Progestins as a Contributing Factor to Hepatocellular Adenoma: A Case Series and Literature Review.

STUDY OBJECTIVE: To explore the role of progestins as potential contributing factors for the development of hepatocellular adenoma (HA) METHODS: We describe 3 cases of adolescents and young adults who developed HA while on norethindrone (NET), as well as their management. In addition, we provide a comprehensive literature review on the association between progestins and HA. RESULTS: Since 1983, 16 cases of HA in patients on progestins have been reported. Ten patients were on NET and 5 on a prodrug of NET (4 on norethindrone acetate [NETA] and 1 on lynestrenol). One individual had a norgestrel implant. Eight subsequently ceased all hormones: 4 experienced a size reduction, and 3 had complete resolution of their HA. Among our patients, 1 ceased NET and instead had a levonorgestrel intrauterine device inserted, and another swapped from NET to oral medroxyprogesterone acetate. Both experienced complete resolution of their HA. The third ceased NET and underwent a hysterectomy, with size reduction of her HA. CONCLUSION: These cases and the literature review suggest an association between progestin exposure, in particular NET and its prodrugs, and the development of HA. The pathophysiology is unknown but may include peripheral conversion of NET and NETA to ethinyl estradiol or a specific action of 19-nortestosterone derivatives on hepatocytes, especially those with higher systemic doses compared with the levonorgestrel intrauterine device. There are no case reports relating to other forms of progestins, such as 17-hydroxyprogesterone, which may be important when considering alternative therapeutic options in females requiring effective menstrual management who have comorbidities.

When you see nothing at all: Outcomes following a negative laparoscopy. A systematic review.

BACKGROUND: Persistent pelvic pain (PPP) is a complex and often debilitating condition. While widely accepted to be multifactorial in nature, the precise aetiology of PPP remains elusive. In many cases, women who undergo laparoscopy for PPP will have no visible pathology identified (a 'negative' laparoscopy). Currently, there are no consensus guidelines which outline the recommended management following a negative laparoscopy, and the woman's experiences and outcomes are not widely known. AIMS: This review aims to identify and summarise the literature surrounding the experiences of women with PPP who have a negative laparoscopy; specifically, their outcomes of pain, quality of life (QoL), satisfaction with care, and their overall management. MATERIALS AND METHODS: A systematic search of the electronic databases Ovid Medline, PubMed and Embase was performed. Studies in English exploring the outcomes of women with PPP following a negative laparoscopy were included. RESULTS: Four studies consisting of a total of 200 women were included. Results were inconsistent. Three studies concluded that the majority of women with PPP had persistent pain following a negative laparoscopy. A single study found that pain significantly improved after negative laparoscopy. QoL outcomes varied, with two studies reporting a positive impact and two studies reporting a deleterious impact on QoL following a negative laparoscopy. CONCLUSIONS: The impact on pain outcomes and QoL following a laparoscopy that does not diagnose pathology remains unknown, and the available evidence is insufficient to guide evidence-based practice. This review highlights a significant gap in our understanding of surgical management for PPP.

Pre-Vaccination Human Papillomavirus Genotypes and HPV16 Variants among Women Aged 25 Years or Less with Cervical Cancer.

BACKGROUND: In 2007, Australia introduced a national human papillomavirus (HPV) vaccination program. In 2017, the onset of cervical screening changed from 18 to 25 years of age, utilising human papillomavirus (HPV) nucleic acid testing. The objective of the study is to describe the HPV genotypes and HPV16 variants in biopsies from women ≤ 25 years of age with cervical carcinoma (CC) (cases), compared with those aged >25 years (controls), in a pre-vaccination cohort. METHODS: HPV genotyping of archival paraffin blocks (n = 96) was performed using the INNO-LiPA HPV Genotyping assay. HPV16-positive samples were analysed for variants by type-specific PCR spanning L1, E2 and E6 regions. RESULTS: HPV16 was the commonest genotype in cases (54.5%, 12/22) and controls (66.7%, 46/69) (p = 0.30), followed by HPV18 (36.3%, 8/22 vs. 17.3% 12/69, respectively) (p = 0.08). Furthermore, 90% (20/22) of cases and 84.1% (58/69) of controls were positive for HPV16 or 18 (p = 0.42); 100% (22/22) of cases and 95.7% (66/69) of controls had at least one genotype targeted by the nonavalent vaccine (p = 0.3). The majority of HPV16 variants (87.3%, 48/55) were of European lineage. The proportion of unique nucleotide substitutions was significantly higher in cases (83.3%, 10/12) compared with controls (34.1%, 15/44), (p < 0.003, χ2, OR 9.7, 95%CI 1.7-97.7). CONCLUSIONS: Virological factors may account for the differences in CCs observed in younger compared with older women. All CCs in young women in this study had preventable 9vHPV types, which is important messaging for health provider adherence to new cervical screening guidelines.

