenital anomalies 11, 12.

Docosahexaenoic acid or DHA, a long-chain polyunsaturated omega-3 fatty acid (C22:6n-3). DHA is an indispensable component of all cell membranes and is incorporated in high concentrations in the membrane phospholipids of brain and retina15. The DHA in NeevoDHA® comes from a vegetarian source (algae), not from fish, grown in an FDA-inspected facility16.

Contraindications Known hypersensitivity to any of the components in this product is a contraindication.

Warnings Ingestion of more than 3 grams per day of omega-3 fatty acids has been shown to have potential antithrombotic effects, including bleeding time and INR. Administration of omega-3 fatty acids should be avoided in patients on anticoagulants and in those known to have an inherited or acquired bleeding diathesis.

12

APRIL 2011 l VOLUME 3, NUMBER 2

Adverse Reactions While allergic sensitization has been reported following both oral and parenteral administration of folic acid, allergic sensitization has not been reported with the use of Metafolin®.

Drug Interactions Pyridoxine hydrochloride should not be given to patients receiving the drug levodopa, because the action of levodopa is antagonized by pyridoxine hydrochloride. However, pyridoxine hydrochloride may be used concurrently in patients receiving a preparation containing both carbidopa and levodopa. While the concurrent use of phenytoin and folic acid may result in decreased phenytoin effectiveness, no such decreased effectiveness has been reported with the use of Metafolin®. Capecitabine (Xeloda®) toxicity may increase with the addition of leucovorin (5-formyltetrahydrofolate) (folate).

Patient Information NeevoDHA should only be used under medical supervision.

NeevoDHA® is certified kosher by Triangle K and Associates.

Dosage and Administration Usual adult dose is 1(one) gelatin capsule daily or as directed by your physician.

How Supplied Available as a blue, soft gelatin capsule with “Neevo DHA” imprinted on one side in white ink. Commercial product (0525-2030-30) is supplied in bottles of 30 capsules. Sample product (0525-2030-04) is supplied in bottles of 4 capsules.

Commercial Product (30 capsules) 0525-0621-30* Sample Product (4 capsules) 0525-0621-04* Professional samples-not for sale

Patients using the intrauterine system are less dissatisfied with it than those undergoing hysterectomy or using endometrial ablation for control of heavy menstrual bleeding; in addition, LRIS is relatively inexpensive and minimally invasive.

“My own practice supports the articles about Mirena. It is very effective in helping women with heavy periods. I also have had success with DepoProvera injection.”

—Donna Freeborn, PhD, FNPBC, CNM

Discussing their results, the researchers wrote, “Although the evidence is not strong, our findings concur with a recent NICE [National Institute for Health and Clinical Excellence] recommendation that women should be offered Mirena before more invasive procedures.”

The 9 LRIS studies included in the Continued on page 13

* Pamlab, LLC does not represent this product code to be a National Drug Code (NDC) number. Instead, Pamlab has assigned a product code formatted according to standard industry practice to meet the formatting requirements of pharmacy and health insurance computer systems.

Storage Store at controlled room temperature 15oC to 30oC (59oF to 86oF) (See USP). Protect from light and moisture. Dispense commercial product in original container. Dispense sample product in original container.

KEEP THIS AND ALL DRUGS OUT OF THE REACH OF CHILDREN. Patents Some or all of the following patents may apply: U.S. Patent No. 6,207,651 U.S. Patent No. 6,254,904 U.S. Patent No. 6,297,224 U.S. Patent No. 6,528,496 and other pending patent applications.

U.S. Patent No. 5,563,126 U.S. Patent No. 5,795,873 U.S. Patent No. 5,997,915 U.S. Patent No. 6,011,040

References 1. Troen A, et al. Unmetabolized folic acid in plasma is associated with reduced natural killer cells cytotoxicity among postmenopausal women. J Nutr 2006; 136:189-194 2. Wu D, Pardridge W. Blood brain barrier transport of reduced folic acid. Pharmaceutical Research 1999; 16(3):415-19.

3. Reynolds E. Benefits and risks of folic acid to the nervous system. J Neurol Neurosurg Psychiatry 2002; 72:567-571.

4. Stroes E, van Faasen E, Circ Res 2000;86:1129-34.

5. Willems FF et al. BR J Pharmacol 2004;141(5):825-30.

6. Wen S, et al. Folic acid supplementation in early second trimester and the risk of preeclampsia. Am J Obstet Gynecol 2008; 198:45.e1-45.e7.

7. Nelen W, et al. Homocysteine and folate levels as risk factors for recurrent early pregnancy loss. Obste Gynecol 2000; 95:519-24.

8. Tamura T, Picciano M. Folate and human reproduction. Am J Clin Nutr 2006; 83:993-1016.

9. Vollset S, et al. Plasma total homocysteine, pregnancy complications, and adverse pregnancy outcomes: the Hordaland Homocysteine Study. Am J Clin Nutr 2000; 71:962-8.

10. Molloy A, et al. Thermolabile variant of 5,10-methylenetetrahydrofolate reductase associated with low red-cell folates: implications for folate intake recommendations Lancet 1997; 349: 1591–93 11. Ulrich CM, et al. Pharmacogenetics of methotrexate: toxicity among marrow transplantation patients varies with the methylenetetrahydrofolate reductase C677T polymorphism. Blood 2001; 98: 231–234.

12. Kirke P, et al. Impact of the MTHFR C677T polymorphism on the risk of neural tube defects: case control study. BMJ 2004; 328:1535-1536.

13. Botto L, et al. 5, 10-methylenetetrahydrofolate Reductase gene variants and congenital anomalies: a HuGE review. Am J Epidemiol 2000; 151:862-77.

14. Gos M, et al. Genetic basis of neural tube defects. J Appl Genet 2002; 43(4):511-524.

15. Krauss-Etschmann S, et al. Effects of fish-oil and folate supplementation of pregnant women on maternal and fetal plasma concentrations of docosahexaenoic acid and eicosapentaenoic acid: a European randomized multicenter trial. Am J Clin Nutr 2007; 85:1392-400.

16. Referenced by Martek Biosciences Corporation, Columbia, Maryland USA Metafolin® is a registered trademark of Merck KGaA, Darmstadt, Germany.

Distributed By PAMLAB, L.L.C. Covington, LA 70433 Manufactured by Accucaps Industries Ltd., Windsor, Ontario N9C 3R5 Made in Canada PC-0053

Revised 02/22

FDA Warns against Use of Terbutaline for Preterm Labor Prevention The US Food and Drug Administration (FDA) has added a warning and contraindications box to the label of terbutaline—a bronchodilator available in oral or injection form—advising clinicians against the off-label use of this product in pregnant women for the prevention of preterm labor or for uterine hyperstimulation. The use of this drug in pregnancy can cause serious adverse events, including death.

Terbutaline is FDA indicated for the treatment of bronchospasms associated with asthma, bronchitis, and emphysema but is also often used offlabel for the prevention of preterm labor or for uterine hyperstimulation.

“Women should be aware that serious and sometimes fatal side effects have been reported after prolonged use of terbutaline in pregnant women,” said Scott Monroe, MD, Director, Division of Reproductive and Urologic Products at the FDA. The product labeling changes are in accordance with the American College of Obstetricians and Gynecologists’ position, which discourages the use of this drug for preventing preterm labor.

Women’s Health

which treatment Is Best... Continued from page 12 meta-analysis were small; in addition, “the substantial levels of [patient] noncompliance make interpretation of outcomes difficult, and casts some doubt on the equivalent-efficacy conclusions,” the researchers wrote.

They recommend that studies be conducted to compare LRIS with hysterectomy and endometrial ablation, and that a consensus statement be developed on optimal outcome measures, because LRIS studies focus on comparing reduction in bleeding, and studies on hysterectomy usually include women’s satisfaction, quality of life, and use of resources.

A randomized controlled trial sponsored by the manufacturer of LRIS (Kaunitz AM, et al. Obstet Gynecol. 2010; 116:625-632) was published shortly before the meta-analysis; it, too, included only 165 patients, was focused on bleeding reduction, and did not compare LRIS with either of the gold standard treatments—hysterectomy or endometrial ablation.

In this trial, LRIS was associated with a significantly greater reduction in median bleeding during 6 menstrual cycles compared with a medroxyprogesterone (Provera, Cycin, Depo-Provera) regimen. LRIS successfully treated 84.8% of the women compared with 22.2% of those using medroxyprogesterone.

“I love this drug [Lysteda]—it’s welltolerated, women only have to take it during their menses, and it is highly effective.”

—Andrea Lukes, MD, MHSc, FACOG

Lead investigator Andrew Kaunitz, MD, FACOG, Associate Chair, Department of Obstetrics and Gynecology, University of Florida College of Medicine-Jacksonville, told the OB/GYN Nurse-NP/PA, “Given the profound efficacy, as well as the safety of the LRIS documented in this large clinical trial, the progestin-releasing IUD (intrauterine device) should be considered first-line therapy for heavy menstrual bleeding, and should be considered with patients prior to proceeding with endometrial ablation or hysterectomy.”

Donna Freeborn, PhD, FNP-BC, CNM, Assistant Professor and Coordinator, Family Nurse Practitioner Program, College of Nursing, Brigham Young University, Provo, UT, offered her comments to this journal, “My own practice supports the articles about Mirena. It is very effective in helping women with heavy periods. I also have

had success with Depo-Provera injection [medroxyprogesterone]; a study comparing Depo with LRIS would be helpful.”

She added that she has also had success with long-term oral contraceptives, which offer women 4 possibly heavy periods a year, but many prefer this to having no periods, as an assurance that they are not pregnant.

tranexamic Acid Another randomized controlled trial investigated tranexamic acid (Lysteda), and was funded by its manufacturer, Xanodyne Pharmaceuticals, and by Ferring Pharmaceuticals. It showed that the 115 women receiving tranexamic acid had a significantly greater mean reduction in menstrual bleeding than those receiving placebo (Luke AS, et al. Obstet

Gynecol. 2010;116:865-875). The formers also had significantly better improvements in quality-of-life parameters.

Lead investigator Andrea Lukes, MD, MHSc, FACOG, with Carolina Women’s Research and Wellness Center, Durham, NC, is enthusiastic about tranexamic acid. “I love this drug—it’s well-tolerated, women only have to take it during their menses, and it is highly effective.” ■

Midwest Reproductive Symposium & Nurse Practicum 2011 Nurse Practicum Day – June 9 • MRS – June 10-11 THE DRAKE HOTEL • CHICAGO, IL

JJoin oin y your our ccolleagues olleagues for a timely and lively discussion of issues releevant to reproductive medicine in a highly interactive, continuing education environment.

And, thanks to last year’s attendees for their feedback! This year’s Practicum Day includes tracked sessions for nurses new to the field and those more experienced and an afternoon ‘en groupe.’ Discounted MRS registration is included.

Some discussion and workshop topics: Age and Body W Weight: eight: A Guide for Establishing Practice Limits; Genetic Counseling and the Genetics of Infertility; OHSS: Current Trends and Treatment Options; IVF Medication Protocols; Health Maintenance for Women of Reproductive Age; Hands-on Ultrasound; Designing and Implementing Effective Studies; The Male Infertility Evaluation; Ethics and Legal Dilemmas; and more!

FACULLTY FACULTY: Y: Barr y Behr, PhD* • Angeline Beltsos, MD** • Lauri Black, MS, CGC • Judy Campisi, LPN* Susan Crockin, JD • Nidhi Desai, JD • Donald Galen, MD • Robert Gilchrist, PhD • Shalini Gunawardena, RN, BSN Karen Hammond, DNP, CRNP • Laurence Jacobs, MD • Maria Jackson, RN, MA • Keith Jarvi, MD • Sue Jasulaitis, RN, MS William Kearns, PhD* • David Keefe, MD • William Kutteh, MD • Carol Lesser, NP • Zsolt Peter Nagyy, MD, PhD Ann Scalia, RN, BSN, CNOR* • Richard Scott, MD • David Seifer, MD • Kaylen Silverberg, MD • Johan Smitz, MD, PhD Tamara TTobias, obias, ARNP *Chairperson **Executive Chairperson

LOWER REGISTRA REGISTRATION RA ATION TION FEES until March 11th: $410 includes the MRS ($250 for the Nurse Practicum Day only) FOR MORE TION about the program, accreditation, RE INFORMA ATION a and TO REGISTER: Go to www www.mwrs.org w.mwrs.org (or call 888-MBM-MTGS, ext.24).

APRIL 2011 l VOLUME 3, NUMBER 2

13

Women’s Health

IoM Calls for Greater leadership role for nurses

By Jessica A. Smith

A

s healthcare reform adds coverage to millions of new patients, significant changes in nursing are needed to meet the increase in demand, as suggested in the new report from the Institute of Medicine (IOM).

The new IOM report issued recommendations for increased leadership roles, responsibilities, and education for nurses.

“The report’s recommendations provide a strong foundation for the development of a nursing work force whose members are well-educated and prepared to practice to the fullest extent of their training…and act as full partners in leading advances in the nation’s healthcare system,” said Donna E. Shalala, President, University of Miami, and chair of the committee that wrote the report.

The key IOM recommendations for the increased role of nurses in healthcare: 1. Remove scope-of-practice barriers.

Advanced practice registered nurses should be able to practice to the full extent of their skills and allow nurses greater authority to prescribe medications, order tests, and perform other medical services for which they have been trained 2. Increase opportunities for nurses to lead collaborative efforts. Recognizing the capacity for nurses to take on increased responsibilities and make significant contributions to collaborative efforts, the IOM calls for nurses to be allowed to spread their wings in leading and managing collaborations to improve the healthcare system; nurses should take a greater part in developing and implementing new patient-centered care models and health information technology 3. Create nurse residency programs.

Nurse residency programs should be implemented to help nurses transition from education to practice; state nursing boards and accrediting bodies should support this effort, and public and private organizations should provide funding for such programs 4. Increase number of nurses with BAs from 50% to 80% by 2020.

