Optimising health after early menopause.

The typical age at menopause is 50-51 years in high-income countries. However, early menopause is common, with around 8% of women in high-income countries and 12% of women globally experiencing menopause between the ages of 40 years and 44 years. Menopause before age 40 years (premature ovarian insufficiency) affects an additional 2-4% of women. Both early menopause and premature ovarian insufficiency can herald an increased risk of chronic disease, including osteoporosis and cardiovascular disease. People who enter menopause at younger ages might also experience distress and feel less supported than those who reach menopause at the average age. Clinical practice guidelines are available for the diagnosis and management of premature ovarian insufficiency, but there is a gap in clinical guidance for early menopause. We argue that instead of distinct age thresholds being applied, early menopause should be seen on a spectrum between premature ovarian insufficiency and menopause at the average age. This Series paper presents evidence for the short-term and long-term consequences of early menopause. We offer a practical framework for clinicians to guide diagnosis and management of early menopause, which considers the nature and severity of symptoms, age and medical history, and the individual's wishes and priorities to optimise their quality of life and short-term and long-term health. We conclude with recommendations for future research to address key gaps in the current evidence.

Long term pregnancy outcomes of women with cancer following fertility preservation: A systematic review and meta-analysis.

OBJECTIVE: As cancer survivorship increases, there is higher uptake of fertility preservation treatments among affected women. However, there is limited evidence on the subsequent use of preserved material and pregnancy outcomes in women who underwent fertility preservation (FP) before cancer treatments. We aimed to systematically review the long-term reproductive and pregnancy outcomes in this cohort of women. PATIENTS: Women who underwent any type of the following FP treatments: embryo cryopreservation (EC), oocyte cryopreservation (OC) and ovarian tissue cryopreservation (OTC)) before any planned cancer treatment. EVIDENCE REVIEW: We searched electronic databases (MEDLINE, Embase, Cochrane CENTRAL, and HTA) from inception until May 2021 for all observational studies that met our inclusion criteria. We extracted data on reproductive and pregnancy outcomes in duplicate and assessed the risk of bias in included studies using the ROBINS-I tool. We pooled data using a random-effects model and reported using odds ratios (OR) with 95% confidence intervals (CI). MAIN OUTCOME MEASURES: Our primary outcome was live birth rate and other important reproductive and pregnancy outcomes. RESULTS: Of 5405 citations, we screened 103 and included 26 observational studies (n = 7061 women). Hematologic malignancy was the commonest cause for seeking FP treatments, followed by breast and gynecology cancers. Twelve studies reported on OTC (12/26, 46 %), eight included EC (8/26, 30 %), and twelve reported on OC (12/26, 46 %). The cumulative live birth rate following any FP treatment was 0.046 (95 %CI 0.029-0.066). Only 8 % of women returned to use their frozen reproductive material (558/7037, 8.0 %), resulting in 210 live births in total, including assisted conceptions following EC/OC/OTC and natural conceptions following OTC. The odds for live birth was OR 0.38 (95 %CI 0.29-0.48 I2 83.7 %). The odds for live birth was the highest among women who had EC (OR 0.45, 95 %CI 0.14-0.76, I2 95.1 %), followed by the OTC group (OR 0.37, 95 %CI 0.22-0.53, I2 88.7 %) and OC group (OR 0.31, 95 %CI 0.15-0.47, I2 78.2 %). CONCLUSIONS: Fertility preservation treatments offered good long-term reproductive outcomes for women with cancer with a high chance to achieve a live birth. Further research is needed to evaluate the long-term pregnancy and offspring outcomes in this cohort.

Menopause knowledge and education in women under 40: Results from an online survey.

