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Clinical News Women’s LDL-C Levels Rise at Menopause, Increasing CHD Risk It has long been known that the risk for coronary heart disease (CHD) increases in women with menopause, but the reason for that was not understood. Now results of a new, prospective study show that low-density lipoprotein cholesterol (LDL-C) and

apolipoprotein (Apo) B levels rise significantly within 1 year of the final menstrual period, consistent with other menopause-induced changes, which explains the increased CHD risk in postmenopausal women (Matthews KA, et al. J Am Coll Cardiol. 2009;54: 2374-2375). The SWAN (Study of Women’s Health Across the Nation) included

3302 white and ethnic (black, Hispanic, Japanese, Chinese) women undergoing menopause. Of these, 1054 women reached natural menopause after 10 examinations. Of all CHD risk factors measured during the study, only LDL-C and ApoB levels rose significantly within 1 year of the final menstruation. Participants’ average LDL-C levels were between 113 mg/dL and

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116 mg/dL in the 3 to 5 years before the last period. At 1 year postmenopause, LDL-C levels increased to an average of >125 mg/dL, before leveling off at just under 130 mg/dL, the level classified as “borderline high” risk for CHD. JoAnn Manson, Chief of Preventive Medicine at Brigham and Women’s Hospital, Boston, commented that the SWAN “helps to understand the role of a woman’s natural estrogen in protecting the heart and affecting risk factors for coronary disease.” She noted that perimenopausal women and their clinicians should follow their lipid profile closely at menopause. Long-term use of estrogen therapy at menopause, however, is controversial, because of the potential risk for breast cancer.

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An analysis of insulinlike growth factor-1 (IGF-1) levels in 531 premenopausal women showed a 10% decline per decade of age in the levels of this hormone (Adami S, et al. Bone. 2010; 46: 244-247). The women (aged 20-50 years) all participated in the 20-site Bone Turnover Range of Normality study, and all had regular monthly menses. Results showed that IGF-1 levels had a significant negative correlation with age. Serum levels of bone-formation markers, such as serum parathyroid hormone, also declined progressively. This is the first time that an association between the progressive, age-related decline in bone formation markers and the IGF-1 hormone was confirmed. The study also showed that exercising for at least 1 hour/week is associated with increased levels of IGF-1.

Childhood Cancer Treatment Can Reduce Fertility in Males Results of a large study investigating the impact of early-age cancer treatment on male fertility have shown significantly reduced fertility in that patient population (Green DM, et al. J Clin Oncol. 2010;28:332-339). The analysis was based on questionnaires completed by 6224 men aged 15 to 44 who had survived childhood cancer. These men were 44% less likely to have sired a pregnancy than their siblings who did not have cancer treatment. All the men were diagnosed before age 21 (between 1970 and 1986) and were treated at one of the 26 American institutions participating in the Childhood Cancer Survivor Study. Having had radiation therapy for testicular cancer (with a dose of >7.5 Gy) was associated with an 88% reduction in the likelihood of the cancersurviving males impregnating their partners. Other factors associated with Continued on page 27

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february 2010 I Vol 2, no 1

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CONTENTS

february 2010

Vol 2, no 1

PUBLISHING STAFF

Managing Director Jack Iannaccone jack@infertilitynurse.org 732-992-1537 Editorial Director Dalia Buffery dalia@greenhillhc.com 732-992-1889 Associate Editor Lara J. Reiman lara@greenhillhc.com 732-992-1892 Editorial Assistant Jessica Smith Director, Client Services Russell Hennessy russell@greenhillhc.com 732-992-1888 Director, Client Services Mark Timko mark@greenhillhc.com Senior Production Manager Lynn Hamilton Business Manager Blanche Marchitto Editorial Contact: Telephone: 732-992-1892 Fax: 732-656-7938

MISSION STATEMENT The OB/GYN and Infertility Nurse is the official publication of the American Academy of OB/GYN and Infertility Nurses. The OB/GYN and Infertility Nurse provides practical, authoritative, cutting-edge information on the physiologic, medical, and psychological aspects of human reproduction, focusing on the role of the OB/GYN, infertility, and urology nurse in patient care. Our journal offers a forum for nurses, nurse practitioners, physician assistants, administrators, researchers, and all others involved in OB/GYN, infertility, and urology to discuss the entire scope of current and emerging diagnostic and therapeutic options, as well as counseling and patient follow-up for men and women throughout their reproductive years and beyond. Written by nurses for nurses, The OB/GYN and Infertility Nurse promotes peer-to-peer collaboration among all nursing professionals toward the advancement of integrated services for optimal care delivery. The journal offers continuing education for all nurses involved in these interrelated fields of patient management. The OB/GYN and Infertility Nurse, ISSN 2151-8394 (print); ISSN 2151-8408 (online), is published 6 times a year by Novellus Healthcare Communications, LLC, 241 Forsgate Drive, Suite 205D, Monroe Twp, NJ 08831. Copyright ©2010 by Novellus Healthcare Communications, LLC. All rights reserved. The OB/GYN and Infertility Nurse 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 The OB/GYN and Infertility Nurse do not necessarily reflect those of the Editorial Board, the Editors, or the Publisher. Publication of an advertisement or other product mentioned in The OB/GYN and Infertility Nurse 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. YEARLY SUBSCRIPTION RATES: United States and possessions: individuals, $105.00; institutions, $135.00; single issue, $17.00. Orders will be billed at individual rates unless proof status is confirmed. SUBSCRIPTIONS/CHANGE OF ADDRESS should be directed to CIRCULATION DIRECTOR, The OB/GYN and Infertility Nurse, 241 Forsgate Drive, Suite 205D, Monroe Twp, NJ 08831; Fax: 732656-7938.

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february 2010 I Vol 2, no 1

CLINICAL NEWS

3 Women’s LDL-C Levels Rise at Menopause IGF-1’s Role in Bone Loss with Aging Childhood Cancer Treatment Can Reduce Fertility in Males 27 Size of American Neonates Decreasing Uterine Fibroid Size Sole Predictor of Growth Rate A Yoga Session a Day Keeps Stress Away

8

THE OB/GYN NURSE

8 9 10 12

Endometriosis—More Than “Killer Cramps” The New Mammography Screening Recommendations Ectopic Pregnancy: Prompt Diagnosis Can Save Your Patient’s Life Rituximab an Alternative to Standard Cyclophosphamide in Patients with Vasculitis 13 Bone Health Concerns in Women Treated for Breast Cancer Antithrombotic Therapy Does Not Improve Pregnancy Outcomes in Women with Unexplained Recurrent Miscarriage

10

CONTINUING EDUCATION

14 Cancer Treatment–Related Bone Loss and Osteoporosis 16 A Fertility Nurse Perspective 17

PHARMACY CORNER

18 Progesterone Support in IVF THE INFERTILITY NURSE

19 Nurses Are Frontline Responders in Ovarian Hyperstimulation 20 21 22 24

Syndrome Management Making Injection Training Personalized and Convenient for Patients Infertile Couples Report High Use of CAM Therapies Midwest Reproductive Symposium Nurse Practicum Navigating the Legal Aspects of Surrogacy Surrogacy in the News: A Complex Process, with Successful Results Exposure to Compound in Plastics a Risk for IVF Failure

26

THE UROLOGY NURSE

25 The Many Faces of Gonadotoxins Linked to Male Infertility NUTRITION

26 More Evidence that Soy Foods Reduce Breast Cancer Recurrence, Death

CORRECTIONS The December 2009 Cover article “Starting CAREN” failed to identify the cover photo as representing nurses from Carolina Conceptions, not from CAREN. The title of the article further created the wrong impression that CAREN had been started by the nurses of Carolina Conceptions. Instead, CAREN was created by a group of nurses from several fertility centers in that region. We regret these errors and any disappointment these might have caused CAREN members. In addition, the Table on page 9 depicted pregnancy rates for Carolina Conceptions from January through August 2009, not from 2006 to 2009.

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From the Editors

Ask the Expert

We invite you to submit a practical question from your actual daily practice in OB/GYN or in Infertility for which you would like to get a “second opinion” or see how your colleagues address it. If neither of us is able to respond to your question, we will get an expert in the appropriate field to respond to it.

Co-Editor-in-Chief Debra Moynihan, WHNP-BC, MSN, Carolina OB/GYN Question: When taking an obstetric history from a patient, I get confused about gravida and parity numbers. What do the individual numbers mean? Answer: Many people get confused about the placement of the numbers. Gravida refers to the total number of pregnancies the patient has had, including the current one. Para is the number of pregnancies that are delivered at ≥20 weeks gestation. When entering gravida and para, the lines look like: G_P_ _ _ _. After the P, the first line is for full-

term births (>36 weeks), the second line is for preterm births (<36 weeks), the third line is for abortions (including spontaneous abortions, elective abortions, and ectopic pregnancies), and the fourth line is for living children. For example, you are interviewing a patient about her obstetric history. This is her sixth pregnancy, and she has 3 children at home. She admits to having

had an abortion at age 16. Her first child was born 38 weeks gestation, and her second child was born at 36 weeks gestation. The patient had an ectopic pregnancy 2 years after the birth of her second child, followed by another child born at 40 weeks gestation. This patient’s history would look like this: G6P2123.

Co-Editor-in-Chief Sue Jasulaitis, RN, MS, Fertility Centers of Illinois Question: I recently attended a nursing conference and overheard several nurses discussing their clinic’s use of cabergoline for the treatment of OHSS. Can you tell me how fertility centers are using it, and what are their results? Answer: Ovarian hyperstimulation syndrome (OHSS) is the most severe complication of controlled ovarian stimulation associated with ART therapy. OHSS is classified as mild, moderate, or severe, depending on symptom prevalence. Those at greatest risk for this syndrome are young, thin women, and patients with polycystic ovarian syndrome (PCOS). The symptoms of OHSS include ovarian enlargement, abdominal distention, and fluid shifts that cause intravascular volume depletion. Management is determined by the type of OHSS: earlyonset OHSS develops after ovarian stimulation with administration of human chorionic gonadotropin (hCG);

EDITORIAL BOARD Co-Editor-in-Chief Debra Moynihan, WHNP-BC, MSN Women’s Health Nurse Practitioner Carolina OB/GYN, SC Co-Editor-in-Chief Sue Jasulaitis, RN, MS Clinical Research Manager Fertility Centers of Illinois, Chicago Donielle Abbruscato, RNC Clinical Nursing Manager Brunswick Hills OB/GYN, NJ Barbara Alice, RN, APN-C, MSN Nursing Manager, IVF Coordinator South Jersey Fertility Center

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late-onset OHSS is associated with a pregnancy from fertility treatment. OHSS is managed with a variety of supportive measures. Traditional measures include fluid replacement therapy, anticoagulation therapy, paracentesis/ thoracentesis, and pharmaceutical therapy. A new pharmaceutical trend involves the use of cabergoline, which in recent years has been used successfully in many fertility centers. Cabergoline is a dopamine agonist that acts to reverse vascular permeability resulting from OHSS. It has been shown to significantly decrease the incidence of moderate and severe OHSS. Cabergoline is currently being used to treat OHSS, as well as prophylactically

to decrease its incidence. Standard dosing varies between clinics; the accepted regimen is an oral dose between 0.5 mg and 1 mg for 5 to 8 days. The initiation of cabergoline therapy varies as well: therapy can begin before hCG administration (when estradiol levels are >4000-5000 pg/mL), on the day of IVF egg retrieval, or with the development of significant OHSS symptoms. The decision to use cabergoline remains physician- and center-specific and should be customized to best treat or prevent OHSS. Cabergoline is a tool recently added to the growing arsenal used to prevent or treat the most severe side effect of fertility treatment.

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

Sandra Fernandez, RPh, PharmD Pharmacist Mandell’s Clinical Pharmacy

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

Nursing Manager IVF Coordinator IVF New Jersey

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

Kit Devine, MSN, ARNP Advanced Nurse Practitioner Fertility & Endocrine Associates, Kentucky Gina Paoletti-Falcone, RN, BSN Clinical Services Manager Freedom Fertility Pharmacy Byfield, MA

Jennifer Iannaccone, RNC

Donna Makris, RN, BSN, IBCLC Parent Education Coordinator OB/GYN, St. Peter’s Medical Center, NJ Jill Marchetti, RN Director, Egg Donor Program IVF New Jersey Mary McGregor, RN IVF Coordinator The Fertility Institute of New Orleans

Patricia Rucinsky, RN, BSN Clinical Nurse Manager IRMS, St. Barnabas, NJ Kriston Ward, RN, MS, NP-C Strong Fertility Center University of Rochester Medical Center, Rochester, NY Joan Zaccardi, MS, DrNP Administrative Practice Manager Urogynecology Arts of New Jersey

february 2010 I Vol 2, no 1

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Clinical Profile

Carolina OB/GYN... women’s health. We mostly engage in OB/GYN, but some of the physicians also become the primary physician for some of our patients. Many women prefer to be taken care of by female physicians, and our practice is staffed by all female providers. Our motto is “Compassionate Care for Women by Women.” We have 2 additional offices that are approximately 25 miles apart. Our main office is where the majority of our patients are seen. Depending on the day of the week, we usually have between 3 and 5 providers working in that office. Our satellite office is very busy and is where we see most of our Medicaid population. That office is staffed with 1 or 2 providers daily. In addition, we share space 2 days a week in a “rural health setting,” where we see women who are more economically disadvantaged. Most days, between all 3 locations, we see about 120 to 130 patients. Services such as surgery and obstetrical deliveries are performed at the 2 area hospitals that are under the Georgetown Hospital System.

What are some of the characteristics of your patient population? Our patient population ranges from adolescent girls aged 13 years to elderly women aged ≥90 years. Many of our young patients are seen for problems such as dysmenorrhea, irregular cycles, birth control, and testing for sexually transmitted diseases (STDs). We also care for a large population of teenage pregnancies. Middle-aged and older patients are seen for a variety of reasons common to women beyond pregnancy. In addition to yearly examinations, which are the most common visits, patients are seen for many problems that require either surgery or referral to other physicians, such as breast care specialists and oncologists. We do see many patients that come in with complaints of breast problems, which turn out to be cancer. Fortunately, we have a great team of neighboring doctors available to see these patients quickly. We also have our own DexaScan machine in the office to screen postmenopausal women for osteoporosis. Diagnostic ultrasounds are offered for both gynecologic problems and for pregnancy. These are performed by the physicians and the midlevel providers. In addition, we offer 4-dimensional ultrasounds to our pregnant patients. Our physicians and midwife deliver approximately 700 babies annually. Our hospital services include a level II nursery for babies born as early as 32 weeks. Women or babies with compli-

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february 2010 I Vol 2, no 1

Continued from page 1

with the patients and can provide an ample amount of education for patients during office visits. Pregnant women are like sponges; they are constantly trying to soak up as much information as possible. They often have all kinds of questions as a result of searching the Internet. We spend a lot of time with patients trying to dispel myths and clear up misinformation from many inaccurate online sources. We provide a comprehensive packet of information to our new obstetric patients, but just like my past experience in the infertility world, I find that many patients don’t read the materials. Esta Hill, CNM; Debbie Moynihan, WHNP-BC, MSN

cations are sometimes transferred to the Medical University of South Carolina, where they have a level III perinatal center.

Is your entire staff trained in OB/GYN? Is it common to have a midwife in an OB/GYN office? In addition to seeing numerous patients on a daily basis, we address a large volume of patient calls daily. Every day we have 3 to 4 clinical staff members working in our “call back” room. All calls are returned on the same day. Some of the problems are simple and can be handled on the phone, but there are other more complicated problems, and we try to fit them in as emergencies that day. It requires a lot of team effort to handle the daily challenges of full schedules, patient calls, and unexpected emergency visits, and make the day run smoothly. Between the 3 locations, we have a staff of 40, including the physicians. This number includes our front office staff, medical records, insurance and billing clerks, and administration and clinical staff. Our clinical staff encompasses 3 licensed practical nurses, 7 medical/nursing assistants, 1 radiology technician, and 2 part-time phlebotomists. Everyone has their own responsibilities, but we all work as a team. Besides the desire to be seen by female physicians, some patients really like the idea of having their baby delivered by a midwife. This is a unique service that our practice has provided for the past 4 years. We are the only practice in the Myrtle Beach area that offers delivery by a midwife. Many women like the idea of minimal intervention during their labor, thus making it feel more natural. The advantage to having midlevel providers, such as midwives and nurse practitioners within the practice, is that they generally have a little more time to spend

Are STDs still common in your area? Education is not limited to our OB population. It is amazing in this day and age that so many young women still fall victim to STDs. After working in the infertility field for 13 years and having 99% of my patients have negative STD screenings, it has been a rude awakening how widespread this problem is, and not only with teenagers. The unnerving thing is that when we call many of the patients to break the news, they barely show any remorse or any signs of being upset. They respond as if it is okay and not a big deal. I cannot stress enough that prevention is key. I often refer to all the patients I have seen in the past with tubal disease because of undiagnosed and untreated Chlamydia infection. Regretfully, this is a daily routine at our clinic: the counseling never stops. In addition to STD prevention, we do a lot of birth control counseling. Today there are so many different methods to choose from. It can be very overwhelming to a first-time user as to what method will be best for her.

What is your specific role at Carolina OB/GYN? I have been employed at Carolina OB/GYN since November 2007. As for my role within the practice, it is well diversified. There is never an opportunity to become bored. In addition to functioning as a nurse practitioner, I am also the Clinical Director, managing the clinical staff and acting as a liaison between administration and the staff. I start each day pretty much the same, by performing rounds at the hospital. Once I arrive at the office, things can change at any moment. Every day has its own unique challenges. On average, I see 20 patients a day. The appointments are varied, but mostly OB related. I see a large number of newly pregnant patients which initially allowed me to maintain my ultrasound skills that I learned while working in infertility. Once I started feeling com-

fortable being back in the world of OB, I wanted to expand my ultrasound skills to the level of 20-week anatomy scans. The physicians welcomed my enthusiasm and sent me for a 1-week course in OB ultrasound. Now I am doing anatomy scans and 36-week ultrasounds for fetal position and estimated fetal weights. This is quite a jump from measuring ovarian follicles and crown– rump lengths. I love it!

How do you deal with emergency situations? At Carolina OB/GYN, we pride ourselves in always being available to our patients. As previously mentioned, sometimes patient problems cannot be handled over the phone. Someone from the “call back” team will come out to the clinical area with a problem and approach one of the physicians or midlevel providers in an effort to have a patient seen that day. A problem such as someone calling who has just noticed a lump in her breast is something that we make time for right away. We know that many times it is probably nothing to worry about, but we also know that the patient will not be able to rest until someone has looked at it and has assured her one way or another that things are probably okay or that we can get her in for a mammography that day to follow up. This shows the patient that we understand her fears. Another example is the pregnant patient that had a miscarriage 3 months ago and has been spotting since last night. She calls in utter panic. Again, we know that she will never rest unless we bring her in to do an ultrasound for her to see that everything is okay. These are the little things that the patients truly appreciate.