The report calls for increased incentives for nurses to pursue higher education, and nursing schools should be required to offer distinct academic conduits that lead nurses toward higher educational attainment 5. Double the number of nurses with PhDs by 2020. The Commission on Collegiate Nursing Education and the National League for Nursing Accrediting Commission should monitor accredited nursing schools to make sure that this objective is met, and academic institutions should create

14

competitive salaries and benefit packages for clinical nurse faculty members 6. Enable nurses to engage in lifelong learning. Education bodies should collaborate to ensure that nurses con-

APRIL 2011 l VOLUME 3, NUMBER 2

tinue their education to maintain their competencies throughout their nursing careers 7. Provide the tools and opportunity for leadership. Nurses should be equipped

with the tools to take on leadership roles in healthcare and be able to apply these tools in leadership positions; healthcare decision makers should ensure that nurses are represented on

Vagifem® is an estrogen (estradiol) indicated for the treatment of atrophic vaginitis due to menopause.

Important Safety Information WARNING: CARDIOVASCULAR DISORDERS, ENDOMETRIAL CANCER, BREAST CANCER and PROBABLE DEMENTIA Estrogen-Alone Therapy Endometrial Cancer There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens.

Adding a progestin to estrogen therapy has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer. Adequate diagnostic measures, including directed or random endometrial sampling when indicated, should be undertaken to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding.

Cardiovascular Disorders and Probable Dementia Estrogen-alone therapy should not be used for the prevention of cardiovascular disease or dementia.

The Women’s Health Initiative (WHI) estrogen-alone substudy reported increased risks of stroke and deep vein thrombosis (DVT) in postmenopausal women (50 to 79 years of age) during 7.1 years of treatment with daily oral conjugated estrogens (CE) [0.625 mg], relative to placebo.

The WHI Memory Study (WHIMS) estrogen-alone ancillary study of WHI reported an increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 5.2 years of treatment with daily CE (0.625 mg) alone, relative to placebo. It is unknown whether this finding applies to younger postmenopausal women.

In the absence of comparable data, these risks should be assumed to be similar for other doses of CE and other dosage forms of estrogens. Estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman.

Estrogen Plus Progestin Therapy Cardiovascular Disorders and Probable Dementia Estrogen plus progestin therapy should not be used for the prevention of cardiovascular disease or dementia.

The WHI estrogen plus progestin substudy reported increased risks of DVT, pulmonary embolism, stroke and myocardial infarction in postmenopausal women (50 to 79 years of age) during 5.6 years of treatment with daily oral CE (0.625 mg) combined with medroxyprogesterone acetate (MPA) [2.5 mg], relative to placebo.

The WHIMS estrogen plus progestin ancillary study of the WHI, reported an increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 4 years of treatment with daily CE (0.625 mg) combined with MPA (2.5 mg), relative to placebo. It is unknown whether this finding applies to younger postmenopausal women.

Breast Cancer The WHI estrogen plus progestin substudy also demonstrated an increased risk of invasive breast cancer.

In the absence of comparable data, these risks should be assumed to be similar for other doses of CE and MPA, and other combinations and dosage forms of estrogens and progestins.

Estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman.

The use of Vagifem® is contraindicated in women who exhibit one or more of the following: undiagnosed abnormal genital bleeding; known, suspected, or history of breast cancer; known or suspected estrogendependent neoplasia; active deep vein thrombosis, pulmonary embolism or history of these conditions; active arterial thromboembolic disease or a history of these conditions; known liver dysfunction or disease, or known or suspected pregnancy.

Vagifem® is intended only for vaginal administration. Systemic absorption occurs with the use of Vagifem®.

The warnings, precautions, and adverse reactions associated with the use of systemic estrogen therapy should be taken into account.

The WHI estrogen plus progestin substudy reported a statistically non-significant increased risk of ovarian cancer.

Other warnings include: gallbladder disease, severe hypercalcemia, loss of vision, severe hypertriglyceridemia, cholestatic jaundice, and vaginal abrasion caused by the Vagifem® applicator. Women on thyroid replacement therapy should have their thyroid function monitored.

In a randomized, double-blind, parallel group, placebo-controlled study for Vagifem® 10 mcg, adverse events with an incidence of ≥5% included vulvovaginal mycotic infection, vulvovaginal pruritus, back pain and diarrhea.

Please see Brief Summary of the Prescribing Information on adjacent pages.

Reference: 1. Vagifem® (estradiol vaginal tablets) prescribing information.

Princeton, NJ: Novo Nordisk Inc; 2009.

Vagifem® is a registered trademark of Novo Nordisk FemCare AG. © 2011 Novo Nordisk. Printed in the U.S.A. 0111-00001636-1 February 2011

Women’s Health boards, executive management teams, and in other leadership positions 8. Build an infrastructure to gather and analyze healthcare data. The National Health Care Workforce Commission, the Government Accountability Office, and the Health Resources and Services Administration should collaborate

“The report’s recommendations provide a strong foundation for the development of a nursing work force whose members are well-educated and prepared to practice to the fullest extent of their training…and act as full partners in leading advances in the nation’s healthcare system.”—Donna E. Shalala

to enhance data collection and analysis on healthcare workforce requirements; by joining forces with state licensing boards, state nursing workforce centers, and the US Department of Labor, the agencies at the helm of the infrastructure can ensure that data are timely and publicly accessible. ■

Low-dose Vagifem® 10 mcg The lowest dose* of local vaginal estrogen commercially available

Minimal systemic absorption There is minimal systemic absorption with Vagifem® 10 mcg,† and systemic estrogen levels remain low throughout treatment.1 Average Daily Serum Concentration (arithmetic mean, Cave(0-24)) of Estradiol During Vagifem® 10 mcg Treatmenta (uncorrected for baseline, N=29)1

a

Day 1

10.09 pg/mL

Day 14

7.35 pg/mL

Day 83

5.50 pg/mL

A 12-week, single-center, randomized, open-label, multiple-dose, parallel group study of 58 patients treated with Vagifem® 10 mcg and 25 mcg.1 Patients received vaginal tablets as a once daily intravaginal treatment for the first 2 weeks and a twice weekly intravaginal maintenance for the following 10 weeks.

Estrone and estrone sulfate parameters were also measured but not shown.

*Based on a 12-week dosing schedule according to Vagifem® Prescribing Information1 †

Clinical relevance of these pharmacokinetic data is unknown.

Call 1-855-NOVO-V10 (668-6810) to order samples and copay cards today.

Please see important safety information and Brief Summary of the Prescribing Information on adjacent pages.

APRIL 2011 l VOLUME 3, NUMBER 2

15

Women’s Health

new Data reinforce potential link between Genital tract Infections in pregnancy and Birth Defects

By Rosemary Frei, MSc

G

enital tract infections in women during the first trimester of pregnancy appear to be significantly associated with certain birth defects in their babies, based on data from a new

National Birth Defects Prevention Study (Carter TC, et al. Birth Defects Res A Clin Mol Teratol. 2010 Dec 7. Epub ahead of print).

Having any genital tract infection in

the first part of pregnancy increased the risk for cleft palate in the baby by nearly 50%; the risk more than doubled in women with chlamydia, gonorrhea, or pelvic inflammatory disease,

Vagifem® (estradiol vaginal tablets) Rx only BRIEF SUMMARY. Please consult package insert for full prescribing information.

WARNING: CARDIOVASCULAR DISORDERS, ENDOMETRIAL CANCER, BREAST CANCER and PROBABLE DEMENTIA: Estrogen-Alone Therapy: Endometrial Cancer: There is an increased risk of endometrial cancer in a woman with a uterus who uses unopposed estrogens. Adding a progestin to estrogen therapy has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer. Adequate diagnostic measures, including directed or random endometrial sampling when indicated, should be undertaken to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding [see Warnings and Precautions]. Cardiovascular Disorders and Probable Dementia: Estrogen-alone therapy should not be used for the prevention of cardiovascular disease or dementia [see Warnings and Precautions]. The Women’s Health Initiative (WHI) estrogen-alone substudy reported increased risks of stroke and deep vein thrombosis (DVT) in postmenopausal women (50 to 79 years of age) during 7.1 years of treatment with daily oral conjugated estrogens (CE) [0.625 mg], relative to placebo [see Warnings and Precautions]. The WHI Memory Study (WHIMS) estrogen-alone ancillary study of WHI reported an increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 5.2 years of treatment with daily CE (0.625 mg) alone, relative to placebo. It is unknown whether this finding applies to younger postmenopausal women [see Warnings and Precautions]. In the absence of comparable data, these risks should be assumed to be similar for other doses of CE and other dosage forms of estrogens. Estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman. Estrogen Plus Progestin Therapy: Cardiovascular Disorders and Probable Dementia: Estrogen plus progestin therapy should not be used for the prevention of cardiovascular disease or dementia [see Warnings and Precautions]. The WHI estrogen plus progestin substudy reported increased risks of DVT, pulmonary embolism, stroke and myocardial infarction in postmenopausal women (50 to 79 years of age) during 5.6 years of treatment with daily oral CE (0.625 mg) combined with medroxyprogesterone acetate (MPA) [2.5 mg], relative to placebo [see Warnings and Precautions]. The WHIMS estrogen plus progestin ancillary study of the WHI, reported an increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 4 years of treatment with daily CE (0.625 mg) combined with MPA (2.5 mg), relative to placebo. It is unknown whether this finding applies to younger postmenopausal women [see Warnings and Precautions]. Breast Cancer: The WHI estrogen plus progestin substudy also demonstrated an increased risk of invasive breast cancer [see Warnings and Precautions]. In the absence of comparable data, these risks should be assumed to be similar for other doses of CE and MPA, and other combinations and dosage forms of estrogens and progestins. Estrogens with or without progestins should be prescribed at the lowest effective doses and for the shortest duration consistent with treatment goals and risks for the individual woman.

INDICATIONS AND USAGE: Treatment of Atrophic Vaginitis due to Menopause CONTRAINDICATIONS: Vagifem® should not be used in women with any of the following conditions: Undiagnosed abnormal genital bleeding; Known, suspected, or history of breast cancer; Known or suspected estrogen-dependent neoplasia; Active deep vein thrombosis, pulmonary embolism or history of these conditions; Active arterial thromboembolic disease (for example, stroke, and myocardial infarction), or a history of these conditions; Known liver dysfunction or disease; Known or suspected pregnancy WARNINGS AND PRECAUTIONS: Risks From Systemic Absorption: Vagifem® is intended only for vaginal administration. Systemic absorption occurs with the use of Vagifem®.

The warnings, precautions, and adverse reactions associated with the use of systemic estrogen therapy should be taken into account. Cardiovascular Disorders: An increased risk of stroke and deep vein thrombosis (DVT) has been reported with estrogen-alone therapy. An increased risk of pulmonary embolism, DVT, stroke, and myocardial infarction has been reported with estrogen plus progestin therapy. Should any of these occur or be suspected, estrogens with or without progestins should be discontinued immediately. Risk factors for arterial vascular disease (for example, hypertension, diabetes mellitus, tobacco use, hypercholesterolemia, and obesity) and/or venous thromboembolism (for example, personal history or family history of venous thromboembolism [VTE], obesity, and systemic lupus erythematosus) should be managed appropriately. Stroke: In the Women’s Health Initiative (WHI) estrogen-alone substudy, a statistically significant increased risk of stroke was reported in women 50 to 79 years of age receiving daily CE (0.625 mg) compared to women in the same age group receiving placebo (45 versus 33 per 10,000 women-years). The increase in risk was demonstrated in year one and persisted.

Should a stroke occur or be suspected, estrogens should be discontinued immediately. Subgroup analyses of women 50 to 59 years of age suggest no increased risk of stroke for those women receiving CE (0.625 mg) versus those receiving placebo (18 versus 21 per 10,000 women-years).In the WHI estrogen plus progestin substudy, a statistically significant increased risk of stroke was reported in all women receiving daily CE (0.625 mg) plus MPA (2.5 mg) compared to placebo (33 versus 25 per 10,000 women-years). The increase in risk was demonstrated after the first year and persisted. Coronary Heart Disease: In the WHI estrogen-alone substudy, no overall effect on coronary heart disease (CHD) events (defined as non-fatal myocardial infarction [MI], silent MI, or CHD death) was reported in women receiving estrogen alone compared to placebo. Subgroup analysis of women 50 to 59 years of age suggests a statistically non-significant reduction in CHD events (CE 0.625 mg compared to placebo) in women with

16

APRIL 2011 l VOLUME 3, NUMBER 2

after controlling for many potential confounding factors.

The risk for bilateral renal agenesis/ hypoplasia increased almost 3-fold and the risk for transverse limb deficiency

less than 10 years since menopause (8 versus 16 per 10,000 women-years). In the WHI estrogen plus progestin substudy, there was a statistically non-significant increased risk of CHD events in women receiving daily CE (0.625 mg) plus MPA (2.5 mg) compared to women receiving placebo (41 versus 34 per 10,000 women-years). An increase in relative risk was demonstrated in year 1, and a trend toward decreasing relative risk was reported in years 2 through 5. In postmenopausal women with documented heart disease (n=2,763), average age 66.7 years, in a controlled clinical trial of secondary prevention of cardiovascular disease (Heart and Estrogen/ Progestin Replacement Study [HERS]) treatment with daily CE (0.625 mg) plus MPA (2.5 mg) demonstrated no cardiovascular benefit. During an average follow-up of 4.1 years, treatment with CE plus MPA did not reduce the overall rate of CHD events in postmenopausal women with established coronary heart disease. There were more CHD events in the CE plus MPA-treated group than in the placebo group in year 1, but not during the subsequent years. Two thousand, three hundred and twenty-one (2,321) women from the original HERS trial agreed to participate in an open label extension of the original HERS, HERS II. Average follow-up in HERS II was an additional 2.7 years, for a total of 6.8 years overall. Rates of CHD events were comparable among women in the CE (0.625 mg) plus MPA (2.5 mg) group and the placebo group in HERS, HERS II, and overall. Venous Thromboembolism (VTE): In the WHI estrogen-alone substudy, the risk of VTE (DVT and pulmonary embolism [PE]) was increased for women receiving daily CE (0.625 mg) compared to placebo (30 versus 22 per 10,000 women-years), although only the increased risk of DVT reached statistical significance (23 versus 15 per 10,000 women-years). The increase in VTE risk was demonstrated during the first 2 years. Should a VTE occur or be suspected, estrogens should be discontinued immediately. In the WHI estrogen plus progestin substudy, a statistically significant 2-fold greater rate of VTE was reported in women receiving daily CE (0.625 mg) plus MPA (2.5 mg) compared to women receiving placebo (35 versus 17 per 10,000 women-years). Statistically significant increases in risk for both DVT (26 versus 13 per 10,000 women-years) and PE (18 versus 8 per 10,000 women-years) were also demonstrated. The increase in VTE risk was observed during the first year and persisted. Should a VTE occur or be suspected, estrogens should be discontinued immediately. If feasible, estrogens should be discontinued at least 4 to 6 weeks before surgery of the type associated with an increased risk of thromboembolism, or during periods of prolonged immobilization. Malignant Neoplasms: Endometrial Cancer: An increased risk of endometrial cancer has been reported with the use of unopposed estrogen therapy in women with a uterus. The reported endometrial cancer risk among unopposed estrogen users is about 2- to 12-fold greater than in non-users, and appears dependent on duration of treatment and on estrogen dose. Most studies show no significant increased risk associated with use of estrogens for less than 1 year. The greatest risk appears associated with prolonged use, with an increased risk of 15- to 24-fold for 5 to 10 years or more and this risk has been shown to persist for at least 8 to 15 years after estrogen therapy is discontinued. Clinical surveillance of all women using estrogen-alone or estrogen plus progestin therapy is important. Adequate diagnostic measures, including directed or random endometrial sampling when indicated, should be undertaken to rule out malignancy in postmenopausal women with undiagnosed persistent or recurring abnormal genital bleeding.