Vaginal bleeding in children: A retrospective audit at a tertiary paediatric gynaecology service.

AIM: The aim of this study was to describe the clinical features and investigations of vaginal bleeding in prepubertal children. METHODS: We performed a retrospective case series of children under the age of 10 who presented with vaginal bleeding to our institution between 2018 and 2019. RESULTS: There were 32 cases identified during the timeframe, with a mean age of 5.5 years (standard deviation 3.2 years, range 5.5 days to 9.6 years). Vulvovaginitis was the most common diagnosis (n = 12, 37.5%), followed by precocious puberty (n = 5, 15.6%). Uncommon but serious causes were vaginal rhabdomyosarcoma (n = 1), and sexual abuse (one patient presenting with gonorrhoea and one with a non-accidental injury). Vaginoscopy was performed in nine patients (28.1%) for various reasons, and a vaginal foreign body was identified in two patients (6.3%). All the patients who had a serious cause of bleeding (neoplasm or sexual assault) or who required specific treatment (precocious puberty, lichen sclerosus, urethral prolapse) presented with red flags on history and/or examination: recurrent episodes of vaginal bleeding, heavy bleeding, associated general symptoms (poor feeding and growth), presence of thelarche, abdominal mass, associated profuse vaginal discharge and abnormal genital examination (skin changes, urethral prolapse or protruding mass from the vagina). CONCLUSIONS: A thorough history-taking and clinical examination aiming at identifying red flags may help to discriminate between benign causes of vaginal bleeding, where no further investigations are indicated, and alternative diagnoses with a poor outcome and/or requiring specific treatment and additional investigations.

Understanding adolescent girls' and young women's health-seeking for female genital cosmetic surgery: How can clinicians help their patients?

AIM: This study aimed to understand why adolescent girls and young women (AGYW) would seek consultation with a health professional about genital appearance concerns and/or request female genital cosmetic surgery (FGCS). The information derived from these participant interviews can inform clinical practice and help clinicians better navigate consultations with young women and girls requesting FGCS. METHODS: A qualitative exploratory study was conducted using in-depth, semi-structured interviews with AGYW (n = 11) in Victoria, Australia. Participants comprised 11 AGYW who sought consultation with a health professional when aged 13-19 years for genital appearance concerns and/or requests for FGCS. Key themes were identified using a thematic analysis approach. RESULTS: Of 11 participants, five had undergone FGCS between the ages of 13 and 23 years. Key reasons for seeking a consultation identified in the interviews included: ideas about what 'normal' genitals look like, experiences of sexual harassment and bullying, and concerns about genital appearance developing before sexual debut. CONCLUSIONS: It is important to understand why AGYW want to access these procedures, given the risks involved, and that FGCS is not recommended by paediatric specialist organisations. Understanding why AGYW seek consultation for FGCS can help inform clinical practice, and the views expressed by participants in this study can help clinicians who work in this area to better support their patients.

Determining a threshold measurement of endometrial thickness for asymptomatic postmenopausal women: A tertiary centre case series.