Do you have any advice to younger nurses in the field? Even after 36½ years of nursing, I still find new challenges and skills to learn. I have found over the years that it is never too late to change your focus or learn new skills. More than 2 years ago, when I left my job of 13 years and moved to South Carolina, it was scary to think that I would have to start all over somewhere else. Friends and colleagues thought that I was moving away to live a life of retirement. Even though I am not old enough or wealthy enough for an early retirement, I was only looking to slow down a little. Fortunately, I have met that challenge, but I can honestly say that I will never allow myself to stop learning new things within the field. I find education exciting and encourage all nurses, no matter what their specialty, to engage in educational programs whenever the opportunity presents itself. ■

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Emerging Questions

The New Mammography Screening... unnecessary additional screening, biopsies, and anxiety. The uproar over the recommendations, especially that women aged less than 50 years need not undergo annual screening, is still being heard, with professional societies and breast cancer groups issuing their own responses (Table). So what should nurses and doctors advise their patients? The answer, although seemingly simple, is not so simple after all. The American College of Obstetricians and Gynecologists (ACOG) noted that although it welcomes the review of the data, the implications for women and physicians require careful evaluation of the data. ACOG suggested that women and their physicians individually assess the benefits and risks of screening, and that gynecologists continue to counsel women that breast self-examination has the potential to detect cancer.

Breast Cancer Experts in Their Own Words: SABCS In December 2009, at the major US meeting of breast cancer experts—the 32nd San Antonio Breast Cancer Symposium (SABCS)—a special session was devoted to the new recommendations. Although many experts rejected them, others found them reasonable, including a breast cancer survivor whose experience of a “false-negative” screening is absent from the current debate. The following quotations are taken directly from the SABCS (and 1 online source, used with permission). A Lot of Patients Are Confused Edith Perez, MD, Professor of Medicine, Director of the Breast Program, Mayo Clinic, Jacksonville, FL “The task force report confused a lot of women. The information is not new. The report is based on a reanalysis and reinterpretation of data that have been available for some time. We know that certainly not women who are screened will develop breast cancer, and we are happy about that. But mammography alone and clinical breast exam have been shown to help reduce mortality in those who do have breast cancer. We cannot abandon the one thing we know works as we search for better strategies to identify women with breast cancer. The recommendations at Mayo Clinic and my own recommendations to patients will not change based on the report.”

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Delaying Screening in Low-Risk Younger Women Eric Winer, MD, Director of the Breast Oncology Center and Chief of the Division on Women’s Cancers, DanaFarber Cancer Center, Boston, MA “If I were a gynecologist, I would try to make enough time in my day to talk to my patients aged 40 to 50 about this topic. I would emphasize the importance of being aware of changes in one’s breast. I would tell them that indeed there are benefits associated with mammography, but there are also ‘harms,’ as the Task Force called them. I don’t think we can entirely dismiss the psychological and physical consequences of false-positives. For women at elevated risk, it seems clear that the benefits outweigh the risks. But for women with usual risk, aged 40 to 50, I think a woman needs to weigh the evidence with her physician and come up with a reasonable choice. It is fine if she decides to undergo mammography. But also, based on the data, it is a reasonable choice to wait a few years to begin screening.” Understanding False-Positives Carolyn Runowicz, MD, Professor of Obstetrics and Gynecology, Director of the Carole and Ray Neag Comprehensive Cancer Center, University of Connecticut Health Center, Farmington, CT “I believe the opposition to the USPSTF recommendations is largely because the Task Force emphasized what they called ‘harms,’ which put their recommendations at odds with those of other professional groups. The timing was also unfortunate, as the implication was healthcare rationing. I believe that women should be informed of the ‘harms,’ but should have them put into perspective. They should also be informed of the benefits of screening mammography.

Table US Organizations Divided on Mammography Recommendations Pro Breast Cancer Action National Breast Cancer Coalition Susan Love Research Foundation The Agency for Healthcare Research and Quality Con American Cancer Society ACOG American College of Radiology Baylor College of Medicine Breastcancer.org Massachusetts General Hospital Mayo Clinic M.D. Anderson Cancer Center National Breast Cancer Foundation, Inc Susan G. Komen for the Cure

Continued from page 1

False-Negative: One Patient’s Experience Musa Mayer, breast cancer survivor, creator of AdvancedBC.org “For many people, the immediate response to the new proposed screening guidelines was a sort of kneejerk, defensive reaction. In fact, the Task Force took a very careful look at the evidence….It has long been controversial to screen women under age 40, as this has never been shown to save lives. The new modeling suggests that we must screen almost 2000 women for 10 to 20 years to save a single life. We all know women diagnosed in their 40s following a mammogram. But here is the interesting thing: these women claim that mammography saved their lives. The reality is that mammography is excellent at picking up slow-growing tumors that tend not to be life-threatening, and does a terrible job at picking up fast-growing tumors or rapidly growing interval cancers that are likely to spread before they are detectable. We have not made much progress in the early detection of tumors that matter, and that is hard to accept.

My own story is illustrative. I was diagnosed 20 years ago with stage II breast cancer at the age of 46, which was 15 months after I had discovered a lump and had a mammogram that revealed nothing at all. Although it was a good-sized lump that could be felt, my doctor called it a cyst and said not to worry. After my next annual visit, when the lump had grown, I was referred to a surgeon, and even then, mammography failed to show it. So my diagnosis was delayed for more than 1 year, yet my cancer remained stage II, with no lymph node involvement. If it were so urgent to look for cancer every year, I would not be here today. I also learned that my mammograms were not informative because of the glandular nature of my breasts—though I was never told. Had I known this, I may have been more proactive. So what is a woman to do? The obvious thing is, talk to her doctor. My concern is that most physicians will not want to change what they are currently doing and they may not have time or inclination to discuss these issues. Women should take charge of their own situation. To do this, they need correct information, otherwise they act out of fear and perhaps do too much.”

My advice to women aged 40 to 50 would be to understand there is a possibility of false-positive results, but there is also a reduction in mortality. Lives are saved through screening. For women over age 75, for whom routine screening was also not recommended, I would still advise annual mammography if they are in good health.”

be at an earlier stage. This is in high-risk patients only.”

The Role of MRI Debu Tripathy, MD, Co-Leader, Women's Cancer Program, Keck School of Medicine, University of Southern California, Los Angeles “The Task Force recommended we focus on high-risk patients. But the fact is, we don’t know how to identify those at high risk other than by family history or presence of the BRCA gene. Everything else is fussy….In a study presented at SABCS investigators compared mammography and MRI in patients thought to be at high risk for breast cancer. They showed that the 2 modalities found the same number of cancers, but MRI found more ductal carcinoma in situ and stage I cancers, and a lower proportion of stage II and III cancers. Mammography, on the other hand, detected more stage II and III cancers. Clinically, this means that if you detect cancer by MRI, it is likely to

A Huge Step Backwards Marisa Weiss, MD, President and Founder of Breastcancer.org, Director of Breast Radiation Oncology and Breast Health Outreach, Lankenau Hospital, Ardmore, PA “The proposed new guidelines are based on research that looks at the effect of breast cancer screening on society from a public health perspective rather than individual women. In proposing the changes, the Task Force members said that starting mammograms later in life and doing mammograms less often would save a large amount of money. It also means that about 3% more women would die from breast cancer each year. The Task Force members felt that the amount of money saved was greater than the value of more lives saved. The 3% decrease in breast cancer survival might seem like an acceptable trade-off when compared with the economic benefits of changing breast cancer screening policies. But the reality is that more women…will die each year from breast cancer, which is neither reasonable nor acceptable.” ■

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The OB/GYN Nurse

Endometriosis—More Than “Killer Cramps” Carol Drury Education Program Coordinator/Associate Director, the Endometriosis Association (Carol@EndometriosisAssn.org)

Y

our next patient may be a woman who has endometriosis. She may mention that she has “bad” menstrual cramps, then laugh, saying, “Don’t we all.” She may mention that she is tired, but explain that away by saying she always feels that way, or blame it on her busy schedule. She probably will not mention that she and her husband/partner avoid intercourse because it is too painful for her, or that she struggles with diarrhea, constipation, or painful defecation. She won’t know that these may be pieces of the puzzling hormonal and immune system disease, endometriosis. More than 6 million girls and women in the United States have this condition, and an estimated 89 million are affected worldwide. Although the symptoms of pelvic pain characteristic of endometriosis concentrate in the reproductive years, the disease can occur before menarche and after menopause. Girls as young as 8 and 9 years old have been diagnosed with endometriosis, as have women who have had hysterectomies. The prevalence of endometriosis has increased dramatically in the past 30 years. In the1980s, the Endometriosis Association (EA) established the world’s largest research registry on endometriosis at the Medical College of Wisconsin to help solve the puzzle. The symptoms of endometriosis can range from none to severe. The severity of the symptoms does not necessarily correlate to the extent of lesions; a woman who has endometriosis and mild symptoms may still be at risk for infertility, and a woman with tiny (petechial) growths may experience severe pain. (Petechial growths have been found to be more active in producing the prostaglandins thought to cause many of the symptoms of endometriosis.) Rupture of cysts, intestinal bleeding or obstruction, and interference of bladder function can also occur, depending on the location of growths. Some women experience symptoms only cyclically, around the time of menses or ovulation, and others suffer constantly. Many women are so disabled from endometriosis that they cannot work, or they lose their jobs because of excessive sick days: 75% of the women included in the EA’s registries (6996 cases) reported that they were sometimes unable to carry on

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their normal work; 25% were incapacitated between 2 and 6 days a month; and 35% for 1 to 2 days a month. Relationships are often strained and broken. Finances can be in shambles. Some women, including teenagers, have committed suicide because of the relentless pain associated with this disease. Earlier diagnosis means more girls and women can find relief sooner.

CFS was >100-fold more common than in the general female population. Hypothyroidism was 7-fold more common, and fibromyalgia was twice as common. Autoimmune inflammatory diseases, including lupus, rheumatoid arthritis, and multiple sclerosis, occur more frequently in these women.3 All these complicate the diagnosis and may result in inappropriate treatment.

The Environmental Connection Endometriosis may have been a mild, mostly tolerable disease in the past, but something has changed. Endometriosis cases are more severe, and new cases are on the rise. What has changed? Modern pollutants are affecting our environment, our food, and our bodies’ functioning. The toxic group of compounds called dioxins, a known human carcinogen, is one culprit. In 1992, EA researchers discovered that dioxin exposure was directly correlated with the incidence of endometriosis in a colony of rhesus monkeys. This link has since been replicated worldwide.1 Exposure to environmental contaminants, especially organochlorines such as dioxin and polychlorinated biphenyls (PCBs), appears to affect fertility. One study showed that in women with infertility, the levels of dichlorodiphenyldichloroethylene (a form of the pesticide DDT) were 90 times higher than in women who conceived.2 Preconception planning should include eliminating—as much as possible—toxic chemicals in food and around the home. This means discontinuing the use of bleach and other harsh chemicals as household cleaners, and the use of pesticides and herbicides on lawns. Fish from most lakes should be taken off the menu. (See www.edf. org for information on safe seafood.)

The Link to Cancer The main concern is not whether endometriosis develops into cancer, although this is possible with endometriomas and ovarian cancer, but rather that endometriosis itself creates a greater risk for cancer. Researchers comparing cancer rates in Swedish women with endometriosis and the entire Swedish female population found that women with endometriosis had significant increases in breast cancer, ovarian cancer, and non-Hodgkin’s lymphoma rates.4 (They also found a slightly reduced risk of cervical cancer and no association with cancer of the endometrium.) Large pathology studies (up to 1000 cases) have revealed ovarian cancer in 5% to 10% of ovarian endometriotic lesions.5 Endometrioid (60%) and clear-cell (15%) tumors predominate in greater proportions in women with a history of endometriosis than in ovarian cancers in general (10%-20% vs 3%-10%, respectively).5 An elevated risk for endocrine tumors, ovarian cancer, kidney cancer, thyroid cancer, brain tumors, malignant melanoma, and breast cancer was found in another large study of 64,630 Swedish women. The study (of women discharged from a hospital from 1969-

The Immune System Analysis of the EA’s registries showed that women with endometriosis have a significantly higher incidence of allergic diseases and yeast infections. Other immune system disorders, such as severe chemical sensitivities, are also common in this patient population. Research has now shown that women with endometriosis are at increased risk for autoimmune inflammatory diseases. A study of women with endometriosis showed that 20% had >1 disease, and of those women, one third had also been diagnosed with either fibromyalgia or chronic fatigue syndrome (CFS).3 Some also had other autoimmune or endocrine diseases.

A woman with endometriosis.

2002 with the diagnosis of endometriosis) showed no difference in the cancer risk between women with endometriosis who had had children and those who had not.6 A French study of 91,965 subjects also showed that a history of endometriosis is significantly associated with an increased risk for melanoma.7 ■ References 1. Bruner-Tran KL, Yeaman GR, Crispens MA, et al. Dioxin may promote inflammation-related development of endometriosis. Fertil Steril. 2008;89(suppl 5): 1287-1298. 2. Environmental panel [eighth world congress on endometriosis]. Endometriosis Association Newsletter. 2002;34:5. 3. Sinai N, Cleary SD, Ballweg ML, et al. High rates of autoimmune and endocrine disorders, fibromyalgia, chronic fatigue syndrome and atopic diseases among women with endometriosis: a survey analysis. Hum Reprod. 2002;17:2715-2724. 4. Brinton L, Gridley G, Persson I, et al. Cancer risk after a hospital discharge diagnosis of endometriosis. Am J Obstet Gynecol. 1997;176:572-579. 5. Nezhat, F. Ask an expert: the association between endometriosis and ovarian cancer. Endometriosis Association Newsletter. 2008;28(4-5):13. 6. Melin A, Sparén P, Bergqvist A. The risk of cancer and the role of parity among women with endometriosis. Hum Reprod. 2007:22:3021-3026. 7. Kvaskoff M, Mesrine S, Fournier A, et al. Personal history of endometriosis and risk of cutaneous melanoma in a large prospective cohort of French women. Arch Intern Med. 2007;167:2061-2065.

The Endometriosis Association (www. EndometriosisAssn.org) is an international self-help organization. Contact: 414-355-2200 or endo@Endo metriosisAssn.org to request brochures or a DVD for healthcare professionals.

What Is Endometriosis? Endometriosis is a hormonal and immune system disease in which endometrial-like tissue is found outside of the uterine cavity (most often in the abdomen), where it develops into “nodules,” “tumors,” “lesions,” or “growths.” In the ovary, these are called “cysts” or “endometriomas.” These growths usually respond to the hormones of the menstrual cycle, building up then breaking down tissue each month, causing internal bleeding. The bleeding causes pain, inflammation, adhesion formation, spread of the disease, and infertility. Endometriosis appears to require estrogen for development, and the estrogen does not have to come from the ovary; endometriosis can produce its own estrogen, because of the presence of the enzyme aromatase. Symptoms

The most common symptoms are dys-

menorrhea, dyspareunia (pain during sexual activity), fatigue, and heavy bleeding. The pain can be debilitating, seriously interfering with the daily life functions. Infertility affects 30% to 40% of women with endometriosis and is a common result of the progression of the disease. Approximately 33% of women with infertility have endometriosis. Diagnosis

A definitive diagnosis can only be made by using laparoscopic surgery for visual observation or to biopsy lesions. The cause of this disease is not fully understood. Treatments

There is no sure cure for endometriosis. Medical treatment is used to reduce pain, remove/destroy growths, and improve fertility. Treatment must be individualized. Options include painkillers, hormones, surgery (eg, removal of growths or hysterectomy), and/or alternative treatments.

www.obgyn-infertility-nurse.com


The OB/GYN Nurse

Female Sexual Dysfunction...

Sheryl A. Kingsberg, PhD

“You really can’t treat the problem if you don’t know what it is.” Ask Questions In a classic study, direct questioning increased patient reporting of sexual dysfunction by 6-fold compared with spontaneous reporting, Dr Kingsberg said at a recent conference on female sexuality held at the Cleveland Clinic. “You really can’t treat the problem if you don’t know what it is,” she pointed out. Questions can take the form of “Do you have any sexual concerns that you would like to discuss?” or “Do you have difficulty with desire, arousal, or orgasm?” A diagnosis of female sexual dysfunction can be challenging, because female sexual response may not follow a linear cycle—excitement followed by plateau and orgasm—as it does in men, especially as women age. For many women, arousal must precede desire and sexual activity. Overlapping Conditions The overlap between the various types of female sexual dysfunctions is considerable, which can also complicate the diagnosis. “If a woman presents and says that she has sexual problems, if you don’t pay attention to the fact that it’s completely overlapping, you may be going down the wrong path,” Dr Kingsberg noted. For example, a woman may say that it hurts to have sex. The immediate temptation may be to prescribe local estrogen, when in fact, low or lack of desire may actually be the cause. “Without desire, the body doesn’t get aroused, and without arousal she won’t have any lubrication, even with vaginal estrogen, and it still hurts,” she said. In other cases, a lack of interest in sex may be the result of pain—also known as dyspareunia—during inter-

course and not a lack of desire; in this case, local estrogen may indeed alleviate the pain and restore desire and sexual function. A 2008 study showed that the prevalence of female sexual dysfunction associated with distress was 8.9% to 14.8%, depending on the woman’s age.1 Most of the women at any age suffered from problems with lack of desire associated with stress.1 According to the DSM IV (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition), an element of distress is required for a diagnosis of female sexual dysfunction, Dr Kingsberg noted. Sex therapists often disagree with the DSM IV in that area. The DSM IV lists the following 6 types of female sexual dysfunctions: • Hypoactive sexual desire disorder (HSDD) • Sexual aversion disorder • Female sexual arousal disorder (lack of sexual desire) • Female orgasmic disorder • Dyspareunia (chronic pain during sexual activity) • Vaginismus. Low Sexual Desire HSDD is the most prevalent sexual disorder in women. According to the DSM IV, HSDD is the persistent or recurrent deficiency or absence of sexual thoughts, fantasies, and/or desire for (or receptivity to) sexual activity, which causes marked personal distress. Surgically menopausal women have the highest rate of HSDD.2 The prevalence of low sexual desire is listed in the Table. “Desire is actually a relatively complicated concept,” Dr Kingsberg said. It has 3 separate but related components: (1) the biologic component, known as drive or spontaneous sexual interest (many diseases, such as diabetes, depres-

Continued from page 1

Table Prevalence of Low/Hypoactive Sexual Desire Disorder in Women Category

Low desire, %

HSDD, %

All Age, y 30-39 40-49 50-59 60-70 Surgical menopausal Natural menopausal Premenopausal

36.2

8.3

30.8 25.3 37.8 60.7 39.7 52.4 26.7

8.3 9.0 9.4 5.8 12.5 6.6 7.7

HSDD indicates hypoactive sexual desire disorder. Source: West SL, et al. Arch Intern Med. 2008;168:1441-1449.

sion, or heart disease and the medicines that treat them can negatively affect sexual drive); (2) expectations and beliefs about sexual behavior and its frequency; and (3) motivation, which reflects the psychological and interpersonal characteristics that create the willingness for sex. Sexual aversion disorder may be mistaken for HSDD, when in fact, women with sexual aversion disorder have a biologic drive but the idea of sexual contact with a partner elicits a phobic response. Treatment Options Therefore, patients with sexual aversion disorder receive psychiatric treatments that often include medical therapies, such as antidepressants (eg, one of the monoamine oxidase inhibitors, selective serotonin uptake inhibitors [SSRIs], or tricyclics) or anxiolytics. Treatment options for arousal disorders in women include: • The Eros vacuum device, the only treatment approved by the Food and Drug Administration for the treatment of female sexual arousal disorder • Hormonal (estrogen) therapy

• Drug therapies, such as phosphodiesterase-5 inhibitors and nitric oxide promoters. The success rate with referral to a sex therapist for the treatment of orgasmic disorder is extremely high, Dr Kingsberg suggests. One beneficial approach is to give the patient permission to practice and explore self-stimulation/masturbation. If orgasmic disorder is caused by a medication (eg, an SSRI), changing the medication within the class, or switching to another class, should be strongly considered. Studies have shown variations in the effects of certain drugs on sexual desire, especially with antidepressants. Progressive muscle relaxation and vaginal dilatation have very high success rates for women with sexual pain disorders. Consider referring nonresponders to a sex therapist “sooner rather than later,” Dr Kingsberg advised. ■ References 1. Shifren JL, Monz BU, Russo PA, et al. Sexual problems and distress in United States women: prevalence and correlates. Obstet Gynecol. 2008;112:970-978. 2. West SL, D’Aloisio AA, Agans RP. Prevalence of low sexual desire and hypoactive sexual desire disorder in a nationally representative sample of US women. Arch Intern Med. 2008;168:1441-1449.