There is no evidence that the use of natural estrogens results in a different endometrial risk profile than synthetic estrogens of equivalent estrogen dose. Adding a progestin to estrogen therapy in postmenopausal women has been shown to reduce the risk of endometrial hyperplasia, which may be a precursor to endometrial cancer. Breast Cancer: The most important randomized clinical trial providing information about breast cancer in estrogen-alone users is the Women’s Health Initiative (WHI) substudy of daily CE (0.625 mg). In the WHI estrogen-alone substudy, after an average follow-up of 7.1 years, daily CE (0.625 mg) was not associated with an increased risk of invasive breast cancer [relative risk (RR) 0.80] . The most important randomized clinical trial providing information about breast cancer in estrogen plus progestin users is the WHI substudy of daily CE (0.625 mg) plus MPA (2.5 mg). After a mean follow-up of 5.6 years, the estrogen plus progestin substudy reported an increased risk of breast cancer in women who took daily CE plus MPA. In this substudy, prior use of estrogen-alone or estrogen plus progestin therapy was reported by 26 percent of the women. The relative risk of invasive breast cancer was 1.24, and the absolute risk was 41 versus 33 cases per 10,000 women-years, for estrogen plus progestin compared with placebo. Among women who reported prior use of hormone therapy, the relative risk of invasive breast cancer was 1.86, and the absolute risk was 46 versus 25 cases per 10,000 women-years for estrogen plus progestin compared with placebo. Among women who reported no prior use of hormone therapy, the relative risk of invasive breast cancer was 1.09, and the absolute risk was 40 versus 36 cases per 10,000 women-years for estrogen plus progestin compared with placebo. In the same substudy, invasive breast cancers were larger and diagnosed at a more advanced stage in the CE (0.625 mg) plus MPA (2.5 mg) group compared with the placebo group. Metastatic disease was rare, with no apparent difference between the two groups. Other prognostic factors, such as histologic subtype, grade and hormone receptor status did not differ between the groups. Consistent with the WHI clinical trial, observational studies have also reported an increased risk of breast cancer for estrogen plus progestin therapy, and a smaller increased risk for estrogen-alone therapy, after several years of use. The risk increased with duration of use, and appeared to return to baseline over about 5 years after stopping treatment (only the observational studies have substantial data on risk after stopping). Observational studies also suggest that the risk of breast cancer was greater, and became apparent earlier, with estrogen plus progestin therapy as compared to estrogen-alone therapy. However, these studies have not generally found significant variation in the risk of breast cancer among different estrogen plus progestin combinations, doses, or routes of administration. The use of estrogen-alone and estrogen plus progestin has been reported to result in an increase in abnormal mammograms requiring further evaluation.

All women should receive yearly breast examinations by a healthcare provider and perform monthly breast self-examinations. In addition, mammography examinations should be scheduled based on patient age, risk factors, and prior mammogram results. Ovarian Cancer: The WHI estrogen plus progestin substudy reported a statistically non-significant increased risk of ovarian cancer. After an average follow-up of 5.6 years, the relative risk for ovarian cancer for CE plus MPA versus placebo was 1.58 (95 percent nCI, 0.77-3.24). The absolute risk for CE plus MPA versus placebo was 4 versus 3 cases per 10,000 women-years. In some epidemiologic studies, the use of estrogen-only products, in particular for 5 or more years, has been associated

Women’s Health almost 2-fold in offspring of mothers with any genital tract infection.

However, none of the findings was significant when an additional statistical analysis was done with the “Bonferroni adjustment.”

“We need to be cautious about any positive findings, because of the lack of significance with the Bonferroni adjustment, and also because these findings were based on the mothers’ self-report of

a genital tract infection and not on clinical data,” said lead investigator Tonia Carter, PhD, member of the Division of Epidemiology, Statistics, and Prevention Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD. “The mothers were interviewed up to 24 months after the end of the pregnancy about illnesses that occurred during the pregnancy.”

with an increased risk of ovarian cancer. However, the duration of exposure associated with increased risk is not consistent across all epidemiologic studies, and some report no association. Probable Dementia: In the estrogen-alone Women’s Health Initiative Memory Study (WHIMS), an ancillary study of WHI, a population of 2,947 hysterectomized women aged 65 to 79 years was randomized to daily CE (0.625 mg) or placebo. In the WHIMS estrogen-alone ancillary study, after an average follow-up of 5.2 years, 28 women in the estrogen-alone group and 19 women in the placebo group were diagnosed with probable dementia. The relative risk of probable dementia for CE-alone versus placebo was 1.49 (95 percent nCI, 0.83-2.66). The absolute risk of probable dementia for CE alone versus placebo was 37 versus 25 cases per 10,000 women-years. In the WHIMS estrogen plus progestin ancillary study, a population of 4,532 postmenopausal women 65 to 79 years of age was randomized to daily CE (0.625 mg) plus MPA (2.5 mg) or placebo. After an average follow-up of 4 years, 40 women in the CE plus MPA group and 21 women in the placebo group were diagnosed with probable dementia. The relative risk of probable dementia for CE plus MPA versus placebo was 2.05 (95 percent nCI, 1.21-3.48). The absolute risk of probable dementia for CE plus MPA versus placebo was 45 versus 22 cases per 10,000 women-years. When data from the two populations in the WHIMS estrogen-alone and estrogen plus progestin ancillary studies were pooled as planned in the WHIMS protocol, the reported overall relative risk for probable dementia was 1.76 (95 percent nCI, 1.19-2.60). Since both substudies were conducted in women aged 65 to 79 years, it is unknown whether these findings apply to younger postmenopausal women. Gallbladder Disease: A 2- to 4-fold increase in the risk of gallbladder disease requiring surgery in postmenopausal women receiving estrogens has been reported. Hypercalcemia: Estrogen administration may lead to severe hypercalcemia in women with breast cancer and bone metastases. If hypercalcemia occurs, use of the drug should be stopped and appropriate measures taken to reduce the serum calcium level. Visual Abnormalities: Retinal vascular thrombosis has been reported in women receiving estrogens. Discontinue medication pending examination if there is a sudden partial or complete loss of vision, or a sudden onset of proptosis, diplopia, or migraine. If examination reveals papilledema or retinal vascular lesions, estrogens should be permanently discontinued. Addition of a Progestin When a Woman Has Not Had a Hysterectomy: Studies of the addition of a progestin for 10 or more days of a cycle of estrogen administration or daily with estrogen in a continuous regimen have reported a lowered incidence of endometrial hyperplasia than would be induced by estrogen treatment alone. Endometrial hyperplasia may be a precursor to endometrial cancer. There are, however, possible risks that may be associated with the use of progestins with estrogens compared to estrogen-alone regimens. These include an increased risk of breast cancer. Elevated Blood Pressure: In a small number of case reports, substantial increases in blood pressure have been attributed to idiosyncratic reactions to estrogens. In a large, randomized, placebo-controlled clinical trial, a generalized effect of estrogens on blood pressure was not seen. Hypertriglyceridemia: In women with preexisting hypertriglyceridemia, estrogen therapy may be associated with elevations of plasma triglycerides leading to pancreatitis. Consider discontinuation of treatment if pancreatitis occurs. Hepatic Impairment and/or Past History of Cholestatic Jaundice: Estrogens may be poorly metabolized in women with impaired liver function. For women with a history of cholestatic jaundice associated with past estrogen use or with pregnancy, caution should be exercised, and in the case of recurrence, medication should be discontinued. Hypothyroidism: Estrogen administration leads to increased thyroid-binding globulin (TBG) levels.

Women with normal thyroid function can compensate for the increased TBG by making more thyroid hormone, thus maintaining free T4 and T3 serum concentrations in the normal range.

Women dependent on thyroid hormone replacement therapy who are also receiving estrogens may require increased doses of their thyroid replacement therapy. These women should have their thyroid function monitored in order to maintain their free thyroid hormone levels in an acceptable range. Fluid Retention: Estrogens may cause some degree of fluid retention.

Women with conditions that might be influenced by this factor, such as a cardiac or renal dysfunction, warrant careful observation when estrogens are prescribed. Hypocalcemia: Estrogen therapy should be used with caution in women with hypoparathyroidism as estrogen-induced hypocalcemia may occur. Exacerbation of Endometriosis: A few cases of malignant transformation of residual endometrial implants have been reported in women treated post-hysterectomy with estrogen-alone therapy. For women known to have residual endometriosis post-hysterectomy, the addition of progestin should be considered. Exacerbation of Other Conditions: Estrogen therapy may cause an exacerbation of asthma, diabetes mellitus, epilepsy, migraine, porphyria, systemic lupus erythematosus, and hepatic hemangiomas and should be used with caution in women with these conditions. Local Abrasion: A few cases of local abrasion induced by the Vagifem® applicator have been reported, especially in women with severely atrophic vaginal mucosa. Laboratory Tests: Serum follicle stimulating hormone and estradiol levels have not been shown to be useful in the management of moderate to severe symptoms of vulvar and vaginal atrophy. Drug-Laboratory Test Interactions: Accelerated prothrombin time, partial thromboplastin time, and platelet aggregation time; increased platelet count; increased factors II, VII antigen, VIII antigen, VIII coagulant activity, IX, X, XII, VII-X complex, II-VII-X complex, and beta-thromboglobulin; decreased levels of antifactor Xa and antithrombin III, decreased antithrombin III activity; increased levels of fibrinogen and fibrinogen activity; increased plasminogen antigen and activity. Increased thyroid-binding globulin (TBG) levels leading to increased circulating total thyroid hormone as measured by protein-bound iodine (PBI), T4 levels (by column or by radioimmunoassay) or T3 levels by radioimmunoassay.

T3 resin uptake is decreased, reflecting the elevated TBG. Free T4 and free T3 concentrations are unaltered. Women on thyroid replacement therapy may require higher doses of thyroid hormone.

Other binding proteins may be elevated in serum, for example, corticosteroid binding globulin (CBG), sex hormone-binding globulin (SHBG), leading to increased total circulating corticosteroids and sex steroids, respectively. Free hormone concentrations, such as testosterone and estradiol, may be decreased. Other plasma proteins may be increased (angiotensinogen/renin

While acknowledging these limitations, 2 other experts applaud this latest effort. “The authors used a robust database, and their methods and statistical analyses are solid,” said Nandor Ács, MD, Professor, Second Department of Obstetrics and Gynecology, Semmelweis University School of Medicine, Budapest, Hungary, whose own studies on a similar link between gential tract infections in pregnancy and congenital

substrate, alpha-1-antitrypsin, ceruloplasmin). Increased plasma HDL and HDL2 cholesterol subfraction concentrations, reduced LDL cholesterol concentrations, increased triglyceride levels. Impaired glucose tolerance.

ADVERSE REACTIONS: The following serious adverse reactions are discussed elsewhere in the labeling: Cardiovascular Disorders [see Boxed Warning, Warnings and Precautions]; Endometrial Cancer [see Boxed Warning, Warnings and Precautions]. Clinical Study Experience: Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trial of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In a 12-month randomized, double-blind, parallel group, placebo-controlled study, a total of 309 postmenopausal women were randomized to receive either placebo or Vagifem® 10 mcg tablets. Adverse events with an incidence of ≥5% in the Vagifem® 10 mcg group and greater than those reported in the placebo group are listed in Table 1.

Table 1: Treatment-Emergent Adverse Events Reported at a Frequency of ≥5% and More Frequent in Women Receiving Vagifem® 10 mcg Body System Adverse Event

abnormalities in the offspring were negative. “But their findings need to be confirmed by other studies, since my team, among other researchers, did not find such an association when we searched for it,” he said.

Marcia Feldkamp, PhD, PA, MSPH, Director, Utah Birth Defect Network, and Assistant Professor, Division of Medical Genetics, University of Utah School of Medicine, Salt Lake City, led an earlier study of gastroschisis in children born to women with self-reported urinary tract infections and sexually transmitted diseases. Her team also used data from the National Birth Defects Prevention Study and found a more than 3-fold increased risk for babies being born with gastroschisis and other birth defects if their mothers had genitourinary infections during pregnancy.

Treatment Number (%) of Women Placebo N = 103 Vagifem® N = 205 n (%) n (%)

Body As A Whole Back Pain 2 (2) 14 (7) Digestive System Diarrhea 0 11 (5) Urogenital System Vulvovaginal Mycotic Infection 3 (3) 17 (8) Vulvovaginal Pruritis 2 (2) 16 (8) N = Total number of women in study. n = Number of women who experienced adverse event.

In a 12-week, randomized, double-blind, placebo-controlled study, 138 postmenopausal women were randomized to receive either placebo or Vagifem® 25 mcg tablets. Adverse events with an incidence of ≥5% in the Vagifem® 25 mcg group and greater than those reported in the placebo group are listed in Table 2.

