P.A.G.E Issue 3 2022

LIMAT HANG C E LIMAT HANG C E TACKLING

take the lead LABIAL

VULVAL &

ADHESION

IN THIS

ISSUE

Message from the Editor and the Editorial Board

Contributors

President’s Message

AOSPAG Activities 2022

First Asia Oceanic Society of Pediatric and Adolescent Gynaecology (AOSPAG)

Virtual Congress - Associate Professor Dr. Ani Amelia Zainuddin

Introducing the new board of AOSPAG 2023-2025. - Dr Noorkardiffa Syawalina Omar

Vulval and vaginal pain in Paediatrics - Professor Dr. Sonia Grover

Vaginal bleeding in Prepubertal Girls - Dr. Noorkardiffa Syawalina Omar

Lower genital tract polyps in Prepubertal Girls - Dr. Karen Ng

Vulvovaginal infections in a Prepubertal Child - Dr Renna Cristina B. de Leon

Vaginal foreign body in children and adolescents in China - Dr HuiHui Gao & Dr Liying Sun

Labial adhesion - Dr Nurkhairulnisa Abu Ishak

Urethral prolapse - Dr Loh Sweet Yee Esther

Precocious puberty in Girls - Associate Professor Dr. Khadija Nuzhat Humayun

Oncofertility in Malaysia - Associate Professor Dr. Anizah Ali

Tackling Climate Change: Why Paediatric Adolescent Gynecology (PAG) should take the lead - Dr. Jerilee Azhary

Prof. Dr. Nur Azurah Abdul Ghani

CONTRIBUTORS

She is a professor in Royal Children’s Hospital Melbourne. She has extensive experience in paediatric and adolescent gynaecology having worked in this field for over 20 years. She has been instrumental in establishing this subspecialty in Australia as well as an Asia and internationally with teaching, providing clinical support and mentoring.

An Associate Professor in Department of O&G, Faculty of Medicine, Universiti Kebangsaan Malaysia (UKM). She is the Head of PAG Unit and developed the Fellowship in PAG training in UKM, together with Prof Dr Nur Azurah Abdul Ghani. She is also the newly elected President of the Asia Oceanic Society of PAG (AOSPAG) for the session 2023-2025.

An Associate Professor and Consultant Paediatric Endocrinologist in the Department of Paediatric and Child Health, Aga Khan University (AKU). She is a trained Paediatric Endocrinologists and has played a lead role in initiation of the first structured fellowship in this specialty in Pakistan and getting it accredited by the College of Physicians and Surgeons Pakistan for subspecialty exams.

Currently serving as Consultant O&G and is sub-specializing in Paediatric Adolescent Gynaecology in Hospital Canselor Tuanku Muhriz UKM, Malaysia. Her passion and areas of interests are Fertility Preservations for children and adolescent, Premature Ovarian Insufficiency (POI), Adolescent Bone Health and Mullerian Anomalies: surgical and non-surgical managements.

An O&G doctor and subspecialized in Paediatric and Adolescent Gynaecology. She also a fellow of IFEPAG. Currently she is the chairman in Department of O&G, MHAM College of Medicine and also the Board Member of Paediatric and Adolescent Gynecology Society of the Philippines.

Dr Huihui Gao and Dr Liying Sun are both from the Paediatric and Adolescent Department in the Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China. Dr Liying Sun is the director of the PAG Department. She is responsible for establishing the first PAG clinic in the mainland of China in the year 2000.

Page 17

An Associate Consultant at Department of O&G, Prince of Wales Hospital and responsible for clinical services for the Reproductive Medicine team including running the PAG services. She is also a trainer for IFEPAG.

Professor Dr. Sonia Grover Page 9

Associate Professor Dr. Ani Amelia Zainuddin

Page 7

Associate Professor Dr. Khadija Nuzhat Humayun Page 21

Associate Professor Dr. Anizah Ali

Page 23

Dr. Renna Cristina B. de Leon Page 15

Dr. Karen Ng Page 13

Dr. HuiHui Gao & Dr. Liying Sun

CONTRIBUTORS

An O&G Specialist and Clinical Lecturer in International Islamic University of Malaysia. She completed Fellowship in Paediatric and Adolescent Gynecology in Hospital Canselor

Tuanku Muhriz (HCTM), Universiti Kebangsaan Malaysia in 2021. Currently she is running her own PAG Unit in her university hospital.

Page 19

Works as a senior clinical lecturer in Obstetrics and Gynaecology at Faculty of Medicine Universiti Malaya, Malaysia. She also serves as O&G specialist in Universiti Malaya Medical Center (UMMC). Currently, she is doing a Fellowship in Paediatric and Adolescent Gynaecology at Hospital Canselor Tuanku Muhriz, UKM, Malaysia.

An O&G Specialist and Clinical Lecturer in Hospital Canselor Tuanku Muhriz (HCTM), Universiti Kebangsaan Malaysia and currently in a fellowship training in Paediatric and Adolescent Gynecology in the same hospital as well.

Page 20

A Clinical Lecturer and Specialist in Obstetrics and Gynecology in Universiti Teknologi MARA, Malaysia and just completed her fellowship training in Paediatric and Adolescent Gynecology in Hospital Canselor Tuanku Muhriz (HCTM), Universiti Kebangsaan Malaysia (UKM). She involves with teaching and research in PAG and also initiates the PAG clinic in Hospital Al-Sultan Abdullah, UiTM, Puncak Alam, Malaysia.

Greetings everyone!

Ramadan Kareem to all Muslims in our society! Thank you for nominating me as the new President of the Asia Oceanic Society of Paediatric & Adolescent Gynecology (AOSPAG) for 2023-2025.

I hope to carry on the good initiatives of the first AOSPAG board led by Past President Dr Sox Bernardino namely the monthly webinars hosted by different countries, preparation of our statutes, participating in international congresses and with FIGIJ and and hopefully we can start planning our own first AOSPAG physical congress soon. Our virtual congress in January 2022 was a great success and brought everyone together! We can use our society as a platform for research collaborations between our different countries, promote advocacy for our young patients, promote and support education and training in PAG and perhaps even starting a database of different conditions in our patients so we can produce baseline statistics for the Asia Oceanic region as well as be the basis for future research.

PRESIDENT’S MESSAGE

I welcome any ideas from all our members on what other activities we can do, please do email me at amelia@ppukm.ukm.edu.my.

Looking forward to working with all of you!

Asst. Prof. Dr. Nurkhairulnisa Abu Ishak

Dr. Jerilee Azhary Page 25

Dr. Loh Sweet Yee Esther

Dr. Noorkardiffa Syawalina Omar Page 11 & 29

ASIA OCEANIC SOCIETY OF PEDIATRIC AND ADOLESCENT GYNAECOLOGY

(AOSPAG) VIRTUAL CONGRESS

15th January 2022

Organized by AOSPAG, PAGSPHIL and Docquity Philippines

Report by Assoc. Prof Ani Amelia Zainuddin Chairman of Organizing Committee

AOSPAG congress was the brainchild of Dr Socorro Bernardino, our President. She collaborated with with Docquity Philippines to be the virtual platform provider for this event and with PAGSPHIL to help with the accounts. Dr Bernardino also worked hard to get sponsorships from various pharmaceutical companies. The Chairperson was me, AP Ani Amelia Zainuddin, Vice President of AOSPAG. There were three committees who worked very hard for this congress; the organizing committee, the scientific committee and the committee for the Fellowship night headed by Dr Ana Vetriana from Malaysia.

Favourable comments were received from participants regarding the lectures. There were several sessions: PAG perspectives in the prepubertals, PAG perspectives in the Adolescents, Best Practices which consisted of two Panel discussions, a talk on IFEPAG exams by A/Prof Symphorosa Chan and Live Forum for Q&A. We also had snack and lunch symposiums. In the evening, we had a wonderful Fellowship night where different countries shared videos showcasing their PAG units and activities and their countries’ beautiful sceneries and which ended joyfully with a fun quiz.

We had a good turnout despite it being a Saturday , and everyone thoroughly enjoyed and benefited from the sessions. The videos of the lectures were available for several months following the congress and was viewed by many.

We were blessed to have fantastic speakers from so many different countries:

As many as 617 people tapped marked going on the Docquity poster when it was posted: consisted of doctors from various fields; pediatrics, O&G, cardiothoracic surgery, general practitioners, family medicine, internal medicine, physical therapy, ENT, oncosurgery, neurology and others, from the Asia Oceania region.

Total attendees were 592! The breakdown is as follows;

A total of 230 Likes were received. From a total of 31 comments, 93.8% were positive (mostly “excellent”) whilst the remainder was neutral, there were no negative comments.

I wish to thank the organizing committees for their hard work in organizing this first successful congress, the scientific committee for their brilliant ideas and the Fellowship committee for their remarkable creativity and wonderful ideas.