BACKGROUND: An incidental finding of a thickened endometrium on ultrasound in the postmenopausal patient without bleeding is a common presentation to gynaecological services; however there is limited evidence to guide clinical practice as to when hysteroscopic evaluation and endometrial sampling is required. AIMS: To determine the endometrial thickness at which endometrial sampling is indicated in asymptomatic postmenopausal women referred with thickened endometrium on ultrasound. MATERIALS AND METHODS: A single-centre retrospective case series of postmenopausal women without bleeding undergoing hysteroscopy was conducted. Logistic regression was used to examine the association between a range of variables and pre-malignant or malignant pathology and endometrial thickness. The optimal endometrial thickness threshold was identified to maximise model sensitivity. RESULTS: A total of 404 postmenopausal women were included in this study, having undergone a hysteroscopy at the study site between 1 July 2008 and 30 June 2018. The mean (SD) age of patients at presentation was 65 (9.09) years and the mean body mass index was 29.86 kg/m2 (6.52). Of these women, nine (2.2%) were diagnosed with endometrial carcinoma and seven (1.7%) had endometrial hyperplasia with atypia. The most common histopathological finding was of a benign endometrial polyp (153: 37.9%). When including hyperplasia with or without atypia in histopathology of interest, a cut-off of ≥9 mm provides the greatest sensitivity (83.3%) and specificity (63.8%) for a diagnosis of pre-malignant or malignant pathology (classification accuracy of 64.8%; area under the receiver operating characteristic: 0.7358, 95% CI: 0.6439, 0.8278) in this cohort. CONCLUSIONS: Using an endometrial thickness of ≥9 mm can be used as a cut-off for endometrial sampling in postmenopausal women without bleeding.

Quality of life of adolescents with menstrual problems in Klang Valley, Malaysia: a school population-based cross-sectional study.

OBJECTIVE: To describe the prevalence of menstrual problems (heavy menses bleeding, dysmenorrhoea and oligomenorrhoea) and its impact towards quality of life among adolescents in Klang Valley, Malaysia. DESIGN: Cross-sectional study. SETTING: Adolescent girls at secondary schools in the Klang Valley, Malaysia. POPULATION: 729 adolescents aged between 13 and 18 years. METHOD: A questionnaire survey using Menorrhagia Questionnaire and Paediatric Quality of Life-Teen Report Ages 13-18 (PedsQL). MAIN OUTCOME MEASURES: Self reports of menstrual bleeding patterns, morbidities and effect on quality of life. RESULTS: The prevalence of menstrual problems among adolescents was 63.9% in the Klang Valley. Adolescents with menstrual problems had significant lower mean total score of PedsQL (70.23±13.53 vs 76.36±14.93, p=0.001), physical health summary score (74.10±16.83 vs 79.00±15.86, p<0.001) and psychosocial health summary score (68.05±14.27 vs 73.21±13.09, p=0.001) compared with those without menstrual problem. Adolescents experiencing heavy menses bleeding had the lowest physical and emotional function. Those with oligomenorrhoea had the lowest social function, whereas those with dysmenorrhoea had the lowest school function. Cigarette smoking, alcohol and medical illness had lower health-related quality of life, whereas taking oral contraceptive pills for menstrual problems was associated with higher scores in these adolescents. CONCLUSION: Menstrual problems among adolescents have a significant impact on their quality of life. It is probably wise to screen them at the school level, to identify those with low functional scores and to refer them for proper management at a tertiary adolescent gynaecology centre.

When pain is not the whole story: Presenting symptoms of women with endometriosis.

BACKGROUND: Endometriosis affects one in nine Australian women of reproductive age, and is often associated with pain and infertility. However, many women may be asymptomatic, or present with alternative symptoms. AIM: To identify reasons for initial specialist referral among patients with endometriosis. MATERIAL AND METHODS: Patients were identified as having endometriosis intraoperatively based on International Classification of Diseases coding. Operation reports were reviewed and graded for severity of disease. This cohort was then retrospectively audited to identify reasons for initial referral to the general gynaecology, endosurgery, gynae-oncology, reproductive medicine outpatient departments (OPD) at the Mercy Hospital for Women in Melbourne between 1 February 2015 and 31 December 2016. RESULTS: Three hundred patients were identified as having endometriosis at laparoscopy, including 90 women with Stage IV disease. Patients were a mean (SD) age of 33.1 (7.6) years. While pain remained a common reason for referral (61.7% of referrals), 36.7% of women with Grade IV disease did not have pain included in their referral letter. Severe disease was associated with increased age (regression coefficient 0.05; 95% CI: 0.03-0.07, P < 0.01), but not with pain symptoms. Women referred with ovarian cysts or masses were more likely to be diagnosed with severe disease (regression coefficient 0.69; 95% CI: 0.37-1.01, P < 0.01). CONCLUSION: Although pelvic pain is not a good predictor for a diagnosis of endometriosis, it remains a common symptom among women with the disease. However, more than one in three patients with Grade IV endometriosis presented without mention of pain symptoms, encouraging clinicians to adopt a broader approach to the presenting symptoms of endometriosis.