Table 2: Treatment-Emergent Adverse Events Reported at a Frequency of ≥5% and More Frequent in Women Receiving Vagifem® 25 mcg Body System Adverse Event

Treatment Number (%) of Women Placebo N = 47 Vagifem® N = 91 n (%) n (%)

Body As A Whole Headache 3 (6) 8 (9) Abdominal Pain 2 (4) 6 (7) Back Pain 3 (6) 6 (7) Respiratory System Upper Respiratory Tract Infection 2 (4) 5 (5) Urogenital System Moniliasis Genital 1 (2) 5 (5) N = Total number of women in study. n = Number of women who experienced adverse event.

Postmarketing Experience: The following adverse reactions have been reported during post approval use of Vagifem® 25 mcg. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Genitourinary System: Endometrial cancer, endometrial hyperplasia, vaginal irritation, vaginal pain, vaginismus, vaginal ulceration Breast: Breast cancer Cardiovascular: Deep vein thrombosis Gastrointestinal: Diarrhea Skin: Urticaria, erythematous/pruritic rash, genital pruritus Central Nervous System: Aggravated migraine, depression, insomnia Miscellaneous: Fluid retention, weight increase, drug ineffectiveness, hypersensitivity, blood estrogen increase. Additional postmarketing adverse reactions have been reported in patients receiving other forms of hormone therapy.

OVERDOSAGE: Overdosage of estrogen may cause nausea and vomiting, breast tenderness, dizziness, abdominal pain, drowsiness/fatigue and withdrawal bleeding in women. Treatment of overdose consists of discontinuation of Vagifem® together with institution of appropriate symptomatic care.

More detailed information is available upon request.

Date of Issue: November 25, 2009 Version: 6 For information contact: Novo Nordisk Inc., 100 College Road West, Princeton, NJ 08540, USA 1-888-824-4336 Manufactured by: Novo Nordisk A/S, 2880 Bagsvaerd, Denmark Vagifem® is a registered trademark owned by Novo Nordisk FemCare AG. © 2003-2010 Novo Nordisk A/S 140373 1/10

“We need to be cautious about any positive findings, because these findings were based on the mothers’ self-report of a genital tract infection and not on clinical data.”

—Tonia Carter, PhD

“Given how common these infections are, particularly among young women, more research is necessary,” Dr Feldkamp told the OB/GYN Nurse-NP/PA. “The additional challenge is obtaining biomarkers to identify the pathogen or pathogens among those women with subclinical infections, in addition to those with clinical infections.”

In the new study, conducted at the Congenital Malformations Registry, New York State Department of Health, Dr Carter and colleagues compared the maternal and infant characteristics of women who gave birth to 12,158 children with birth defects and another group of women who gave birth to 5913 children who did not have birth defects.

They focused on infections contracted by women between 1 month before conception and the end of the first trimester.

They found that the association was present only among women with untreated genital tract infections, not in those with treated infections. ■

APRIL 2011 l VOLUME 3, NUMBER 2

17

Pharmacy Corner

First FDA-Approved At-Home Conception Kit

By Sandra Fernandez, PharmD Pharmacist, Mandell’s Clinical Pharmacy, Somerset, NJ

M

any couples today are struggling with the challenge of achieving fertility. This devastating life crisis of unknown causes and solutions can lead to physical, emotional, and financial hardship.

Although there is no way of completely eliminating anxiety during this journey, providing affected couples with comprehensive information on insurance coverage, as well as alternative options for making their infertility treatment affordable, may lessen anxiety and make it easier to cope.

It is a common misconception among infertile couples that there are no therapeutic options between at-home ovulation tracking and undergoing in vitro fertilization (IVF). In 2007, the US Food and Drug Administration approved the first at-home insemination tool based on cervical cap technology to aid in conception—the Conception Kit. The key component of the kit is the Conception Cap, which when used in conjunction with the other components in the kit, may increase the likelihood of becoming pregnant. The kit is available only with a valid prescription from a physician.

Instruction Manual The comprehensive instruction manual, provided in English and in Spanish, allows women to track the entire cycle, from choosing a 3-month window during which they would like to deliver to determining their most fertile time of the month.

Couples are instructed to use the collection condom during intercourse to collect semen, and then carefully transfer its contents to the provided Conception Cap. The cap is then inserted into the vagina and placed on the cervix for 4 to 6 hours.

This technique shields sperm from the acidic vaginal environment, which normally kills sperm. Capping the semen on the cervix also allows slowswimming sperm and semen that contains a low sperm count an opportunity to swim up the uterus and fallopian tubes to fertilize an egg. The cervical cap technology may also help to address fertility issues resulting from a tilted cervix, position during intercourse, low sperm mobility, and an irregular position of the penis opening.

Cervical caps have been used for decades, with the medical literature documenting their use back to the 1950s.

The Conception Cap. Photo used with permission from Conceivex, Inc.

More recent research eventually gave way to new technology to treat infertility complications, leading to assisted reproductive technology and IVF.

With the rising costs of using such modern treatments, and the current economic status of many couples facing infertility, the cervical cap technology has made its way back to the market.

With the rising costs of using such modern treatments, and the current economic status of many couples facing infertility, the cervical cap technology has made its way back to the market. It is a more private, cost-effective, and natural method of trying to conceive before moving on to more expensive and invasive clinical procedures, such as IVF. publicly Available product Information Cost listed on the company’s website (www.conceptionkit.com), $299.95; $285.00 at any DesignRx pharmacy (www.designrx.net/pharmacies.aspx).

The Conception Kit is now covered by many health insurance plans, with a $25 to $50 copayment, depending on the plan and coverage.

Contents of kit: • 3 Conception Caps • 1 practice Conception Cap • 24 Conceivex Ovulation Predictors • 3 Conceivex Pregnancy Tests • 3 latex-free Conceivex Semen Collectors • 3 sperm-friendly intimate moisturizers • 1 conception journal • 1 instruction manual • 1 Conceivex Ovulation Predictor instructions • 1 Conceivex Pregnancy Test instructions • 1 sperm-friendly intimate moisturizer instructions • 1 Conception Wheel • 1 medical provider note/envelope.

Contents of 1 kit are designed to be used for 3 complete cycles.

Product information: Conceivex Conception Kit; National Drug Code number, 08597-1111-13.

Patients should be instructed that the Conception Kit will not overcome infertility caused by age or certain medical conditions, including azoospermia, blocked fallopian tube(s), cervical stenosis, endometriosis, fibroids, genital warts, low amount of follicle-stimulating hormone, luteal phase defect, polycystic ovarian syndrome, polyps, scarred uterus, and other serious medical conditions. ■

Clinical news Sex Disparities in Asthma For reasons that remain unclear, the incidence of asthma is greater in women than in men, and women have worse asthma-related outcomes than men, including deaths, new data show (Kynyk JA, et al. Curr Opin Pulm Med. 2011;17:6-11). American women with asthma also have poorer quality of life and greater healthcare utilization than men. In 2006, of the 3613 asthmarelated deaths, 64% were women.

Age plays a large role in asthma mortality in this sex disparity: women’s increased mortality rate only exceeds that of men after age 65 years; men’s highest asthma mortality is before age 35 years. Hospitalization for asthma also varies by sex and age: those hospitalized at age >15 years are 3 times more likely to be female; those hospitalized at age <15 years are twice as likely to be male.

Black women have the highest ageadjusted asthma mortality and have more exacerbations that require hospitalization than white women or men.

Asthma’s incidence in women decreases after menopause, but hormone replacement therapy is associated with increased rates of newly diagnosed asthma.

Fetal Heart rate Monitoring Cuts neonatal Morbidity, Mortality Electronic fetal heart rate (FHR) monitoring significantly decreases neonatal morbidity and mortality, according to results of the largest study to date on this topic, which was presented at the 2011 Society for Maternal–Fetal Medicine meeting.

The use of electronic FHR monitors during labor reduced early neonatal mortality by 53%. The study included 47% (N = 1,945,789) of all live births in 2004, of which 88% had electronic FHR monitoring. The risk for neonatal and infant mortality was 3.0 per 1000 births with electronic FHR compared with 3.8 per 1000 births for babies not subjected to electronic FHR. That magnitude of the reduction in infant and neonatal mortality rate was slightly affected by gestational age.

In addition, infant mortality, neonatal morbidity, low Apgar scores at 5 minutes, and neonatal seizures were also reduced with electronic FHR monitoring.

Criteria for exclusion included multiple gestations, anomalous newborns, foreign residents, gestational age <24 weeks or ≥45 weeks, implausible birth weights, and births for which use of electronic FHR monitoring was unknown.

opioids linked to Birth Defects risk Women who are using opioid analgesics 1 month before or 3 months after Continued on page 27

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APRIL 2011 l VOLUME 3, NUMBER 2

Progesterone # Fact 5 Only one progesterone is FDA approved for progesterone replacement.

Itâ&#x20AC;&#x2122;s a fact.

When you need to replace progesterone in your patients undergoing donor egg cycles, only CRINONE offers the confidence of FDA approval for progesterone replacement.1 In fact, CRINONE has demonstrated comparable pregnancy rates to IM P in a prospective, randomized trial of women in a donor egg cycle.2 Before you prescribe, check the facts.

The only

Meetings

Upcoming Meetings APRIL

MAY

JUNE

New England Fertility Society

American Urological Association

Midwest Reproductive Symposium

4/29-4/30 Westbrook, CT Contact: (978) 640-9176 michellepicher@nefs.org www.nefs.org

5/14-5/19 Washington, DC Contact: (800) 908-9414 www.aua2011.org

6/10-6/11 Chicago, IL Contact: (888) MBM-MTGS www.mwrs.org

American College of Nurse-Midwives

ACOG 59th Annual Clinical Meeting

5/24-5/28 San Antonio, TX Contact: (240) 485-1800 info@acnm.org http://am.midwife.org

Cancer Survivorship and Sexual Health Symposium

4/30-5/4 Washington, DC Contact: acm@acog.org www.acog.org/acm/

Crinone® 4% Crinone® 8% (progesterone gel) For vaginal use only.

Rx only

BRIEF SUMMARY For full prescribing information, see package insert.

INDICATIONS AND USAGE Assisted Reproductive Technology Crinone 8% is indicated for progesterone supplementation or replacement as part of an Assisted Reproductive Technology (“ART”) treatment for infertile women with progesterone deficiency.

Secondary Amenorrhea Crinone 4% is indicated for the treatment of secondary amenorrhea. Crinone 8% is indicated for use in women who have failed to respond to treatment with Crinone 4%.

CONTRAINDICATIONS Crinone should not be used in individuals with any of the following conditions: known sensitivity to Crinone (progesterone or any of the other ingredients); undiagnosed vaginal bleeding; liver dysfunction or disease; known or suspected malignancy of the breast or genital organs; missed abortion; active thrombophlebitis or thromboembolic disorders, or a history of hormone-associated thrombophlebitis or thromboembolic disorders.

WARNINGS The physician should be alert to the earliest manifestations of thrombotic disorders (thrombophlebitis, cerebrovascular disorders, pulmonary embolism, and retinal thrombosis).

Should any of these occur or be suspected, the drug should be discontinued immediately.

Progesterone and progestins have been used to prevent miscarriage in women with a history of recurrent spontaneous pregnancy losses. No adequate evidence is available to show that they are effective for this purpose.

PRECAUTIONS General 1. The pretreatment physical examination should include special reference to breast and pelvic organs, as well as Papanicolaou smear.

2. In cases of breakthrough bleeding, as in all cases of irregular vaginal bleeding, nonfunctional causes should be considered. In cases of undiagnosed vaginal bleeding, adequate diagnostic measures should be undertaken.

3. Because progestogens may cause some degree of fluid retention, conditions which might be influenced by this factor (e.g., epilepsy, migraine, asthma, cardiac or renal dysfunction) require careful observation.

4. The pathologist should be advised of progesterone therapy when relevant specimens are submitted.

5. Patients who have a history of psychic depression should be carefully observed and the drug discontinued if the depression recurs to a serious degree.

6. A decrease in glucose tolerance has been observed in a small percentage of patients on estrogen-progestin combination drugs. The mechanism of this decrease is not known. For this reason, diabetic patients should be carefully observed while receiving progestin therapy.

Information for Patients The product should not be used concurrently with other local intravaginal therapy. If other local intravaginal therapy is to be used concurrently, there should be at least a 6-hour period before or after Crinone administration. Small, white globules may appear as a vaginal discharge possibly due to gel accumulation, even several days after usage.

Drug Interactions No drug interactions have been assessed with Crinone.

Carcinogenesis, Mutagenesis, Impairment of Fertility Nonclinical toxicity studies to determine the potential of Crinone to cause carcinogenicity or mutagenicity have not been performed. The effect of Crinone on fertility has not been evaluated in animals.

Pregnancy Crinone 8% has been used to support embryo implantation and maintain pregnancies through its use as part of ART treatment regimens in two clinical studies (studies COL1620-007US and COL1620-F01). In the first study (COL1620-007US), 54 Crinonetreated women had donor oocyte transfer procedures, and clinical pregnancies occurred in 26 women (48%). The outcomes of these 26 pregnancies were as follows: one woman had an elective termination of pregnancy at 19 weeks due to congenital malformations (omphalocele) associated with a chromosomal abnormality; one woman pregnant with triplets had an elective termination of her pregnancy; seven women had spontaneous abortions; and 17 women delivered 25 apparently normal newborns.

In the second study (COL1620-F01), Crinone 8% was used in the luteal phase support of women undergoing in vitro fertilization (“IVF”) procedures. In this multi-center, openlabel study, 139 women received Crinone 8% once daily beginning within 24 hours of embryo transfer and continuing through Day 30 post-transfer.

Clinical pregnancies assessed at Day 90 post-transfer were seen in 36 (26%) of women.

Thirty-two women (23%) delivered newborns and four women (3%) had spontaneous abortions. Of the 47 newborns delivered, one had a teratoma associated with a cleft palate; one had respiratory distress syndrome; 44 were apparently normal and one was lost to follow-up.

Geriatric Use The safety and effectiveness in geriatric patients (over age 65) have not been established.

Pediatric Use Safety and effectiveness in pediatric patients have not been established.

Nursing Mothers Detectable amounts of progestins have been identified in the milk of mothers receiving them. The effect of this on the nursing infant has not been determined.