Looking forward to the next congress, hopefully it will be a physical one so we can meet each other!

Introducing the new board of AOSPAG 2023-2025

By Dr Noorkardiffa Syawalina Omar

AOSPAG General Assembly was held virtually on 20th March 2023 and was attended by the representatives from the countries in Asia-Oceanic region which includes China, Hong Kong, Australia, New Zealand, Indonesia, Philippines, Japan, Bangladesh, South Korea and Malaysia (2 representatives from Pakistan and India were unable to attend).

Attendees

4.

Did not attend

Dr Iffat Ahmed

Dr Hafizur Rahman

Following the fruitful assembly, we are so excited to announce the new board for AOSPAG 2023-2025 as below:

President

Assoc. Prof Dr Ani Amelia Zainuddin

Vice President

Prof Dr Hideya Sakakibara

Secretary

Dr Karen Ng

Treasurer

Prof Dr Angela Aguilar

Education

Prof Dr Sonia Grover

Assistant Education

Prof Dr Lan Zhu

Dr Kohinoor Begum

8.

9. Assoc. Prof Dr Ani Amelia

10. Dr Saman Moeed

11. Dr Karen Ng

12. Dr Dyana Velies

On behalf of AOSPAG, we would like to congratulate the new faces of the AOSPAG board. We are looking forward for the future activities and events with this recent elected board lead by Assoc. Prof Dr Ani Amelia Zainuddin.

1. Prof Dr Socorro C. Bernardino

2. Prof Dr Lan Zhu

3. Prof Dr Angela Aguilar

Prof Dr Sonia Grover

5. Prof Dr Hideya Sakakibara

6. Prof Dr Mee-Hwa Lee

7. Prof Dr Begum Kohinoor

Assoc. Prof Dr Symphorosa Chan Shing Chee

Grover

VULVAL AND VAGINAL IN PAEDIATRICS

Vulval problems in adult women can be more readily divided into the skin or dermatological problems and those vulval conditions associated with pain in the absence of a skin problem. In children, this is not always so easy to separate these 2 issues. In adult women, vulval pain problems are often divided into vulvodynia, and vestibulodynia – depending on the location of the altered sensation, and can be classified as provoked pain or unprovoked. It is also recognised in adult women that it can be an altered sensation or dysaesthesia.

In young children, these altered skin sensation conditions also exist

– but have hardly been reported in the literature until recently(1-5). As the children who experience these symptoms may be quite young it is sometimes challenging to localise or get an accurate description of the pain.

At the Royal Children's Hospital in Melbourne, we realised we were increasingly recognising young prepubertal girls who were reporting distressing genital sensations. The words used to describe the sensations included a "bubbly feeling", "a tickly sensation", stinging, burning, and funny feeling. Some of the girls were referred with questions raised as to whether they were masturbating – as they were rubbing their genital area, but questioning revealed that they were doing this to relieve an uncomfortable sensation.

When we explored the associated symptoms in this cohort, we uncovered that over 60% had also experienced, or were currently experiencing urinary symptoms, most often in the form of urinary frequency and urgency.

Examination of the genital area reveals no skin changes and no evidence of lichen sclerosus or other dermatological problems. Even very young girls of 3 years of age have been able to assist with the diagnosis. By using cotton wool tipped ( usually the same as the swabs used for taking specimens) we gently touched the inner thighs, the mons pubis and then progressively the labia majora, labia minora – outer then inner aspects, then periurethral and perihymenal areas – looking for areas that replicate was distressing the young person. Repeating the testing usually provokes the same response in the same area, suggesting that there is a specific area that has altered sensation or dysaesthesia.

Our approach to this problem after exclusion of other possibilities such as sexual

abuse, vulvovaginitis, and vulval lichen sclerosis was usually the use of tricyclics ( amitriptyline) starting at 5 mg at night, increasing to 10 and occasionally 20 mg. Treatment is often required for a few months – to break the cycle, and then the dose is gradually reduced. Flareups of symptoms or relapses tend to occur at times of stress, but for the vast majority of young girls, this approach resulted in a resolution of symptoms.

The other far more distressing pain symptom that is seen only in prepubertal girls is a condition that we used to call 'vaginal shooting pain" – which turned out to be "lost worms". Threadworms which live in the anal region and cause perianal itch can get lost and wander into the vagina. Usually, the perianal itch is nocturnal, due to the worms

laying their eggs at this time in the perianal area. Likewise, the movement of the worms from the vagina over the very sensitive skin of the prepubertal hymen appears to provoke a considerable distressing pain – waking girls at night. The distress often lasts a few hours, with girls requiring baths, and cool washes to the perineum to relieve their distress. Once we realised that the problem was "lost worm" we instituted treatment with mebendazole once weekly for 3 weeks, in association with the usual measures of treating other family members and washing bed linen – and trying to encourage good hand hygiene to avoid re-infection.(6)

References

Reed B, Cantor LE. Vulvodynia in Preadolescent Girls. J Low Genital Tract Dis 2008; 12(4): 257-261

Powell J. Paediatric vulval disorders. J Obstet Gynecol 2006; 26(7): 596-602

Landry BA, Bergeron S. How Young Does Vulvo-vaginal Pain Begin? Prevalence and characteristics of dyspareunia in adolescents. J sexual Med 2009; 6(4): 927-935

Greenstein A, Sarig J, Chan J, Matzkin H, Lessing J, Abramov L. Childhood Nocturnal Enuresis in Vulvar Vestibulitis Syndrome. The Journal of Reproductive Medicine. 2005; 50(1): 49-52

Dunford, A., D. Rampal, M. Kielly and S. Grover. Vulval pain in paediatric and adolescent patients. J Pediatr Adolesc Gynecol 2019;32(4): 359-362.

Dennie J, Grover SR. distressing perineal and vaginal pain in prepubescent girls; An aetiology. J Paed and Child Health 2013; 49: 138-140

Vaginal pain caused by pelvic floor muscle spasms or cramps can also occur – but this is not a condition usually seen in young children.

VAGINAL IN PREPUBERTAL GIRLS BLEEDING

by Dr. Noorkardiffa Syawalina Omar

Vaginal bleeding is a common gynecology symptom. However, vaginal bleeding in prepubertal girls is rare.(1) During childhood, vaginal bleeding after one week of age until before menarche usually abnormal and necessitate urgent attention. The causes vary from benign cause like vulvovaginitis and more ominous like sexual abuse or malignancy.

Clinical assessment of vaginal bleeding in prepubertal girls require a thorough targeted history taking and examination to reach to the diagnosis. History can be taken from both child and caretaker. Firstly, need to determine the nature of the bleeding whether it is acute or chronic, and just spotting or actual bleeding. Severity of the bleeding is crucial to determine the anemia status. Further history should include other associated symptoms like foul smelling vaginal discharge which suggests presence of foreign body; itchiness and scratching at the genital area which can be due to vulvovaginitis and constitutional symptoms like weight loss and reduce appetite which may related to possible malignancy.

Minor genitourinary trauma also can cause significant bleeding. Status of toilet training as well as personal hygiene habit like cleaning up after toileting is also an important clue to condition like chronic dermatitis which also can be presented with vaginal bleeding.(2) Sexual abuse is an alarming cause of vaginal bleeding and should not be overlooked especially if the history is suspicious. A girl may not disclose sexual abuse as she is too young to understand or has been threatened by the perpetrator.(3) Any change of behavior or frequent genital complaints need to be addressed.

In order to do appropriate assessment, clinicians need to be equipped with pediatric-specific gynecology examination skills.(2) It is important for the clinicians attending to these cases to be familiarized with normal variant of normal pediatric genitourinary anatomy and also able to identify an estrogenized hymen. Without recognizing the normal prepubertal genital anatomy, pathological findings will be a challenge to identify.(3) In a prepubertal girl without estrogen exposure, the hymen and mucosa are atrophic, red and highly vascular and the labia minora are flat and thin. (Fig.1(A)) After estrogen exposure, the hymen becomes thick, redundant and pale. The labia minora are enlarged and hyperpigmented (Fig.1(B)).

Furthermore, physical examination and further work up should be done with caution to prevent so that no further trauma to the child.(4) Vaginal examination can be a distressing event for the small girl and usually limited to inspection only. If the source of bleeding cannot be seen by inspecting externally, it is advisable to do examination under anesthesia (EUA) where the situation is under control and appropriate examination could be done.(2) Nasal speculum or vaginoscopy can be used for a better visualization especially in the upper vagina.(5) To avoid trauma to the hymen, pediatric Foley’s catheter is another alternative to look for lesion or foreign body at the level of hymen.(6)

Figure 1: Normal female genital anatomy; (A) prepubertal (B) pubertal (picture taken from the internet)

A complete physical examination is important to identify extragenital causes of vaginal bleeding. Palpable abdominal mass like ovarian cyst can be benign autonomous cyst or malignant like juvenile granulosa cell tumour. Identification of café au lait macules with ovarian cyst is associated with McCune Albright syndrome. Additional signs of soft tissue trauma like bruises and abrasions may be associated with sexual abuse. Presence of other secondary sexual characteristics like pubic hair and breast development with increase height velocity needs further evaluation to rule out precocious puberty.