BACKGROUND: All women experience the menopause, yet education around the topic is limited. Studies conducted in women aged over 40 show that women have limited knowledge about the menopause. OBJECTIVES: This study aims to understand what women under 40 know about the menopause, how they have acquired this knowledge and where they think menopause education should be taught. This data will help to determine how to effectively deliver menopause education. DESIGN: A survey was designed that asked women under 40 what they know of, and their attitudes to, the menopause, using Qualtrics XM software. METHODS: The survey was advertised for 5 weeks on social media. Six questions related to menopause education were analysed. Responses between age groups under 20, 21-30 and over 30 were compared using a chi-square test. A thematic-style analysis was also conducted on a free-text question where answers referred to education. RESULTS: A total of 738 women's responses were included in the analysis; over 80% had no knowledge or just some knowledge of the menopause. Women over 30 used official websites (p = 0.017) and scientific literature (p = 0.047) significantly more than other age groups to learn about the menopause, while women under 20 were more likely to learn from family members (p = 0.002). These women felt education should start in schools. CONCLUSION: Many women under 40 have limited education of the menopause. Women under 20 are more passive in their approach to learning about the menopause compared with those over 30, who are more proactive. Menopause education strategies must start at school and extend beyond schools adopting a multifaceted approach; it is recommended that the workplace, social media and public health campaigns are used to deliver menopause education moving forward.

Variability of response to early puberty induction demonstrated by transverse uterine diameter measurement and a novel method of 3D breast imaging.

OBJECTIVE: Induction of puberty with exogenous oestrogen results in considerable variability in final uterine and breast volumes. We set out to quantify the variability of these two outcome measures with a view to establishing monitoring methods that could be used to individualise treatment protocols. DESIGN: A prospective observational study. PARTICIPANTS: Sixteen participants with pubertal delay and primary amenorrhoea, due to hypogonadism were recruited from paediatric gynaecology and endocrinology clinics at University College London Hospital. A standardised protocol of transdermal 17ß oestradiol (17ßE) was used (Evorel™), with a starting dose of 12.5 mcg increasing to 25 mcg (patch changed twice weekly) after 4 months. Follow up was every 2 months for a total of 8 months. MEASUREMENTS: Uterine dimensions using ultrasound, oestradiol concentrations and breast development assessed by both Tanner staging and 3D photographic imaging. RESULTS: After 8 months of treatment, the changes in oestradiol concentrations (0-174 pmol), uterine volume growth (4.4-16.4 ml) and breast volume (1.76-140.1 ml) varied greatly between individuals. Of uterine parameters, transverse uterine diameter was most closely associated with serum oestradiol levels at 8 months (beta standardised coefficient = 0.80, p = .001). Change in breast volume was associated with age of treatment initiation (beta standardised coefficient 0.55 p = .04). CONCLUSIONS: We demonstrate variation in response to exogenous oestrogen, emphasising the necessity for individualised dose titration. In the absence of sensitive oestradiol assays, uterine transverse measurements may be used as a surrogate marker of oestrogen sensitivity to guide early dose adjustment. 3D breast imaging may provide a quantitative assessment of breast development to complement Tanner breast staging.

SARS-CoV-2 infection in the first trimester and the risk of early miscarriage: a UK population-based prospective cohort study of 3041 pregnancies conceived during the pandemic.