The New Mammography Screening Recommendations A Women’s Health Nurse Practitioner Perspective Karen N. Healy, APN, MSN

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hile having my breakfast one morning in November 2009, I was shocked to hear about the new recommendations of the US Preventive Services Task Force for mammography screening (see Emerging Questions, page 1). I have been a women’s health nurse practitioner in private practice for 15 years. There has

certainly been some variation from different medical groups regarding when to start screening and at what frequency, but never to this extent. These recommendations are very confusing for patients and insulting to women. In my practice, we have many women in their 40s who have been diagnosed with breast cancer solely as a

result of a screening mammogram. I would be hard-pressed to find any woman among them who feels that a biopsy or additional testing “harmed” her rather than helped diagnose early, curable breast cancer. I have also seen many women, especially those younger than age 50, who by doing a self-breast examination discovered their breast Continued on page 10

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february 2010 I Vol 2, no 1

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The OB/GYN Nurse

Ectopic Pregnancy: Prompt Diagnosis Can Save Your Patient’s Life, Preserve Her Fertility Debra Moynihan, WHNP-BC, MSN Women’s Health Nurse Practitioner, Carolina OB/GYN

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iagnosis of ectopic pregnancy presents one of the most tedious challenges to the clinician. In ectopic pregnancy, the fertilized egg implants itself outside of the uterus, most often within the fallopian tube if there is interference in normal ovum transport. A prompt and accurate diagnosis will not only save a patient’s life, but will also play a major part in preserving her fertility. Ectopic pregnancy occurs in approximately 20 per 1000 pregnancies and is a leading cause of maternal mortality. Although the mortality rate from ectopic pregnancy has decreased over the years in the United States, the actual number of ectopic pregnancies has increased. Some contributing factors are infection of the fallopian tubes (50% of cases), previous ectopic pregnancy, structural defects of the tubes, endometriosis, and tubal surgeries, such as tubal reversal and bilateral tubal ligation. Other risks include in vitro fertilization, the intrauterine device with progesterone, the “mini pill,” emergency contraception, and a history of pelvic inflammatory disease (PID). Recognizing the Symptoms In most cases, when a woman achieves pregnancy, her first sign is amenorrhea, but vaginal bleeding or spotting is common in the first trimester. If bleeding is associated with lower-abdominal pain, the patient must be evaluated immediately. Always consider ectopic pregnancy in any woman of childbearing age who reports mild or severe abdominal symptoms. Initially, the pain may be unilateral, but as the pregnancy progresses, it can become

more sharp and severe, and the patient may complain of a more generalized discomfort. Other associated symptoms are malaise, syncope, and gastrointestinal disturbances. The patient may present with tachycardia, hyperpnea, hypotension, and/or a rigid abdomen. Sometimes the presentation may be atypical. The patient may report vague or subacute symptoms. Amenorrhea may not be obvious, because of spotting, which can mimic a normal menses. At times, the symptoms do not correlate with the severity of the condition. The most classic symptom is pain radiating to the shoulder. This is called Kehr’s sign and may indicate abdominal bleeding, causing phrenic nerve irritation. Abdominal bleeding leads to shock, which is the first symptom in 20% of cases.

The most classic symptom of ectopic pregnancy is pain radiating to the shoulder. A physical examination may reveal unilateral tenderness in the adnexa. On pelvic examination, the cervix will appear normal, but usually with marked tenderness. Vaginal tenderness and blood in the vaginal vault may be present. Depending on gestational age, diagnosis is made using serial quantitative beta-hCG (human chorionic gonadotropin) levels and pelvic ultrasound. In early pregnancy, beta-hCG levels should double every 48 to 72 hours. Low or abnormally rising levels are

suggestive of ectopic pregnancy. If levels are from 1500 to 2000 mIU/mL at 35 days gestation and the pregnancy is intrauterine, a gestational sac should be present. Absence of a sac is suggestive of an ectopic pregnancy. The differential diagnosis includes intrauterine pregnancy, recent spontaneous abortion, ovarian cyst or tumor, acute appendicitis, or PID. Medical Therapy Once the diagnosis is confirmed, treatment must be initiated immediately to avoid rupture of the tube and hemorrhage. The choice of treatment is dependent on the gestational age, symptoms, location of implantation, and whether the fallopian tube is intact or ruptured. If the woman is in the very early stage of pregnancy, medical management is the preferred option, using methotrexate (Trexall), a chemotherapeutic agent that clears the trophoblastic tissue. The necessary criteria for this therapy are: • The patient must be hemodynamically stable • The mass must not be ruptured and <4 cm in diameter • Also consider any contraindications to methotrexate and the woman’s commitment to follow-up care. Contraindications include known sensitivity to methotrexate, breastfeeding, hematologic abnormalities, alcoholism or evidence of chronic liver disease, immunodeficiency states (eg, HIV), and renal or active pulmonary disease. Common side effects with metho-

Ectopic pregnancy.

trexate therapy include abdominal cramping, vaginal bleeding/spotting, nausea/vomiting, fatigue, lightheadedness, headache, body aches, and lowgrade fever. Instruct the patient to stop prenatal vitamins, all sources of folic acid, and alcohol use. She should also refrain from having intercourse. She may want to avoid gas-forming foods temporarily. Penicillin and non-steroidal anti-inflammatory drugs should be used with caution, because they may delay the excretion of methotrexate from the kidneys. Before giving methotrexate, a betahCG level, complete blood count (CBC), comprehensive metabolic panel (CMP), and blood type and antibody screening should be drawn. The betahCG should be repeated on day 4. The level is expected to rise before decreasing. On day 7, the beta-hCG, CBC, and CMP are to be repeated. A 15% decline in the beta-hCG level is expected; if a decline does not occur, a second injection may be given, with a repeat in protocol. If the levels drop appropriately, biweekly beta-hCG levels should be repeated until <100 mIU/mL, and then weekly until <10 mIU/mL. When beta-hCG levels do not decline after 2 doses, surgical intervention must be considered. ■

The New Mammography Screening Recommendations... Continued from page 9 cancer. Counseling women not to examine themselves takes away their ability to be proactive, and discredits the very important fact that women should know their own bodies. The systematic review of the evidence that prompted this change found that women in their 40s and 50s did benefit equally from routine screening. Why the change, then? Are women in their 40s not statistically significant? These women are in their prime, often with young children, important jobs, and many people dependent on them. Wouldn’t it make

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sense to emphasize early detection in this group rather than disregard them? I would beg to differ from the notion

every other year at age 50? Finally, are women older than age 74 just not worth the effort? We will lose 30 years

Counseling women not to examine themselves takes away their ability to be proactive, and discredits the very important fact that women should know their own bodies. that extra testing in this case causes harm. We also all know women who have a change in their mammogram from one year to the next. Why skip to

of gain if we are forced to follow the new government recommendations. My first gut reaction to this news was that the government funded this study

to have a basis for providing less-expensive screening protocols. From a public health standpoint, it will save a lot of money, but we cannot disregard human life to save a little money. And at the end we will not save healthcare dollars, because treatment of more advanced disease will become more expensive and more deadly. We need to empower women to be proactive in the detection of breast cancer, but to do this we need healthcare providers to be able to order appropriate screening tests, without worrying whether these tests will be covered by insurance. ■

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She depends on your guidance...

Only ONE vaginal progesterone is proven as effective as IM It’s a fact. CRINONE is proven equivalent to IM progesterone in the largest prospective, randomized, well-controlled clinical trial study ever conducted comparing vaginal to IM progesterone.1

CRINONE 8% (progesterone gel) is indicated for progesterone supplementation or replacement as part of an Assisted Reproductive Technology (ART) treatment for infertile women with progesterone deficiency. Important Safety Information The most common side effects of CRINONE 8% include breast enlargement, constipation, somnolence, nausea, headache, and perineal pain. CRINONE 8% is contraindicated in patients with active thrombophlebitis or thromboembolic disorders, or a history of hormone-associated thrombophlebitis or thromboembolic disorders, missed abortion, undiagnosed vaginal bleeding, liver dysfunction or disease, and known or suspected malignancy of the breast or genital organs.

www.crinoneusa.com

This study, conducted at Brigham and Women’s Hospital, adds to the 12 prior trials 2-13 demonstrating the comparable efficacy of CRINONE and IM progesterone. No other vaginal progesterone can make this claim. In fact, CRINONE is the single most studied and widely used vaginal progesterone worldwide. When she asks about progesterone, give her the facts.

The only ONE

Toll-free support line: 1-888-PRO-GEL8 (1-888-776-4358) Please see brief summary of full prescribing information on the adjacent page. © 2009, Columbia Laboratories, Inc.

CRI8-PAD-005


The OB/GYN Nurse

Rituximab an Alternative to Standard Cyclophosphamide in Patients with Vasculitis By Alice Goodman

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ituximab was as effective as cyclophosphamide for inducing remission in antineutrophil cytoplasmic antibodies (ANCA)-associated

vasculitis, with fewer toxicities, in particular, genitourinary malignancies and infertility-related adverse events. The study, which was presented at the 2009

CRINONE® 4% CRINONE® 8% (progesterone gel)

See package insert for full prescribing information. 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 hormoneassociated 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 Crinone-treated 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, open-label 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. 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 more 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 reported in 5% or more of women treated with Crinone

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annual meeting of the American College of Rheumatology, showed that rituximab was superior to cyclophosphamide for induction of remission in patients with severe flares of vasculitis. Cyclophosphamide has been the standard of care for induction of remis-

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. This brief summary is based on the current Crinone package insert (Version 40405010007, Revised December 2006). How Supplied Crinone is available in the following strengths: 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-55056-0806-2 - 6 Single-use prefilled applicators. NDC-55056-0818-2 - 18 Single-use prefilled applicators. Each applicator is wrapped and sealed in a foil overwrap. Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F). Rx only. U.S. Patent Number 5,543,150. Manufactured for: Columbia Laboratories, Inc. Livingston, NJ 07039 Manufactured by: Fleet Laboratories Ltd., Watford, United Kingdom © 2007, Columbia Laboratories, Inc. Printed in USA 6/07

References: 1.Yanushpolsky EH. Comparison of Crinone 8% intravaginal gel and intramuscular progesterone (IMP) for luteal phase support: largest prospective randomized trial to date. Slides presented at: American Society for Reproductive Medicine, 2009. 2. Berger B, Phillips JA. A retrospective analysis of pregnancy outcomes in recipients of anonymously donated oocytes at a large ART center. Fertil Steril. 2008;89:S11–S12. Abstract P-7. 3. Saucedo LLE, Batiza V, Arenas L, et al. Progesterone for luteal support: randomized, prospective trial comparing vaginal and i.m. administration. Paper presented at the 19th Annual Meeting of the European Society for Human Reproduction & Embryology; July 2003; Madrid, Spain. Abstract P-383. 4. Anserini P, Costa M, Remorgida V, Sarli R, Guglielminetti E, Ragni N. Luteal phase support in assisted reproductive cycles using either vaginal (Crinone 8) or intramuscular (Prontogest) progesterone: results of a prospective, randomized study [in Italian]. Minerva Ginecol. 2001;53:297–301. 5. Coutifaris C, Patrizio P, Schafer D, Bunso S, Bucci J, Barnhart K. Is the use of Crinone for support of the luteal phase detrimental to pregnancy outcome after transfer of non-cryopreserved embryos in good prognosis patients? A preliminary report. Fertil Steril. 2000;74(suppl 1):S205. Abstract P-350. 6. Alper MM, Penzias AS. Crinone® offers excellent implantation rates in patients undergoing IVF. Paper presented at the 16th Annual Meeting of the European Society for Human Reproduction & Embryology; June 2000; Bologna, Italy. Abstract P-059. 7. Schoolcraft WB, Hesla JS, Gee MJ. Experience with progesterone gel for luteal support in a highly successful IVF programme. Hum Reprod. 2000;15:1284–1288. 8. Saucedo LLE, Galache VP, Hernández AS, Santos HR, Arenas ML, Patrizio P. Randomized trial of three different forms of progesterone supplementation in ART: preliminary results. Fertil Steril. 2000;74(suppl 1):S150. Abstract P-175. 9. Williams SC, Donahue J, Muasher SJ. Vaginal progesterone therapy during programmed cycles for frozen embryo transfer: an analysis of serum progesterone levels and pregnancy rates. Fertil Steril. 2000;74(suppl 1):S209. Abstract P-363. 10. Levine H. Luteal support from the vaginal progesterone (P) gel Crinone 8%: preliminary results of multicenter trial show higher pregnancy rates than historical controls. J Soc Gynecol Investig. 2000;7(suppl). Abstract 571. 11. Chantilis SJ, Zeitoun KM, Patel SI, et al. Use of Crinone vaginal progesterone gel for luteal support in in vitro fertilization cycles. Fertil Steril. 1999;72:823– 829. 12. 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. 13. Berger BM, Phillips JA. A retrospective analysis of pregnancy outcomes in recipients of frozen/thawed embryos (FET) from donated oocytes at a large assisted reproductive technology (ART) center. Fertil Steril. 2008;90(suppl 1):S459. Abstract A-260.

Columbia Laboratories, Inc. Livingston, NJ 07039

sion for ANCA-associated vasculitis for many decades. However, oral cyclophosphamide is associated with serious toxicities, including genitourinary malignancies, infertility, infections, and neutropenia. “Rituximab is the first proven alternative to cyclophosphamide in severe ANCA-associated vasculitis, and the drug is effective and well tolerated. This is particularly relevant for patients with severe disease and those of child-bearing age,” said Ulrich Specks, MD, of the Mayo Clinic, Rochester, MN. ANCA vasculitis is an umbrella term for an autoimmune disease that includes Wegener granulomatosis, microscopic polyangiitis, and ChurgStrauss syndrome.

“Rituximab is the first proven alternative to cyclophosphamide in severe ANCA-associated vasculitis, and the drug is effective and well tolerated.” —Ulrich Specks, MD

The multicenter, randomized, double-blind, placebo-controlled Rituximab for ANCA-Associated Vasculitis (RAVE) trial assigned 99 patients to rituximab (375 mg/m2 intravenous weekly for 4 weeks) and 98 patients to cyclophosphamide (2 mg/kg/day orally): 75% had Wegener granulomatosis and 25% had microscopic polyangiitis. The primary end point of the study was disease remission. The rate of disease remission was 63.6% in the rituximab group compared with 53.1% in those taking cyclophosphamide. A reduction in disease activity was seen in 70.7% of the rituximab group versus 62.2% of the cyclophosphamide group. The difference between the 2 treatment groups was not significant in newly diagnosed patients (n = 96), but rituximab was superior in achieving complete disease remission in the 101 patients who had severe disease flares—66.7% with rituximab versus 42% with cyclophosphamide, an almost 25% absolute improvement. The rate of adverse events was similar in the 2 groups, with no difference in infection rate. The study is good news for patients with vasculitis, Dr Specks noted. Long-term treatment with oral cyclophosphamide can be difficult for patients to tolerate, and a 10% to 15% incidence of genitourinary transitional cell carcinoma has been reported with long-term (10-15 years) treatment with cyclophosphamide. ■

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The OB/GYN Nurse

Bone Health Concerns in Women Treated for Breast Cancer A Gynecologist’s Perspective Elyse Erlich, MD Dr Erlich is a Gynecologist in Private Practice, Arlingon Heights and Buffalo Grove, IL

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here has been much progress in the early detection and treatment of breast cancer. This (in association with a drop in hormone replacement therapy use) is responsible for much of the decrease in deaths from breast cancer since the 1990s. The American Cancer Society estimates that there are about 2.5 million survivors of breast cancer alive in the United States today. Consequently, clinicians today are seeing many women who survive their breast cancer and who are now faced with other health issues, such as osteoporosis, which might have been exacerbated by the treatment that has kept them alive. Peak bone mass is reached in women by age 30 to 35 years. After that age, there is a steady but small loss of bone mineral density (BMD) until menopause. At menopause, bone loss is accelerated, often significantly. Women may lose up to 20% of their bone mass in the

first 5 to 7 years after menopause. Thereafter, they will continue to lose BMD, but at a slower rate. In addition, chemotherapy often leads to premature menopause, which not only advances the normal menopausal effects of a hypoestrogenic state but may also be compounded by cancer treatment– induced bone loss (CTIBL).