Pelvic pain: What are the symptoms and predictors for surgery, endometriosis and endometriosis severity.

BACKGROUND: Chronic pelvic pain (CPP) is a common condition which significantly impacts the quality of life and wellbeing of many women. Laparoscopy with histopathology is recommended for investigation of pelvic pain and identification of endometriosis with concurrent removal. Never-the-less, the association between endometriosis and pelvic pain is challenging, with endometriosis identified in only 30-50% of women with pain. AIMS: To explore the predictors for undergoing surgery, for identifying endometriosis and endometriosis severity in a cohort of women with CPP. MATERIALS AND METHODS: This study forms part of the Persistent Pelvic Pain project, a prospective observational cohort study (ANZCTR:ACTRN12616000150448). Women referred to a public gynaecology clinic with pain were randomised to one of two gynaecology units for routine care and followed for 36 months with 6-monthly surveys assessing demographics, medical history, quality of life, and pain symptoms measured on a Likert scale. Operative notes were reviewed and endometriosis staged. RESULTS: Of 471 women recruited, 102 women underwent laparoscopy or laparotomy, of whom 52 had endometriosis (n = 37 stage I-II; n = 15 Stage III-IV). Gynaecology unit, pelvic pain intensity and lower parity were all predictors of surgery (odds ratio (OR) 0.342; 95% CI 0.209-0.561; OR 1.303; 95% CI: 1.079-1.573; OR 0.767; 95% CI: 0.620-0.949, respectively). There were no predictors identified for endometriosis diagnosis and the only predictor of severity was increasing age (OR 1.155; 95% CI: 1.047-1.310). CONCLUSIONS: Gynaecology unit and pain intensity were key predictors of undergoing laparoscopy; however, pain severity did not predict endometriosis diagnosis or staging. These findings indicate the need to review current frameworks guiding practice toward surgery for pelvic pain.

Role of cross-campus multidisciplinary team meetings in decision-making for children and adolescents with differences of sex development/intersex.

AIM: Management of children with differences/disorders of sex development (DSD) is complex with limited evidence to guide clinical decisions. Regular multidisciplinary team meetings were set up in Sydney and Melbourne paediatric hospitals to enable systematic peer review of complex decision-making. We aim to describe the workload and role of these meetings. METHODS: The multidisciplinary team forum includes invited representatives from endocrinology, urology, gynaecology, genetics, psychology, social work, clinical ethics, laboratory and hospital executive and meetings occur 1-3 times monthly. Descriptive data were collected from de-identified meeting referrals and minutes between August 2012 to August 2018 (Sydney) and January 2014 to August 2018 (Melbourne). RESULTS: A total of 192 referrals (142 new and 50 follow-ups) aged 1 week to 17 years were discussed across the two sites. 46, XY DSD (n = 81) was the most common sub-classification. Consideration of surgical options and optimal management of gonads with malignant potential were amongst the common reasons for referral to the multidisciplinary team meetings. Surgical interventions were considered but not recommended after review for 38 of 154 (24.7%) procedures. Gonad retention to allow potential functional benefit was recommended in 15/46 (32.6%) referrals. Evidence of premalignant or malignant changes was found in 20/57 (35%) gonads removed, with dysgenetic features and atrophy/streak features in 6 (10.5%) and 27 (47.4%) gonads respectively. CONCLUSION: Formal DSD multidisciplinary team meetings provide a framework and opportunity for multi and interdisciplinary discussions amongst representatives from several specialities to help make complex decision-making.

The persistent pelvic pain study: Factors that influence outcomes in women referred to a public hospital with chronic pelvic pain - A study protocol.