STUDY QUESTION: Does maternal infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the first trimester affect the risk of miscarriage before 13 week's gestation? SUMMARY ANSWER: Pregnant women with self-reported diagnosis of SARS-CoV-2 in the first trimester had a higher risk of early miscarriage. WHAT IS KNOWN ALREADY: Viral infections during pregnancy have a broad spectrum of placental and neonatal pathology. Data on the effects of the SARS-CoV-2 infection in pregnancy are still emerging. Two systematic reviews and meta-analyses reported an increased risk of preterm birth, caesarean delivery, maternal morbidity and stillbirth. Data on the impact of first trimester infection on early pregnancy outcomes are scarce. This is the first study, to our knowledge, to investigate the rates of early pregnancy loss during the SARS-CoV-2 outbreak among women with self-reported infection. STUDY DESIGN, SIZE, DURATION: This was a nationwide prospective cohort study of pregnant women in the community recruited using social media between 21 May and 31 December 2020. We recruited 3545 women who conceived during the SARS-CoV-2 pandemic who were <13 week's gestation at the time of recruitment. PARTICIPANTS/MATERIALS, SETTING, METHODS: The COVID-19 Contraception and Pregnancy Study (CAP-COVID) was an on-line survey study collecting longitudinal data from pregnant women in the UK aged 18 years or older. Women who were pregnant during the pandemic were asked to complete on-line surveys at the end of each trimester. We collected data on current and past pregnancy complications, their medical history and whether they or anyone in their household had symptoms or been diagnosed with SARS-CoV-2 infection during each trimester of their pregnancy. RT-PCR-based SARS-CoV-2 RNA detection from respiratory samples (e.g. nasopharynx) is the standard practice for diagnosis of SARS-CoV-2 in the UK. We compared rate of self-reported miscarriage in three groups: 'presumed infected', i.e. those who reported a diagnosis with SARS-CoV-2 infection in the first trimester; 'uncertain', i.e. those who did not report a diagnosis but had symptoms/household contacts with symptoms/diagnosis; and 'presumed uninfected', i.e. those who did not report any symptoms/diagnosis and had no household contacts with symptoms/diagnosis of SARS-CoV-2. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 3545 women registered for the CAP-COVID study at <13 weeks gestation and were eligible for this analysis. Data for the primary outcome were available from 3041 women (86%). In the overall sample, the rate of self-reported miscarriage was 7.8% (238/3041 [95% CI, 7-9]). The median gestational age (GA) at miscarriage was 9 weeks (interquartile range 8-11). Seventy-seven women were in the 'presumed infected' group (77/3041, 2.5% [95% CI 2-3]), 295/3041 were in the uncertain group (9.7% [95% CI 9-11]) and the rest in the 'presumed uninfected' (87.8%, 2669/3041 [95% CI 87-89]). The rate of early miscarriage was 14% in the 'presumed infected' group, 5% in the 'uncertain' and 8% in the 'presumed uninfected' (11/77 [95% CI 6-22] versus 15/295 [95% CI 3-8] versus 212/2669 [95% CI 7-9], P = 0.02). After adjusting for age, BMI, ethnicity, smoking status, GA at registration and the number of previous miscarriages, the risk of early miscarriage appears to be higher in the 'presumed infected' group (relative rate 1.7, 95% CI 1.0-3.0, P = 0.06). LIMITATIONS, REASONS FOR CAUTION: We relied on self-reported data on early pregnancy loss and SARS-CoV-2 infection without any means of checking validity. Some women in the 'presumed uninfected' and 'uncertain' groups may have had asymptomatic infections. The number of 'presumed infected' in our study was low and therefore the study was relatively underpowered. WIDER IMPLICATIONS OF THE FINDINGS: This was a national study from the UK, where infection rates were one of the highest in the world. Based on the evidence presented here, women who are infected with SARS-CoV-2 in their first trimester may be at an increased risk of a miscarriage. However, the overall rate of miscarriage in our study population was 8%. This is reassuring and suggests that if there is an effect of SARS-CoV-2 on the risk of miscarriage, this may be limited to those with symptoms substantial enough to lead to a diagnostic test. Further studies are warranted to evaluate a causal association between SARS-CoV-2 infection in early pregnancy and miscarriage risk. Although we did not see an overall increase in the risk of miscarriage, the observed comparative increase in the presumed infected group reinforces the message that pregnant women should continue to exercise social distancing measures and good hygiene throughout their pregnancy to limit their risk of infection. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by a grant from the Elizabeth Garrett Anderson Hospital Charity (G13-559194). The funders of the study had no role in study design, data collection, data analysis, data interpretation or writing of the report. J.A.H. is supported by an NIHR Advanced Fellowship. A.L.D. is supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: support to J.A.H. and A.L.D. as above; no financial relationships with any organizations that might have an interest in the submitted work in the previous 3 years; no other relationships or activities that could appear to have influenced the submitted work. TRIAL REGISTRATION NUMBER: N/A.

Relationship and sexual experiences in women with early-onset oestrogen deficiency: Comparison between women with Turner syndrome and premature ovarian insufficiency.