We need to remember the important sequelae that premature menopause and cancer treatment itself could have on a woman’s bone health. One way to think about this is to consider that a woman has a “bone biological clock.” The average clock is set at age 51—considered the average age of menopause in the United States. If a

woman’s clock is prematurely set off as a result of chemotherapy-induced menopause (the same would be true for surgical menopause), we are advancing her biological clock by up to 10 years. Therefore, the acceleration of bone loss happens much earlier than it should have, and that speeds up the development of osteoporosis. Furthermore, if a patient suffers from CTIBL, this will further exacerbate bone loss. Because the largest decreases in death rates from breast cancer have been for women in their 40s, this is a real and present danger for cancer survivors. When considering treatment for osteopenia and osteoporosis, the goal is fracture prevention. The World Health Organization’s tool, the FRAX calculator, allows estimation of a woman’s risk of fracture and helps determine the individual 10-year risk of fracture, taking into account her age, height, weight, family history, medical risk factors, tobacco and alcohol use, and her current BMD of the femoral neck. When a patient’s 10-year risk of hip fracture reaches 3%, or the 10-year risk of major fracture reaches 20% , a more aggressive medical treatment is indicated, such as the use of bisphosphonates.

Osteoporosis is a major health concern that is starting to get the attention it deserves. Surprisingly, a woman’s risk of hip fracture is equal to her combined risk of breast, uterine, and ovarian cancer. As a practicing gynecologist, I am faced daily with patients’ concerns over breast cancer and ovarian cancer, but not over osteoporosis. As clinicians, we need to share with our patients that 1 of 2 women age ≥50 will have an osteoporotic fracture during their remaining lifetime. Of those who have a hip fracture, one quarter will die in the subsequent year, and many of the survivors will suffer from loss of independence, loss of mobility, and permanent disability. Clinicians working with women see breast cancer survivors for routine follow-up visits, and we need to remember the important sequelae that premature menopause and cancer treatment itself could have on a woman’s bone health, and start regular bone density testing early. Prevention is of utmost importance, including adequate intake of calcium and vitamin D, as well as exercise, combined with appropriate intervention with pharmacologic agents when indicated. ■

Antithrombotic Therapy Does Not Improve Pregnancy Outcomes in Women with Unexplained Recurrent Miscarriage By Wayne Kuznar

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ntithrombotic therapy does not improve the chance of live birth in women with unexplained recurrent miscarriage, according to findings from a new study presented at the 2009 annual meeting of the American Society of Hematology. Recurrent miscarriage occurs in 1% to 3% of women, of which about half is unexplained. In women with recurrent miscarriages and antiphospholipid syndrome, heparin and aspirin appear to improve pregnancy outcomes, but there is no evidence to the benefit of these medications for women with unexplained recurrent miscarriages. Many clinicians in the United States prescribe aspirin and low-molecular-weight heparin (LMWH) for women with unexplained recurrent miscarriage, because they believe that the mechanism behind recurrent miscarriage may be similar to that of antiphospholipid syndrome, despite the lack of evidence. This new randomized, placebo-controlled trial was conducted in the Netherlands, said lead investigator Stef

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P. Kaandorp, MD, Research Fellow, Department of Obstetrics and Gynecology, Academic Medical Center, Amsterdam, because “colleagues in the United States are stating that they couldn’t do this kind of trial, because the women get treatment already.”

relatively high incidence of unexplained fetal loss. We don’t know if there is a similar level of unexplained fetal loss in families without a history of deep vein thrombosis. It’s that bit of a correlation and the desire to try to figure out what’s going on and fix it

“Aspirin combined with heparin and aspirin alone do not prevent recurrent, unexplained miscarriages…we should not needlessly put these women through the inconvenience and risks associated with these bloodthinning medications.” —Stef P. Kaandorp, MD “There are a number of things that hint that blood clots may be contributing to these unexplained pregnancy losses,” said Bradford Schwartz, MD, Professor of Medicine and Biochemistry, and Dean, University of Illinois College of Medicine at UrbanaChampaign. “When we do family histories of people who have unexplained blood clots, we find that in a family where there are a lot of deep venous thromboses, there also seems to be a

that has pointed our therapy in the direction of antithrombotic therapy.” But the evidence from this new study suggests otherwise. The study enrolled 364 women (aged 18-42) who were attempting to conceive or were <6 weeks pregnant. All had previously had at least 2 unexplained miscarriages by their 20th week of pregnancy. Women with a history of thromboembolism, endocrine disorders, or other indications for anticoagulant therapy in preg-

nancy were excluded from the study. The women were randomized to 1 of 3 groups—aspirin plus LMWH (nadroparin), aspirin alone, or placebo, given once daily until the woman reached 36 weeks of gestation, or until miscarriage, ectopic pregnancy, or premature delivery occurred. Results showed that the rate of live births did not differ significantly among the 3 treatment groups. Live birth rates were: • 54.5% in the group of aspirin plus nadroparin • 50.8% in the aspirin-alone group • 57% in the placebo group. Adverse effects, such as bruising and skin reactions occurred more often in women assigned to the aspirin and nadroparin group. “The study clearly demonstrates that aspirin combined with heparin and aspirin alone do not prevent recurrent, unexplained miscarriages, and that we should not needlessly put these women through the inconvenience and risks associated with these blood-thinning medications,” said Dr Kaandorp. ■

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PROGRAM OGI1 • RELEASE DATE: FEBRUARY 26, 2010 • EXPIRATION DATE: FEBRUARY 26, 2011 • ESTIMATED TIME TO COMPLETE: 1.0 HOUR

Cancer Treatment–Related Bone Loss and Osteoporosis A Concern for Women with Breast Cancer By Rita Wickham, PhD, RN, AOCN Rush University College of Nursing, Oncology and Palliative Care Consultant, Chicago, IL

STATEMENT OF NEED As women treated for breast cancer are living longer, their bone health is a major concern. Healthcare providers should be able to identify risk factors for bone loss to determine who may benefit from current management options. TARGET AUDIENCE Advanced practice nurses, registered nurses, and other interested healthcare professionals. LEARNING OBJECTIVES After completing this activity, the reader should be better able to: • Explain normal bone physiology and the effects of cancer therapies on bone health • Identify risk factors for bone loss • Discuss current recommendations for pharmacologic and nonpharmacologic interventions to prevent and treat bone loss in patients with cancer

EDITORIAL BOARD Marcia Hilse, RNC, MSN IVF Coordinator Fertility Center of Illinois 900 N. Kingsbury, Suite RW6 Chicago, IL 60610 Rita Wickham, PhD, RN, AOCN Assistant Professor Rush University College of Nursing 600 S. Paulina Street Armour Academic Center, Suite 1080 Chicago, IL 60612 PLANNING COMMITTEE Gloria Mui Medical Director Veritas Institute for Medical Education, Inc. 611 Route 46 West Hasbrouck Heights, NJ 07604 Julie Ann Tagliareni CME Director Veritas Institute for Medical Education, Inc. 611 Route 46 West Hasbrouck Heights, NJ 07604 Anne L. Finger President Veritas Institute for Medical Education, Inc. 611 Route 46 West Hasbrouck Heights, NJ 07604 Dalia Buffery Editorial Director Novellus Healthcare Communications, LLC 241 Forsgate Drvie Monroe Twp, NJ 08831

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reast cancer is a disease of women: only 1% of cases occur in men. Risk for breast cancer increases with age, and 95% of new cases are diagnosed in women aged 40 years or older.1 The median age at diagnosis is 61 years,1 so half of all cases occur in younger women—who may be premenopausal. Women are more likely than men to develop osteoporosis, because they have smaller bones with proportionally less bone volume and density. In addition, women with breast cancer may be at high risk for cancer treatment–induced bone loss (CTIBL), leading to low bone mass (formerly called osteopenia) or osteoporosis.1 The effects of CTIBL can occur independently of bone metastases and pathologic fractures. Because women treated for localized or metastatic breast cancer are living longer, their bone health is a major concern. Healthcare providers must have an understanding of normal bone turnover, patient- and treatment-related risk factors for bone loss, measurement of bone mineral density (BMD), and implications for clinical practice. Patients at risk for bone loss should be identified early so that care interventions can be planned to decrease risks for osteoporosis, maintain or restore normal BMD, sustain functional independence, and prevent potentially fatal low-impact (fragility) fractures. Normal Bone Turnover Bones are stiff, flexible, lightweight,

and strong to aid in body movement, support and protect vital organs, produce blood cells, and serve as rapid stores for body minerals. Sixty percent of bone is mineralized as calcium hydroxyapatite in a collagen matrix. There are 2 types of bone: the outer compact (or cortical) bone that makes up most of the long bones (femur, tibia, humerus) and pelvis, as well as the outer covering of flat bones (ileum, vertebrae, ribs), and the inner trabecular (cancellous or spongy) bone found near the ends of the long bones and within flat bones.2 Bone turnover continues over a lifetime to maintain strength and integrity, and all bone undergoes remodeling depending on the forces placed on it. Only a small portion of total bone is remodeled at a given time; areas of greatest stress—vertebral bodies, femoral head and hip, and long bones—are the sites of most frequent remodeling. Turnover is greater in trabecular than in compact bone. Bone homeostasis is tightly regulated and, in general, bone resorption and bone synthesis are coupled. During childhood and after fractures, more bone is synthesized than resorbed, but in young adults, bone resorbed equals bone made. After about age 30 to 35 years, slightly less bone is formed, and gradual bone density loss continues into old age. This uncoupling in bone turnover increases dramatically in women during menopause because of the sudden loss of estrogen. This pro-

CONTINUING NURSING EDUCATION ACCREDITATION AND CONTACT HOURS STATEMENT Veritas Institute for Medical Education, Inc., is approved by the California Board of Registered Nursing Provider #13986 for 1.0 Contact Hours. METHOD OF PARTICIPATION 1. Read the article in its entirety 2. Log on to www.obgyn-infertility-nurse.org 3. Click on “CE Credits” 4. Click on “Click here to complete the posttest and obtain a CE certificate online” 5. Register to participate 6. Enter program number OGI1 7. Complete and submit the CE posttest and CE Activity Evaluation and Request for Credit Form online 8. Print your Statement of Completion This activity is provided free of charge to participants. FINANCIAL DISCLOSURES Veritas Institute for Medical Education, Inc., is required to disclose to the activity audience

nounced uncoupling wanes after 5 to 10 years, and bone loss in postmenopausal women and men older than 55 years is equivalent (about 0.5%-1% per year).3,4 There are 3 types of bone cells: osteocytes, osteoclasts, and osteoblasts. Osteocytes are the functional bone cells, osteoclasts (c for bone consuming) break down bone, and osteoblasts (b for bone building) synthesize new bone cells and differentiate into osteocytes. Each bone cell influences the activity of the other cell types, which are also influenced by hormones, cytokines, and local growth factors, as well as the central and peripheral nervous system.5,6 For example, osteoclasts and osteoblasts of women and men express estrogen receptors and androgen receptors. Estrogen is more important and may prevent bone loss by regulating cytokine production, maintaining coupled bone turnover, and suppressing the rate of turnover.3 Loss of estrogen increases and intensifies osteoclast activity and may impair osteoblast activity, thereby uncoupling bone homeostasis with more bone resorbed than formed and decreasing bone mass.7,8 Bone remodeling occurs over 3 to 6 months in phases of initiation, transition, and termination. Initiation begins when microcracks in bone, loss of mechanical loading (as caused by prolonged inactivity), or altered hormones or cytokines cause monocytes to gather and differentiate into preosteoclasts. These subsequently fuse into large,

the relevant financial relationships of the planners and faculty involved in the development of CE content. An individual has a relevant financial relationship if he or she has a financial relationship in any amount occurring in the last 12 months with a commercial interest whose products or services are discussed in the CE activity content over which the individual has control. In addition, all faculty are expected to openly disclose any unlabeled/unapproved/investigational uses of drugs or devices discussed in this activity. Disclosures are as follows: • Rita Wickham, PhD, RN, AOCN, has nothing to disclose. • Marcia Hilse, RNC, MSN, has nothing to disclose. The staffs of Veritas Institute for Medical Education, Inc., and Novellus Healthcare Communications, LLC, have nothing to disclose. DISCLAIMER The opinions expressed in this activity are those of the presenters and do not necessarily reflect the opinions or recommendation of Veritas Institute for Medical Education, Inc. Copyright © 2010 Veritas Institute for Medical Education, Inc. All rights reserved.

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WWW.OBGYN-INFERTILITY-NURSE.COM multinucleated osteoclasts that have powerful proteases to demineralize and resorb damaged bone. Resorption lasts about 3 weeks.7,9 During transition (or reversal), osteoclasts stimulate local mesenchymal stem cells to differentiate into preosteoblasts and then osteoblasts, at which point osteoclasts undergo apoptosis and stop resorbing bone. During termination (or formation), osteoblasts begin to form new bone. Layering of osteoblasts continues until the resorbed cavity fills in over 3 to 4 months. Osteoblasts ultimately flatten and differentiate into osteocytes and become encased in hydroxyapatite. New bone is not as mineralized (or strong) as older bone. Risk Factors for BMD Loss Bone strength depends on BMD and bone quality (mineralization, hydroxyapatite matrix, altered repair, and microdamage).3 Only BMD can be measured, and evaluation of BMD is recommended in individuals at high risk for osteoporosis and low-intensity fractures. These fractures can result from a fall from a height no more than the person’s standing height or occur spontaneously with coughing, sneezing, or abrupt movement.10 Aging inevitably leads to bone loss, so elderly women and men have less bone strength than young adults. Some risk factors for osteoporosis, such as genetic predisposition and early menopause (<45 years of age), are unchangeable; however, other factors, including sedentary lifestyle, low calcium and vitamin D intake, cigarette smoking, and alcohol intake, can be changed.10,11 Bone architecture is altered with bone loss, and osteoporotic compact bone is thin and brittle, whereas cancellous bone loses many trabeculae; both loss of trabeculae and compact bone greatly weaken bone.12 Cancer medications that can cause CTIBL, autologous bone marrow/ stem-cell transplantation, and multiple myeloma are all high-risk factors for patients with cancer. Chronic corticosteroid treatment (eg, 5 mg prednisone per day for ≥3 months) can also induce bone loss and osteoporosis. Chemotherapy and hormones may indirectly cause bone loss by leading to loss of estrogen. Ovarian damage and premature menopause occur in 63% to 96% of premenopausal women within 1 year after adjuvant chemotherapy that includes cyclophosphamide, and older women receiving higher cumulative doses are at greatest risk for bone loss.7 More than two thirds of breast cancers are estrogen receptor–positive, and hormones—particularly selective estrogen-receptor modulators (SERMs) and aromatase inhibitors (AIs) that are given to treat or prevent breast cancer by inducing menopause or further reducing estrogen levels—also affect

bone remodeling.13 Tamoxifen, a SERM, is an estrogen antagonist on bone and increases bone loss in premenopausal women, but is an agonist on bone and spares bone in postmenopausal women.7,14 AIs block the action of aromatase, the enzyme that converts adrenally produced androgens into estrogen in postmenopausal women. Anastrozole, letrozole, and exemestane increase bone loss and fracture rates, but this effect is reversible shortly after the AI is stopped. It is not known, however, whether lost bone is regained or over what period. Similarly, a gonadotropin-releasing hormone agent such as goserelin dramatically decreases circulating estrogen, as does oophorectomy or sudden menopause. Detection and Management of Osteoporosis It is critical to identify patients at risk for bone loss because osteoporosis is asymptomatic until a fracture occurs. The best single test for BMD is central dual-energy x-ray absorptiometry (DXA or DEX), which provides 2-dimensional views of the hip and spine, or total body bone.7,10 DXA results, reported as T-scores, represent the differences in standard deviations (SDs) in the patient’s BMD and a standard comparison group of young adult women. BMD may be normal, low bone mass (osteopenia), osteoporosis, or severe osteoporosis (Table 1).11 Fracture risk is inversely correlated with BMD and increases by 1.6 to 2.2 times for each fall in T-score SD.15 In 2003, the American Society of Clinical Oncology published updated guidelines for management of bone health in women with breast cancer (Table 2). The guidelines stress the importance of early detection and therapy for osteoporosis.16 Management involves both nondrug and pharmacologic therapies.10-12 First, healthcare providers must identify at-risk patients who may benefit from lifestyle changes that can decrease bone loss. For example, current recommendations from the National Osteoporosis Foundation for daily intake of calcium and vitamin D are 1200 mg/day and 800 IU/day to 1000 IU/day, respectively, and many individuals will need supplements to attain these levels.11 Supplemental calcium should not exceed 1500 mg/day (in divided doses), however, because of risks for kidney stones and cardiovascular problems. Patients should also be counseled on strategies to stop smoking and limit alcohol intake, and the benefits of regular weight-bearing exercise (walking or jogging, stair climbing, Tai-Chi) and muscle-strengthening exercise (weight training, resistive exercises), which may decrease the risk of falls and modestly increase BMD, should be emphasized.11

Raloxifene, estrogen (not used in patients with breast cancer), calcitonin, parathryroid hormone, and some bisphosphonates have US Food and Drug Administration approval to treat postmenopausal osteoporosis (Table 3).10,11 Bisphosphonates, which suppress osteoclast activity to slow bone resorption, are the most commonly used agents in patients with cancer. An evidence-based review of bisphosphonates for CTIBL in breast cancer patients confirmed that clodronate, ibandronate, pamidronate, risedronate, and zoledronic acid have protective effects against bone loss secondary to chemotherapy-induced menopause, ovarian ablation with goserelin, or treatment with an AI.13 When using pamidronate and zoledronic acid, it is important to remember that the doses used to treat osteoporosis are lower than those commonly used for hypercalcemia. It is also important to assess vitamin D levels in patients who are prescribed a bisphosphonate for osteoporosis, because vitamin D insufficiency, which is common in patients with cancer, can worsen hypocalcemia and lead to secondary hyperparathyroidism, low bone mass, and fractures.17 Patients with low vitamin D levels thus require instruction about vitamin D supplementation during bisphosphonate therapy. To take an oral bisphos-

phonate, patients must be able to take it with tap water on an empty stomach and to sit or stand for 30 minutes after taking it because of the potential for reflux, esophageal irritation, and gastritis. Some oral bisphosphonates are given weekly or monthly to simplify administration, but adherence is problematic, and up to 50% of patients stop taking oral agents after less than 1 year.18 Ibandronate and zoledronic acid can be administered intravenously. This may enhance adherence but can also cause acute flulike symptoms, which can be alleviated by acetaminophen. Conclusion Osteoporosis is likely to become an increasingly important issue in survivorship care plans for patients with breast cancer. Early identification of patients at risk—particularly as they age—and counseling about maintaining healthy weight, regular exercise, calcium and vitamin D intake, moderate alcohol use, and avoidance of smoking are essential for preventing this complication. Some patients will also need pharmacologic management of CTIBL, which will require nurses, pharmacists, and others caring for these patients to maintain upto-date knowledge about current recommended therapies to teach patients about drug benefits and burdens and aid patient adherence.