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APRIL 2011 l VOLUME 3, NUMBER 2

6/17-6/19 Washington, DC Contact: (847) 517-7225 info@smsna.org

ADVERSE REACTIONS Assisted Reproductive Technology In a study of 61 women with ovarian failure undergoing a donor oocyte transfer procedure receiving Crinone 8% twice daily, treatment-emergent adverse events occurring in 5% or more of the women were: bloating (7%), cramps not otherwise specified (15%), pain (8%), dizziness (5%), headache (13%), nausea (7%), breast pain (13%), moniliasis genital (5%), vaginal discharge (7%), pruritus genital (5%).

In a second clinical study of 139 women using Crinone 8% once daily for luteal phase support while undergoing an IVF procedure, treatment-emergent adverse events reported in 5% or greater of the women were: abdominal pain (12%), perineal pain female (17%), headache (17%), constipation (27%), diarrhea (8%), nausea (22%), vomiting (5%), arthralgia (8%), depression (11%), libido decreased (10%), nervousness (16%), somnolence (27%), breast enlargement (40%), dyspareunia (6%), nocturia (13%).

Secondary Amenorrhea In three studies, 127 women with secondary amenorrhea received estrogen replacement therapy and Crinone 4% or 8% every other day for six doses. Treatment-emergent adverse events during estrogen and Crinone treatment that occurred in 5% or more of women treated with Crinone 4% or Crinone 8% respectively were: abdominal pain (5%, 9%), appetite increased (5%, 8%), bloating (13%, 12%), cramps not otherwise specified (19%, 26%), fatigue (21%, 22%), headache (19%, 15%), nausea (8%, 6%), back pain (8%, 3%), myalgia (8%, 0%), depression (19%, 15%), emotional lability (23%, 22%), sleep disorder (18%, 18%), vaginal discharge (11%, 3%), upper respiratory tract infection (5%, 8%), and pruritus genital (2%, 6%).

Additional adverse events reported in women at a frequency of less than 5% in Crinone ART and secondary amenorrhea studies and not listed above include: autonomic nervous system–mouth dry, sweating increased; body as a whole–abnormal crying, allergic reaction, allergy, appetite decreased, asthenia, edema, face edema, fever, hot flushes, influenza-like symptoms, water retention, xerophthalmia; cardiovascular, general–syncope; central and peripheral nervous system–migraine, tremor; gastro-intestinal–dyspepsia, eructation, flatulence, gastritis, toothache; metabolic and nutritional–thirst; musculo-skeletal system– cramps legs, leg pain, skeletal pain; neoplasm–benign cyst; platelet, bleeding & clotting– purpura; psychiatric–aggressive reactions, forgetfulness, insomnia; red blood cell– anemia; reproductive, female–dysmenorrhea, premenstrual tension, vaginal dryness; resistance mechanism–infection, pharyngitis, sinusitis, urinary tract infection; respiratory system–asthma, dyspnea, hyperventilation, rhinitis; skin and appendages–acne, pruritus, rash, seborrhea, skin discoloration, skin disorder, urticaria; urinary system–cystitis, dysuria, micturition frequency; vision disorders–conjunctivitis.

OVERDOSAGE There have been no reports of overdosage with Crinone. In the case of overdosage, however, discontinue Crinone, treat the patient symptomatically, and institute supportive measures.

As with all prescription drugs, this medicine should be kept out of the reach of children.

DOSAGE AND ADMINISTRATION Assisted Reproductive Technology Crinone 8% is administered vaginally at a dose of 90 mg once daily in women who require progesterone supplementation. Crinone 8% is administered vaginally at a dose of 90 mg twice daily in women with partial or complete ovarian failure who require progesterone replacement. If pregnancy occurs, treatment may be continued until placental autonomy is achieved, up to 10-12 weeks.

Secondary Amenorrhea Crinone 4% is administered vaginally every other day up to a total of six doses. For women who fail to respond, a trial of Crinone 8% every other day up to a total of six doses may be instituted.

It is important to note that a dosage increase from the 4% gel can only be accomplished by using the 8% gel. Increasing the volume of gel administered does not increase the amount of progesterone absorbed.

HOW SUPPLIED Crinone is available in the following strengths: 4% gel (45 mg) in a single use, one piece, disposable, white polyethylene vaginal applicator with a twist-off top. Each applicator contains 1.45 g of gel and delivers 1.125 g of gel.

NDC 52544-283-24 - 6 Single-use prefilled applicators.

8% gel (90 mg) in a single use, one piece, disposable, white polyethylene vaginal applicator with a twist-off top. Each applicator contains 1.45 g of gel and delivers 1.125 g of gel.

NDC 52544-284-12 - 15 Single-use prefilled applicators.

Each applicator is wrapped and sealed in a foil overwrap.

Store at 20-25°C (68-77°F). [See USP controlled room temperature.]

Rx only References: 1. CRINONE® prescribing information. Morristown, NJ: Watson Pharmaceuticals, Inc. June 2010. 2. Gibbons WE, Toner JP, Hamacher P, Kolm P. Experience with a novel vaginal progesterone preparation in a donor oocyte program. Fertil Steril.

1998;69:96-101.

AWHONN Convention 6/25-6/29 Denver, CO Contact: (800) 673-8499 customerservice@awhonn.org www.awhonn.org

JULY Controversies in Women’s Health 7/14-7/16 Wisconsin Dells, WI Contact: (800) 323-2688 cme@mayo.edu www.mayo.edu/cme

AUgUST Pathways to Clinical Excellence in OB/GYN 8/12-8/14 Orlando, FL Contact: (904) 674-0751 cfilbert@flobgyn.org www.obgpathways.com

SEPTEMBER American Urogynecologic Society 9/14-9/17 Providence, RI Contact: (202) 367-1167 info@augs.org www.augs.org

American Gynecological & Obstetrical Society 9/15-9/17 Chicago, IL Contact: (804) 924-9937 www.agosonline.org

Association of Reproductive Health Professionals Reproductive Health 2011 9/15-9/17 Las Vegas, NV Contact: (202) 466-3825 ARHP@arhp.org www.reproductivehealth2011.org

NAMS Annual Meeting 9/21-9/24 Washington, DC Contact: (440) 442-7550 info@menopause.org www.menopause.org

OCTOBER American College of Osteopathic Obstetricians & Gynecologists Fall Conference 10/12-10/16 Philadelphia, PA Contact: (817) 377-0421 www.acoog.com

National Association of Nurse Practitioners in Women’s Health 10/12-10/15 Austin, TX Contact: (202) 543-9693 info@npwh.org www.npwh.org

ASRM Annual Meeting Address medical inquiries to: WATSON Medical Communications P.O. Box 1953 Morristown, NJ 07962-1953 800-272-5525 Distributed by: Watson Pharma, Inc., Morristown, NJ 07962 USA Manufactured by: Fleet Laboratories Ltd., Watford, Herts WD18 7JJ UK Revised: July 2010

10/15-10/19 Orlando, FL Contact: (866) 471-7224 asrmregistration@jspargo.com www.asrm.org

North American Forum on Family Planning 10/22-10/24 Washington, DC Contact: info@societyfp.org www.societyfp.org

WWW.INFERTILITYREPRONEWS.COM

CONTINUING EDUCATION

PROGRAM CE14 • RELEASE DATE: APRIL 20, 2011 • EXPIRATION DATE: APRIL 20, 2012 ESTIMATED TIME TO COMPLETE: 1.0 HOUR

Hypoactive Sexual Desire Disorder in women: An Evolving Understanding Pamela Fawcett Pressman, MEd, LPC; Nancy Gambescia, PhD, RN Ms Pressman is a Licensed Professional Counselor in private practice, Voorhees, NJ; Dr Gambescia is a Clinical Associate Professor, Department of Psychiatry, University of Pennsylvania School of Medicine, and Director, Postgraduate Sex Therapy Program, Council for Relationships, Philadelphia, PA. STATEMENT OF NEED Many clinicians have little knowledge regarding female sexuality and its impact on a woman’s overall health.

Low sexual desire in women is a complex condition involving a variety of issues. Social and religious influences have often defined women, and genital mutilation continues to exist in some cultures. Low desire may be particularly high among women with certain medical diagnoses, and women often do not report low sexual desire because of shame, embarrassment, or a discomfort discussing sexual issues.

Untreated desire disorders may have profound implications for a woman and her partner. Hypoactive sexual desire disorder (HSDD), defined as “the deficiency or absence of sexual fantasies and desire for sexual activity,” causes “marked distress or interpersonal distress.” HSDD is the most common sexual disorder in women, affecting up to 1 in 10 women in the United States. Concern about low sexual desire may be present in 30% to 40% of women. Clinicians involved in women’s health and infertility should be familiar with the issues related to HSDD and its potential impact on a woman’s well-being, as well as the treatment modalities available to address this disorder.

TARgET AUDIENCE Nurses whose primary interest is women’s health and infertility.

LEARNINg OBJECTIVES After completing this activity, the reader should be able to: • Describe the growing understanding of female sexuality and the implications of low sexual desire in women on their overall health and well-being and interpersonal relationships • Discuss the prevalence of low sexual disorder in women and its causes, including body shame, domesticity, and cultural, social, and religious influences • Review the approaches to a comprehensive assessment of women with low sexual desire and the treatment modalities available today CONTINUINg NURSINg EDUCATION ACCREDITATION AND CONTACT HOURS STATEMENT Science Care is approved by the California Board of Registered Nursing, Provider number 15559, for 1.0 contact hour.

T

he high incidence of low sexual desire in women has caught the attention of mental health professionals who are seeking clarity about the etiology of this phenomenon. Low desire may be particularly high among women with a medical diagnosis, such as infertility, polycystic ovarian syndrome, or dyspareunia (pain during intercourse). Women may not report low sexual desire and avoidance of sex because of shame, embarrassment, or a discomfort discussing sexual issues.1 Untreated desire disorders may have profound implications for a woman and her husband or partner.2 Clinicians helping women may need to consider this issue, which can have implications on a woman’s overall health and well-being, and when appropriate, consider the option of sex therapy or other avenues to explore sexual desire issues. This article reviews the current literature on low sexual desire in women, as well as the current psychotherapeutic interventions available to women with low desire.

There is an increasing awareness of the need for accurate assessment and treatment of low sexual desire in women. This article addresses the limitations of the current classification of hypoactive sexual desire disorder

(HSDD) in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR),2 and proposes a different model for the assessment of women’s low sexual desire.

It also reviews the current literature on treating low sexual desire in women.

Throughout history, the experience of women has been misunderstood. Social, political, economic, and religious influences have often defined women and dictated what they want and should be experiencing. It is little wonder that women’s sexuality has been the subject of speculation, exploitation, and pathologizing. For example, Freud promoted a valuative judgment about “mature” female orgasm, which has influenced concepts of normalcy, femininity, and pathology.3 Genital mutilation continues to exist in some cultures, and the cosmetic and pharmaceutical industries are robust with business from women who have been acculturated to believe that they need to fix themselves.4 Clinicians dealing with women’s health must question the cultural assumptions from which these premises are based. What is normal? How is a woman’s sexual experience different from or similar to a man’s experience?

How do we learn about this disparity?

And how do these issues affect women’s well-being? All these issues serve to make the study of women’s sexuality complex, difficult, and interesting. the Early Models of Female Sexuality In the United States, research on human sexuality has historically focused on the experience of men.5,6 In 1966, Masters and Johnson were the first investigators to systematically study the physiology of the human sexual response in men and women in the United States.7 They described a 4-stage linear model of sexual behavior— excitement, arousal, plateau, and resolution (orgasm). This model presumed that an internal biological drive would propel the individual toward self or partner sexual stimulation, which would lead to orgasm. Moreover, Masters and Johnson looked for similarities in the sexual response between genders. In 1979, Kaplan added the integral concept of “desire” to the physiologic model of Masters and Johnson.8 Kaplan recognized that the mind and body were intertwined with physiologic sexual responses.8 In both linear models, however, experts assumed the male and female sexual response cycle as identical.

Continued on page 22

METHOD OF PARTICIPATION 1. Read the article in its entirety 2. Go to www.infertilityrepronews.com 3. Select “Continuing Education” 4. Click on this article’s title from the list shown 5. Select “Click here to complete the posttest and obtain a CE certificate online” 6. Complete and submit the CE posttest and CE activity evaluation 7. Print your Certificate of Credit This activity is provided free of charge to participants.

FACULTY DISCLOSURES As a provider accredited by the California Board of Registered Nursing, Science Care must ensure balance, independence, objectivity, and scientific rigor in all its activities.

All course directors, faculty, planners, and any other individual in a position to control the content of this educational activity are required to disclose to the audience any relevant financial relationships with any commercial interest.

Science Care must determine if the faculty’s relationships may influence the educational content with regard to exposition or conclusion and resolve any conflicts of interest prior to the commencement of the educational activity. Disclosures are as follows: • Nancy Gambescia, PhD, RN, has nothing to disclose.

• Pamela Fawcett Pressman, MEd, LPC, has nothing to disclose.

• Margaret-Rose Agostino, DNP, MSW, RN-BC, IBCLC, has nothing to disclose.

• Dalia Buffery, MA, ABD, has nothing to disclose.

• The staff members of Science Care have nothing to disclose.

DISCLAIMER The opinions and recommendations expressed by faculty, authors, and other experts whose input is included in this program are their own and do not necessarily represent the viewpoint of Science Care or Novellus Healthcare Communications, LLC.

COPYRIGHT STATEMENT Copyright © 2011 Science Care. All rights reserved.

EDITORIAL BOARD Nancy gambescia, PhD, RN Director, Postgraduate Sex Therapy Program Council for Relationships 1062 E. Lancaster Avenue, Suite 26 Rosemont, PA 19010 Pamela Fawcett Pressman, MEd, LPC Licensed Professional Counselor 1202 Laurel Oak Road, Suite 207 Voorhees, NJ 08043 Margaret-Rose Agostino, DNP, MSW, RN-BC, IBCLC Assistant Professor Department of Nursing Delaware State University 1200 N. DuPont Highway, Price 117C Dover, DE 19901

APRIL 2011 l VOLUME 3, NUMBER 2

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Hypoactive Sexual Desire Disorder... Continued from page 21 Future theorists have considered the more complex nature of women’s subjective sexual experience; moreover, questions about the role of motivation in determining women’s sexual behavior have emerged, and these broadened the understanding of the female sexual experience.9,10 Basson recognized the differences between genders in the sexual response and identified the need for intimacy as a motivator of sexual behavior in women.9 This is a significant departure from the aforementioned linear models.