OBJECTIVE: Age at first date and sexual intercourse have been observed to be delayed in women with Turner syndrome (TS), with delayed puberty being the main factor. We sought to assess relationship and sexual experiences comparing women with TS and premature ovarian insufficiency (POI). DESIGN: Cross-sectional observational study. PATIENTS: 302 women with TS and 53 women with karyotypically normal POI (median age 33.0 [15.0-78.4] and 26.3 [17.8-52.3], respectively). MEASUREMENTS: A self-reporting questionnaire was used to collect data on relationship and sexual experiences. RESULTS: Women with TS were older than women with POI (P = .002). Compared to women with POI, a smaller proportion of women with TS had ever had vaginal sexual intercourse (VSI) (40 [78.4%] vs 169 [58.1%], respectively, P = .006) and women with TS exhibited a delay in the median age at first relationship and VSI (POI 19.3 ± 0.4 vs TS 22.2 ± 1.1, P = <.001). Start of oestrogen replacement therapy at ≤ 14 years of age compared with > 14 years did not result in earlier relationship and sexual debut. After adjusting for age and diagnosis, induction of puberty, as opposed to spontaneous puberty, was associated with a delay in the median age at first relationship and VSI and a reduced probability of having VSI (Hazard ratio = 0.44 [95% confidence interval: 0.32-0.60], P = <.001). CONCLUSIONS: Turner syndrome and induction of puberty are associated with a reduced likelihood and a delay in relationship and sexual experiences. Women needing puberty induction and women with TS more than POI have a delayed mean age at first VSI compared to the general population.

Fracture rate in women with oestrogen deficiency - Comparison of Turner syndrome and premature ovarian insufficiency.

OBJECTIVE: Women with early-onset oestrogen deficiency are at risk of reduced bone mineral density (BMD). We sought to assess fracture history and BMD in women with Turner syndrome (TS) and premature ovarian insufficiency (POI). DESIGN: A cross-sectional observational study. PATIENTS: Two hundred and sixty seven women with TS (median age 34.3 years) and 67 women with POI (median age 28.1 years). MEASUREMENTS: A questionnaire was used to collect data on fracture history, co-morbidities and drug history including age at first oestrogen exposure. Clinical data included height, weight, serum vitamin D and hip and spine T-scores, which were adjusted for height and age. Fractures were subdivided into major osteoporotic fractures (MOF) and 'other' fracture types. RESULTS: Overall fracture rate was similar in women with TS and POI (82 [30.5%] vs 22 [32.8%] respectively, P = .74). Compared to women with POI, those with TS had more fractures at MOF sites (30.2% vs 52.7%, P = .012) and fewer phalangeal fractures (27.9% vs 9.8%, P = .005). There was no difference in BMD between women who sustained a fracture compared to those who did not. Women with TS who fractured were more likely to suffer from hearing impairment compared to those with no fracture (62.2% vs 48.1%, P = .045). CONCLUSIONS: TS is not associated with an overall excess risk of bone fracture. The higher rate of fractures at MOF sites in women with TS may be secondary to hearing impairment, thin cortical bone and abnormal bone remodelling.

Reduced uterine volume after induction of puberty in women with hypogonadism.

OBJECTIVE: Adequate uterine growth is an essential component of pubertal induction with exogenous oestradiol in those with hypogonadism. Poor uterine development will render the individual vulnerable in the context of fertility. We assessed uterine size using ultrasound in those who had undergone pubertal induction treatment compared with a reference group who had experienced spontaneous puberty. DESIGN: This is a single-centre, retrospective, cross-sectional study of women who underwent pubertal induction compared with a reference group. PATIENTS: Ninety-five women with hypogonadism who had previously undergone pubertal induction and were receiving maintenance oestrogen replacement as adults were recruited: 48 women with Turner syndrome, 32 with premature ovarian insufficiency and 15 with gonadotrophin deficiency. The reference group consisted of 35 nulliparous women attending with male factor subfertility with a normal pelvis on ultrasonography. MEASUREMENTS: Pelvic ultrasound was performed by a single observer. Uterine dimensions (total length, anterior-posterior (AP), transverse, uterine volume and fundal cervical AP ratio (FCR) measurements) were recorded. Clinical details were also recorded. RESULTS: Those with hypogonadism had significantly reduced uterine dimensions compared with the reference group (uterine length 64 mm vs 71 mm P = <.05, uterine volume 28.9 mL vs 43.9 mL P = <.05). All women in the reference group attained a mature uterine configuration with a FCR >1, compared with 84% of those with hypogonadism (P = .01). A total of 24% and 48% of the diagnostic group had total uterine length and uterine volume measurements less than the 5th percentile of the reference group, respectively. In a subgroup of 22 women in whom serum oestradiol concentrations could be analysed, there was a positive correlation between this parameter and uterine volume. CONCLUSION: Despite standard oestrogen therapy, uterine growth is often compromised in those with hypogonadism. Uterine health has historically been overlooked in pubertal induction protocols; however, with increasing options for fertility treatment, adequate uterine development is crucial. Given the variation in uterine size witnessed, a more tailored approach to treatment with regular monitoring of uterine dimensions should be advocated.