Table 1 T-Scores and BMD Category

Definition

T-score

Normal Low bone mass (osteopenia) Osteoporosis

BMD within 1 SD of young normal adult BMD between 1 and 2.5 SDs below that of young normal adult BMD is 2.5 SD or more below that of young normal adult BMD is 2.5 SD or more below that of young normal adult Has had ≥1 low-impact (fragility) fracture

–1.0 and above Between –1.0 and –2.5 Below –2.5

Severe osteoporosis

Below –2.5

BMD indicates bone mineral density; SD, standard deviation. Source: Reference 11.

Table 2 ASCO Recommendations for Patients with Nonmetastatic Breast Cancer Low risk High risk T-score –1.0 and above T-score –1.0 to –2.5 T-score –2.5 and below

DXA hip ± spine Not recommended

Management Monitoring Lifestyle advice; calcium Annual history and vitamin D for risk status

Recommended

Lifestyle advice; calcium Annual BMD and vitamin D Lifestyle advice; calcium Annual BMD and vitamin D Lifestyle advice; calcium Annual BMD and vitamin D; begin bisphosphonate or raloxifenea

Recommended Recommended

a Raloxifene, a selective estrogen-receptor modulator, is not recommended in patients who have taken tamoxifen. ASCO indicates American Society of Clinical Oncology; BMD, bone mineral density; DXA, dual-energy x-ray absorptiometry. Source: Reference 16.

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Continued from page 15 References

Table 3 Agents that May Be Used in Patients with Breast Cancer and Osteoporosis Dosing Class/Agent

Indications

Prevention

Treatment

Comments

Bisphosphonates Alendronate (Fosamax, Fosamax D)

Postmenopausal osteoporosis

Tablet: 5 mg/day or 35 mg/week

Tablet or liquid: 10 mg/day or 70 mg/week Tablet: 70 mg/week with 2800 IU or 5600 IU of vitamin D

Take upon rising in AM with 8 oz water, empty stomach; do not eat or drink, and stay upright for 30 minutes

Ibandronate (Boniva)

Postmenopausal osteoporosis

Tablet: 2.5 mg/day or Tablet: 2.5 mg/day or 150 mg/month 150 mg/month

Take upon rising in AM with 8 oz water, empty stomach; do not eat or drink, and stay upright for 60 minutes

Risedronate (Actonel, Actonel with calcium)

Postmenopausal osteoporosis; increase bone mass in men with osteoporosis; prevent, treat osteoporosis in men and women starting or taking glucocorticoid

Tablet: 5 mg/day or 35 mg/week or 75 mg on 2 consecutive days or 150 mg once a month

Take upon rising in AM with 8 oz water, empty stomach; do not eat or drink, and stay upright for 30 minutes

Zoledronic acid (Reclast)

Postmenopausal osteoporosis

IV: 5 mg once a year

Administer over at least 15 minutes

Calcitonin Salmon calcitonin Women at least 5 years (Miacalcin, Fortical) postmenopausal

Single daily intranasal Alternate nares spray 200 IU

Parathyroid hormone PTH (1-34) Teriparatide Postmenopausal women at high (Forteo) risk for fracture

Daily subcutaneous injection: 20 µg

Contraindicated: patients receiving skeleton or bone radiotherapy to metastases, history of skeletal malignancy, hypercalcemia

IV indicates intravenous.

1. Breast Cancer Facts and Figures 2007-2008. Atlanta, GA: American Cancer Society; 2008. 2. Datta HK, Ng WF, Walker JA, et al. The cell biology of bone metabolism. J Clin Pathol. 2008;61:577-587. 3. Almeida M, Han L, Martin-Millan M, et al. Skeletal involution by age-associated oxidative stress and its acceleration by loss of sex steroids. J Biol Chem. 2007; 282:27285-27297. 4. Lønning PE. Endocrine therapy and bone loss in breast cancer: time to close in the RANK(L)? J Clin Oncol. 2008;26:4859-4861. 5. Borovecki F, Pecina-Slaus N, Vukicevic S. Biological mechanisms of bone and cartilage remodeling—genomic perspective. Int Orthop. 2007;31:799-805. 6. Elefteriou F. Regulation of bone remodeling by the central and peripheral nervous system. Arch Biochem Biophys. 2008;473:231-236. 7. Michaud LB, Goodin S. Cancer-treatment-induced bone loss, part 1. Am J Health Syst Pharm. 2006;63: 419-430. 8. Zallone A. Direct and indirect estrogen actions on osteoblasts and osteoclasts. Ann N Y Acad Sci. 2006; 1068:173-179. 9. Matsuo K, Irie N. Osteoclast-osteoblast communication. Arch Biochem Biophys. 2008;473:201-209. 10. Institute for Clinical Systems Improvement. Health Care Guideline: Diagnosis and Treatment of Osteoporosis. September 2008. www.icsi.org/osteoporosis/ diagnosis_and_treatment_of_osteoporosis__3.html. Accessed November 20, 2009. 11. National Osteoporosis Foundation. Clinician’s Guide to Prevention and Treatment of Osteoporosis. 2008. http://nof.org/professionals/NOF_clinicians_guide. pdf. Accessed November 20, 2009. 12. Turner Biomechanics Laboratory. Osteoporosis/ biomechanics. 2005. www.engr.iupui.edu/~turnerch/ biomech.htm. Accessed November 20, 2009. 13. Saad F, Adachi JD, Brown JP, et al. Cancer treatment-induced bone loss in breast and prostate cancer. J Clin Oncol. 2008;26:5465-5476. 14. Bjarnason NH, Hitz M, Jorgensen NR, Vestergaard P. Adverse bone effects during pharmacological breast cancer therapy. Acta Oncol. 2008;47:747-754. 15. Johnell O, Kanis JA, Oden A, et al. Predictive value of BMD for hip and other fractures. J Bone Miner Res. 2005;20:1185-1194. 16. Hillner BE, Ingle JN, Chlebowski RT, et al. American Society of Clinical Oncology 2003 update on the role of bisphosphonates and bone health issues in women with breast cancer. J Clin Oncol. 2003;21:4042-4057. 17. Wang-Gillam A, Miles DA, Hutchins LF. Evaluation of vitamin D deficiency in breast cancer patients on bisphosphonates. Oncologist. 2008;13:821-827. 18. Boonen S, Vanderschueren D, Venken K, et al. Recent developments in the management of postmenopausal osteoporosis with bisphosphonates: enhanced efficacy by enhanced compliance. J Intern Med. 2008;264:315-332.

COMMENTARY: Cancer Treatment–Related Bone Loss and Fertility

A Fertility Nurse Perspective Marcia Hilse, RNC, MSN IVF Coordinator Fertility Centers of Illinois, Chicago

A

ccording to different reports, only about 20% to 30% of patients newly diagnosed with cancer are given information regarding fertility preservation before cancer treatment begins.1-3 Many of the treatments available affect not only bone loss but fertility as well, leading to ovarian dysfunction, premature ovarian failure, and egg or sperm loss or production failure.4,5 Bone loss that may accompany cancer treatment can have adverse effects on future pregnancies.6 Treatment with bisphosphonates (which break down and reform bone)—prescribed as a common adjunct to cancer therapy—are traditionally contraindicated in planned pregnancy resulting from potential complications in fetal development.6 Preventing bone loss should be a primary focus of the oncology nurse, and education on diet and exercise will aid

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in patient lifestyle modifications. Such early interventions may decrease potential complications of osteoporosis in the future. In addition to the immediate concern of bone loss associated with cancer therapy, preservation of fertility should be a subsequent concern for all healthcare providers when dealing with a patient of childbearing age. Advising patients on fertility preservation options should be considered by all those caring for patients with cancer. Sperm banking before cancer treatment is a simple way for men to preserve their option of becoming a biologic parent in the future, but what options are available to a woman who is currently single or to a couple that has not yet completed a family? Keep in mind that even if a woman’s ovarian function is not affected dramatically by the cancer treatment, attempting pregnancy is often contraindicated for 2 to 5 years after the cancer is eradicated.7 Because fecundity declines with advancing maternal age, this 2- to 5-

year time frame can mean that the woman has to face decreased options and decreased successful pregnancy rates in the future. Postponing traditional fertility treatment until after cancer treatment could result in a woman’s age precluding her success in achieving pregnancy with her own eggs. Embryo cryopreservation for couples and oocyte vitrification for single women are now available at many fertility clinics around the world; using these options before cancer treatment can help offset the chronological and treatment-induced biological clock. Different fertility clinics offer a variety of options for patients dealing with cancer. One example is the Fertility Centers of Illinois in Chicago, which has developed a Cancer Fast Track program to offer women an opportunity to preserve their option of becoming a biologic parent after successful cancer treatment. This program was developed with the knowledge that time is a slim commodity for patients with cancer.

Women can see a physician within 2 to 3 days of contacting the clinic, and (menstrual cycle permitting) may be able to complete an in-vitro fertilization cycle within 2 to 4 weeks if they so desire. Not all women choose to pursue this treatment, but having the opportunity to do so can give them a measure of hope that there is “life after cancer.” ■ References 1. Kesic V. Fertility after the treatment of gynecologic tumors. Recent Results Cancer Res. 2008;178:79-95. 2. Nieman CL, Kazer R, Brannigan RE, et al. Cancer survivors and infertility: a review of a new problem and novel answers. J Support Oncol. 2006;4:171-178. 3. Partridge AH, Gelber S, Peppercorn J, et al. Webbased survey of fertility issues in young women with breast cancer. J Clin Oncol. 2004;22:4174-4183. 4. Su HI, Lin K, Gracia CR. Early menopause in cancer survivors: fertility options. Menopausal Med. 2008; 16:S1-S6. 5. Sonmezer M, Oktay K. Fertility preservation in female patients. Hum Reprod. 2004;10:251-266. 6. Djokanovic N, Klieger-Grossman C, Koren G. Does treatment with bisphosphonates endanger the human pregnancy? J Obstet Gynaecol Can. 2008;30:1146-1148. 7. Petrelli NJ, Winer EP, Brahmer J, et al. Clinical cancer advances 2009: major research advances in cancer treatment, prevention, and screening—a report from the American Society of Clinical Oncology. J Clin Oncol. 2009;27:6052-6069.

www.obgyn-infertility-nurse.com


Clinic Spotlight

Shady Grove Fertility Center...

Debbie Rice, RN

ductive endocrinologists and more than 100 nurses who see patients in 12 office locations in the Washington/Baltimore metropolitan areas. Our physicians perform >4000 IVF cycles a year, with an equivalent number of intrauterine insemination and ovulation induction cycles annually. We have 2 state-of-theart IVF laboratories—one in our Rockville, MD, office and the other in our Baltimore office. The Rockville office houses our ambulatory surgery center, where our physicians perform egg retrievals and hysterosalpingograms. In addition to doctors and nurses, our clinical staff includes embryologists, andrologists, geneticists, and researchers. Our center is open 365 days a year and is accredited by the Joint Commission and by the Accreditation Association for Ambulatory Health Care. Shady Grove Fertility has one of the largest donor egg programs in the United States. We have a very dedicated team of nurses and administrators whose primary focus is donor egg. They are responsible for recruiting donors, matching donors and recipients, and administering medication protocols for the donors and recipients.

What sets Shady Grove apart and contributes to its success? Everyone in this organization is dedicated to seeing our patients succeed in their “fertility journey” and have the best outcome possible—a healthy baby. From a nursing perspective, we focus on a holistic, relationship-based approach by putting the patient first. Most of our patients have direct contact with our clinical staff through e-mail and direct phone calls. We want to make sure that we are always available to answer any questions a patient may have. Every patient’s treatment protocol is individualized to the patient’s specific diagnosis. Although patients may see one physician for their treatment, our team of physicians is always collaborating to help maximize the success of their patients. Our physicians meet weekly as a group in the Rockville office, where they discuss clinical issues and new

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Continued from page 1

academic teaching. Many of our physicians lecture and teach residents at Georgetown University School of Medicine. We are a partner in the combined National Institutes of Health and Walter Reed Fellowship Program, in which fellows rotate through our center to get hands-on experience in reproductive endocrinology. Our new partnership with the University of Maryland provides another opportunity for patients to participate in multidisciplinary research based at a major university medical school, while giving medical students/ residents a chance to learn from a wide variety of fertility patient cases from top reproductive endocrinologists.

advances in fertility treatment. We also have innovative financial programs that have contributed greatly to our success. The biggest has been our Shared Risk 100% Refund Program, which provides patients with up to 6 IVF or donor egg cycles for one flat fee, with a 100% refund for those who either do not have a baby or choose to stop treatment at any point. Patients who opt for this program can also choose to include their standard IVF medication in the flat-fee program, and have those costs refunded if they do not succeed in having a baby or decide to stop treatment. Our Shared Donor Egg program is unique in that it provides an opportunity for couples seeking this treatment to share the donated eggs and the cost. Couples who choose this option reduce the cost of donor egg treatment by up to 50%. These programs make fertility treatment affordable for more people. Although the majority of our patients come from the Mid-Atlantic states, we have had patients come from all 50 states and from more than 35 countries worldwide to take advantage of our unique programs. Another contributor to our success is that we strive to hire the very best staff. Our bar is high, and our staff is very well-trained. Nobody can operate independently; we are all integrated and work well together. Everyone is trained with a generous orientation for each new position, and we make sure that new hires are a good fit with our culture and philosophy, so people work here for a long time.

lite offices. It is a great setup for patients and is made available to all those who wish to take advantage of it. In addition, we have in our building a holistic fertility group called Pulling Down the Moon, which offers our patients adjunct complementary therapy. Through this group, patients can participate in yoga classes, nutrition counseling, massage, or acupuncture, all of which are focused on helping patients get pregnant. We offer many opportunities for patients who choose to take part in this great group.

How does Shady Grove support its patients throughout the process?

Shady Grove Fertility Center’s nurses, front to back: Jenny Dufresne, RN; Sharon Morey, RN; Jessica Buggs, RN; Lindsey Wiesler, RN; Krystal Lewis, RN; Dew Jamandre, RN; Kathy Bugge, RN; Marsha Deweese, RN, Clinical Operations Director; Debbie Rice, RN, Clinical Operations Supervisor.

Every patient has an entirely different reason for being here, so we make sure that we give every patient individualized care. In our nursing model, each of our physicians has a team of primary nurses and a clinical assistant. When patients come to our center for an initial consultation, they meet with a physician and are then assigned a primary nurse who works with them throughout the entire process. Although we all understand that we are not going to be successful in getting all our patients pregnant, we are successful in supporting them in their decisions along the way. Sometimes patients go through the infertility process and then decide that adoption or remaining childless is okay; in these cases, we know that we have helped and supported them to get to that point. One of our unique support systems is provided by our psychological services department, which is focused on infertility. It offers patients free support groups in Rockville and at all our satel-

Are you active in the research community? Shady Grove Fertility Center has been a national leader in fertility research and is one of the few fertility centers in the country to employ a full-time dedicated research staff, under the leadership of Kevin Richter, PhD. As the largest clinic in the country, our size gives us the ability to gain insight into the best fertility practices within a few months of patient care that may take many other

clinics, or groups of clinics, years to gather. We take the responsibility to give back to our field seriously, for the benefit of all patients, not just our own. All the physicians and many of the laboratory staff at Shady Grove Fertility began their training, and often part of their careers, in academic medical centers. Coming from that background, we realize that an invigorating, stimulating atmosphere can contribute to clinical excellence. Therefore, we have reconstructed that academic atmosphere within the privacy and patient-oriented setting of our practice, melding the best of both worlds. Every year, our center is a major contributor to the annual meeting of the American Society for Reproductive Medicine (ASRM). Last year, we had 9 submissions to the 2009 ASRM annual meeting, and some of those studies were published in Fertility and Sterility. In addition, our center participates in

What does your role as assistant nursing supervisor entail? I always laugh and say that I am a jack of all trades and master of none. Primarily, I am responsible for most of the nurse staffing in our Rockville center, along with precepting and helping to orient new nurses to the practice. New nurses that join the practice spend

their first few weeks with me learning infertility basics, types of medications and protocols, and our electronic medical records system before they move to their home offices. We fine-tune their training based on their, and our, needs. Being the supervisor, I do not have patients of my own, which enables me to be the go-to person in any area where help is needed. For example, if an instructor is unable to come in for an injection class during the week, I will teach the injection class. If we have a busy day and one office is overwhelmed with the number of patient results they have, I will assist with the callbacks. I also assist our Clinical Operations Director, Marsha DeWeese, RN, according to her needs, such as writing policy and procedures and reviewing new clinical initiatives. I have the kind of cross-training that allows me to work in any area. It is a great job, and there is never a boring day. ■

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The Pharmacy Corner

Progesterone Support in IVF Brett Pine President and COO, Braun PharmaCare, Chicago, IL

lowers the incidence of miscarriage. The best route of administration, however, has not been clearly established. In the pharmacy setting we see that all formulations are prescribed, with an average slightly higher use of the injectable form. When Braun PharmaCare started compounding injectable progesterone many years ago, the suspending base used was sesame oil. With increasing feedback and more studies

women had fewer adverse effects. But a main problem remained. Both forms of the oil are viscous, require the use of a large needle, and are sometimes difficult to inject. This has paved the way for administering progesterone in ethyl oleate. This form carries all of the positive attributes of cottonseed oil, but is much less viscous. A less-painful needle can be used for injection, and ease of administration can be accomplished.