Thus, female sexual desire is viewed as a process that is responsive rather than biologically driven. Often, the motivation for sexual intimacy in a partnered relationship is related to the desire for emotional closeness rather than a biological hunger for sex. The emphasis in Basson’s conceptualization is on the woman’s “willingness” to become aroused.1 Multiple factors may facilitate arousability, she says, “including feeling desired rather than feeling used, feeling accepted by the partner, the partner’s behavior, and the woman’s body image and mood.”1 Hypoactive Sexual Desire Disorder The DSM-IV-TR classifies HSDD as “the deficiency or absence of sexual fantasies and desire for sexual activity,” which causes “marked distress or interpersonal distress.”2 This disorder may be lifelong or acquired, generalized or situational.

HSDD is the most common sexual disorder in women,11 affecting up to 1 in 10 women in the United States.12 Moreover, concern about low sexual desire may be present in 30% to 40% of women, according to Basson.1 The important issue that arises from this emerging body of research is the reality that the range of sexual desire is extremely inconsistent for women; thus, some women with low desire may actually fall within a wide range of normal variability.

A 1998 International Consensus Committee meeting expanded upon the DSM-IV-TR’s definition of HSDD to propose the concept of receptivity in its provisional definition.13 It defines HSDD as the “persistent or recurrent deficiency (or absence) of sexual fantasies, thoughts and/or desire for or receptivity to, sexual activity, which causes personal distress.”9 This revision appears to more accurately describe the range of “normalcy” with respect to sexual desire in women.

The disparity between women’s physiologic arousal and the subjective experience of their arousal has been an area of recent investigation.9,14-16 In 2003, changes to the DSM-IV-TR were rec-

ommended that would include a woman’s subjective experience of being arousable as the marker for identifying a disorder, rather than a physiologic response alone. Thus, if a woman is not distressed about her lack of arousability, she would not be classified as having a disorder.17 In addition, orgasm would not be essential to a woman’s subjective experience of sexual satisfaction.9 In 2000, a group of feminist scholars, therapists, and researchers convened, resulting in the “new view” campaign of women’s sexuality.18 They proposed new classifications for women’s sexual problems, suggesting that female sexual problems are influenced by, or are associated with, several factors, including: • Sociocultural, political, or economic components • Partner and relationship factors • Psychological aspects • Medical conditions.

This model contextualizes women’s sexuality in a much broader perspective than what was initially proposed by earlier theorists, and provides more accurate and specific information to guide in the assessment and treatment of women’s sexual disorders. low Sexual Desire in women Toates examined the role of inhibition in attenuating the sexual behavior of women.19 Inhibition can prevent sexual desire or sexual behavior, and can be caused by myriad factors, including aversion, conflict, relational factors, and medical or psychological issues.

Hertlein and colleagues proposed an “intersystemic model” to reflect their understanding and assessment of HSDD, which combines individual, interactional, and intergenerational factors.20,21 This comprehensive paradigm recognizes the historical, psychological, and relational influences that contribute to a woman’s sexual identity and ability for sexual responsiveness.

The roles of “body shame” and selfconsciousness diminish a woman’s ability to enjoy partner-related sexual activity22; in a small yet provocative recent study, women were able to identify multiple factors that significantly contributed to their diminishing desire.10 The issue of domesticity was thematic in reducing the wish for sexual intimacy. It appeared difficult to be “turned on” by a person with whom one pays the bills, cares for children, and is overly familiar.10 Messages internalized from one’s culture are very influential in determining the acceptability of certain sexual behaviors in women.23 Assessment of low Sexual Desire In addition to the diagnostic criteria for HSDD,2 a comprehensive assess-

ment of HSDD would have to include a woman’s sexual experience within the context of her life.24 Assessment of HSDD should therefore include24: 1. Family and early developmental histories, including information about gender influences, exposure to sexual themes, and sexual experiences and trauma 2. A complete psychological history to identify other axis I and II disorders (ie, coexisting mood or personality disorders), as well as a medical history to identify biological or medication influences on desire, arousal, and orgasm 3. History of the presenting problem, and information about ways in which it may have changed over time, or with different partners 4. Beliefs and cognitions about sex, intimacy, identity, and power/lack of power within her relationships 5. Sexual history, including sexual experiences and preferences 6. A review of her current relationship, if applicable, including conscious and unconscious emotional patterns, negotiations, beliefs, and agreements; look for a history of affairs or emotional disloyalty.

In addition, the issues of balance of power, emotional safety, openness, and acceptance should be explored as part of a comprehensive assessment. Basson suggests assessing the quality of the sexual interaction, as well as the thoughts that occur during the sexual interaction.1 Cognitive distractions or preoccupations with antisexual thoughts could impair a woman’s sexual experience.

Approaches to treatment Discussion of low sexual desire in women must presuppose that there is much that we do not yet understand, and any therapeutic model should only serve as a starting point from which to launch a treatment plan for the individual or the partners. During the assessment, the clinician collates information about life experiences that serve as pearls of insight for constructing a treatment strategy.

Sex Therapy In the context of sex therapy, the therapist incorporates the individual experiences of each partner and notes their interactions (if partnered). Sorting out the jigsaw puzzle that comprises any relationship is always the task of therapy. Each partner brings her/his story to the relationship, and the relationship, of course, has its own story as well.

A woman’s sexual self is, in many ways, consistent with her identity; therefore, an intimate exploration of

her history vis-à-vis identity formation is a useful guide in treatment. Because self-objectification may have obscured her ability to know herself accurately, cultivating healthy boundaries is one way to gain clarity and perspective about her experience as a sexual being.21 The therapist or the clinician must challenge the woman’s limiting assumptions about the self and her relational possibilities. Resolving past issues of abuse, trauma, parentification, or exploitation can provide release from an identity of “victim” or sense of powerlessness. The clinician can help the patient to become responsible for her own sensual experience and to give up self-imposed limitations.

In a survey assessing what was considered the greatest sexual “turn on” for women, Ogden found that 4 of 5 women said it was “love.”25 In this same survey, many male respondents similarly described themselves as wanting connection, feelings, and meaning in their sexual relating.25 Ultimately, a major goal for successful treatment of HSDD is to help the woman understand and develop her authentic sexual identity and to choose partners with whom she would be fully permitted to experience it. The “intersystems model” mentioned earlier views HSDD as a relational issue.20 There is no “identified patient,” and the treatment addresses the complex individual, intergenerational, and interpersonal issues that collectively have an impact on the relating of the system that is the couple.21

The Partner Component This treatment approach will help partners to recognize feelings and thoughts as they relate to one another, as well as increase their capacity for effective communication. In addition, ongoing discussions with a professional sex therapist will dispel myths and misinformation about sexuality and increase comfort with an expanded repertoire of sexual activity.

Perel identifies the difficulty of melding the domestic with the erotic in long-term relationships.23,26 As a couple becomes overly familiar, they lose the mystery and lack of predictability that once facilitated sexual excitement. In this model of treatment, the therapist explores each individual’s background and its impact on sexuality. Previously held yet unconscious limiting beliefs, assumptions, and inhibitions are illuminated. The partners are helped to see how they enact such irrational beliefs in the shared space of the relationship.

The therapist challenges these assumptions and supports the removal Continued on page 23

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Hypoactive Sexual Desire Disorder... Continued from page 22 of self-imposed prohibitions, promoting new and different opportunities for intimate sexual relating. Perel states that “the rules for desire are not the same as the rules for good citizenship.”25 Each individual is encouraged to explore the fantasy and eroticism that may exist in the quiet recesses of a mind wrapped in a blanket of taboo. The couple is encouraged to explore these fantasies and permit flexibility in their relational dynamics to promote a new eroticism in their relationship.

Mindfulness Cognitive-Behavioral Therapy Mindfulness-based cognitive-behavioral therapy is a means for facilitating body awareness and changing negative automatic thoughts about the self or about sexual activity.27 Theoretically, this approach could result in changes in sexual behavior, because negative thoughts about sex or body image are repeatedly replaced with more positive cognitions. Mindfulness may also permit a woman to become more aware of her physiologic arousal, thereby facilitating integration with her cognitive and affective experiences.28 Often, mindfulness and other sensually focused homework exercises are recommended for the woman and her partner.29 The work of therapy requires a commitment

to cognitive and behavioral change, something that is reinforced outside of the office setting.

Conclusion Low sexual desire in women is a complex condition involving a variety of issues. Current classifications for diagnosing HSDD fail to consider the larger context in which sexuality is experienced. Furthermore, this condition is extremely common in women; therefore, a reconceptualization of what constitutes a disorder of desire is prudent.

This process has ignited a movement toward a more accurate description of the broad range of female sexuality, allowing for its variability and difference from men’s sexual functioning.

This will assist clinicians in better treatment of women’s sexual difficulties, without being constrained by the ongoing debate over what constitutes a female sexual disorder.

Regardless of the classification debate, there is an increasing interest in treatment of women with HSDD; furthermore, sexuality experts have identified exciting possibilities for successful treatment of women and their partners.

Newer approaches to treatment recognize the many forces that comprise a woman’s sexual identity, such as her culture, family of origin, psychological

issues, personality, and life experiences.

All these factors contribute to our understanding of how she sees herself as a sexual being and as a sexual partner.

Furthermore, depathologizing women’s low sexual desire permits a more accurate portrayal of women’s sexuality as fluid, responsive, and contextual.

Successful treatment of HSDD will only be possible when this rich context is acknowledged. ■ references

1. Basson R. Chapter 2: Sexual desire/arousal disorders in women. In: Leiblum S, ed. Principles and Practice of Sex Therapy. 4th ed. New York: Guilford Press; 2006.

2. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (Text Revision). Washington, DC: American Psychiatric Association; 2000.

3. Freud S. Three Essays on the Theory of Sexuality.

Standard Edition. London: Hogarth Press; 1953:125-243.

4. Tiefer L. Sex therapy as a humanistic enterprise. Sex Relationship Ther. 2006;21:359-375.

5. Wood JM, Koch PB, Mansfield PK. Women’s sexual desire: a feminist critique. J Sex Res. 2006;43:236-244.

6. Irvine JM. Disorders of Desire: Sex and Gender in Modern American Sexology. Philadelphia: Temple University Press; 1990.

7. Masters WH, Johnson VE. Human Sexual Response.

Boston: Little, Brown; 1966.

8. Kaplan HS. Disorders of Sexual Desire and Other New Concepts and Techniques in Sex Therapy. New York: Brunner/Mazel; 1979.

9. Basson R. The female sexual response: a different model. J Sex Marital Ther. 2000;26:51-65.

10. Sims KE, Meana M. Why did passion wane? A qualitative study of married women’s attributions for declines in sexual desire. J Sex Marital Ther. 2010; 36:360-380.

11. Kingsberg SA, Altman AM, Parish SJ. Sexuality, assessment and treatment of hypoactive sexual desire disorder. Sex Reprod Menopause. 2010;(Feb suppl):26-28.

12. Simon JA. Low sexual desire—is it all in her head?

Pathophysiology, diagnosis, and treatment of hypoactive sexual desire disorder. Postgrad Med. 2010;122:128-136.

13. Basson R, Berman J, Bernett A, et al. Report of the international consensus development conference on female sexual dysfunction: definitions and classifications. J Urol. 2000;163:888-893.

14. Laan E, Everaerd W. Physiological measures of vaginal vasocongestion. Int J Impot Res. 1998;10(suppl 2): S107-S110.

15. Lieblum S. Principles and Practice of Sex Therapy, 4th ed. New York: Guilford Press; 2007.

16. Chivers ML, Seto MC, Blanchard R. Gender and sexual orientation differences in sexual response to sexual activities versus gender of actors in sexual films.

J Pers Soc Psychol. 2007;93:1108-1121.

17. Laumann EO, Paik A, Rosen RC. Sexual dysfunction in the United States: prevalence and predictors.

JAMA. 1999;281:537-544.

18. Kaschak E, Tiefer L. A New View of Women’s Sexual Problems. New York: Haworth Press; 2001.

19. Toates F. An integrative theoretical framework for understanding sexual motivation, arousal, and behavior.

J Sex Res. 2009;46:168-193.

20. Hertlein KM, Weeks GR, Gambescia N. The treatment of hypoactive sexual desire disorder. In: Hertlein K, Weeks GR, Gambescia, N, eds. Systemic Sex Therapy.

New York: Routledge; 2009.

21. Weeks GR, Gambescia N. Hypoactive Sexual Desire: Integrating Sex and Couple Therapy. New York: W.W. Norton & Company; 2002.

22. Steer A, Tiggemann M. The role of self-objectification in women’s sexual functioning. J Soc Clin Psychol.

2008;27:205-225.

23. Perel E. Mating in Captivity: Reconciling the Erotic and the Domestic. New York: Harper Collins; 2006.

24. Tiefer L. The “consensus” conference on female sexual dysfunction: conflicts of interest and hidden agendas. J Sex Marital Ther. 2001;27:227-236.

25. Ogden G. The Return of Desire: A Guide to Rediscovering Your Sexual Passion. Boston: Trumpeter; 2008.

26. Perel E. The double flame: reconciling intimacy and sexuality, reviving desire. In: Leiblum SR, ed. Treating Sexual Desire Disorders: A Clinical Casebook. New York: Guilford Press; 2010.

27. Brotto LA, Woo JT. Cognitive-behavioral and mindfulness-based therapy for low sexual desire. In: Leiblum S, ed. Treating Sexual Desire Disorders: A Clinical Casebook. New York: Guilford Press; 2010.

28. Brotto LA, Basson R, Luria M. A mindfulness-based group psychoeducational intervention targeting sexual arousal disorder in women. J Sex Med. 2008;5:1646-1659.

29. Gambescia N, Weeks GR. Sexual dysfunction. In: Kazantzis N, L’Abate L, Gerard F, eds. Handbook of Homework Assignments in Psychotherapy: Research, Practice, and Prevention. New York: Springer; 2007.