Pelvic ultrasound is the first imaging modality to be used. Ovarian cyst usually can easily be seen on ultrasound. Polyp can be seen as thickening of the endometrial lining or lesion. However, pelvic ultrasound does not always aid in identifying foreign body especially small objects. If the history is highly suggestive, X-ray maybe helpful if the object is radiopaque. If imaging is negative and symptom persists or recur then it is necessary to proceed with vaginoscopy as mentioned.

Further assessment may include hormonal evaluation and serum tumour markers. In young girls with secondary sexual characteristics development and having high levels of luteinizing hormone (LH) and follicular-stimulating hormone (FSH) indicates central precocious puberty. Prepubertal levels of FSH and LH in girls with some signs of pubertal changes may indicates precocious pseudo-puberty.(7) Tumour markers like estradiol and inhibin are useful markers for granulosa cell tumour.(8)

Pre-pubertal vaginal bleeding is a rare condition, but it can cause anxiety and concern to the girl and her caretakers regardless of whether it occurs as a single, transient or recurrent event. The differential diagnosis is broad and it can be benign or malignant. It is critical for the healthcare providers to assess pubertal progression, identify its pathology and the differences in sexual differentiation to narrow the differential diagnosis of pre-pubertal vaginal bleeding. The clinical workup requires careful pediatric-specific gynecological examination followed by relevant investigations and appropriate treatment.

References

1. Ng SM, Apperley LJ, Upradrasta S, Natarajan A. Vaginal Bleeding in Pre-pubertal Females. J Pediatr Adolesc Gynecol. 2020;33(4):339-42.

2. Howell JO, Flowers D. Prepubertal Vaginal Bleeding: Etiology, Diagnostic Approach, and Management. Obstet Gynecol Surv. 2016;71(4):231-42.

3. Hadley J, Moore J, Goldberg A. Sexual Abuse as a Cause of Prepubertal Genital Bleeding: Understanding the Role of Routine Physical Examination. J Pediatr Adolesc Gynecol. 2021;34(3):288-90.

4. Merritt DF. Evaluation of vaginal bleeding in the preadolescent child. Semin Pediatr Surg. 1998;7(1):35-42.

5. Nayak S, Witchel SF, Sanfilippo JS. Vaginal foreign body: a delayed diagnosis. J Pediatr Adolesc Gynecol. 2014;27(6):e127-9.

6. Dwiggins M, Gomez-Lobo V. Current review of prepubertal vaginal bleeding. Curr Opin Obstet Gynecol. 2017;29(5):322-7.

7. Wei C, Davis N, Honour J, Crowne E. The investigation of children and adolescents with abnormalities of pubertal timing. Ann Clin Biochem. 2017;54(1):20-32.

8. Kottarathil VD, Antony MA, Nair IR, Pavithran K. Recent advances in granulosa cell tumor ovary: a review. Indian J Surg Oncol. 2013;4(1):37-47.

LOWER GENITAL TRACT POLYPS

IN PREPUBERTAL GIRLS by Dr. Karen Ng

Vaginal polyp is rarely found in pre-pubertal girls and newborns. The finding of an interlabial lesion in this age group should prompt one to review other possible diagnosis including hymenal tag, prolapsed ectopic ureterocele, urethral prolapse, paraurethral Skene cyst, müllerian papilloma and the more serious botryoid sarcoma of the vagina.

History, physical examination and investigation

The girl with the polyp usually presents with finding of a mass during examination after birth, or observed by the family. There have only been a few case reports on fibroepithelial polyps in prepubertal girls [1-5]. None of them presented with vaginal bleeding and they were usually painless and presented as incidental findings.

For physical examination, one can consider utilizing the pull-down technique to visualize the hymen and vaginal opening. It is important to differentiate whether the mass is originating from the urethra or paraurethral region, from the hymen, or whether it is originating from inside the vagina, as there can be different differential diagnosis.

For fibroepithelial polyps, they will present as a mass protruding from the vagina, whereas for hymenal tags or polyps, they can present as incidental findings of an elongated projection of hymenal tissue protruding beyond the hymenal rim or extending from the rim [6].

Benign müllerian papillomas are rare polypoid masses which can be found on the cervix or vaginal wall. It can have a similar appearance to rhabdomyosarcoma [7] and often presents with painless vaginal bleeding. For sarcoma botryoides, they can present in the prepubertal girl with a rapidly growing ‘grape-like’ vaginal mass along with vaginal bleeding. MRI should be considered if there is concern for sarcoma, so as to delineate the extent of the disease hence guide the treatment plan.

Whereas for urothelial polyps, commonly present as a mass protruding from the urethral opening, along with symptoms such as urinary retention, pain and bleeding [8].

Differentiating the benign fibroepithelial polyp or müllerian papilloma from the most concerning diagnosis of botryoid rhabdomyosarcoma of the genital tract can be difficult. History may give some clues as to the possible diagnosis as fibroepithelial polyps rarely presents with bleeding and sarcoma usually presents as a rapidly enlarging mass. However, if the girl presents with vaginal bleeding and no obvious mass can be visualized, it may be prudent to perform an examination under anaesthesia after ruling out other causes of bleeding such as vulvovaginitis, trauma, presence of foreign body, infection or precocious puberty.

Examination under aneasthesia can be performed with the aid of a vaginoscope, so as to preserve the integrity of the hymen, which can be socially, culturally or religiously important for some families. Biopsy is often required, as obtaining a sample for histopathological diagnosis is important to rule out the diagnosis of sarcoma. In the case where there is high suspicion of sarcoma, obtaining a biopsy rather than excision of the mass, may be prudent at the first instance as treatment of rhabdomyosarcoma can require more extensive surgery along with adjuvant therapy such as chemotherapy and radiotherapy [7].

Fibroepithelial polyp is a polypoid lesion with a central fibrovascular core covered by squamous epithelium. It is rare and is mostly seen in adult women. The mainstay of treatment is simple excision. Recurrence is uncommon after complete excision [3], and there have been no reports of malignant transformation [2, 3].

Benign müllerian papilloma is a rare tumor of the female genital tract which can involve the cervix or vagina, or both. On histopathological examination, the müllerian papilloma has multiple thin papillary processes covered by a layer of epithelial cells. Majority of the cases occurred in prepubertal girls with a median age at presentation of 5 years old [7]. Most presented with intermittent vaginal bleeding. Histopathological diagnosis is important and obtaining a biopsy of the mass is crucial to differentiate it from sarcoma. Though rare, borderline malignant change or malignant transformation has been reported [9, 10], therefore complete excision is still the recommendation once biopsy confirmed the diagnosis of müllerian papilloma.

Whereas for the other diagnosis of hymenal polyps or tags, they are usually found in newborns or in early childhood and are not uncommon. Neonatal cases are probably due to estrogen stimulation in the fetal period [6]. They are usually discovered during physical examination of the genitalia. Hymenal polyps are usually less than 5mm [11]. Most of them will disappear by age of 3 years, and very rarely they can persist and increase in size. Therefore, most hymenal polyps can be managed conservatively.

In conclusion, it is important to have a thorough history and physical examination to identify the origin of the interlabial mass as the management can vary. Vaginoscopy and biopsy should be considered especially in cases where girls presented with vaginal bleeding after all other causes have been ruled out.

References

1. Alev Suzen, N.E., Ozgur Ilhan Celik, Fibroepithelial polyp of vagina ina two-year-old girl and review of the literature. Pediatric Urology Case Reports, 2016. 3(2): p. 4.

2. Alotay, A.A., et al., Fibroepithelial vaginal polyp in a newborn. Urology Annals, 2015. 7(2): p. 277-278.

3. Jallouli, M., et al., Vaginal polyp in a newborn. European Journal of Pediatrics, 2008. 167(5): p. 599-600.

4. Pul, M., et al., Vaginal Polyp in a Newborn. Clinical Pediatrics, 1990. 29(6): p. 346-346.

5. Smart, V.A., et al., Fibroepithelial Vaginal Polyps in a Newborn Female. Urology, 2019. 132: p. 161-163.

6. Frikha, F., et al., Hymenal polyps in two infants. Pediatr Dermatol, 2018. 35(6): p. e412-e413.

7. McQuillan, S.K., et al., Literature Review of Benign Mullerian Papilloma Contrasted With Vaginal Rhabdomyosarcoma. Journal of Pediatric and Adolescent Gynecology, 2016. 29(4): p. 333-337.