All this information continues to support the use of progesterone therapy when a woman goes through IVF, but an ideal form of administration has yet to be determined.

conducted to monitor this route of administration, patients were receiving the benefit needed from the progesterone, but many patients also encountered typical side effects, such as injection-site pain and allergic reactions. When we replaced the sesame oil base with a cottonseed oil base, many

Why is progesterone being given to a patient undergoing treatment for infertility? There are several hypotheses explaining the need for progesterone administration during an IVF cycle. A woman is being prescribed various medications during this time, which may alter the amount of progesterone her

Table Available Forms of Progesterone FDA-approved for use in Average ART/pregnancy monthly cost

@Copyright iStockphotos.com/drbouz

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hat comes to mind when you hear the word “progesterone”? In most cases, it would not be given much thought. To an individual undergoing infertility treatment, however, “progesterone” takes on a very powerful meaning. Both men and women produce the hormone progesterone. Although men do not menstruate, they do have shifts in hormone levels. Men produce estrogen and progesterone, each taking part in the regulation of sex hormones. Progesterone and estrogen are major factors in the menstruation cycle of a woman; each of these hormones plays a dominant role, depending on the phase of the cycle. Progesterone levels increase after ovulation occurs, to prepare for a fertilized egg to implant. If this is a natural response, then why does progesterone mean more to an individual undergoing infertility treatment? The answer is simple—progesterone support. Progesterone can be prescribed in various formulations—oral, injectable, or as a vaginal suppository or cream (Table). Case studies show pros and cons to all these forms, but the consensus is that progesterone is integral to the success of early pregnancy, and that it

body produces. Gonadotropin-releasing hormone (GnRH) antagonists and GnRH agonists are often used to prevent ovulation. Either medication may suppress pituitary production of luteinizing hormone, which is required for progesterone production. Also, during oocyte retrieval some of the granulosa cells lining the follicles are removed or disrupted, which could be another reason why luteal-phase supplementation is needed in an IVF cycle. Progesterone therapy proves effective for increasing pregnancy rates among women with luteal-phase defects. Studies show pregnancy rates as high as 77% in women receiving progesterone therapy. All this continues to support the use of progesterone therapy when a woman goes through IVF, but an ideal form of administration has yet to be determined. Until one form rises above the rest, we are fortunate to have multiple avenues for physicians and nurses to choose from for additional progesterone support. Patients should be advised to consult their provider to determine which formulation is the most appropriate fit for their goals. ■

Product

Mode of administration Compound

Progesterone in oil

Intramuscular injections

Micronized progestin: Sesame oil Cottonseed oil Ethyl oleate

Venous absorption Maximum absorption 8-11 hrs after administration

No

Once daily, $150.00

Endometrin

Vaginal

Micronized effervescent suppositories

Vaginal absorption Maximum absorption 17-24 hrs after administration (dosedependent)

Yes

Once daily, $165.00 Twice daily, $330.00 3 times daily, $495.00

Coming in April

Vaginal absorption Maximum absorption after 4-14 hrs (dosedependent)

Yes

Once daily, $360.00 Twice daily, $720.00

• Reproductive Depression • Lifestyle Choices that Influence Fertility

Crinone/Prochieve Vaginal

Bio-adhesive gel

Mode of absorption

Progesterone vaginal suppositories

Vaginal

Compounded micronized progestin

Vaginal absorption Maximum absorption after 6-8 hrs

No

Once daily, $35.00

Oral progesterone

Oral

Micronized progestin

GI absorption Maximum absorption after 1-3 hrs

No

Once daily, $35.00 Twice daily, $70.00

Prometrium

Oral

Micronized progestin

GI absorption Maximum absorption after 1-2 hrs

No

100 mg/day, $60 200 mg/day, $110 400 mg/day, $220

ART indicates assisted reproductive technology; FDA, US Food and Drug Administration; GI, gastrointestinal.

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• The Pap Smear Debate

• Elective Single Embryo Transfer Success: The Ultimate Measure of Efficacy and Safety for an IVF Center • First Case of Term Stillbirth from Oral Bacteria • Effect of Vaginal Estrogen on Women with Breast Cancer • Childbirth after Breast Cancer Affects Mortality Risk

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The Infertility Nurse

Nurses Are Frontline Responders in Ovarian Hyperstimulation Syndrome Management Cutting-Edge Strategies from the Nurses Professional Group, ASRM 2009 By Wayne Kuznar

T

he medical treatment of ovarian hyperstimulation syndrome (OHSS) is aimed at managing symptoms and mitigating the cascade of events that can occur in this syndrome, said Shalini S. Gunawardena, RN, BSN, with the Kaiser Permanente Center for Reproductive Medicine, Fremont, CA. Ms Gunawardena participated in the Nurses Professional Group session on cutting-edge strategies for preventing/managing OHSS at the 2009 American Society of Reproductive Medicine annual meeting. “As nurses we are the frontline responders,” she said. “Through education, assessment, and vigilance, we can help mitigate the effects of this potentially life-threatening complication of ovarian stimulation.” After administration of human chorionic gonadotropin (hCG), patients on the verge of OHSS will exhibit telltale signs—especially abdominal distention—that nurses must recognize to effectively manage the syndrome. The role of the nurse in the management of OHSS is critical, not only as a conduit between physicians and patients but also as educators, she said. “An informed patient is an active participant in care,” she said. “We are also the patient’s support system. We are patients’ counselors; sometimes just listening means the difference between a positive and a negative experience.” Maintaining Fluid Balance OHSS is characterized by a fluid shift from the capillaries to the third space (ie, abdomen and lungs) as a result of increased vascular permeability. Fluid management is one of the basic tenets of treatment, said Ms Gunawardena. “It’s one of the preliminary teachings we all received as new [inductees] to the work of IVF and reproductive medicine,” she said. The 5 essential parameters for maintaining fluid balance are: • Urine output should mirror fluid intake • Baseline body weight should be maintained • Hematocrit and hemoglobin concentrations should be measured • Abdominal girth, which can provide valuable information regarding the development of ascites, should be monitored immediately after oocyte retrieval • An accurate account of oral and intravenous fluid intake should be

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obtained, which can help determine if the patient is collecting fluid in places she should not be. Crystalloid use (0.9% normal saline with or without dextrose) should be routine, because of the tendency for patients to develop hyponatremia.

is an option to albumin. Its cost is a fraction of the cost of albumin and carries no risk of contaminants or infectious disease, unlike albumin. “Like albumin, it will not prevent OHSS; it will only lessen the degree of symptoms,” Ms Gunawardena said.

“As nurses we are the frontline responders…we can help mitigate the effects of this potentially lifethreatening complication of ovarian stimulation.” —Shalini S. Gunawardena, RN, BSN Dietary Guidelines Information on appropriate diet for the management of OHSS is “extremely limited,” said Ms Gunawardena. “We encourage a high-protein diet, due to the finding that increased vascular permeability causes high levels of protein-rich fluid to enter the intravascular space. It’s important to empower our patients and have them be part of the solution. When we have an actively engaged participant, regardless of outcome, they walk away with a positive feeling.” A low-potassium diet is also recommended to mitigate potential cardiac complications. “Beyond this, the rest is truly debatable,” she said, including appropriate sodium intake. The diet Ms Gunawardena recommends to patients limits sodium and encourages electrolyte drinks. For patients who experience nausea and have difficulty with a high-protein diet, nutrition drinks (eg, Ensure), powdered whey protein, or whey protein in tablet form can be tried. “In our clinic, if we have a patient who has a demonstrated history of OHSS or fits the clinical picture, we’ll recommend starting it early,” she said. The Table lists dietary options for OHSS. OHSS and Infertility Treatment Volume expanders (albumin) are used to increase osmotic pressure and pull fluid back into the cellular space, thereby decreasing hemoconcentration. Albumin also increases diuresis and improves renal function. If albumin is used, it is given as 20% human albumin, 50 mL after egg retrieval, and it can be repeated every 2 to 12 hours as needed. Cost is the major drawback to the use of albumin, because 1 infusion costs $800 to $4000. A synthetic plasma expander (6% hydroxyethyl starch) after egg retrieval

A widely used option in the management of OHSS is paracentesis of abdominal ascites specific to OHSS. Early outpatient paracentesis has been shown to be a more cost-effective strategy than hospitalization for moderateto-severe OHSS. Cryopreservation may have value in preventing late-onset OHSS, but has not been shown to prevent early-onset OHSS, said Ms Gunawardena. According to a recent Cochrane review, the evidence is insufficient to support routine cryopreservation to prevent OHSS. Recent data indicate that elective cryopreservation as a result of OHSS does not decrease the rates of implantation or clinical pregnancy compared with fresh embryo transfer. “As freezing rates at clinics continue to improve, offering a ‘freeze all’ cycle becomes more viable,” she said. “Although it will not prevent early-onset OHSS, it will stop the potential for lateonset OHSS related to implantation.” Table Diet Options in OHSS Foods high in protein (encouraged) Meats: red, chicken, lamb Fish Eggs Tofu Nuts Peas Soy products

Foods high in potassium (restricted) Bananas Apricots Avocados Cantaloupe Honeydew melon Nectarines Plantains Tangelos Artichokes Butter beans Dried peas, beans, lentils Potatoes: baked, commercial French fries Sweet potatoes Swiss chard

A retrospective case-controlled study conducted at her institution comparing patients undergoing a frozen embryo transfer cycle after OHSS in the fresh cycle (group A) with patients having a fresh embryo transfer (group B) showed comparable implantation rates between the 2 groups, and clinical pregnancy rates of 72% (group A) and 62% (group B). Emerging Treatments: Cabergoline, GnRH antagonists Without a medication to prevent OHSS, a few new treatments are receiving close inspection. Two such promising medications are cabergoline, a dopamine agonist, and gonadotropinreleasing hormone (GnRH) antagonists, Ms Gunawardena said. Dopamine agonists have been shown to reduce vascular permeability significantly, thereby decreasing the risk and severity of OHSS. Cabergoline has proven favorable effects on peritoneal fluids and ascites, abdominal distention, and discomfort. Different protocols for the use of cabergoline have emerged, although none appears to be a “silver bullet.” One double-blind study in which cabergoline was administered at 0.5 mg/day from the day of hCG administration and continued for 8 days showed significant decreases in thrombin clot time and levels of hemoglobin and ascites, as well as significant reductions in vascular permeability and extravascular leakage. The benefits appeared only in patients with moderate OHSS, noted Ms Gunawardena, and not in those with severe OHSS. No teratogenic effects have been observed with the different protocols. GnRH antagonists after oocyte retrieval may also have a role in OHSS suppression, with potential treatment candidates being donors and patients intending to freeze all embryos. “With the use of the antagonist we see a significant drop in estradiol levels, which can impact the potential for pregnancy, so it is not indicated for fresh transfers,” she said. In a pilot study, the effect of a postretrieval GnRH antagonist on the incidence of severe OHSS in highrisk donors was assessed. Compared with untreated controls, those receiving GnRH antagonists postretrieval had a lower incidence of moderate-tosevere OHSS, and none of the GnRH antagonist recipients developed severe OHSS. ■

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The Infertility Nurse

Making Injection Training Personalized and Convenient for Patients Gina Paoletti-Falcone, RN, BSN Clinical Services Manager, Freedom Fertility Pharmacy, Byfield, MA

O

ne of the scariest things for patients about starting infertility treatments is learning how to prepare and administer injectable medications. The thought of handling something alone at home that is typically associated with being done by doctors and nurses can seem overwhelming. Women tend to worry about their ability to stick a needle into their body, and men worry that they will inject it incorrectly and cause permanent harm to their wives. When I started working at a small community hospital–based infertility practice in 1989, one of my first responsibilities was to provide injection training for our patients. At that time, we used Pergonal, Humegon, Lupron Depot, Profasi, and progesterone in oil, all given as intramuscular (IM) injections. Because it was a small practice, I scheduled appointments with each couple to go over their treatment plan, including how to prepare and administer injectable medications. I reassured patients that being anxious about it was perfectly normal, that the manual skills required were not difficult, and that they would be just fine. I demonstrated how to snap the top off of a glass ampule, withdraw diluents, mix vials, and administer an IM injection. I developed written, step-by-step instructions for injecting medications. We have made great progress in the ease of use of many fertility drugs over the past 20 years. We have premixed, prefilled pen devices, and prefilled cartridges and syringes that make preparation simpler for patients. Pharmaceutical companies provide tear sheets with instructions and videos for their products. But teaching patients to prepare and inject their medications remains a challenging, time-consuming, and repetitive responsibility for fertility nurses. Some practices require couples to attend in-office medication instruction on a one-to-one basis with a nurse or in a group setting. For patients, this means finding time to fit yet another appointment into a life already complicated by the treatment cycle requirements. For nurses, this means finding available nursing time away from the phones and office procedures to repeatedly teach the same information. Group instruction is certainly more efficient, but class size must be reasonable, and a classroom setting puts con-

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fidentiality at risk for IVF patients. Finally, for scheduling purposes, couples may attend their medication training class several weeks before they ever do an injection, which can decrease their recall and confidence when actually doing that first injection.

Teaching patients to prepare and inject their medications remains a challenging, timeconsuming, and repetitive responsibility for fertility nurses. When I joined Freedom Fertility Pharmacy 5 years ago, one of my first projects was to develop our injection training website—Freedom MedTEACH. I believe that fertility specialty pharmacies should provide medication education and support for patients and the nurses who entrust them to our care. Fertility patients routinely surf the Web for information, so attending a “virtual class” online should be a comfortable option. We know that people have different learning styles. Some are visual learners who respond to pictorial/written materials; others learn best by auditory instructions. An online streaming video provides both audio and visual stimulation. Studies support multimedia patient learning of injection training, because: • Patients who experience fear or stress about injections may forget even the simplest verbal instructions1 • Providing learning material in a variety of media for at-home learning reinforces and complements inoffice teaching2 • Video learning programs increase short-term knowledge and may be superior to written materials alone or even individual counseling.3 The many patient benefits of online medication instruction are that it: • Is versatile and can be used as a primary education resource, in preparation for or during an in-office class or as a resource after the office class • Offers the convenience of learning at home when patients can focus their attention • Affords privacy and confidentiality • Allows unlimited access to instruction. Patients can watch the video

many times, including while preparing and administering their medication • Provides easy-to-understand, step-bystep instruction for each medication • Can offer the audio portion in other languages. Freedom MedTEACH is available in English and in Spanish. Online medication training is also beneficial to nurses; it: • Provides consistent, high-quality, clinically reviewed instruction that can be utilized to replace, supplement, or reinforce traditional inoffice instruction • Decreases the time nurses spend on medication training, allowing nurses to use their time more efficiently in patient care • Improves patient competency and confidence, reducing anxiety and the need for phone follow-up. We recently added a new feature to our MedTEACH. Patients receive personal e-mail notification when their order ships, with customized training for the medication protocol. The link brings them to a personalized webpage

with videos for the medications they will be taking so they know exactly what to watch. We understand that nurses feel the burden of responsibility for patients’ competency in administering their medications. Using online video medication instruction is, I believe, the closest thing to being with the patient. Our patient survey consistently tells us that after watching video instruction, patients feel “more confident” in doing their injections. At a recent RESOLVE meeting, a couple shared with me that he watched the progesterone in oil video every night before he gave her the injection, saying that it made him feel better to see it being done before doing it himself. It was very satisfying to hear. ■ References 1. The Canadian MS Nurses Network. The Canadian MS Nursing Care Plan. Mississauga: Ontario; 2000. 2. Kolton KA, Piccolo P. Patient compliance: a challenge in practice. Nurse Pract. 1988;13:37-50. 3. Gagliano ME. A literature review on the efficacy of video in patient education. J Med Educ. 1988;63:785-792.

See also Pharmacy Corner, page 18.

Infertile Couples Report High Use of CAM Therapies By Wayne Kuznar

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ore than one fourth of couples seeking infertility treatment have tried complementary and alternative medicine (CAM), and the likelihood of trying CAM therapies increases if no pregnancy occurs after 18 months, according to results of a new study presented at the 2009 annual meeting of the American Society of Reproductive Medicine. This prospective cohort study from the University of California, San Francisco, included 428 infertile couples who were treated at 8 community and academic infertility practices. They were asked about their use of acupuncture, herbal therapy (ie, Chinese medicine, herbal therapy, or homeopathy), massage, chiropractic, or meditation. After 18 months of observation, 29% of the couples had reported trying CAM for treatment of infertility, including acupuncture (22%), herbal therapies (17%), body work (5%), and meditation (1%). In this study, the wealthier couples were more likely to try CAM. Couples with a household income of >$200,000 were almost 3 times as likely to try

CAM compared with those earning <$100,000. Those who did not achieve pregnancy within 18 months were 2.3-fold more likely to try CAM. Of note, CAM therapies were not associated with an increase in the rate of achieving pregnancy. A survey conducted at Cornell Medical Center, New York City, also showed a high rate of CAM use among 301 infertility patients. This survey was completed by 120 patients undergoing IVF, 45 patients undergoing controlled ovarian hyperstimulation (COH)/intrauterine insemination (IUI), 34 patients who were trying timed intercourse, and 102 patients who presented for infertility evaluation. Overall, 47% of the patients reported using some form of CAM while undergoing assisted reproductive technology. Of those undergoing IVF, 61.7% reported using some form of CAM. The percentage of those trying CAM was 35.5% in the COH/IUI group and 32.4% in the timed intercourse group. Acupuncture was used by >90% of patients undergoing IVF and nearly 80% undergoing IUI. ■

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The Infertility Nurse

Midwest Reproductive Symposium Nurse Practicum: A New Educational Initiative Judith Rosen Farrar, PhD, FAAAAI Dr Farrar is Executive Director, Midwest Reproductive Symposium, Chicago, IL

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pecialty nursing education is critical for professional development and for best care of patients. This is especially true in reproductive medicine, a field that is rapidly evolving in terms of technology and therapy and that involves complex issues, separate from medical care, that can affect every aspect of a patient’s, or a couple’s, life. Review of the available programs for nurses in reproductive medicine reveals gaps in advanced and introductory level offerings and, particularly, a need for more workshops and interactive sessions. Recognizing this, the 2010 Midwest Reproductive Symposium (MRS) will for the first time include a special program for nurses—the MRS Nurse Practicum. Nurses have been an integral part of the MRS since its inception in 2005, accounting for up to 40% of MRS attendees. Early on, input from nurse attendees led to the development of MRS workshops for nurses (eg, managing patients with polycystic ovary disease, dealing with stress in the clinic, a nurse’s guide to PGD). It has become a successful collaboration. For nurses, the MRS has provided an opportunity to network with colleagues and experts in reproductive medicine; in return, nurses have provided invaluable feedback on educational needs and interests. “We carefully evaluate all attendee feedback,” commented MRS Chairperson Barry Behr, PhD. “The nurse comments definitely have helped shape our programming.” MRS Chairperson William Kearns, PhD, agreed, saying, “We worked hard to create opportunities for interaction and expect that this year will be similar to 2009, when 200 physicians, nurses, and embryologists participated in dynamic, sometimes controversial, sessions.” The MRS Nurse Practicum takes that collaboration up another notch. In light of new regulations for continuing education in the United States, and using the MRS as a model of interactive programming, the Practicum Planning Committee identified 3 critical conditions for success: 1. Direct and practical relevance to the nurse practicing in reproductive medicine 2. Necessary knowledge about new technologies and therapeutic approach-

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es on the horizon identified as having an important potential impact on the clinical practice of IVF and assisted reproductive technology 3. Involvement of the attendees in lively discourse about current issues relevant to their practices.