COMMENTARY

Female Sexual Health: Breaking the Silence in provider–Client Interactions

By Margaret-Rose Agostino, DNP, MSW, RN-BC, IBCLC, Assistant Professor, Delaware State University, Dover

T

he age-old adage, “Ask me no questions, and I’ll tell you no lies” could very well be applied to the lack of discourse between providers and their adult female patients regarding sexual health (ie, sexual functioning). Time constraints of the proverbial 15 minutes of reimbursed time per contact compound the issue.

Providers are left with the quandary of starting a very sensitive discussion and not having enough time to provide the safe environment of conducting this discussion in the privacy of the office versus in the examination room, nor the resources to refer the patient if a problem is identified.

Our society claims to be sophisticated regarding sexual freedom, yet the subject of female sexual functioning or sexual health is still viewed as “private” and “taboo” on an individual basis.

How do women know what is normal and healthy regarding their sexuality?

The classic groundbreaking work of Masters and Johnson in the 1960s did much to dispel the myths regarding female sexual function, yet here we are more than 40 years later, and a clear definition of “normal” remains elusive.

Richard Balon,1 as well as the present article by Pamela Fawcett Pressman and Nancy Gambescia, provide insight into the lack of clarity that still exists in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision regarding this topic, and the need to more clearly define not only what is normal but also the variances that cause distress for women.

But what is normal? Does the preponderance of sex-laden reality series and sitcoms on television provide a realistic portrayal of women and normal sexual functioning? We are also bombarded with commercials for products dealing with everything from birth control to urinary incontinence. Often

these commercials portray conditions that should be discussed with a healthcare provider as part of normal aging; instead, their message is to use an “X, Y, or Z” product and “get on with your active life.” The popularity of the television shows by Dr Oz and Dr Phil suggest that the public is hungry for accurate information from a credible source regarding their “whole health,” including those “private issues” that many cultures still view as taboo for individual discussion.

The burden of breaking this silence clearly falls on the provider. Sexuality experts Kingsberg and Althof suggest that although data indicate a high prevalence of female sexual disorders, including hypoactive sexual desire disorder, few providers include even a brief screening of sexual health on a routine basis.2 Kingsberg and Althof further suggest that even with the time constraints of today’s provider, a brief

assessment can be linked to the assessment of the woman’s current reproductive stage.2 When these screenings are practiced universally with all female patients, screening becomes normative, and the burden of revealing an area of dysfunction shifts away from the patient to the provider.

Depending on the cultural and religious upbringing, some women may still hold to the belief that the plight of women should be borne in silence, so as not to live with shame. An informed, culturally competent approach, which is individualized to the presenting patient, provides the opportunity to break the silence surrounding female sexual health. ■ references 1. Balon R. The DSM criteria of sexual dysfunction: need for a change. J Sex Marital Ther. 2008;34:186-197.

2. Kingsberg S, Althof SE. Evaluation and treatment of female sexual disorders. Int Urogynecol J Pelvic Floor Dysfunct. 2009;20(suppl 1):33-34.

APRIL 2011 l VOLUME 3, NUMBER 2

23

Urology News

Shock-wave therapy Improves Severe Erectile Dysfunction

By Jill Stein

L

ow-intensity shock-wave therapy applied to the penis seems to be an effective treatment for men with severe erectile dysfunction (ED) who have failed standard therapy with an oral phosphodiesterase type 5 (PDE-5) inhibitor, investigators said at the 2011 European Association of Urology Congress.

An earlier study by the same group showed that the treatment can improve ED in men who respond to PDE-5 inhibitor therapy.

“All currently available ED treatments enhance sexual function, by improving the quality of erections, but none is curative,” said Yoram Vardi, MD, Director, Neuro-Urology Department, Rambam Medical Center, Haifa, Israel. “PDE-5 inhibitors, clearly the most popular ED treatment, are associated with unpleasant side effects and poor compliance.”

Dr Vardi said that the results are very encouraging, noting that “this modality seems to have the potential to be a rapid and curative therapy for ED.” The study involved 29 men with vasculogenic ED who had not responded to PDE-5 inhibitor therapy; 60% of the men had diabetes, and 85% had cardiovascular disease.

Low-intensity shock-wave therapy is increasingly being used to induce neovascularization in patients with angina who are not candidates for coronary surgery or angioplasty. The approach has

3 weeks, which were repeated 3 weeks later. During each treatment session, lowenergy shock-wave therapy was applied on the penile shaft and crus for 3 minutes at 5 different anatomic sites. The shock-

“Low-intensity shock-wave therapy was able to convert most nonresponders into PDE-5 inhibitor responders, thereby enabling non–sexually functioning men to achieve vaginal penetration and full intercourse.”

—Yoram Vardi, MD

proved effective in other conditions that result from impaired vascularity, such as chronic diabetic foot ulcers.

Because shock-wave therapy can improve the vasculature of the heart, the research team concluded that it might also be effective in the penis, because ED usually has a vascular origin.

The shock-wave therapy protocol involved 2 weekly treatment sessions for

wave intensity is roughly one tenth of that used to pulverize kidney stones.

Patients were assessed at 1 month without the use of a PDE-5 inhibitor, and then again at 2 months, while they were using on-demand PDE-5 inhibitor therapy.

The coprimary end points were changes in the erectile function domain of the International Index of Erectile

Function (IIEF) score and the change in penile rigidity score.

Overall, a total of 21 patients (72.4%) achieved a penile rigidity score ≥3, meaning that they were able to achieve vaginal penetration and full intercourse.

At the 2-month visit, the mean IIEF erectile function domain score increased to 18.8 ± 1.1. Eight patients had normalized erectile function at the second follow-up visit, and were able to function sexually without medication.

No patient reported any pain related to treatment or any other adverse event during follow-up.

“The findings mean that low-intensity shock-wave therapy was able to convert most nonresponders into PDE-5 inhibitor responders, thereby enabling non–sexually functioning men to achieve vaginal penetration and full intercourse,” Dr Vardi observed.

Based on his experience, most men who are treated with a PDE-5 inhibitor eventually seek alternative treatments that will improve or cure their ED. “If the results are confirmed in larger, long-term, randomized, controlled studies, this treatment may prove to be the first to actually restore erectile function,” he said. ■

Botox Helps Control Idiopathic Detrusor overactivity in women

N

ew findings presented at the 2011 European Association of Urology Congress demonstrate “conclusively” that botulinum toxin A (BoNT-A)—better known as Botox in this country—is effective for the treatment of women with idiopathic detrusor overactivity who have failed conventional anticholinergic therapy.

The UK investigators say that their study of 240 women is the largest to date to test the use of BoNT-A in refractory idiopathic detrusor overactivity, which leads to incontinence. At the time of enrollment, all patients had at least 8 voids and 2 urgency episodes within a 24-hour period.

“The data clearly confirm the efficacy of BoNT-A for symptoms of idiopathic detrusor overactivity,” said Douglas G. Tincello, MB ChB, MD, Senior Lecturer/ Honorary Consultant Gynecologist, Leicester Royal Infirmary.

Treatments for detrusor overactivity include behavioral therapy and anticholinergic drugs that have moderate

24

efficacy and are limited by side effects, including constipation, dry mouth, and blurred vision, which lead to a high rate of treatment discontinuation, he explained.

“The magnitude of effects occurring in the BoNT-A group was far greater than the improvements that have been reported for any of the available anticholinergic drugs.”

—Douglas G. Tincello, MB ChB,

MD

BoNT-A, which is an established treatment for muscle spasticity disorders, including cervical dysplasia and cerebral palsy, has been used to treat neurogenic detrusor overactivity and,

APRIL 2011 l VOLUME 3, NUMBER 2

more recently, idiopathic detrusor overactivity.

All patients had undergone 8 weeks of anticholinergic treatment and had only slight improvement or actual deterioration, or had stopped treatment prematurely for different reasons. The primary end point of the study was voiding frequency per 24 hours at 6 months.

The women were divided into 2 similar groups, with 116 women receiving 200 IU of BoNT-A and 111 women receiving placebo. Results showed a significantly lower voiding frequency with BoNT-A than in the placebo group (8.71 vs 10.52 episodes per 24 hours, respectively).

Similarly large reductions were observed in 6-month outcomes with urgency episodes (4.39 vs 6.82) and leakage episodes (3.28 vs 5.74).

At 6 months, 30% of the women treated with BoNT-A were continent, with a complete absence of leaks, compared with 12% of the women who received placebo, a significant difference.

Eighteen (16%) women in the BoNTA group and 4 (4%) women in the placebo group required an indwelling catheter or training in intermittent selfcatheterization. Thirty-six (31%) women and 12 (11%) women in the 2 groups, respectively, developed a urinary tract infection.

“The magnitude of effects occurring in the BoNT-A group was far greater than the improvements that have been reported for any of the available anticholinergic drugs, and the effects were persistent at 6 months’ follow-up, with clear differences between women in the treated arm and placebo arm,” Dr Tincello commented. He added that the safety data concur with published reports, concluding that BoNT-A is a safe treatment and that the major side effects are voiding dysfunction and urinary tract infection.

Dr Tincello concluded that the size of the study allows practitioners to counsel patients accurately about the efficacy and safety of this agent.—JS ■

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Nutrition

Choline Essential During Pregnancy

By Jessica A. Smith

C

holine is an essential amino acid that is important for overall well-being in men and women, and is especially crucial for pregnant women, because the dietary levels of choline in the mother directly affect the fetal brain development, similar to folic acid, according to Zeisel (Zeisel SH. J Nutr. 2011 Jan 26. Epub ahead of print).

Table Foods Rich in Choline Serving size

Choline, mg

Beef liver

3 oz

355

Chicken liver

3 oz

308

Toasted wheat germ

1 cup

172

Egg

1 large

126

Pork loin

3 oz

103

Chicken breast

3 oz

73

Atlantic cod

3 oz

71

Lean beef

3 oz

67

Brussels sprouts

1 cup

63

Broccoli

1 cup

62

Canned shrimp

3 oz

60

Salmon

3 oz

56

Cauliflower

1 cup

47

Skim milk

1 cup (8 fl oz)

38

Peanut butter

2 Tbsp

20

Milk chocolate

1.5 oz

20

Food

Along with its overall roles of protecting the structure of cell membranes, helping in the breakdown and use of fat for energy, and transporting and eliminating cholesterol from the body, choline is also important to female and male fertility.

Studies in animals have shown that choline plays an essential role in developing the memory center in the brain by helping to increase the number of cells in that area during fetal development.

Although it is well-known that folic acid supplementation decreases the risk for embryonic neural tube defects (NTDs), the role of choline in this area is not as widely known. According to the current literature, choline deficiency increases the risk for NTDs, which develop between the third and fourth weeks of gestation, often before a woman is aware that she is pregnant.

Women with diets rich in choline have a decreased risk for NTDs. Choline is often included in daily vitamin supplementations, and a large variety of healthy foods provide good amounts of choline (Table). The recommended daily intake of choline for pregnant women is 450 mg; for lactating women, the recommended amount increases to 550 mg (Higdon J. Linus Pauling Institute, Oregon State University, http:/lpi.oregonstate.edu/infocenter/ othernuts/choline).

A woman’s need for choline does not end after her childbearing years, however. As suggested by Zeisel, postmenopausal women must ensure that they are consuming sufficient dietary

Isoflavones Decrease Postmenopausal Insomnia

T

he insomnia that often plagues postmenopausal women can be alleviated with isoflavones, according to results of a new study (Hachul H, et al. Menopause. 2011;18:178-184).

In this controlled, double-blind study, investigators examined changes in sleep parameters in postmenopausal women with insomnia before and after treatment with isoflavones.

Isoflavones are found in abundance in soybeans and soy products and to a lesser degree in some other plants; isoflavones are naturally occurring phytohormones (or estrogen-like plant hormones) that have been shown in previous research to produce estrogenlike health benefits in women.

In this new study, 38 postmenopausal women with insomnia received either 80 mg of isoflavones daily or a placebo

26

for a period of 4 months. Sleep parameters were measured through questionnaires and with polysomnography.

Polysomnography revealed a significant improvement in overall sleep parameters in the women receiving isoflavones—from 77.9% to 83.9% compared with from 77.6% to 81.2% for those receiving placebo. The reduction in moderate or intense insomnia was also significant in those receiving isoflavones—from 89.5% to 36.9% compared with from 94.7% to 63.2% for those receiving placebo.

Another significant finding was the reduction in the intensity and frequency of hot flashes in those taking isoflavones.

Isoflavones are available in many forms of supplementations in addition to food products. ■

APRIL 2011 l VOLUME 3, NUMBER 2

choline to avoid liver or muscle dysfunction that is associated with a deficiency of this nutrient.

Furthermore, according to Zeisel and colleagues, before menopause more than 50% of women are resistant to organ dysfunction associated with choline deficiency, because estrogen induces the gene phosphatidylethanolamine-N-methyltransferase (PEMT), which triggers the synthesis of choline.

Other premenopausal women are unresponsive to estrogen induction of PEMT, which makes it important for these women to receive dietary supplementation of choline. ■ For more information consult the US Department of Agriculture’s Database for the Choline Content of Common Foods at www.nal.usda.gov/fnic/ foodcomp/Data/Choline/Choline.pdf.

Recipe for a Healthy Pregnancy Low-Fat Broccoli Mushroom Leek Quiche Courtesy of Stephanie Laudien

What you will need: 1 pie shell, preferably whole wheat 1 tbsp olive oil 1 leek 8 mushrooms 2 cloves garlic 1 broccoli crown 2 stems fresh rosemary 3 eggs 1¼ cup skim milk ½ tsp salt ¼ tsp pepper ½ cup Swiss cheese (optional) Directions: 1. If using a frozen pie shell, remove from the freezer; preheat oven to 350° 2. Place a pan on medium heat, add olive oil; slice the leek and add to pan 3. Slice the mushrooms and mix with the leeks; add garlic and stir often. Do not cover the pan; cook for 5 minutes 4. Cut the broccoli crown into small pieces, add to the pan. Cook for another 5 minutes, then add fresh rosemary; mix well and cook for 1 minute; remove from heat 5. In a separate bowl, crack the eggs, scrambling slightly; add milk, salt, and pepper and stir well 6. Pour the vegetable mixture into the pie shell 7. Place the pie shell on a foil-covered cookie sheet and carefully pour in the egg mixture; top with Swiss cheese if you’d like, and bake for 40 minutes 8. Allow to cool for 10 minutes before slicing Health Benefits This easy, low-fat recipe provides nutrients essential especially during pregnancy. The eggs provide iron and protein, and the skim milk and cheese provide calcium. Known as “super vegetable,” broccoli also provides calcium and a high amount of vitamin C, as well as folic acid, which is critical during pregnancy. Leeks are another source of folic acid and vitamin C, as well as iron and vitamin B6. Mushrooms, although often overlooked for their nutritional benefits, are a source of iron, vitamin C, and vitamin D. Garlic enhances the immune system, promotes circulation, and contains antioxidants. Even rosemary imparts benefits, with its antioxidant and anti-inflammatory properties.