8. Goel, P., et al., Urothelial polyps from anterior urethra in a prepubertal female child: a rare entity. Journal of Pediatric Surgery, 2012. 47(12): p. E13-E15.

9. Dobbs, S.P., et al., Borderline malignant change in recurrent mullerian papilloma of the vagina. Journal of Clinical Pathology, 1998. 51(11): p. 875-877.

10. Zou, J., et al., Cervicovaginal Mullerian papilloma malignant transformation in a prepubertal girl. Journal of Clinical Pathology, 2019. 72(12): p. 836.

11. Borko, E., et al., A large hymenal polyp in a 21-year-old virgin. Acta Dermatovenerol Alp Pannonica Adriat, 2009. 18(4): p. 173-5.

VULVOVAGINAL INFECTIONS

in a Prepubertal Child

by Dr Renna Cristina B. de Leon

Vulvovaginitis, which refers to an inflammation of the vulva and vagina, is generally considered the most common gynecologic problem in prepubertal girls. It constitutes about 62% of pediatric gynecologic problems seen in primary care. The most frequent age of referral is between 3–10 years old. The majority of these girls are diagnosed and treated by their general practitioner and only come to the attention of a gynaecologist when the condition is resistant to treatment or is recurrent. In practice, the terms vulvitis, vaginitis, and vulvovaginitis are often used interchangeably by physicians in diagnosing inflammatory conditions of the lower female genital tract. Diagnosing infection is confounded by the overlap between normal flora and potential pathogens. The presence of an organism does not itself signify the cause of the condition. The clinical picture, as well as microbiology, should be considered before the infection is assumed.

The hypoestrogenic hormonal milieu

in a prepubertal girl is a major factor in making her vaginal mucosa susceptible to infection. There is a lack of labial fat pads or pubic hair, small labia minora, thin, atrophic and delicate mucosa which lacks cornification, has an alkaline pH and is therefore susceptible to invasion from pathogens. Other factors putting the girl at risk are the close proximity of the rectum thus the risk of faecal contamination, which can lead to infection, children's tendency to poor local hygiene and to explore their bodies, spread of respiratory bacteria from hand to the perineum, and local irritants such as nylon underwear.

A detailed and thorough history and comprehensive examination, including inspection of the genital area, are essential. Gynaecological examination of the prepubertal girl must be done with sensitivity and gentleness. If the child is very young, then the examination can be done with the child on the mother’s lap. If the child is older and cooperative, then she can be instructed to assume the frog-leg position. Gentle separation and retraction of the labia should allow visualization of the external genitalia, introitus and hymen. Any discharge can pool in the posterior fourchette and a small, wire, cotton-tipped swab can be used and specimen obtained from this area for gram staining, microscopy and culture. If visualization is difficult, then the child may be

placed in the knee-chest position to allow a better view. Instrumentation of the vagina in an awake, pre-pubertal child can be uncomfortable, painful and stressful for the child and her caregiver and should therefore be avoided If inspection of the upper vagina is essential for diagnosis, like in the presence of vaginal bleeding or suspicion of a foreign body, then this should be done under anaesthesia.

The most common symptom of vulvovaginitis is vaginal discharge, which occurs in the majority of girls (62–92%). The discharge can be clear, yellow or green and may be offensive smelling. Other symptoms of

vulvovaginitis include redness and soreness (74–82%), pruritus (45–58%) and dysuria (19%). Vaginal bleeding is an unusual symptom of vulvovaginitis (5–10%) and must be investigated appropriately. More serious causes, such as tumours, precocious puberty and sexual abuse, must be excluded before attributing bleeding to vulvovaginitis.

Most cases (70%–80%) have nonspecific causes and require only reassurance and improved vulvar hygiene. Symptoms resolve in most children within two to three weeks. General vulvovaginal hygiene measures include keeping the vulva clean, dry and well aerated. Nightgowns and loose clothing are advised at night to allow air to circulate, and in the morning avoid tights, leotards, and leggings. Cotton instead of nylon underwear is advised to be used. Underwear should be doubly rinsed after washing to avoid residual irritants. Then, avoid letting children sit in wet swimsuits for long periods. For bathing, advise caregivers not to use bubble baths or perfumed soaps. Then allow the child to soak in clean water for 10 to 15 minutes. Use soap to wash regions other than the genital area just before taking the child out of the tub. Limit the use of any soap on genital areas. Rinse the genital area well and gently pat dry. A hair dryer on the cool setting may be helpful to assist with drying the genital region. If the vulvar area is tender or swollen, cool compresses may relieve the discomfort. Emollients may help protect the skin. It is also important to review toilet hygiene with the child. Children younger than 5 should be supervised or assisted in hygiene. Have children sit with knees apart to reduce reflux of urine into the vagina. If they have trouble with this position because of the small size, they can use a smaller detachable seat or sit backwards on the toilet seat (facing the toilet). Emphasize wiping front to back after bowel movements. Wet wipes can be used instead of toilet paper for wiping as long as they don't cause a "stinging" sensation.

About 25% of cases are infectious vulvovaginitis. Children may pass respiratory flora from the nose and oral pharynx to the vulvar area and enteric flora from the anal area has also been identified. The challenge for clinicians is to determine whether the bacteria found on cultures represent pathogens causing infection or are part of the vaginal flora in a young female presenting with symptoms. Respiratory and enteric bacteria cultured in prepubertal females with vulvovaginitis include Respiratory bacteria: Streptococcus pyogenes (group A streptococcus), Staphylococcus aureus, Haemophilus influenza, Streptococcus pneumoniae, Neisseria meningitides, Moraxella catarrhalis; and enteric bacteria: Escherichia coli, Enterococcus faecalis, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas species, Shigella species and Yersinia species. Although sometimes isolated, Candida species and Gardnerella vaginalis are not usually associated with vulvovaginitis in prepubertal females. Less commonly, prepubertal vulvovaginitis results from sexual abuse, and additional evaluation is necessary.

References

1. Van Eyk N, Allen L, Giesbrecht E, et al. Pediatric vulvovaginal disorder: a diagnostic approach and review of the literature. J Obstet Gynaecol Can 2009;31:850-62.

2. Vilano SE, Robbins CL. Common prepubertal vulvar conditions. Curr Opin Obstet Gynecol 2016;28:359-65.

3. Jill M. Jasper, Vulvovaginitis in the Prepubertal Child, Clinical Pediatric Emergency Medicine, Volume10,Issue1,2009,Pages10-13,ISSN15228401,https://doi.org/10.1016/j.cpem.2009.01.003.

4. StrickerT, Navratil F, Sennhauser FH. Vulvovaginitis in prepubertal girls. Arch Dis Child 2003;88:324–6. doi:10.1136/adc.88.4.324

5. Joishy M, Ashtekar C, Jain A, Gonsalves R. Do we need to treat vulvovaginitis in prepubertal girls? BMJ 2005;330:186–8. doi:10.1136/bmj.330.7484.186

Other known causes of childhood vulvovaginitis include parasites. The most common is E. vermicularis. Increased itching of the perianal or perineal region at night, and crowded and poor hygiene conditions should make us consider worm infestation. A slight irritation and vaginal discharge can also be seen in addition to itching because of the movements of the larvae on the vulva. Diagnosis is made thru the Gaita with the Sellotape slide method or scotch tape method. In children with threadworm infection, a course of Mebendazole is useful. Chronic vulvovaginitis in childhood is most commonly due to psoriasis, dermatitis (atopic, allergic, seborrheic or irritant) and lichen sclerosis. All of these conditions may present with scaling and erythema of the external vulva with or without vaginitis.

In the management of vulvovaginitis in prepubertal girls, current evidence suggests that, in addition to advising about hygienic measures, vaginal secretions should be obtained for microbiological investigations and that antibiotics should be used only if a pure or predominant growth of a pathogen is identified.

6. Ranđelović, G., Mladenović, V., Ristić, L. et al. Microbiological aspects of vulvovaginitis in prepubertal girls. Eur J Pediatr 171, 1203–1208 (2012). https://doi.org/10.1007/s00431-012-1705-9

7. Cuadros J, Mazon A, Martinez R, Gonzalez P, Gil-Setas A, Flores U, et al for the Spanish Study Group for Primary Care Infection. The aetiology of paediatric inflammatory vulvovaginitis. Eur J Pediatr 2004;163: 105-7.

8. Baiulescu M, Hannon PR, Marcinak JF,

Janda WM, Schreckenberger PC. Chronic vulvovaginitis caused by antibiotic-resistant Shigella flexneri in a prepubertal child. Pediatr Infect Dis J 2002;21: 170-2.