BACKGROUND: Persistent pelvic pain affects between 10-20% of women with a significant impact on their physical and mental health, sexual relationships, families and society. Estimates of the cost to women and the community is over $9 billion/annum. Although endometriosis is considered a leading cause of pelvic pain, no symptoms reliably allow the identification of those with and without endometriosis. Furthermore, the significance of mild endometriosis is now debated. The optimal clinical approach for pelvic pain and endometriosis remains unclear, with increasing evidence of other contributing factors such as central sensitisation. Studies to date have significant limitations due to their sample size, relatively short follow-up, and inclusion of only women with laparoscopically identified endometriosis. AIMS: To undertake a real-world study of women referred with pain to gynaecology outpatients of a women's hospital and explore factors influencing three-year outcomes. MATERIALS AND METHODS: Five hundred women will be randomised to one of two gynaecology units. The units will provide routine clinical care but their approaches to management of women with pelvic pain and endometriosis differ: one with skilled endoscopic gynaecologists has greater emphasis on surgery, the other, gynaecologists have more medical expertise in managing pain and menstrual problems. Participants will complete six-monthly questionnaires regarding pain and quality of life for three years. This information will not be available to clinicians. Their medical care will be followed from their medical records. The cost of outpatient care and admissions will be calculated. Data will be analysed using STATA software with appropriate post hoc tests. Australian and New Zealand Clinical Trials Registry (ANZCTR:ACTRN12616000150448).

A Challenge in Diagnosis and Management: Uterine Torsion in Childhood.

BACKGROUND: Uterine torsion is a rare event, which mostly reported in females with a gravid uterus and is exceptionally rare in children. CASE: A 9-year-old girl presented with 3 days of intermittent lower abdominal pain. Ultrasound revealed an ovarian mass, but laparotomy revealed an ischemic enlarged ovary and uterus rotated 180°. No reperfusion occurred after 60 minutes. A subtotal hysterectomy and right salpingoophorectomy were thus performed. CONCLUSION: Uterine and adnexal torsion presents with symptoms similar to those of adnexal torsion. Delays in diagnosis and referral continue to be an issue, resulting in suboptimal outcomes. Uterine torsion, although exceedingly rare in childhood, appears to occur only in the setting of ovarian masses, which provide the impetus for the rotational force to the elongated cervix of the prepubertal uterus.

Cardiometabolic Risk Factors in Adolescents with Polycystic Ovary Syndrome.

It is well-established that adults with polycystic ovary syndrome (PCOS) have an increased prevalence of several cardiometabolic risk factors, including obesity, insulin resistance, type 2 diabetes mellitus, and dyslipidemia. Accumulating data suggest that these risk factors are already present in adolescence in patients with PCOS. This has major implications for the management of this population since the timely identification of these risk factors is essential for preventing cardiovascular disease in adulthood. The present review summarizes the existing evidence regarding the prevalence of traditional and non-traditional cardiometabolic risk factors in adolescents with PCOS.

A Multicenter Cross-Sectional Study of Malaysian Females With Congenital Adrenal Hyperplasia: Their Body Image and Their Perspectives on Feminizing Surgery.

OBJECTIVE: To explore the impact of congenital adrenal hyperplasia (CAH) on body image in Malaysian females with CAH and to understand the perspectives of these young women and their parents toward feminizing genitoplasty (FG). DESIGN: Multi-center cross-sectional study. SETTING: Two tertiary medical centers in Malaysia. PARTICIPANTS: A total of 59 patients with CAH who were raised as females and more than 10 years old, and their parents. METHODS: The CAH respondents completed the validated and translated Body Image Disturbance Questionnaires (BIDQ). All CAH respondents and their parents underwent semi-structured interviews to explore their views on FG. MAIN OUTCOME MEASURES: Body image disturbance score and perspectives on FG. RESULTS: The 59 CAH respondents consisted of 12 children, 29 adolescents, and 18 adults. The majority were of Malay ethnicity (64.4%) with classical CAH (98.3%) and had undergone FG (n = 55, 93.2%). For the BIDQ scores, the median score (interquartile range) for general body image was 1.29 (0.71), range 1.00-3.29, whereas the genital appearance score was 1.07 (0.39), range 1.00-4.29, revealing a greater concern for general body parts over genitalia. With regards to FG, it was perceived as necessary. Infancy and early childhood were perceived as the best timing for first FG by both respondents and parents, most preferring single-stage over 2-stage surgery. CONCLUSIONS: General body appearance concerns were greater than for genital appearance, with more impact on the patients' lives. Contrary to much international opinion, feminizing surgery was perceived as necessary and appropriate by CAH respondents and their families, and should be offered in infancy or early childhood. Future qualitative studies are recommended.

Gynaecology problems in puberty.