Send Us Your Healthy Recipes for Women If you have a recipe that is especially beneficial to women’s health, pregnant women, lactating mothers, or newborns, please send it to lara@novellushc.com.

Include a brief explanation of the health benefits of the recipe and any other tips you wish to share with your colleagues, as well as your name, and e-mail or phone number.

To submit online, go to www.infertilityrepronews.com/submit-recipe and upload the file.

Clinical News opioids linked...

Continued from page 18

conception place their offspring at increased risk for some birth defects, a recent analysis of data from the ongoing National Birth Defects Prevention Study (NBDPS) shows (Broussard CS, et al. Am J Obstet Gynecol. 2011 Feb 11.

Epub ahead of print).

Codeine, hydrocodone, and oxycodone were the most often reported prescription opioid analgesics used in the case-control NBDPS population; 2.6% of the 17,449 mothers of infants with birth defects (case mothers) and 2.0% of the 6701 control mothers reported therapeutic opioid use just before, or during, the first trimester of their pregnancies.

The risk for heart defects, including hypoplastic left heart syndrome, was approximately doubled, representing the largest increase in risk with opioid use. Other risks linked to opioid use included spina bifida, congenital hydrocephaly, congenital glaucoma, and gastroschisis.

“It’s important to acknowledge that although there is an increased risk for some types of major birth defects from an exposure to opioid analgesics, that absolute risk for any individual woman is relatively modest,” said lead investigator Cheryl S. Broussard, PhD, of the Centers for Disease Control and Prevention’s National Center on Birth Defects and Developmental Disabilities.

FDA Updated Antipsychotics labeling for risks in pregnancy In February 2011, the US Food and Drug Administration (FDA) updated the Pregnancy Section on the drug labels of all antipsychotics, providing consistent information on the risks for the offspring of mothers using these medications during pregnancy; these risks include extrapyramidal signs (ie, abnormal muscle movements) and withdrawal symptoms.

Symptoms of extrapyramidal signs and withdrawal in newborns could include agitation, abnormally increased or decreased muscle tone, tremor, tiredness, and severe difficulty breathing and feeding. In some babies, these symptoms dissipate within hours or days and therefore do not require treatment; for other newborns whose symptoms last, longer hospital stays are required.

The FDA advises providers to counsel women about the risks and benefits of taking antipsychotics during pregnancy, keeping in mind that these drugs cross the placenta. Neonates who show signs of extrapyramidal or withdrawal symptoms should be closely monitored, and any adverse events should be reported to

the FDA MedWatch program, by calling 800-332-1088.

Vitamin A Supplementation Does not prevent Motherto-Child HIV transmission, Improves Birth weight Previous studies have shown an association between low vitamin A levels in the mother’s blood and increased risk for mother-to-child transmission of HIV. A

new meta-analysis shows that using vitamin A supplements has little effect on the risk for mother-to-child transmission of the virus (Wiysonge CS, et al.

Cochrane Database Syst Rev. 2011 Jan 19;CD0036481).

The analysis included 5 randomized controlled trials conducted in Africa between 1995 and 2005, involving 7528 pregnant or postpartum women with HIV, to assess for HIV transmission dur-

Crinone® 4% Crinone® 8% (progesterone gel) For vaginal use only.

Rx only

BRIEF SUMMARY For full prescribing information, see package insert.

INDICATIONS AND USAGE Assisted Reproductive Technology Crinone 8% is indicated for progesterone supplementation or replacement as part of an Assisted Reproductive Technology (“ART”) treatment for infertile women with progesterone deficiency.

Secondary Amenorrhea Crinone 4% is indicated for the treatment of secondary amenorrhea. Crinone 8% is indicated for use in women who have failed to respond to treatment with Crinone 4%.

CONTRAINDICATIONS Crinone should not be used in individuals with any of the following conditions: known sensitivity to Crinone (progesterone or any of the other ingredients); undiagnosed vaginal bleeding; liver dysfunction or disease; known or suspected malignancy of the breast or genital organs; missed abortion; active thrombophlebitis or thromboembolic disorders, or a history of hormone-associated thrombophlebitis or thromboembolic disorders.

WARNINGS The physician should be alert to the earliest manifestations of thrombotic disorders (thrombophlebitis, cerebrovascular disorders, pulmonary embolism, and retinal thrombosis).

Should any of these occur or be suspected, the drug should be discontinued immediately.

Progesterone and progestins have been used to prevent miscarriage in women with a history of recurrent spontaneous pregnancy losses. No adequate evidence is available to show that they are effective for this purpose.

PRECAUTIONS General 1. The pretreatment physical examination should include special reference to breast and pelvic organs, as well as Papanicolaou smear.

2. In cases of breakthrough bleeding, as in all cases of irregular vaginal bleeding, nonfunctional causes should be considered. In cases of undiagnosed vaginal bleeding, adequate diagnostic measures should be undertaken.

3. Because progestogens may cause some degree of fluid retention, conditions which might be influenced by this factor (e.g., epilepsy, migraine, asthma, cardiac or renal dysfunction) require careful observation.

4. The pathologist should be advised of progesterone therapy when relevant specimens are submitted.

5. Patients who have a history of psychic depression should be carefully observed and the drug discontinued if the depression recurs to a serious degree.

6. A decrease in glucose tolerance has been observed in a small percentage of patients on estrogen-progestin combination drugs. The mechanism of this decrease is not known. For this reason, diabetic patients should be carefully observed while receiving progestin therapy.

Information for Patients The product should not be used concurrently with other local intravaginal therapy. If other local intravaginal therapy is to be used concurrently, there should be at least a 6-hour period before or after Crinone administration. Small, white globules may appear as a vaginal discharge possibly due to gel accumulation, even several days after usage.

Drug Interactions No drug interactions have been assessed with Crinone.

Carcinogenesis, Mutagenesis, Impairment of Fertility Nonclinical toxicity studies to determine the potential of Crinone to cause carcinogenicity or mutagenicity have not been performed. The effect of Crinone on fertility has not been evaluated in animals.

Pregnancy Crinone 8% has been used to support embryo implantation and maintain pregnancies through its use as part of ART treatment regimens in two clinical studies (studies COL1620-007US and COL1620-F01). In the first study (COL1620-007US), 54 Crinonetreated women had donor oocyte transfer procedures, and clinical pregnancies occurred in 26 women (48%). The outcomes of these 26 pregnancies were as follows: one woman had an elective termination of pregnancy at 19 weeks due to congenital malformations (omphalocele) associated with a chromosomal abnormality; one woman pregnant with triplets had an elective termination of her pregnancy; seven women had spontaneous abortions; and 17 women delivered 25 apparently normal newborns.

In the second study (COL1620-F01), Crinone 8% was used in the luteal phase support of women undergoing in vitro fertilization (“IVF”) procedures. In this multi-center, openlabel study, 139 women received Crinone 8% once daily beginning within 24 hours of embryo transfer and continuing through Day 30 post-transfer.

Clinical pregnancies assessed at Day 90 post-transfer were seen in 36 (26%) of women.

Thirty-two women (23%) delivered newborns and four women (3%) had spontaneous abortions. Of the 47 newborns delivered, one had a teratoma associated with a cleft palate; one had respiratory distress syndrome; 44 were apparently normal and one was lost to follow-up.

Geriatric Use The safety and effectiveness in geriatric patients (over age 65) have not been established.

Pediatric Use Safety and effectiveness in pediatric patients have not been established.

Nursing Mothers Detectable amounts of progestins have been identified in the milk of mothers receiving them. The effect of this on the nursing infant has not been determined.

ing pregnancy or via breastfeeding in relation to vitamin A supplementation, as well as on infant and maternal morbidity and mortality.

The mother’s use of vitamin A supplementation did not affect her risk of transmitting HIV to her infant, and did not improve preterm outcomes or mortality. However, prenatal vitamin A supplementation significantly improved birth weights. ■

ADVERSE REACTIONS Assisted Reproductive Technology In a study of 61 women with ovarian failure undergoing a donor oocyte transfer procedure receiving Crinone 8% twice daily, treatment-emergent adverse events occurring in 5% or more of the women were: bloating (7%), cramps not otherwise specified (15%), pain (8%), dizziness (5%), headache (13%), nausea (7%), breast pain (13%), moniliasis genital (5%), vaginal discharge (7%), pruritus genital (5%).

In a second clinical study of 139 women using Crinone 8% once daily for luteal phase support while undergoing an IVF procedure, treatment-emergent adverse events reported in 5% or greater of the women were: abdominal pain (12%), perineal pain female (17%), headache (17%), constipation (27%), diarrhea (8%), nausea (22%), vomiting (5%), arthralgia (8%), depression (11%), libido decreased (10%), nervousness (16%), somnolence (27%), breast enlargement (40%), dyspareunia (6%), nocturia (13%).

Secondary Amenorrhea In three studies, 127 women with secondary amenorrhea received estrogen replacement therapy and Crinone 4% or 8% every other day for six doses. Treatment-emergent adverse events during estrogen and Crinone treatment that occurred in 5% or more of women treated with Crinone 4% or Crinone 8% respectively were: abdominal pain (5%, 9%), appetite increased (5%, 8%), bloating (13%, 12%), cramps not otherwise specified (19%, 26%), fatigue (21%, 22%), headache (19%, 15%), nausea (8%, 6%), back pain (8%, 3%), myalgia (8%, 0%), depression (19%, 15%), emotional lability (23%, 22%), sleep disorder (18%, 18%), vaginal discharge (11%, 3%), upper respiratory tract infection (5%, 8%), and pruritus genital (2%, 6%).

Additional adverse events reported in women at a frequency of less than 5% in Crinone ART and secondary amenorrhea studies and not listed above include: autonomic nervous system–mouth dry, sweating increased; body as a whole–abnormal crying, allergic reaction, allergy, appetite decreased, asthenia, edema, face edema, fever, hot flushes, influenza-like symptoms, water retention, xerophthalmia; cardiovascular, general–syncope; central and peripheral nervous system–migraine, tremor; gastro-intestinal–dyspepsia, eructation, flatulence, gastritis, toothache; metabolic and nutritional–thirst; musculo-skeletal system– cramps legs, leg pain, skeletal pain; neoplasm–benign cyst; platelet, bleeding & clotting– purpura; psychiatric–aggressive reactions, forgetfulness, insomnia; red blood cell– anemia; reproductive, female–dysmenorrhea, premenstrual tension, vaginal dryness; resistance mechanism–infection, pharyngitis, sinusitis, urinary tract infection; respiratory system–asthma, dyspnea, hyperventilation, rhinitis; skin and appendages–acne, pruritus, rash, seborrhea, skin discoloration, skin disorder, urticaria; urinary system–cystitis, dysuria, micturition frequency; vision disorders–conjunctivitis.

OVERDOSAGE There have been no reports of overdosage with Crinone. In the case of overdosage, however, discontinue Crinone, treat the patient symptomatically, and institute supportive measures.

As with all prescription drugs, this medicine should be kept out of the reach of children.

DOSAGE AND ADMINISTRATION Assisted Reproductive Technology Crinone 8% is administered vaginally at a dose of 90 mg once daily in women who require progesterone supplementation. Crinone 8% is administered vaginally at a dose of 90 mg twice daily in women with partial or complete ovarian failure who require progesterone replacement. If pregnancy occurs, treatment may be continued until placental autonomy is achieved, up to 10-12 weeks.

Secondary Amenorrhea Crinone 4% is administered vaginally every other day up to a total of six doses. For women who fail to respond, a trial of Crinone 8% every other day up to a total of six doses may be instituted.

It is important to note that a dosage increase from the 4% gel can only be accomplished by using the 8% gel. Increasing the volume of gel administered does not increase the amount of progesterone absorbed.

HOW SUPPLIED Crinone is available in the following strengths: 4% gel (45 mg) in a single use, one piece, disposable, white polyethylene vaginal applicator with a twist-off top. Each applicator contains 1.45 g of gel and delivers 1.125 g of gel.

NDC 52544-283-24 - 6 Single-use prefilled applicators.

8% gel (90 mg) in a single use, one piece, disposable, white polyethylene vaginal applicator with a twist-off top. Each applicator contains 1.45 g of gel and delivers 1.125 g of gel.

NDC 52544-284-12 - 15 Single-use prefilled applicators.

Each applicator is wrapped and sealed in a foil overwrap.

Store at 20-25°C (68-77°F). [See USP controlled room temperature.]

Rx only References: 1. CRINONE® prescribing information. Morristown, NJ: Watson Pharmaceuticals, Inc. June 2010. 2. Gibbons WE, Toner JP, Hamacher P, Kolm P. Experience with a novel vaginal progesterone preparation in a donor oocyte program. Fertil Steril.

1998;69:96-101.

Address medical inquiries to: WATSON Medical Communications P.O. Box 1953 Morristown, NJ 07962-1953 800-272-5525 Distributed by: Watson Pharma, Inc., Morristown, NJ 07962 USA Manufactured by: Fleet Laboratories Ltd., Watford, Herts WD18 7JJ UK Revised: July 2010

APRIL 2011 l VOLUME 3, NUMBER 2

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Progesterone # Fact 5 Only one progesterone is FDA approved for progesterone replacement.

Itâ&#x20AC;&#x2122;s a fact.

When you need to replace progesterone in your patients undergoing donor egg cycles, only CRINONE offers the confidence of FDA approval for progesterone replacement.1 In fact, CRINONE has demonstrated comparable pregnancy rates to IM P in a prospective, randomized trial of women in a donor egg cycle.2 Before you prescribe, check the facts.

The only