9. Zuckerman A, Romano M, Clinical Recommendation: Vulvovaginitis. J Pediatr Adolesc Gynecol.2016;29(6):673. Epub 2016 Sep 21.

Vaginal Foreign Body Vaginal Foreign Body

in Children and Adolescents: Our Experience in China

By Dr Huihui Gao(Amy) & Dr Liying Sun (Lynn)

The occurrence of vaginal foreign bodies (VFB) among children and adolescents is not common. However, the rate of VFB among girls in China has been increasing in recent years. About 21%-34.1% of girls in China who presented with vaginal discharge or bleeding were found to have VFB.

The Pediatric and Adolescent Gynecology (PAG) Department of the Children’s Hospital of Zhejiang University School of Medicine (ZJU) was the first PAG training and research center in mainland of China and was recognized by FIGIJ in 2017. The center has carried out clinical gynecologic work and provided outpatient services to more than 100,000 children and adolescents for nearly 20 years.

We wanted to describe the age and distribution of characteristics of girls with VFB over time, thus we retrospectively reviewed medical record information of patients who had VFB in our hospital between the years 2005 to 2019. The results showed that there was a total of 353 patients with the diagnosis of VFB in the PAG department in our hospital between 2005 to 2019. The actual number of patients with VFB was likely to be greater because not all patients were recorded in the medical record information system.

The patients came from different provinces in China. We collected the geographical distribution data of 254 patients which is shown in Fig.

Our patients’ ages ranged from 1-14 years old with a mean ± standard deviation (SD) of 6.15 ± 2.46 years old. Based on WHO's definition of children and adolescents, we divided children aged 0-18 into three categories: children (0-6 years old), pre-adolescence (prepuberty, 7-9 years old), and late adolescence (late puberty, 10-18 years old). The age distribution of VFB is shown in Table.

Table Age distribution of patients with Vaginal foreign body

Most of the patients visited the PAG department for genital inflammation, vaginal discharge or irregular vaginal bleeding which may last for several days or even several months. Most required 2-3 visits before their problem could be solved.

The most common foreign bodies were small hard objects, followed by bits of cloth or toilet tissue. One patient who had a disk battery as a foreign body had the most severe symptoms. 72.2% of patients had concomitant genital inflammation. A few patients had associated urinary infections.

Gynecological examination is crucial for diagnosis, especially recto-abdominal examination by an experienced gynecologist. Ultrasound and pelvic radiographs can help distinguish different VFBs. Neglected foreign bodies in the vagina can lead to persistent infection, vaginal discharge, tissue fibrosis, and even ureterovaginal fistula.

VFB also has negative psychological impacts on girls. A previous study by our team suggested that the social anxiety level of patients with VFB was higher. These girls were found to have shorter times of outdoor activities and longer screen time. Poor family cohesion, poor emotional expression, and high levels of control and social anxiety in girls were associated with the occurrence.

An attentive and caring environment, more comfortable parenting styles, more time for outdoor exercise, and necessary psychological referral and intervention are needed for these girls.

LABIAL ADHESION (LA) LABIAL ADHESION

Asst. Prof. Dr. Nurkhairulnisa Abu Ishak

is the fusion of the labia minora or majora. It starts at the back of the fourchette and moves towards the clitoris. Most often, labial adhesions are encountered in prepubertal age group due to hypoestrogenic state. It occurs most commonly between 3 months and 3 years of age. Parents most often diagnose incidentally while changing diapers. Some patients may present with symptoms involving urinary tract like dysuria, increased frequency, inability to pass urine or dribbling.

The labial adhesions may range from small partial fusion to complete fusion that can occlude the vaginal orifice. These adhesions are related to local irritation and inflammation at an age when estrogen levels are low. Other postulations of adhesions are thinning of the vulva, lack of good and proper hygiene, lichen sclerosis, vulva coming in touch with urine, local infection, and physical irritants. Diagnosis is usually clinical and there is hardly any need for detailed investigations. The differential diagnosis should include hymenal skin tags, imperforate hymen, transverse vaginal septum, and vaginal atresia. This can easily be done by careful history and detailed clinical examination.

For the parents to notice such a condition in their child is worrisome. Most of them are not convinced with the conservative treatment offered to them and demand prompt cure. Therefore, it is important to make them understand the fact that if the patient is clinically asymptomatic, there is no requirement for treatment. Initial management of every case is reassurance as most of the adhesions resolve naturally with time or with onset of puberty. It is reported that up to 80% resolve spontaneously without any treatment before puberty as estrogen levels increase and the vaginal epithelium becomes multi-layered and cornified.

Previously LA would have been treated with estrogen cream or by manual separation. Recent studies have shown that success rates for both estrogen cream and manual separation are quite low. There were concerned on the use of estrogen cream in young girls as it was associated with breast tenderness, vaginal bleeding and vulvar pigmentation. However, most studies have reported that the side effects were mild and transient. An alternative to estrogen therapy is topical betamethasone.

Surgical separation should only be reserved for those who were resistant to conservative treatment or those who presented with urinary retention. Surgical separation preferably be done under general anaesthesia to reduce the psychological trauma to these young girls. Recurrences are common with labial adhesions, regardless of the mode of treatment used. Labial adhesions may keep reforming until the female patient goes through puberty. Some studies report a rate of recurrence from 11% to 14% with either topical or surgical management.

In conclusion, despite being a benign entity, labial adhesion in prepubertal girls may be a cause of severe concern and a source of great parental anxiety. To avoid repetitive treatment, reassurance and conservative management is the best approach if the patient is asymptomatic.

References

1. Gonzalez D, Anand S, Mendez MD (2021) Labial adhesions. In: StatPearls. StatPearls Publishing, Treasure Island

2. Eroğlu E, Yip M, Oktar T, Kayiran SM, Mocan H (2011) How should we treat prepubertal labial adhesions? Retrospective comparison of topical treatments: estrogen only, betamethasone only, and combination estrogen and betamethasone. J Pediatr Adolesc Gynecol 24:389–391.

3. Granada C, Sokkary N, Sangi-Haghpeykar H, Dietrich JE (2015) Labial adhesions and outcomes of office management. J Pediatr Adolesc Gynecol 28:109–113.

4. Bussen, S., Eckert, A., Schmidt, U., & Sütterlin, M. (2016). Comparison of Conservative and Surgical Therapy Concepts for Synechia of the Labia in Pre-Pubertal Girls. Geburtshilfe Und Frauenheilkunde, 76(04), 390–395.

5. Srivastava, S., Pandey, A., Kumar, P. et al. Management of labial adhesion in a developing country—an observational study. Egypt Pediatric Association Gaz 69, 41 (2021).

By

Dr. Loh Sweet Yi Esther

URETHRAL PROLAPSE

is a rare condition characterised by the circumferential protrusion of the urethral mucosa through the urethral meatus. Recent epidemiological data is lacking but older reports estimate a prevalence of 1:3000 children. Urethral prolapse is commonly known to occur in pre-pubertal girls with a peak incidence between 7 to 8 years old. However, cases have also been reported among infants as young as 11 months old and adolescents aged 18 years old.

The exact cause of urethral prolapse in the paediatric and adolescent population remains unknown. Various theories have been conjectured including congenital weakness of the pelvic or urethral structures, increased intra-abdominal pressure as a result of chronic cough or constipation, trauma and oestrogen deficiency.

Diagnosis is made clinically. The majority of patients with urethral prolapse present with an asymptomatic periurethral mass discovered on routine examination. In advanced cases, patients may complain of bleeding or pain. They may also report urinary symptoms such as dysuria or voiding difficulties.

Careful examination of the perineum will reveal a classic doughnut-shaped mass surrounding the urethral meatus (Figure 1 and 2). Often, the mass is erythematous, tender to palpation and bleeds upon contact. The presence of the centrally-located urethral meatus can be confirmed by either direct visualization, insertion of an instrument tip, catheterization or observation of voiding.

Extensive investigations are rarely needed. The differential diagnoses of urethral prolapse include urethral caruncles or polyps, condyloma, rhabdomyosarcoma or urethral malignancy. Patients who present late may develop necrosis, ulceration and gangrene of the mass.

In mild and asymptomatic cases, conservative and medical therapy is acceptable. Sitz bath, topical antibiotics, topical oestrogens or steroids have all been shown to help eradicate infection and reduce oedema with subsequent resolution of the prolapse. However, the rate of treatment failure and recurrence is high.

Surgical management is most effective with a high cure rate. It is indicated in advanced, refractory or recurrent cases. Most studies recommend the modified Kelly-Burnham technique which involves circular excision of the prolapsed urethral mucosa and re-approximation of the muco-cutaneous junction of the urethra. Ligation of the prolapsed urethral mucosa over a Foley catheter is also effective. However, this method is associated with more pain and longer hospital stay. Complications from surgical management include urethral stenosis, stricture, urinary incontinence and recurrence of the prolapse.