With these conditions, MRS Founder and Chairperson Angeline Beltsos, MD, said that the practicum meets the original goal of the MRS—“to provide an opportunity for attendee input on issues of relevance presented in an interactive educational setting.” In

addition, combining the practicum with the MRS provides programming and cost efficiencies. The first day of the June practicum will consist of programming developed by nurses for nurses; day 2 will be the first clinical day. ■

The Midwest Reproductive Symposium (MRS)

Nurse Practicum 2010 June 3-4 • The Drake Hotel (Chicago, IL) June 3rd: Sessions developed by nurses for nurses June 4th: Required sessions at the MRS OPTIONAL - June 5th MRS sessions at no extra cost!

Join your colleagues for a timely and lively discussion of issues relevant to reproductive medicine in a highly interactive, continuing education environment. Discussion and workshop topics include Reproductive Medicine Essentials Update; Managing Infertility – the Nurse Perspective; A Nurse’s Guide to the Embryology Lab; Optimizing Ultrasound; Clinical Dilemmas (PCOS, OHSS, RPL); Male Infertility; Ethics and Legal Dilemmas; Telemedicine; and more! Some of our distinguished faculty: Barry Behr, PhD • Angeline Beltsos, MD • Mark Bush, MD • Ken Cadesky, MD Judy Campisi, LPN • Susan Crockin, JD • Alan DeCherney, MD • Kevin Doody, MD • Melinda Henne, MD • Lawrence Jacobs, MD • Sue Jasulaitis, RN, MS William Kearns, PhD • William Keye, MD • Monica Kuuspalu • Ruth Lathi, MD • Carol Lawrence • Juergen Lieberman, PhD • Craig Niederberger, MD Kutluk Oktay, MD • Ann Scalia, RN, BSN • William Schoolcraft, MD • Peter Schlegel, MD • Christopher Scott • Richard Scott, MD • Al Yuzpe, MD

LOWER REGISTRATION FEES until May 5th: $380 (After May 5th: $440)

FOR MORE INFORMATION about the program, accreditation, and TO REGISTER: Go to www.mwrs.org (or call 888-MBM-MTGS, ext.24).

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The Infertility Nurse

Navigating the Legal Aspects of Surrogacy Melissa B. Brisman, Esq Ms Brisman is owner of Reproductive Possibilities, and Surrogate Fund Management, Montvale, NJ. She offers a full range of legal services for gestational carriers; ovum, sperm, and embryo donation; and adoption.

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he New York Times (NYT) article “Building a Baby, With Few Ground Rules” (December 13, 2009; www.nytimes.com/2009/12/13/us/ 13surrogacy.html) has created quite a stir in my reproductive law firm. Imagine the panic that bubbles up when prospective parents find out that someone has lost the right to parent their child who was born by a gestational surrogate. The cases cited in that article were fraught with legal issues from their inception; such disastrous scenarios can be avoided with proper guidance and legal support. The article selected a handful of cases of intended parents and their surrogates who exercised poor judgment and a lack of caution: these cases, however, are the exception, not the rule. As an experienced reproductive attorney and a mother of children born through surrogacy, I must share the knowledge that although these few cases have failed miserably, an estimated 6000 successful surrogacy arrangements are made in the United States annually. Court battles are few, and most infertile couples and individuals involved in surrogacy have good odds for a smooth and successful arrangement. There are 2 forms of surrogacy—traditional and gestational. A traditional surrogate carries a child that is created using her own eggs, and sperm is provided by the intended father. This child is biologically related to the surrogate parents. In contrast, a gestational surrogate is a woman who carries an already developing embryo, created by ova from an intended mother or donor and the sperm of the intended father or donor. There is no biological connection between a gestational surrogate and the baby she is carrying. When challenged in a court of law, traditional surrogacy arrangements will often result in the courts favoring the biological and birth mother. I advocate for gestational carrier arrangements in which the carrier has no biological relationship to the child, which results in significantly fewer legal risks to intended parents. In the article, Mr and Mrs Kehoe are presented in a sympathetic manner, but the overall view is negative toward intended parents who need the services of a surrogate to build a family. The author appears to hold an attitude of commercialism toward surrogacy, sug-

gesting that it is “now essentially possible to order up a baby,” especially because neither of the Kehoes are biologically related to the babies. In almost all gestational surrogacy cases, at least 1 of the intended parents is biologically related to the child. George J. Annas, bioethicist, describes in the article how children born through surrogacy are viewed as a “consumer product” or “like pets.” This is insulting and dehumanizing, when so many infertile individuals view surrogacy as their only hope for a family.

An estimated 6000 successful surrogacy arrangements are made in the United States annually. When intended parents come to my office seeking assistance after they have tried repeatedly and unsuccessfully to have children on their own, it is very clear that any child born to them will be viewed by them as miracles, not as a new handbag, pair of shoes, or a pet. Legal Aspects of Surrogacy The first step for intended parents should be to get legal advice and assistance to guide them through surrogacy. Some people fail to do that, as suggested in the article, “Prospective parents with no genetic link often create their own baby first, then ask for legal approval, potentially leaving judges with little alternative.” However, intended parents must create a baby first and seek legal approval later, as the legal system requires. Whether intended parents seek a birth order or complete an adoption, either action necessarily will be filed after conception, and in the case of adoption, after a live birth. The acknowledgment that “most” surrogacy arrangements are “less complicated” than the Kehoes’ should offer comfort to many intended parents. It is unfortunate that the Kehoes no longer have custody of their twins, but these intended parents chose to handle their arrangement almost entirely on their own, and as a result, did not adequately protect themselves and their rights to the twins. Significantly, the Kehoes live in

Michigan and selected a carrier who lives there—a state with public policy against surrogacy. Michigan law criminalizes certain aspects of surrogacy and states explicitly that surrogacy agreements are unenforceable. I do not know whether the Kehoes researched Michigan law before entering into their surrogacy arrangement, but by entering into their surrogacy arrangement in Michigan, they left themselves vulnerable to a custody dispute with their carrier; any contract between the 2 parties was virtually meaningless. It appears that the Kehoes found their surrogate through an online surrogate website, a method I would not recommend, largely because it is so difficult for intended parents to screen their surrogate on their own. The use of a law firm or surrogate agency would be recommended as best practice for intended parents to ensure that their gestational carrier has been screened appropriately. This case suggests that several important screening safeguards were missed. The surrogate made the decision to seek custody of the twins after she learned, belatedly, of Mrs Kehoe’s psychological history. Medical/Psychological Disclosure When entering into a surrogacy arrangement, all parties should undergo full medical and psychological screenings. Intended parents want to

know that their surrogate has a good medical history and the psychological and emotional health to handle gestating and then surrendering a child. Similarly, a surrogate wants to know that the intended parents do not have diseases that could be passed on to her through the transfer of embryos. A surrogate may also want to know that the intended parents are not only medically and psychologically fit, but with whom she is comfortable entrusting a child. Full medical and psychological disclosure is therefore the best policy. The other cases highlighted in the article demonstrate similar mistakes. The use of a relative as a surrogate is not uncommon, but it presents its own potential problems. Intended parents using a relative as a surrogate tend not to listen to the professionals around them, and go forward despite warning signals. Surrogacy is an extremely emotional journey, and there are times when complications may arise that are negatively affected by the family dynamics. These pitfalls are all avoidable if intended parents enlist the guidance of a team of professionals in surrogacy and follow their advice. I would strongly advise against a “do-it-yourself” approach to surrogacy. Although it is potentially less expensive, the risk of being vulnerable to legal challenges and the potential loss of the child are simply too high. ■

Surrogacy in the News: A Complex Process, with Successful Results Monica R. Benson, BSN, RNC Nurse Manager, Third Party Reproduction, Reproductive Medicine Associates of New Jersey

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he New York Times (NYT) article discussed by Ms Brisman outlines 3 cases of ill-planned surrogacy, with disturbing outcomes. In the first case, the Kehoes had twin boys by donor eggs, donor sperm, and a gestational carrier, all found online. They lose the custody battle when the carrier discovers a history of mental illness in the intended mother. In the second case, a single, eccentric 62-year-old male has twin girls through surrogacy and ends up in court when the carrier charges him of neglect. The third case, a woman agrees to be a surrogate for

her brother and his male partner who donated sperm; they are now fighting in the courts over the 3-year-old twins. As a reproductive endocrinology nurse, I was disappointed to see such a one-sided representation of surrogacy, focusing on few unfortunate cases that were ill-planned, and with no mention of the many successful stories with a happy ending. Deciding to use a surrogate is not easy. All patients go through much pain before choosing this difficult option. Every day, I witness our patients’ anguish. Typically patients enter the Continued on page 24

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february 2010 I Vol 2, no 1

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IVF New Jers ey

EMERGING QUESTIONS

How Should Pregnant WoWe Advise the H1N1 Flu men Regarding Vaccine? Donna Makris, RN, BSN, IBCLC Paren

Transitioning to Infertility Nu Interview with rsing Jenni fer Iannaccone , RN

• A

to The OB/GYN and Infertility Nurse, . Written for nurses by nurses, it covers current and pertinent information on the physiologic, medical, and psychological aspects of human reproduction, with special emphasis on the nurse’s role in patient care ($150 value).

on all American Academy of OB/GYN and Infertility Nurses™ educational activities, including more than $200 off future Annual Meeting registration fees.

t Education Coord inator, Saint Peter’ s

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bstetricians, midwi ves, and nurse practitioners in the Unite d States agree with the recen national recom t mend nant women shoul ations that prega vaccine for the d have priority once novel H1N1 influe za virus (also know nn as the swine flu) becomes availa ble. At Saint Peter’ s University Hospi tal

for issues such as coverage and reimbursement.

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CLINIC SPO TLIGHT

IVF New Jersey Roychowdhury, nurses outside the clinic (from left): Jamie Thom Lauren Noble, Jennifer Iannaccone, Zofia Mance as, Leslie Meincke, ra, Cathy Ovacz Ella Terri Nelson. , Jill Marchetti,

Research

Interview with Sue Jasulaitis, RN, MS n her role as Clinic ue Jasulaitis is New Jersey, Jennif al Manager at IVF dure, which Clinic Manager at Fertil al Research precepted many er Iannaccone has has a lower is less intrusive but also ity Centers of nurses to the field success rate. If Illinois (FCI), infertility. In the IUI fails, of the coupl River North, this interview, Chicago. In this e in describes the steps she dure, which then tries an IVF proceinterview she discusses key features has a very good ic to help a new she takes at her clin- rate of the center success nurse at our center. nurse get famili and how s can improve ar with the demands of patient care by The nurse is this field. gesting problem the areas to study basedsugnates the patien one who coordi- their on own t’s daily IVF Do you do only experience. cycle. She writes up the patient’s IVF at IVF New Jerse IVF procedures We assign y? the start dates protocol. What are some Actually we have of medicaof the special tions and once features of FCI? a lot more coupl a protocol is who are doing deterintrauterine insem es mined, schedule her FCI has 10 IVF orientation tion (IUI) than ina- and make offices aroun in d the (IVF). The reason vitro fertilization the appro sure she has undergone all Chicago area, with 2 fully staffed in is that IVF is a priate testing. vitro fertilization intrusive proce (IVF) centers. dure; it is a surgic more dinate with the husba We also coor- one of the FCI is largest al pro- semen cedure that requir nd to have his frozen es general anesth the country, and fertility centers in and involves esia day of retrie , which is used if on the has provided more treatInside River North more couples begin risk. Therefore, a specim val he is unable to produce ment to >100,000 patients . during the matel en. All past with an IUI proce y 60 - of knowledge. this involves a new set specia25 years. We have 11 physic ians support clinical staff, as well as 120 Basic infertility lized in reprod staff employed uctive medicine, may be large at FCI. a team of embry Our main Continued on page ologists, appro 6 xi- quality care goal is to combine the best that expertise, technology,

I

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Inside

Pharmacy Corn Latex allergies in er infertility drugs

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Newborn Umb Cord Blood ilical The case of Chloe Levine

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Fertility Center s of Illinois Influence Infertilit y

How Nurses Can

Page 14

• Obtain to the enhanced, member-only sections at www.obgyn-infertility-nurse.org to network with your peers in a community of OB/GYN, Infertility, and Urology Nursing Professionals. Discuss current and emerging diagnostic and therapeutic options, as well as strategies for counseling and follow-up of patients.

Medical Cente r, New Brunswick, NJ in New Bruns wick, New Jersey offer a wide array , we of classes for expec tant families, and, as the Paren Education Coord inator, I am certai t that many of n our asking about the participants will be H1N1 flu vaccin fall. OB/GYN nurses and other e this working with pregnant wome nurses n should be prepared to provide inform ation to

Page 15

Continued on page

Polar Bodies Screening New techniques enhance genetic diagnosis

Page 17

Obesity and Reproduction What nurses need to know

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VOL 1, NO 1

The official pu blication of the American Academy of OB/GYN and Infertility Nu rses

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The Infertiltiy Nurse

Surrogacy in the News...

Continued from page 22

world of surrogacy after several years of infertility treatment failure, or they are cancer survivors and are unable to carry a pregnancy on their own. A few of our recent cases are good examples. Julie is a 33-year-old woman who had a uterine abruption at delivery, followed by a hysterectomy; she needed to use a carrier for a subsequent pregnancy. Tara is a 37-year-old breast cancer survivor who had to undergo surgical procedures, including total mastectomy and then received chemotherapy before coming to us; she was well informed and froze embryos before her chemotherapy. Carolyn has a bicornuate uterus; she was able to get pregnant and carry 1 pregnancy in each horn, but both were delivered at 24 weeks, and neither survived. Another group is the gay male couples who have few choices for parenthood. Most adoption agencies will not allow men to adopt or foster children.

is rare case to have both donor egg and donor sperm. The NYT article uses a litany of references to paying for eggs, sperm, hiring a fertility clinic, and a “designer baby.” It is clearly aimed at sensationalizing a very serious and emotionally charged issue. Many people may wonder why those undergoing infertility treatment do not adopt instead. If only adoption was so simple. Many of our intended parents have attempted to adopt, without success.

The Surrogacy Process Once the decision to use surrogacy is made, the process is not simple. Traditional surrogacy uses the egg of the woman carrying the pregnancy. Today, “gestational carrier” (GC) and “intended parents” are the terms used, because many states have laws against traditional surrogacy. In GC, the carrier has no genetic link to the child. Often, the sperm and egg from the intended parents are used. Usually, at least 1 of the intended parents’ gametes is used, such as a partner’s sperm with a donor egg. It

The article, however, does highlight the importance of following proper guidelines when entering into surrogacy. Patients need to be educated and choose a reputable fertility center and a reproductive attorney or a surrogacy agency with much experience to assist patients in finding and screening a gestational carrier. At Reproductive Medicine Associates of NJ, we take surrogacy very seriously and have a third-party team of nurses and coordinators who focus solely on this. Once it is established by a

physician that a patient needs to use a GC, a meeting with a mental health professional is set up to discuss the process. The couple will then be referred to a reputable reproductive attorney/agency, unless they already have one. The next step is to find the carrier via the reproductive attorney/agency. When a potential match is found, we obtain all the potential carrier’s medical records from all previous deliveries (both OB/GYN and labor and delivery

As a reproductive endocrinology nurse, I was disappointed to see such a one-sided representation of surrogacy. —Monica R. Benson, BSN, RNC

records). These are first reviewed by a third-party nurse to make sure the potential carrier meets our guidelines. For instance, the carrier must have had: • At least 1 previous delivery • Uneventful OB history • No preterm births • A limit of 5 previous deliveries • Body mass index <35 m2/kg • No systemic/psychiatric diseases. Then 2 separate prescreening phone calls are set up, one with the patient’s attending physician and another with our mental health professional. The

doctor will review all records and discuss her history with the potential carrier for any “red flags.” The mental health professional will focus on the carrier’s mental health during previous pregnancies (eg, history of postpartum depression), family situation, and feelings toward surrogacy. If the carrier passes screening, she is set up for an all-day evaluation, including complete medical history, physical examination, blood tests, and uterine cavity evaluation by saline sonogram. She then undergoes a full psychological screening, including a standardized personality assessment test and an extensive interview with her, and then with the intended parents, first separately and then together. Once screening is back and the carrier is approved, we await legal contracts before initiating any treatment. This extensive process aids in avoiding the pitfalls noted in the NYT article. Although the cases profiled there ended badly, it is important to remember that such cases constitute only a fraction of regular surrogacy arrangements, the vast majority. I am confident that our patients who have gone through such an ordeal to have a child share my feeling that there is nothing more precious than a child. But the NYT article would lead one to believe that people who choose to have a child through surrogacy are somehow unworthy of having children. This could not be further from the truth. ■

Exposure to Compound in Plastics a Risk for IVF Failure By Wayne Kuznar

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ncreased urinary concentrations of bisphenol A (BPA), a substance found in many consumer plastics, decreases the chance of uterine implantation of embryos from women undergoing IVF, said Shelley R. Ehrlich, MD, MPH, Research Fellow at Harvard School of Public Health, at the 2009 American Society for Reproductive Medicine annual meeting. “It’s reported to leach out into the food, so the main route of exposure is through dietary ingestion,” said Dr Ehrlich. The Centers for Disease Control and Prevention (CDC) recently found detectable levels of BPA in 93% of urine samples from the US population. BPA binds to estrogen receptor subtypes alpha and beta. It can also increase the expression of progesterone receptor proteins in the hypothalamus, thereby altering the receptivity of the uterus. BPA can be found in:

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• Polycarbonate plastic baby bottles • Water bottles • Epoxy resin lining of food and beverage cans • Some dental sealants and composites. “Very recently, a Canadian group published findings in mice given bisphenol A, and found that the litter size was reduced and implantation sites were less,” said Dr Ehrlich. In this study, urinary BPA concentrations were measured during controlled ovarian hyperstimulation (once at the beginning of the cycle and once on the day of egg retrieval) in 79 women (average age, 35.6 years) who were seeking evaluation for fertility treatment. Implantation failure was defined as a negative beta human chorionic gonadotropin(hCG) test (hCG <6 mIU/mL) 2 weeks after embryo transfer. The primary diagnosis (34%) type, based on the Society of Assisted

Reproductive Technology criteria, was female factor. The distribution of BPA exposure was similar to that found

The CDC found detectable levels of BPA in 93% of urine samples from the US population. “As urinary levels of bisphenol A increased, there was a trend toward an increase of embryo implantation failure in women.” —Shelley R. Ehrlich, MD, MPH

among participants in the CDC’s National Health and Nutrition Exami-

nation surveys—more than 90% had detectable levels of BPA in the urine. Urinary BPA concentrations were divided into tertiles. “As urinary levels of bisphenol A increased, there was a trend toward an increase of embryo implantation failure in women,” she said. Implantation failure occurred in 45% of cycles in women with BPA levels in the highest tertile compared with 37% of cycles in women with levels in the lowest tertile. A similar trend toward higher implantation failure with increased urinary BPA levels was seen when adjusting for age and day of embryo transfer. More urine samples are being incorporated into the analysis to determine the strength of the association, Dr Ehrlich said. ■ See also Gonadotoxins that Affect Male Fertility, page 25.