With the onset of puberty a range of problems may be encountered by the young girl. Some of these include a range of gynaecological issues relating to delayed onset of puberty, delayed menarche, atypical pubertal changes and the identification of anomalies of the genital tract. The distinction between physiological events and pathological problems is important to avoid unnecessary distress and anxiety. The onset of cyclic hormonal changes also provokes a number of "non-gynaecological" problems - where the link to cyclic hormonal events is often overlooked and an important opportunity to potentially intervene and assist is missed. From a global perspective there are a range of problems that are particularly encountered with the onset of puberty including the risks of sexual violence, which in the setting of having achieved the age of reproductive potential result in unplanned pregnancies, unsafe abortions and adolescent pregnancy all of which pose life threatening risks. Sex education in its broadest sense is important for all young people. Access to contraception for adolescents is vital, such that clinicians across all streams of health care who are involved in the care of young people should take the opportunity to educate and provide this care.

Malaysian Females With Congenital Adrenal Hyperplasia: Surgical Outcomes and Attitudes.

Background: Girls born with congenital adrenal hyperplasia have virilized external genitalia. There is considerable debate regarding both the outcomes of feminizing genitoplasty and timing of the surgery in this population. Objective: To investigate outcomes of females 46,XX individuals with CAH in Malaysia, the surgical outcomes of feminizing genitoplasty (FG) and their attitudes toward surgery. Study Design: This is a cross-sectional study involving the two main tertiary centers in Malaysia. All 46,XX patients with CAH and raised female, who had undergone FG were identified and invited to participate. Data on socio-demographic, medical profiles, and attitudes toward surgery were collected. A standardized evaluation of the external genitalia was undertaken including the anatomic and cosmetic evaluation by independent gynecologists. Results: Of 61 individuals identified, 59 participated-consisting of children (n = 12), adolescents (n = 29) and adults (n = 18). All but one had classical CAH (98.3%) and had undergone FG (n = 55, 93.2%) with surgery mostly undertaken by pediatric surgeons trained in DSD work (n = 44, 74.6%). Complications overall were low (20.3%), with repeat surgery rate of 9.1%. External genital examination was performed in 38 participants. Overall 36.8% had absent clitoral glands and 39.5% had a persistent urogenital sinus and in 10.5%, no vaginal orifices were seen. Poor cosmetic outcomes were present in 42.1% with 55.3% recommended for further assessment under general anesthetic. Almost half participants did not venture an opinion on FG, those who did varied from having a positive attitude toward it (18 participants) to 3 opining that it should not be done, or avoided or delayed. From the participants, 35.5% preferred FG to be done early in life compared to 44.0% of the parents. Conclusions: The reoperation rates of the feminizing genitoplasty surgeries were low however due to the anatomic and cosmetic outcomes, reassessment of the external genitalia of these CAH patients may be required once they consider becoming sexually active as they may require further treatment. Many factors such as cultural sensitivities and access to medical treatment and late diagnoses have an impact on attitudes toward FG.

TP63-truncating variants cause isolated premature ovarian insufficiency.

Premature ovarian insufficiency involves amenorrhea and elevated follicle-stimulating hormone before age 40, and its genetic basis is poorly understood. Here, we study 13 premature ovarian insufficiency (POI) patients using whole-exome sequencing. We identify PREPL and TP63 causative variants, and variants in other potentially novel POI genes. PREPL deficiency is a known cause of syndromic POI, matching the patients' phenotype. A role for TP63 in ovarian biology has previously been proposed but variants have been described in multiorgan syndromes, and not isolated POI. One patient with isolated POI harbored a de novo nonsense TP63 variant in the terminal exon and an unrelated patient had a different nonsense variant in the same exon. These variants interfere with the repression domain while leaving the activation domain intact. We expand the phenotypic spectrum of TP63-related disorders, provide a new genotype:phenotype correlation for TP63 and identify a new genetic cause of isolated POI.

The characteristics of women recommended a laparoscopy for chronic pelvic pain at a tertiary institution.