References

1. Ninomiya T, Koga H. Clinical characteristics of urethral prolapse in Japanese children. Paeds Int. 2017;59(5):578-82.

2. Liu C, Lin Y, Chen X, et al. Urethral prolapse in prepubertal females: Report of seven cases. J Obstet Gynaecol Res. 2017;44(1):175-78. https://doi.org/10.1111/jog.13467

3. Olumide A, Kayode Olusegun A, Babatola B. Urethral mucosa prolapse in an 18-year-old adolescent. Case Rep Obstet Gynecol. 2013;2013:231709. doi: 10.1155/2013/231709

4. Wei Y, Wu SD, Lin T, et al. Diagnosis and treatment of urethral prolapse in children: 16 years’ experience with 89 Chinese girls. Arab J Urol. 2017;15(3):248–53. https://doi.org/10.1016/j.aju.2017.03.004.

Figure 1

Figure 2

By Associate Professor Dr. Khadija Nuzhat Humayun

PRECOCIOUS

PUBERTY IN GIRLS

Puberty starts with reawakening of the hypothalamic pituitary gonadal axis (HPG). After birth, the HPG axis shows a neonatal surge and then goes into a long quiescent period during childhood. Precocious puberty (PP) is development of pubertal changes before the age of 8 years in girls due to increase in gonadotropins and / or estrogens leading to accelerated body development and bone age. PP is classified as gonadotropin dependent (central, true PP) or gonadotropin independent (peripheral,

Precocious puberty(PP)

Early puberty

Thelarche

Pubarche

Adrenarche

Gonadarche

CPP

Gn-independent PP

Idiopathic CPP

Onset before 8 years old in girls, deserves evaluation

Normal variant, onset at approximately 8–9 years old in girls

Onset of breast development

Onset of pubic hair

Onset of adrenal androgen production

Onset of gonadal activity

Central, true, GnRH-dependent precocious puberty

Incomplete, peripheral, or GnRH-independent PP; pseudo puberty

Central precocity without other cause, common in girls

CPP, central precocious puberty; GnRH, gonadotropin-releasing hormone;

Central precocious puberty (CPP) is due to the early maturation of the HPG axis. Many cases of CPP in girls are idiopathic. Central nervous systems (CNS) pathology may be seen only in a small number of girls with CPP and is more likely in girls who manifest puberty before 4 years. CNS pathology includes hydrocephalus, meningomyelocele, neurofibromatosis, hypothalamic hamartomas, etc. Hamartomas are nonneoplastic, congenital lesions, containing GnRH neurons.

CPP may be the first sign of optic glioma/ astrocytoma. Girls receiving cranial radiation for malignancy are at higher risk of CPP. Environmental estrogen (cosmetic products, insecticides, bioengineered food products) can disturb the HPG axis. Childhood obesity, intrauterine growth retardation, parental obesity, and diabetes are associated with early thelarche which may progress to CPP.

Peripheral precocious puberty (PPP) or gonadotropin-independent precocious puberty is due to endogenous or exogenous estrogen excess. McCune-Albright syndrome manifests with Cafe’ au lait spots, polyostotic fibrous dysplasia, and PPP. It should be considered in children who present with recurrent follicular cysts and irregular vaginal bleeding. Primary hypothyroidism may also manifest with thelarche and vaginal bleed in

Table. 1 Glossary of terms used with precocious puberty

Table 2. Causes of precocious puberty in girls

Central precocious puberty

Idiopathic

Central nervous system aberrations

• Hypothalamic hamartoma

• Astrocytoma and glioma

• Cerebral palsy

• Hydrocephalus

• Irradiation

• Environmental estrogens

• Trauma

• Infection

• Subarachnoid cyst

• Pineal cyst

• Neurofibromatosis type 1

• Tuberous sclerosis

• Sturge–Weber syndrome

Peripheral precocious puberty

Functional ovarian cysts

McCune–Albright syndrome

Ovarian tumor (granulosa cell)

Exogenous estrogen

Profound primary hypothyroidism

Premature thelarche starts before 2 years of age and can be unilateral. It is not associated with rapid growth or advanced bone age and usually regresses with time. Uterine and ovarian sizes are in the prepubertal range. Premature thelarche which starts after 2 years of age may progress to CPP.

Premature adrenarche is the increase in adrenal androgens. It may be associated with premature pubarche (increase in pubic and axillary hair). It occurs as a result of increased secretion of androgens from the adrenal glands. The conditions that need to be considered in girls with premature adrenarche are adrenal tumors and congenital adrenal hyperplasia. Premature adrenarche may be an early sign of metabolic syndrome or polycystic ovary syndrome and may be associated with hyperinsulinism and dyslipidemia.

Diagnosis

These are the clinical scenarios which may present to us:

Case 1: A 7-year-old girl with pubic or axillary hair only

Case 2: A female infant with breast development only

Case 3: A 6-year-old girl having breast development, with or without pubic hair.

The initial evaluation includes detailed medical history – the onset of symptoms, rate of progression, growth, and family history of PP.

Physical examination includes anthropometry and pubertal staging.

Laboratory evaluation will be defined by the clinical findings and may include measurement of LH, FSH, E2 GnRH stimulation test and pelvic ultrasound for ovaries and uterus, and X-ray for bone age.

Additional investigations may be needed like 17-Hydroxyprogesterone, DHEAS, etc. depending on the clinical presentation.

Cranial magnetic resonance imaging (MRI) should be done in cases of CPP to exclude CNS pathology, especially in girls younger than 6 years.

Treatment

It will depend on the exact etiology of precocious puberty. GnRH analogues can be considered safe in CPP depending on age at diagnosis, predicted height, anxiety about early menarche, and psychological and behavioral problems. Girls less than 7 years of age show good height gain when treated. Anti-estrogens or aromatase inhibitors can be used in McCune–Albright syndrome.

Conclusion

It is very important for the clinicians to be aware of normal pubertal timing and patterns so that any deviation from the norms is picked up early and investigated in order to save the child from facing issues in the long run.

References

1. Eugster EA. Update on precocious puberty in girls. Journal of Pediatric and Adolescent Gynecology. 2019 Oct 1;32(5):455-9.

2. Cesario SK, Hughes LA. Precocious puberty: a comprehensive review of literature. Journal of Obstetric, Gynecologic & Neonatal Nursing. 2007 May 1;36(3):263-74.

3. Chittwar S, Ammini AC. Precocious puberty in girls. Indian Journal of Endocrinology and Metabolism. 2012 Dec;16(Suppl 2):S188.

ONCOFERTILITY IN MALAYSIA

By Associate Prof Dr Anizah Ali, PAG Malaysia

Remarkable improvements in childhood cancer therapies have witnessed a rise in the number of survivors entering adulthood. Reduced fertility, premature menopause and osteoporotic bones may profoundly impact their self-esteem and overall quality of life. Unfortunately, the crippling aftermath of gonadotoxic therapies onto fertility potential is a bitter pill these childhood cancer survivors had to swallow.

“Oncofertility” a term coined from oncology and fertility was first described by Therese K Woodruff. It refers to an interdisciplinary field of science dedicated to addressing the reproductive future of young men, women, and children facing a life-preserving but fertility-threatening cancer diagnosis. The emergence of oncofertility promises hopes for future childhood cancer survivors. This is achieved via options to conserve fertility before possible gonadotoxic therapies. In 2006, The American Society of Clinical Oncology (ASCO) recommended that cancer patients of childbearing age be routinely referred to a reproductive endocrinologist for fertility preservation (FP) discussion, counselling and services. Thereafter, there was notable interest and focus globally on oncofertility, both in terms of research and clinical service provision.

OUR MALAYSIAN CHAPTER of oncofertility

was initiated by a shared interest in improving care provision for cancer survivors with hopes for fertility preservation; in adults and children alike. Training and networking with established oncofertility institutions worldwide were fostered. Subsequently, the Malaysian Society for Fertility Preservation (MSFP) was founded on 2nd July 2020 to generate awareness of FP among the medical fraternity and the general population. 26th August 2020 was a milestone in the Malaysian oncofertility journey as it marks the launching of Malaysian’s first oncofertility referral centre based in Advanced Reproductive Centre (ARC), Hospital Canselor Tuanku Muhriz (HCTM UKM), Kuala Lumpur.

Oncofertility services in HCTM concerted efforts involving multiple disciplines. Paediatric and adolescent gynaecologists liaise with reproductive specialists to provide oncofertility services for children, adolescents and young adults. Oncofertility services among children and adolescents are led by Associate Prof Dr Anizah Ali, while adults and male oncofertility services are manned by the ARC team reproductive specialist; Associate Prof Dr Faizal Ahmad. Our oncofertility team works under close mentorship and guidance from Professor Dr Nao Suzuki of the Japanese Society of Fertility Preservation (JSFP).