A critical assessment of case reports describing absent uterus in subjects with oestrogen deficiency.

OBJECTIVE: The dual diagnosis of hypoplastic uterus in association with ovarian dysgenesis is regularly reported but the pathogenesis of the association is unclear. The uterus, however, may be invisible to all imaging modalities without at least six months of exogenous oestrogen exposure in complete ovarian failure. We assessed all available case reports in this category to estimate whether the apparent association between primary ovarian insufficiency or Turner syndrome and Mullerian agenesis can be largely accounted for by oestrogen deficiency. DESIGN: A literature review of all cases in which an association between ovarian insufficiency or Turner syndrome and hypoplastic uterus has been reported. PATIENTS: PubMed was searched for all case reports associated with relevant key terms. In total, 22 publications with a total of 25 patients were identified and reviewed; 14 subjects had the normal female karyotype (46,XX), and 11 subjects had Turner Syndrome. MEASUREMENTS: Proportion of subjects who had been exposed to adequate oestrogen prior to the absent uterine diagnosis. RESULTS: A diagnosis of absent uterus was made prior to exposure to exogenous oestrogen in 22/25 (88%) of subjects with primary hypogonadism including 14/14 females with normal karyotype and 8/11 females with Turner syndrome. CONCLUSIONS: Oestrogen deficiency is a possible explanation for most subjects being reported as having Mullerian agenesis in association with Turner syndrome or primary ovarian insufficiency. In the presence of oestrogen deficiency, no conclusion can be made about the status of the uterus until adequate exposure to exogenous oestrogen has been completed and we suggest reassessment of the uterus when full adult dose has been reached towards the end of induction of puberty.

Effects of Estrogen Therapies on Outcomes in Turner Syndrome: Assessment of Induction of Puberty and Adult Estrogen Use.

CONTEXT: Turner syndrome (TS) is often associated with delayed puberty. To induce puberty, estrogen is administered in incremental doses at an age determined by age of presentation. After puberty, various types of maintenance estrogen replacement therapy (ERT) are used. OBJECTIVE: We sought associations between age of induction of puberty and type of ERT on adult health outcomes. DESIGN: Health surveillance data included blood profiles, bone density, and blood pressure. We assessed interactions between these data and age at first estrogen exposure in women with primary amenorrhea. We also assessed these data according to ERT subgroups [combined oral contraceptive pill (OCP), oral estrogen (OE), and transdermal estradiol (TE)] using data from each of 6679 clinic visits, controlling for age, body mass index, and height. SETTING: Adult TS clinic at University College London Hospital. PATIENTS: Of 799 women with TS, 624 had primary amenorrhea and 599 had accurate maintenance ERT data. MAIN OUTCOME MEASURES: Parameters of health surveillance derived from clinical guidelines. RESULTS: Estrogen start age was negatively correlated with adult bone density (spine: r = -0.20 and hip: r = -0.022; P ≤ 0.001). OCP users had higher blood pressure and an adverse lipid profile compared with other ERT subgroups. TE was associated with elevated liver enzymes and hemoglobin A1c compared with OE (P ≤ 0.01). CONCLUSIONS: An earlier age of induction of puberty may be beneficial for adult bone density. Given the high prevalence of hypertension in TS, the use of OCP for ERT should be limited. OE may be a benefit for steatohepatitis.

Outcome of ovarian stimulation for oocyte cryopreservation in women with Turner syndrome.