BACKGROUND: Clinician and patient factors impact on the management of chronic pelvic pain (CPP) with medical, surgical or combined approaches possible, although none have proven superior. AIMS: To understand the characteristics of women offered laparoscopic pelvic surgery for CPP. MATERIALS AND METHODS: We performed an observational study of women referred with CPP. They were asked to complete a study questionnaire regarding their symptoms, medical history, quality of life and pain catastrophisation. Examination and ultrasound findings were collected from patient records. Gynaecologists who recommended a laparoscopy completed a survey detailing their reasoning at the time of booking. The outcomes were investigated using a Cox proportional hazards ratio (HR) model. RESULTS: Of 211 participants, 59 (28%) were booked for laparoscopic surgery during the study timeframe. Factors increasing the rate of laparoscopy included severe dysmenorrhoea (Cox HR = 1.94; P = 0.017), unsuccessful trial of hormonal therapy (Cox HR = 1.81; P = 0.044), prior abdominal surgery (Cox HR = 1.79; P = 0.030), prior pelvic laparoscopy (Cox HR = 2.00; P = 0.007) and past diagnosis of endometriosis (Cox HR = 5.44; P = 0.010). Abnormal vaginal examination (Cox HR = 2.86; P = 0.019) and ultrasound probe tenderness (Cox HR = 2.52; P < 0.001) also increased the likelihood of surgery. Surgical and non-surgical patients did not differ in family history, quality of life or pain catastrophisation. Of gynaecologists' questionnaires, 75% were returned. Results indicated they were most influenced by the severity or duration of pain and least by examination or ultrasound findings. CONCLUSIONS: The characteristics of women booked for surgery were in keeping with the features evidence suggests increases the risk of pathology. There were some discrepancies between patient characteristics elicited in the questionnaires and those indicated by gynaecologists to influence their decision.

Identification of variants in pleiotropic genes causing "isolated" premature ovarian insufficiency: implications for medical practice.

Next-generation sequencing (NGS) is increasingly being used in a clinical setting for the molecular diagnosis of patients with heterogeneous disorders, such as premature ovarian insufficiency (POI). We performed NGS of ~1000 candidate genes in four unrelated patients with POI. We discovered the genetic cause of "isolated" POI in two cases, both of which had causative variants in surprising genes. In the first case, a homozygous nonsense variant in NBN was causative. Recessive function-altering NBN variants typically cause Nijmegen breakage syndrome characterized by microcephaly, cancer predisposition, and immunodeficiency, none of which are evident in the patient. At a cellular level, we found evidence of chromosomal instability. In the second case, compound heterozygous variants in EIF2B2 were causative. Recessive EIF2B2 function-altering variants usually cause leukoencephalopathy with episodic decline. Subsequent MRI revealed subclinical neurological abnormalities. These cases demonstrate that variants in NBN and EIF2B2, which usually cause severe syndromes, can cause apparently isolated POI, and that (1) NGS can precede clinical diagnosis and guide patient management, (2) NGS can redefine the phenotypic spectrum of syndromes, and (3) NGS may make unanticipated diagnoses that must be sensitively communicated to patients. Although there is rigorous debate about the handling of secondary/incidental findings using NGS, there is little discussion of the management of causative pleiotropic gene variants that have broader implications than that for which genetic studies were sought.

Spontaneous resolution of labial adhesions in pre-pubertal girls.

AIMS: This study sought to observe the rate and timing of spontaneous resolution of labial adhesions that had been diagnosed in pre-pubertal girls. The secondary aim was to evaluate the conservative approach to management of labial adhesions that has been advocated by the Gynaecology Department, by assessing the rates of concurrent uro-gynaecological symptoms in this population, as well as parent satisfaction with their child's management. METHODS: A retrospective chart review was performed of all patients diagnosed with labial adhesions in the Department of Paediatric and Adolescent Gynaecology between 2000 and 2017. Patients and their parents (depending on the age of the patient at the time of this study) were then invited to participate in follow-up surveys and questionnaires and clinical examination. RESULTS: Of 148 girls identified, the median age of the follow-up participants (n = 45) was 6.1 years (2.6-27.2 years), compared with that of the entire cohort of 7.4 years (1-27 years). After a median follow-up period of 2.6 years (0.4-20.7 years), 40% (18/45) of girls reported and/or had findings that supported resolution of labial adhesions without treatment. Two parents (4%) sought treatment elsewhere after their appointment. A history of UTI was reported in 30% (14/45) of patients, and 16% (7/45) had a known history of vulvovaginitis. CONCLUSIONS: Our findings support the natural history of spontaneous resolution of labial adhesions. Concurrent uro-gynaecological conditions that developed were successfully treated according to standard treatments. A conservative approach to the management of labial adhesions is associated with very low rates of parental concern and intervention.