Fertility preservation services in HCTM start from fertility preservation counselling for patients and family members to the provision of various FP options. The oncofertility clinic runs every Friday morning from 9 am to 12 noon. This clinic manages referrals from within the hospital as well as external cases. In terms of FP services catering to the paediatric, adolescent and young adults’ population, these include:

i. Oocytes cryopreservation

This option may cryopreserve either mature or immature oocytes. Mature oocytes require ovulation induction and oocyte retrieval, as is done for IVF. This is followed by mature oocyte retrieval, which is subsequently frozen. The potential advantage of freezing immature oocytes is that they are smaller and metabolically less active than mature oocytes. Alternatively, cryopreservation of immature oocytes may be an option for pre-pubertal girls. These immature oocytes would need to undergo in-vitro maturation; which is widely still experimental.

ii. Ovarian tissue cryopreservation (OTC)

The technique involves freezing ovarian cortex segments for later thawing and transplanting either back to the ovarian site (orthotopically) or to some other location (heterotopically). The ovarian cortex is used because this part of the ovary is particularly rich in primordial follicles.

iii. Hormonal suppression with GnRH agonists

This method is applied on the basis that GnRH agonists may inhibit chemo-therapy-induced ovarian follicular depletion by chemotherapy agents. It does not involve any delay in cancer treatment initiation. It is an attractive option given the wide availability of the agent involved (GnRH agonist).

To date, we have performed a total of eight OTCs and a single case of oocyte cryopreservation for children, adolescent and young adult cohorts.

iv. Fertility-sparing surgeries

This involves a surgical approach aiming to preserve fertility where ovaries and/or uterus are preserved

As expected, with any new service provision, there would be challenges. Even though the overall response to oncofertility services was good ever since we commenced the services, the knowledge gap on oncofertility was still apparent among both patients and parents and healthcare providers. Efforts to increase both knowledge and awareness of oncofertility among the public and healthcare providers were initiated via public webinars, continuous medical education sessions targeting healthcare providers and mass media appearances discussing oncofertility.

Deciding for fertility preservation for cancer patients is never an easy task, let alone involving children and adolescents. This challenging feat takes a toll on parents and caretakers. Acknowledging this, Associate Professor Dr Anizah Ali is currently conducting research looking at factors facilitating oncofertility decision-making in children, adolescents and young adults; towards developing a decision aid. It is hoped that this decision aid would facilitate decision-making among parents and caretakers contemplating FP for their children.

The availability of oncofertility services in Malaysia is an achievement to be embraced. Albeit our oncofertility journey has just started, we are stepping slowly but surely into a future of promises and hopes for preserving fertility among childhood cancer survivors and other affected children and adolescents.

References

Badawy, A., Elnashar, A., El-Ashry, M., & Shahat, M. (2009). Gonadotropin-releasing hormone agonists for prevention of chemotherapy-induced ovarian damage: prospective randomized study. Fertility and Sterility, 91(3), 694–697. https://doi.org/10.1016/j.fertnstert.2007.12.044

Benedict, C., Thom, B., & Kelvin, J. F. (2016). Fertility preservation and cancer : challenges for adolescent and young adult patients. 87–94. https://doi.org/10.1097/SPC.0000000000000185

Christopher J. Long, Jill P. Ginsberg, T. F. (2016). Fertility Preservation in Children and Adolescents with Cancer. Urology. https://doi.org/10.1016/j.urology.2015.10.047

Diesch, T., Rovo, A., Weid, N. Von Der, Faraci, M., Pillon, M., Dalissier, A., Dalle, J., & Bader, P. (2017). Fertility preservation practices in pediatric and adolescent cancer patients undergoing HSCT in Europe : a population- based survey. January, 1022–1028. https://doi.org/10.1038/bmt.2016.363

Estes, S. J. (2015). Fertility Preservation in Children and Adolescents. Endocrinology and Metabolism Clinics of North America, 44(4), 799–820. https://doi.org/10.1016/j.ecl.2015.07.005

Mccracken, K., & Nahata, L. (2017). Fertility preservation in children and adolescents : current options and considerations. 283–288. https://doi.org/10.1097/GCO.0000000000000395

Melo, C., Moura-Ramos, M., Canavarro, M. C., & Almeida-Santos, T. (2019). The time is now: An exploratory study regarding the predictors of female cancer patients’ decision to undergo fertility preservation. European Journal of Cancer Care, 28(4), 1–10. https://doi.org/10.1111/ecc.13025

Salsman, J. M., Yanez, B., Snyder, M. A., Avina, A. R., Clayman, M. L., Smith, K. N., Purnell, K., & Victorson, D. (2021). Attitudes and practices about fertility preservation discussions among young adults with cancer treated at a comprehensive cancer center: patient and oncologist perspectives. Supportive Care in Cancer, 29(10), 5945–5955. https://doi.org/10.1007/s00520-021-06158-0

Vadaparampil, S., Quinn, G., King, L., Wilson, C., & Nieder, M. (2008). Barriers to fertility preservation among pediatric oncologists. 72, 402–410. https://doi.org/10.1016/j.pec.2008.05.013

Woodruff, T. K., & Snyder, K. A. (2007). Oncofertility : Ferility Preservation for Cancer Survivors. Springer.

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TACKLING CLIMATE CHANGE:

WHY PEDIATRIC ADOLESCENT GYNECOLOGY (PAG) SHOULD TAKE THE LEAD.

by Dr. Jerilee Azhary, PAG Fellow Year 1 & Arya Mishal Nadrah, Primary student Year 6

My 12-going-on-13-year-old, self-proclaimed-environmentalist niece and I were binge-watching The National Geographic's Air Crash Investigation docuseries. She said, "Doctors and pilots both do their best to provide safety for the people they serve. They are similar in many ways, except…ONE". “Oh yeah? And what will that be?" I asked, intrigued. "Well…" she started with confidence. "Every time a pilot flies a plane, it burns enough fuel to heat the planet. But doctors don't do that". Perplexed, I asked her what she meant. She elaborated that doctors' jobs "Do not warm up the world because doctors do not deal with burning fuels ". I gave her a long silence. "Think about it…" she looked at me. And 'think about it' was exactly what I did.

While the next episode was loading on my TV screen, I excused myself to the kitchen and secretly googled ‘greenhouse emission,’ ‘carbon dioxide (CO2) emission’ and ‘climate change.’ According to The Growth in Greenhouse Gas Emissions from Commercial Aviation (2022) (1), aviation produces 2.4% of the total CO2 emissions globally. I have little idea how much 2.4% is. But on a global scale, I think it is huge. I was even more alarmed to learn that health care facilities are responsible for around 4.4% of global greenhouse gas emissions (2), twice that of the aviation industry! Such emissions may originate from medical waste, unsustainable materials, and anesthetics used in surgeries (3) In disbelief, I began my literature search. I noticed that each article relating to climate change and its effects on human health begins with a worrying statement: "Climate change is the single biggest health threat facing humanity" (4); “Climate change is one of the major global health threats to the world's population” (5). This global threat is comparable to that of COVID-19 and may prove even more damaging in the long run (6). However, some of these articles were not open-access and therefore not easily accessible unless you have an institutional account or an extra USD 24.95 (exclude taxes) to spend.

Climate change refers to a long-term shift in temperature and weather patterns. Similar shifts in the past have been attributed to various factors, including variations in the solar cycle. However, since the 1800s, human activities and industrial development have been the leading contributor. Greenhouse gases, such as CO2 and methane, are produced from burning fuels and collect in the atmosphere, preventing heat from escaping and thus raising the temperature of the planet. As the emissions continue to increase, the earth gets warmer. Earth is now 1.1 ⁰C warmer than it was in the late 1800s. This slight rise in temperature, which seems "of little concern" to many of us, has created extreme heat and fires in the Western United States, floods in Central Europe, droughts in Africa, wildfires in Australia, and hurricanes across the globe. This 1.1 ⁰C increase in earth temperature has displaced people from their homes, increased the risk of vector-borne diseases, created clean-water shortages and drought, limited health care accessibility, reduced food production, and threatened food and shelter security (7, 8).

The health impact of climate change, climate disaster, or displacement threatens human lives. Worse, the climate-sensitive health risks are greatest for the most vulnerable: women, especially pregnant women, and children, ethnic minorities, marginalized persons, the elderly, and those with underlying health comorbidities (7). In Bangladesh (9), for example, women are more vulnerable because of their socially determined roles, lack of food and shelter, and lack of access to hygiene. Of the 1.3 billion people living below the poverty line in low-resource countries, 75% are women, and climate change will place this group in the most vulnerable position (10).