OBJECTIVE: To study the safety and efficacy of ovarian stimulation and oocyte cryopreservation as a method of fertility preservation in women with Turner syndrome (TS). DESIGN: Retrospective cohort study. SETTING: Reproductive medicine clinic. PATIENT(S): Seven women with TS who attended the clinic between 2011 and 2017. INTERVENTION(S): Ovarian stimulation and oocyte cryopreservation. MAIN OUTCOMES MEASURE(S): Number of oocytes cryopreserved, ovarian hyperstimulation syndrome. RESULT(S): The oocyte retrieval rates (mean ± SD, 9 ± 3.16) in women with TS were comparable to the published data from healthy women. The oocyte yield was higher than expected based on the low antimüllerian hormone levels. There was no correlation between baseline antimüllerian hormone or antral follicle count levels and the number of oocytes retrieved. CONCLUSION(S): Oocyte cryopreservation after ovarian stimulation appears to be safe and successful in women with mosaic TS who wish to consider fertility preservation.

Efficacy of intravaginal dehydroepiandrosterone (DHEA) for symptomatic women in the peri- or postmenopausal phase.

OBJECTIVE: There is uncertainty whether treatment with dehydroepiandrosterone (DHEA) decreases menopausal symptoms for women in the peri- or postmenopausal phase. A previous systematic review considering this subject suggested that DHEA may slightly improve sexual function compared with placebo (CS. Scheffers, S. Armstrong, AEP. Cantineau, C. Farquhar, V. Jordan Dehydroepiandrosterone for women in the peri- or postmenopausal phase. Cochrane Database of Systematic Reviews 2015, Issue 1. Art. No.: CD011066. DOI: https://doi.org/10.1002/14651858.CD011066.pub2). The purpose of this article is to review recent research investigating whether the use of DHEA, and in particular intravaginal DHEA (Prasterone®), improves sexual function. METHODS: We conducted an online search using Medline OVID for recent articles related to DHEA and menopause. We found 48 relevant publications, out of which 14 papers were original research, all related to the development and licensing of intravaginal DHEA. We critically analysed these 14 articles in relation to sexual function. RESULTS: All the randomised controlled trials assessed the efficacy of vaginal DHEA in women with vulvovaginal atrophy and showed that sexual dysfunction improved with treatment regardless of the level of dyspareunia at baseline. Treatment with DHEA was found to be superior to placebo and at least as efficacious as vaginal oestrogens in improving symptoms. CONCLUSION: Intravaginal DHEA appears to be a safe and effective treatment for menopausal vulvovaginal atrophy and dyspareunia in most women. Further studies are required before it can be recommended for women with a history of thrombosis, cardiovascular disease or hormone-sensitive neoplasms.

Risks of ovarian, breast, and corpus uteri cancer in women treated with assisted reproductive technology in Great Britain, 1991-2010: data linkage study including 2.2 million person years of observation.

OBJECTIVE: To investigate the risks of ovarian, breast, and corpus uteri cancer in women who have had assisted reproduction. DESIGN: Large, population based, data linkage cohort study. SETTING AND PARTICIPANTS: All women who had assisted reproduction in Great Britain, 1991-2010, as recorded by the Human Fertilisation and Embryology Authority (HFEA). INTERVENTIONS: HFEA fertility records for cohort members were linked to national cancer registrations. MAIN OUTCOME MEASURES: Observed first diagnosis of ovarian, breast, and corpus uteri cancer in cohort members were compared with age, sex, and period specific expectation. Standardised incidence ratios (SIRs) were calculated by use of age, sex, and period specific national incidence rates. RESULTS: 255 786 women contributed 2 257 789 person years' follow-up. No significant increased risk of corpus uteri cancer (164 cancers observed v 146.9 cancers expected; SIR 1.12, 95% confidence interval 0.95 to 1.30) was found during an average of 8.8 years' follow-up. This study found no significantly increased risks of breast cancer overall (2578 v 2641.2; SIR 0.98, 0.94 to 1.01) or invasive breast cancer (2272 v 2371.4; SIR 0.96, 0.92 to 1.00). An increased risk of in situ breast cancer (291 v 253.5; SIR 1.15, 1.02 to 1.29; absolute excess risk (AER) 1.7 cases per 100 000 person years, 95% confidence interval 0.2 to 3.2) was detected, associated with an increasing number of treatment cycles (P=0.03). There was an increased risk of ovarian cancer (405 v 291.82; SIR 1.39, 1.26 to 1.53; AER 5.0 cases per 100 000 person years, 3.3 to 6.9), both invasive (264 v 188.1; SIR 1.40, 1.24 to 1.58; AER 3.4 cases per 100 000 person years, 2.0 to 4.9) and borderline (141 v 103.7; SIR 1.36, 1.15 to 1.60; AER 1.7 cases per 100 000 person years, 0.7 to 2.8). Increased risks of ovarian tumours were limited to women with endometriosis, low parity, or both. This study found no increased risk of any ovarian tumour in women treated because of only male factor or unexplained infertility. CONCLUSIONS: No increased risk of corpus uteri or invasive breast cancer was detected in women who had had assisted reproduction, but increased risks of in situ breast cancer and invasive and borderline ovarian tumours were found in this study. Our results suggest that ovarian tumour risks could be due to patient characteristics, rather than assisted reproduction itself, although both surveillance bias and the effect of treatment are also possibilities. Ongoing monitoring of this population is essential.