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Urology Nurse

The Many Faces of Gonadotoxins Linked to Male Fertility Inform Patients on Potential Damage from Common Habits By Wayne Kuznar

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number of gonadotoxins can affect male fertility, and it is important to identify any substances that may be present in the patient’s hobbies, workplace, or lifestyle that may impact testicular function, said Larry I. Lipshultz, MD, Professor, Department of Urology, and Chair of Reproductive Medicine, Baylor College of Medicine, Houston, TX, at the 2009 annual meeting of the American Society for Reproductive Medicine. The list of gonadotoxins includes: • Alcohol (ethanol) • Tobacco • Illicit drugs • A variety of prescribed medicines • Anabolic steroids • Environmental toxins.

Alcohol’s Effects on the Testes Ethanol has a direct effect on the hypothalamic-pituitary-gonadal (HPG) axis; disturbances to the HPG axis are a common cause of sexual dysfunction in men and women. In men, ethanol acts as a direct toxin on the testes. Alcohol reduces sperm count, the number of sperm with progressive motility, and the number of sperm with normal morphology. Alcohol consumption also causes a reduction in antioxidant levels, leading to an increase in the production of reactive oxygen species, which have a direct effect on the sperm membrane. Alcohol can also have a negative effect on sex steroid production and gonadal function. “The effect of ethanol is dose-dependent and can be irreversible in chronic abusers,” said Dr Lipshultz. “If I have a patient who does drink, I try to minimize it, if not get the patient to stop using alcohol during the time he is trying to initiate a pregnancy.” Nicotine Nicotine can alter the HPG axis through stimulation of growth hormone, vasopressin, oxytocin, and cortisol. Nicotine and other carcinogens have been found in the sperm of smokers. “Carcinogens have also been found in embryos that resulted from IVF cycles in which the male was identified as a smoker,” Dr Lipshultz said. There is a greater presence of reactive oxygen species and increased oxidative stress in the semen of smokers, in addition to a greater proportion of immature sperm compared with nonsmokers. A delay of >6 months in natural conception has been observed

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in couples in which either individual is a smoker. Illicit Drugs Recreational drug use is also important to identify in the male history. Heavy use of marijuana can cause a decrease in the levels of serum testosterone, impaired sperm production, and oligospermia (ie, low sperm count), as well as pyospermia (ie, pus in the semen). Cocaine use has been associated with a reduction in sperm count, impaired sexual function, and delayed or inhibited ejaculation.

all of those that we legitimately prescribe (ie, testosterone cypionate, testosterone enanthate, and testosterone gel),” he said. Whereas the anabolic to androgenic ratio is 1 for the anabolic steroids prescribed in clinical practice, this ratio can be as high as 30 for anabolic steroids used for muscle enhancement, such as stanozol. “The problem with those that are abused, and this is especially true of the injectables, is that they cause a decrease in the HDL [high-density lipoprotein] to LDL [lowdensity lipoprotein] ratio, and often we see polycythemia in these patients,

“The effect of ethanol is dose-dependent and can be irreversible in chronic abusers….If I have a patient who does drink, I try to minimize it, if not get the patient to stop using alcohol during the time he is trying to initiate a pregnancy.” —Larry I. Lipshultz, MD Prescription Drugs Among prescription drugs, the antihypertensive drug spironolactone has antiandrogenic activity, causing reduced semen quality. “Calcium channel blockers have been more recently identified as having a reversible functional defect in sperm, and interfering with the ability of those sperm to fertilize eggs; however, this is not something you are going to see in a sperm count or in a routine semen analysis,” said Dr Lipshultz. Among the antibiotics, nitrofurantoin, erythromycin, tetracyclines, and gentamicin are often implicated in impaired fertility, but there are no invivo studies to support this contention, he said. Among the immunotherapeutic agents, sulfasalazine, used for the treatment of ulcerative colitis, has been shown to cause reversible defects in sperm concentration and motility. Colchicine, often used to treat gout, can cause oligospermia if used for a long period. Anabolic Steroids Impair Sperm Quality: Testosterone a Male Contraceptive “The data are overwhelming on the effect of anabolic steroids on semen quality,” said Dr Lipshultz. Anabolic steroids are testosterone derivatives that are used (or abused) to enhance the metabolic state. “All testosteronederived products have both anabolic and androgenic properties, including

which has to be closely monitored, in addition to gynecomastia and infertility,” Dr Lipshultz noted. No matter how testosterone is taken, it serves as a male contraceptive, he reminded. It suppresses gonadotropin-releasing hormone, follicle-stimulating hormone, and luteinizing hormone. Azoospermia (ie, complete absence of sperm in the ejaculate) can occur in as little as 10 weeks of testosterone use; sperm counts often do not rebound for as long as 18 months after cessation of testosterone use. Permanent azoospermia occurs in 4% to 10% of anabolic steroid users.

months in previous users of transdermal testosterone, said Dr Lipshultz. Preliminary data indicate that hypogonadal males who must use testosterone replacement therapy can maintain spermatogenesis by using low-dose hCG (500 U every other day) during their testosterone replacement treatment. Impact of Pthalates in Consumer Goods on Reproductive Health Endocrine-disrupting chemicals with estrogenic or anti-androgenic activity found in consumer goods can lead to male (and female) reproductive dysfunction. Pthalates are a type of endocrine disruptors that are used widely in plastics to improve flexibility, and in cosmetics to bind fragrances. Examples of pthalates include: • Plastic water bottles • Intravenous tubing • Baby toys • Polyvinyl chloride tubing • Carpet backing. Pthalate syndrome, identified prenatally in rats, leads to a host of medical problems, including (1) malformations of the epididymis, vas deferens, seminal vesicles, and prostate; (2) hypospadias; (3) a decrease in the anogenital distance (a sign of estrogenic effect on male offspring); as well as (4) cryptorchidism. Reduced sperm motility and sperm concentration have been found in a dose-dependent manner with pthalate exposure, Dr Lipshultz said. “Anything that is microwaveable in a plastic container can leach pthalates,” as can squeezable plastic water bottles, he said, and these should be avoided by men trying to initiate pregnancy. ■

“Carcinogens have also been found in embryos that resulted from IVF cycles in which the male was identified as a smoker.” —Larry I. Lipshultz, MD In steroid-suppressed patients, sperm has been recovered in the ejaculate by discontinuing exogenous testosterone and immediately administering human chorionic gonadotropin (hCG), 3000 U every other day, and continued for at least 3 months. An aromatase inhibitor or tamoxifen (Soltamox) can also be given to prevent the occurrence of gynecomastia. Sperm recovery takes about 3 months in previous users of intramuscular testosterone, and 7

“There’s nothing to laugh about but I laugh all the time.”

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Nutrition

More Evidence that Soy Foods Reduce Breast Cancer Recurrence, Death By Rosemary Frei, MSc

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ating soy-based foods appears to be very good for the health of women with breast cancer. Results of a new study show that consuming about 11 g of soy protein daily lowers breast cancer–related death rate by 29% and recurrence rate by 32% (Shu XO, et al. JAMA. 2009;302:24372443). This beneficial effect occurs in all women with breast cancer, regardless of their estrogen receptor status (positive/negative) or tamoxifen use status. It does not take much to ingest 11 g of soy protein, as can be seen from the following list: • 1/2 cup tempeh (partially cooked, fermented soybeans) = 15 g soy protein • ½ cup tofu = 10 g soy protein • 1 bowl cereal with soy milk = about 26 oz soy protein. “In addition to its anticancer property, soy food also has many other healthy benefits,” lead investigator Xiao Ou Shu, MD, PhD, Professor of Medicine, Vanderbilt University School of Medicine, Nashville, TN, told The OB/GYN and Infertility Nurse. “It is a healthy diet, with sufficient soy protein, that women should be encouraged to adopt.”

“In addition to its anticancer property, soy food also has many other healthy benefits….It is a healthy diet, with sufficient soy protein, that women should be encouraged to adopt.”

viewed in person 2 weeks after entering the study. The questions covered age, height, weight, cancer stage, tumor estrogen-receptor, and progesteronereceptor status, as well as patterns of consumption of soy-containing foods, meat, fish, and cruciferous vegetables. They were also interviewed 36 and 60 months later; those results are contained in the JAMA article. Women who consumed relatively little soy protein (<5.32 g/day) had a

29% greater risk of dying during the follow-up period than those who consumed ≥15.31 g/day of soy protein. The women consuming little soy protein also had a 32% greater chance of cancer recurrence. There was no difference between soy isoflavone and soy protein intake in terms of breast cancer survival. Further analyses revealed that the salubrious effects peaked at intake levels of 11 g/day of soy protein and 40 mg/day of

soy isoflavones. Dr Shu noted that they are following up with the women in this cohort “to investigate the long-term effects of soy food intake on health among breast cancer survivors, including bone density, fracture, and coronary heart disease.” ■

CONTINUING EDUCATION CREDITS Current activities at www.COEXM.com include:

—Xiao Ou Shu, MD, PhD

Only one other study had examined the association between soy intake and the outcomes of women with breast cancer. The Life After Cancer Epidemiology study showed that women with a high intake of soy isoflavone had a reduced breast cancer recurrence rate (Guha N, et al. Breast Cancer Res Treat. 2009;118:395-405). To take a closer look at this association, Dr Shu and colleagues analyzed the outcomes of 5042 women participating in the Shanghai Breast Cancer Survival Study. The women were diagnosed with primary breast cancer between March 2002 and April 2006 (aged 20-75 years at time of diagnosis). They were recruited into the study approximately 6 months after their cancer diagnosis. The women were inter-

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february 2010 I Vol 2, no 1

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Clinical News Continued from page 3

Childhood Cancer Treatment... a significantly reduced ability to procreate were having a higher cumulative alkylating agent dose, or treatment with cyclophosphamide or procarbazine. Those who had been diagnosed with Hodgkin lymphoma were least likely to have sired a pregnancy—a 66% lower probability than their siblings with no history of cancer. Those who had Wilms’ tumor or neuroblastoma, however, had procreating probabilities equal to their siblings.

A Yoga Session a Day Keeps Stress Away Recent findings highlight the physiologic benefits of regular yoga practice, showing that novice yoga-practicing persons are 4.75-fold more likely to have detectable C-reactive protein (CRP) levels and 41% higher interleukin (IL)-6 levels than those with extensive yoga practice (Kiecolt-

Glaser JK, et al. Psychosom Med. 2010 Jan 11. Epub ahead of print). A total of 25 novice and 25 expert female yoga practitioners (aged 30-65 years) performed yoga during a 30minute session. They underwent a battery of psychological and physiologic tests immediately before, during, and after the session. This was repeated with 2 control forms of exercise, movement

CRINONE® 4% CRINONE® 8% (progesterone gel)

Size of American Neonates Decreasing New evidence shows a marked trend toward lower birth weight and gestational length among US neonates, but no one reason has been elucidated (Donahue SM, et al. Obstet Gynecol. 2010;115[2 Pt 1]:357-364). Researchers used data from the National Center for Health Statistics to examine 36,827,828 singleton neonates born between 1990 and 2005, at 37 to 41 weeks gestation. The results showed decreased birth weight in 2005 compared with 1990 (–52 g in the overall study population), and decreases in neonates that were large for gestational age (–1.4% overall). Gestational length also decreased during the 15-year period. The steepest decline occurred after 1999. The changes in weight were not affected by maternal or neonate characteristics, gestational length, or delivery factors. Gestational length decreases were not influenced by route of delivery or induction of labor, according to the researchers.

Uterine Fibroid Size Sole Predictor of Growth Rate In premenopausal women, the size of fibroids is the only significant independent predictor of the future growth rate of these benign tumors (Mavrelos D, et al. Ultrasound Obstet Gynecol. 2010;35:238-242.). This new study included 122 women who had been diagnosed with uterine fibroids between July 1997 and July 2006. Inclusion criteria included age between 25 and 45 years at the time of initial examination, no previous surgery for fibroids, and no use of hormonal contraception or medications that affect ovarian hormone production. The difference in median increase rate of the largest fibroid was not significant between the older and younger women. Small- and large-size fibroids at presentation grew at annual rates of 51.3% and 40.7%, respectively, compared with 16.8% for intermediate-size fibroids, the only significant difference in the study that independently predicted fibroid growth rate.

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See package insert for full prescribing information. 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 hormoneassociated 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 Crinone-treated 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, open-label 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. 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 more 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 reported in 5% or more of women treated with Crinone

control, and passive-video control. Test results revealed that in addition to the differences in IL-6 and CRP levels, yoga experts produced less lipopolysaccharide-stimulated IL-6 in response to stress than novices. Having shown that increased IL-6 level promotes CRP production, the investigators concluded that regular yoga practice could have substantial health benefits. ■

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. This brief summary is based on the current Crinone package insert (Version 40405010007, Revised December 2006). How Supplied Crinone is available in the following strengths: 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-55056-0806-2 - 6 Single-use prefilled applicators. NDC-55056-0818-2 - 18 Single-use prefilled applicators. Each applicator is wrapped and sealed in a foil overwrap. Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F). Rx only. U.S. Patent Number 5,543,150. Manufactured for: Columbia Laboratories, Inc. Livingston, NJ 07039 Manufactured by: Fleet Laboratories Ltd., Watford, United Kingdom © 2007, Columbia Laboratories, Inc. Printed in USA 6/07

References: 1.Yanushpolsky EH. Comparison of Crinone 8% intravaginal gel and intramuscular progesterone (IMP) for luteal phase support: largest prospective randomized trial to date. Slides presented at: American Society for Reproductive Medicine, 2009. 2. Berger B, Phillips JA. A retrospective analysis of pregnancy outcomes in recipients of anonymously donated oocytes at a large ART center. Fertil Steril. 2008;89:S11–S12. Abstract P-7. 3. Saucedo LLE, Batiza V, Arenas L, et al. Progesterone for luteal support: randomized, prospective trial comparing vaginal and i.m. administration. Paper presented at the 19th Annual Meeting of the European Society for Human Reproduction & Embryology; July 2003; Madrid, Spain. Abstract P-383. 4. Anserini P, Costa M, Remorgida V, Sarli R, Guglielminetti E, Ragni N. Luteal phase support in assisted reproductive cycles using either vaginal (Crinone 8) or intramuscular (Prontogest) progesterone: results of a prospective, randomized study [in Italian]. Minerva Ginecol. 2001;53:297–301. 5. Coutifaris C, Patrizio P, Schafer D, Bunso S, Bucci J, Barnhart K. Is the use of Crinone for support of the luteal phase detrimental to pregnancy outcome after transfer of non-cryopreserved embryos in good prognosis patients? A preliminary report. Fertil Steril. 2000;74(suppl 1):S205. Abstract P-350. 6. Alper MM, Penzias AS. Crinone® offers excellent implantation rates in patients undergoing IVF. Paper presented at the 16th Annual Meeting of the European Society for Human Reproduction & Embryology; June 2000; Bologna, Italy. Abstract P-059. 7. Schoolcraft WB, Hesla JS, Gee MJ. Experience with progesterone gel for luteal support in a highly successful IVF programme. Hum Reprod. 2000;15:1284–1288. 8. Saucedo LLE, Galache VP, Hernández AS, Santos HR, Arenas ML, Patrizio P. Randomized trial of three different forms of progesterone supplementation in ART: preliminary results. Fertil Steril. 2000;74(suppl 1):S150. Abstract P-175. 9. Williams SC, Donahue J, Muasher SJ. Vaginal progesterone therapy during programmed cycles for frozen embryo transfer: an analysis of serum progesterone levels and pregnancy rates. Fertil Steril. 2000;74(suppl 1):S209. Abstract P-363. 10. Levine H. Luteal support from the vaginal progesterone (P) gel Crinone 8%: preliminary results of multicenter trial show higher pregnancy rates than historical controls. J Soc Gynecol Investig. 2000;7(suppl). Abstract 571. 11. Chantilis SJ, Zeitoun KM, Patel SI, et al. Use of Crinone vaginal progesterone gel for luteal support in in vitro fertilization cycles. Fertil Steril. 1999;72:823– 829. 12. 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. 13. Berger BM, Phillips JA. A retrospective analysis of pregnancy outcomes in recipients of frozen/thawed embryos (FET) from donated oocytes at a large assisted reproductive technology (ART) center. Fertil Steril. 2008;90(suppl 1):S459. Abstract A-260.

Columbia Laboratories, Inc. Livingston, NJ 07039

february 2010 I Vol 2, no 1

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She depends on your guidance...

Only ONE vaginal progesterone is proven as effective as IM It’s a fact. CRINONE is proven equivalent to IM progesterone in the largest prospective, randomized, well-controlled clinical trial study ever conducted comparing vaginal to IM progesterone.1

CRINONE 8% (progesterone gel) is indicated for progesterone supplementation or replacement as part of an Assisted Reproductive Technology (ART) treatment for infertile women with progesterone deficiency. Important Safety Information The most common side effects of CRINONE 8% include breast enlargement, constipation, somnolence, nausea, headache, and perineal pain. CRINONE 8% is contraindicated in patients with active thrombophlebitis or thromboembolic disorders, or a history of hormone-associated thrombophlebitis or thromboembolic disorders, missed abortion, undiagnosed vaginal bleeding, liver dysfunction or disease, and known or suspected malignancy of the breast or genital organs.

www.crinoneusa.com

This study, conducted at Brigham and Women’s Hospital, adds to the 12 p prior trials 2-13 demonstrating the comparable efficacy of CRINONE and IM progesterone. No other vaginal progesterone can make this claim. In fact, CRINONE is the single most studied and widely used vaginal progesterone worldwide. When she asks about progesterone, give her the facts.

The only ONE

Toll-free support line: 1-888-PRO-GEL8 (1-888-776-4358) Please see brief summary of full prescribing information on the adjacent page. © 2009, Columbia Laboratories, Inc.

CRI8-PAD-005

February 2010 Vol 2, No 1  

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