Closer to home, an increase in rainfall has led to a series of flash floods over the years. Studies in Malaysia have shown that increased rainfall is associated with dengue and malaria transmission, as flooded environments provide excellent breeding grounds for vector-borne diseases (11). Additional local data suggested the sea level along the Malaysian coast is rising at a rate of 0.1 to 3.5 mm/year (12). The negative impacts of rising sea level include beach erosion, inundation of land, increased flood and storm damage, increased salinity of coastal aquifers, and coastal ecosystem loss. An increase in rainfall, sea levels, and temperature further leads to a reduction in agriculture production. For every 1% rise in the temperature, local rice production declines by 4.6-6.1% (13). Additionally, in December 2006, flood-related problems in southern Malaysia had decreased the production of crude palm oil to 1.1 million metric tons.(14)

Children born today will live in an environment 4 °C warmer and therefore will be exposed to health risks related to climate change (7). Without adequate nutrition, shelter, and clean water, children will be more susceptible to diarrheal disease and experience the most severe effects of dengue fever. Girls facing climate change risk losing their access to education (15). By 2025, climate change will be a contributing factor in preventing 12.5 million girls from completing their education annually (15). A lack of education leads to less knowledge about contraception, abortion (16), and adverse maternal and birth outcomes for pregnant adolescents. In addition, robust data has indicated that climate change itself may have adverse effects on sexual and reproductive health in adult females (5,17).

The editorial board of the Journal of Pediatric and Adolescent Gynecology has called for leadership in tackling climate change for the future health of girls (4). We, as health care providers, could do a few things individually. This includes opting for a plant-based diet, eating less meat, recycling and reusing, using a little less water for showering, and taking public transport. When I ran out of ideas, I sought help from my climate-anxious niece. In a common social event like an office celebration and events (which is very much part of the Malaysian culture), "you could use flowers instead of balloons for decoration, potted plants instead of the conventional mugs as gifts, paper cups and plates. Even better to bring your own cutlery, coffee flask, or straws" she added. Then she asked me a question I did not have the answer to: "How many pairs of gloves do you use a day in the hospital?"

Children and adolescents are and will be among those worst-affected by climate change.

Gloves are essential for clinicians to protect ourselves and our patients. I must admit there have been times when sterilized gloves were disposed of in an unused condition – when the wrong size or powered/non-powdered gloves were "mistakenly" opened. A simple act of choosing the correct one before any procedure can make a difference. During one of our surgical procedures with Professor Nur Azurah (PAG consultant in Hospital Canselor Tuanku Muhriz Universiti Kebangsaan Malaysia (HTCM-UKM), I learned that she would cut off the individual fingers from a new pair of gloves and use one over her donned gloves every time she needed to perform a per-rectal examination (instead of using a new glove for each per-rectal). In addition to all these baby steps towards improving the environment, we could opt for reusable instead of disposable instruments and switch off machines we are not using.

Education is a powerful tool. A recent study has provided evidence that if 16% of high school students in highand middle-income countries were to receive climate-change education, we could see a 19-gigaton reduction in carbon dioxide emission by 2050 (18). As PAG providers, we have the opportunity to become advocates for climate change. A simple routine clinic consultation would be a golden opportunity for us to educate not only our underaged patients but also their accompanying adults, parents, or guardians.

On a bigger scale, there is a huge opportunity and significant advantage for the PAG society, such as the Asian Oceanic Society of Pediatric Adolescent Gynecology (AOSPAG), in the fight against global warming. The members of the AOSPAG originated from countries affected directly and indirectly by the changing climate; Australia, China, Hong Kong, Indonesia, Thailand, Bangladesh, Malaysia and Japan. And as a society, the AOSPAG could lead in education, research, and advocacy in responding to climate-sensitive health risks, training professional healthcare providers, patients, the lay public, and other leaders, and making the changes necessary to address this crisis.

One year into my PAG fellowship training program, I learned to create and maintain a vagina, remove a cyst or a uterus, suppress or regulate menses, induce or suppress puberty, and underwent 6 months of training in pediatric endocrinology and adolescent medicine.

References

By the end of my 2-year training fellowship, I will be considered trained, skilled, and knowledgeable enough to provide the best care for young girls. However, such training does not include managing girls’ ‘future health’ and that has to change. In November last year, the International Federation of Gynecology and Obstetrics (FIGO) Committee on Climate Change called for obstetricians and gynecologists to be leaders in addressing climate change. The leaders of climate justice today are young adolescent girls: Greta Thunberg, 19, Xiye Bastida, 19, Autumn Peltier, 17 and my niece, 12-going-on-13. If our patient's peers are leading the fight against climate change, then we, as professionally trained health providers for girls of this age group, should step up and lead with them, for their reproductive health in the future.

Overton J. Issue Brief | The Growth in Greenhouse Gas Emissions from Commercial Aviation (2019, revised 2022) https://www.eesi.org/papers/view/fact-sheet-the-growth-in-greenhouse-gas-emissions-from-commercial-aviation#1

World Health Organization 2021 WHO Health and Climate Change Global Survey Report, 2021. Geneva Licence: CC BY-NC-SA 3.0 IGO .

Mercer C. How health care contributes to climate change. CMAJ. 2019 Apr 8;191(14): E403-E404. doi: 10.1503/cmaj.109-5722. PMID: 30962202; PMCID: PMC6453681.

Roos EJ. Call for Leadership: Climate Change and the Future Health of Girls. J Pediatr Adolesc Gynecol. 2022 Apr; 35(2):107-108. doi: 10.1016/j.jpag.2021.12.015. Epub 2022 Jan 6. PMID: 34999232.

"Sprinkle a little climate change in everything you do", my niece would say. However small the effects of these actions, they will snowball into a greater impact in the long run.

Giudice LC, Llamas-Clark EF, DeNicola N, Pandipati S, Zlatnik MG, Decena DCD, Woodruff TJ, Conry JA; FIGO Committee on Climate Change and Toxic Environmental Exposures. Climate change, women's health, and the role of obstetricians and gynaecologists in leadership. Int J Gynaecol Obstet. 2021 Dec; 155(3):345-356. doi: 10.1002/ijgo.13958. Epub 2021 Oct 25. PMID: 34694628.

Climate Change Is An Even Bigger Health Threat Than COVID-19 – International Red Cross. https://healthpolicy-watch.news/climate-change-country-risk-behind/

Watts N , Amann M , Arnell N , et al : The 2019 report of the Lancet Countdown on health and climate change: ensuring that the health of a child born today is not defined by a changing climate. Lancet 2019; 394:1836–78 .

Centers for Disease Control and Prevention [website]. The National Institute for Occupational Safety and Health (NIOSH). Heat Stress –Heat Related Illness. Accessed September 27, 2021. https://www.cdc.gov/niosh/ topic s/heat s tress/ heatr elill ness.html

Cannon T. Gender and climate hazards in Bangladesh. Gend Dev. 2002;2002(10):45-50.

Denton F. Climate change vulnerability, impacts, and adaptation: why does gender matter? Gend Dev. 2002; 10:10-20

Rahman HA. Climate change scenarios in Malaysia: Engaging the public. International Journal of Malay-Nusantara Studies. 2018;1(2), 55-77

Ami Hassan Md Din, Kamaludin Mohd Omar, Marc Naeije & Sahrum Ses.2 March 2012. Long-term sea level change in the Malaysian seas from multi-mission altimetry data. International Journal of Physical Sciences, 7(10): 1694 – 1712.

Singh S. Amartalingam R., Wan Harun W.S & Islam T. 1996. Simulated impact of climate change on rice production in Peninsular Malaysia. Proceedings at National Conference on Climate Change, University of Putra Malaysia, 41-49. www.met.gov.my/.../metmalaysia/.../socioeconomicimpactsofextremeweatherandclimate).

The Malala Fund A Greener Fairer future: Why Leaders Need to Invest in Climate and girls' education, 2021. March Available: www.malala.org/newsroom/ archive/malalafund- publishes- report- on- climate- change- and- girls- education Accessed July 15, 2022 .

World Bank: Female Education and Childbearing: A Closer Look at the Data, 2015. Available: https://blogs.worldbank.org/health/ female- education- and- childbearingcloser- look- data Accessed November 26, 2021 .

Women Deliver The Link Between Climate Change and Sexual and Reproduc- tive Health and rights, an Evidence Review, January 2021. Available: www. womendeliver.org Accessed November 20, 2021 .

Cordero EC, Centeno D, Todd AM. The role of climate change education on individual lifetime carbon emissions. PLoS One. 2020 Feb 4;15(2):e0206266. doi: 10.1371/journal.pone.0206266. PMID: 32017773; PMCID: PMC6999882.