Fertility preservation for medical reasons in girls and women: British fertility society policy and practice guideline.

Fertility preservation in the female poses several challenges due to the invasive nature of the techniques available to achieve it. The guideline aims to bring together the evidence available for the measures for fertility preservation and their outcome. The guideline addresses fertility preservation for medical reasons and includes both oncological and non-oncological causes. The techniques that the guideline considers are: (i) embryo and oocyte cryopreservation; (ii) ovarian tissue cryopreservation; (iii) GnRH agonist suppression and (iv) ovarian transposition. Although ovarian tissue cryopreservation is still considered experimental, the availability of this technique is gaining momentum as more live births from auto-transplanted tissue are reported. The guideline also highlights use of current treatment modalities for benign and malignant conditions that have a better fertility sparing profile. The guideline recommends a multidisciplinary approach in counselling women and girls about the risk to their fertility and available techniques. The role of psychological support in assisting women and girls with decision-making is highlighted. The guideline also highlights the risks associated with these techniques. Women need to be medically fit to undergo invasive procedures. Fertility preservation techniques are appropriate when treatment has curative intent. Fertility preservation is a subject of on-going research on outcomes of different techniques and at the time of publication, studies are still likely to emerge adding to the available literature.

The Turner syndrome life course project: Karyotype-phenotype analyses across the lifespan.

INTRODUCTION: Turner syndrome (TS) is associated with a variety of morbidities affecting nearly every body system, some of which increase in prevalence in adult life. The severity of clinical features in TS is roughly in parallel with the magnitude of the deficit of X-chromosome material. The aim of this study was to extend the established karyotype-phenotype relationships using data from a large adult cohort. MATERIALS AND METHODS: Karyotypes were available in 656 women with TS. 611 of whom could be classified into five major groups within the cohort: 45,X; 45,X mosaicism (45,X/46,XX); isochromosome X (isochromosome Xq); mosaicism 45,X/46,XY and ring X. Continuous variables such as blood pressure and biochemical markers from clinic data were binarised allocating those in the upper quartile to represent at-risk individuals. With the exception of bone mineral density T-score for which the lower quartile was allocated as at risk. For comorbidities, initiation of formal treatment was recorded. RESULTS: 45,X/46,XX had considerably lower frequency of comorbidities compared to 45,X. The isochromosome group experienced similar outcomes to 45,X. Novel associations were found between the XY mosaic karyotype group and a decreased prevalence of thyroid disease and severe hearing loss. A previously unreported increased incidence of metabolic syndrome was noted within the ring chromosome subgroup. CONCLUSIONS: Karyotype may play an important factor against stratifying risk of comorbidity in TS and should be taken into consideration when managing adults with TS. Further investigations of the isochromosome (Xq) and ring groups are necessary to further clarify their associations with comorbidities.

Oocyte cryopreservation: where are we now?

INTRODUCTION: Since the first live birth from oocyte cryopreservation three decades ago, oocyte cryopreservation has become an important component of ART. Cryopreservation techniques have evolved, leading to higher success rates and the introduction of oocyte cryopreservation into IVF clinics worldwide. Concurrently, there has been an increase in patient demand, especially for so-called 'social egg freezing' that allows women to preserve their fertility in anticipation of age-related fertility decline. This review addresses a need to evaluate the current status of oocyte cryopreservation. It explores current techniques and success rates, clinical applications, the rise of elective oocyte cryopreservation, and future implications. METHODS: A search was performed using Web of Science and PubMed databases for publications between January 1980 and December 2015. Keywords used included 'egg freezing', 'oocyte freezing', 'oocyte cryopreservation', 'oocyte vitrification', and 'fertility preservation'. RESULTS: The success rate of oocyte cryopreservation has risen, and the increasing use of vitrification offers has improved outcomes, with IVF pregnancy rates now similar to those achieved with fresh oocytes. There are conflicting opinions about the comparative success rates of open and closed vitrification. Patients are accessing and receiving oocyte cryopreservation for a wide range of indications, and there has been a marked increase in patient numbers and oocyte cryopreservation cycles. Oocyte cryopreservation for circumventing age-related infertility is becoming more widely accepted. CONCLUSION: Oocyte cryopreservation is an established component of ART, with vitrification now being the cryopreservation technique of choice. Increasing numbers of women undergo oocyte cryopreservation for both medical and social reasons. It is important to continue auditing outcomes and reporting long-term follow-up of children born from frozen-thawed oocytes.

Fertility preservation in women undergoing treatment for breast cancer in the UK: a questionnaire study.

OBJECTIVE: Fertility preservation is an important survivorship issue for women treated for breast cancer. The aim of this work was to examine the referral practices of health care professionals who treat women with breast cancer in the United Kingdom, and to investigate their understanding and knowledge of the fertility preservation options available. METHOD: An invitation to participate in a confidential, online questionnaire was e-mailed to surgeons, oncologists, and clinical nurse specialists who manage patients with breast cancer in the United Kingdom. RESULTS: n = 306 respondents. Factors which influenced whether fertility preservation options were discussed with a patient included the following: patient's age (78%), final tumor/nodes/metastasis status (37.9%); concern that fertility preservation would delay chemotherapy (37.3%); whether the patient had children (33.5%) or a partner (24.7%); estrogen receptor expression (22.6%), lack of knowledge regarding the available options (20.9%); and concern that fertility preservation would compromise the success of cancer treatment (19.8%). Twenty-seven percent did not know whether fertility preservation was available for their patients on the National Health Service. Nearly half (49.4%) of respondents said that gonadotropin-releasing hormone agonists were used for fertility preservation outside the setting of a clinical trial. Knowledge regarding the available options varied according to different members of the multidisciplinary team, with consultant oncologists better informed than consultant surgeons or clinical nurse specialists (p < .05). CONCLUSIONS: Many health care professionals have incomplete knowledge regarding the local arrangements for fertility preservation for patients with breast cancer. This may result in patients receiving inadequate or conflicting information regarding fertility preservation.

What is the best management strategy for a 20-year-old woman with premature ovarian failure?

The diagnosis of premature ovarian failure (POF) for a 20-year-old woman is devastating and will impact on many areas of her life. She deserves prompt confirmation of the diagnosis and accurate, honest information about the condition including the chances of conception and long-term health issues. She should be offered investigation of aetiology, although this may be hard to establish, and assessment of associated medical conditions. Oestrogen replacement should be advised for long-term use until the normal age of menopause, and she should be fully counselled on the benefits and risks of hormone replacement and her options of which preparation to take. Long-term follow-up is needed, and this is likely to require multidisciplinary input, including that from a gynaecologist, clinical psychologist and fertility team. POF may not be the appropriate terminology for this condition. Ovarian function often fluctuates in young women with POF, who may continue to menstruate occasionally and even conceive spontaneously. In view of this unpredictability, 'premature ovarian insufficiency' is a better description of the condition and carries a less negative connotation than 'ovarian failure' which can cause great distress. We recommend that the condition is termed 'premature ovarian insufficiency' (Clinical Endocrinology 2008;68:499).