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Ulipristal acetate (UPA) was introduced as a novel progesterone receptor modulator as effective therapy for symptomatic fibroids. Randomised clinical trials established its effectiveness in the management of heavy menstrual bleeding due to uterine leiomyomas. The trials did not find any significant evidence of clinical harm to the participants. Recently, however, there have been reports of liver injury necessitating liver transplant in women who have had UPA treatment. This has led to the suspension of UPA as one of the medical therapies in the treatment for uterine fibroids while the European Medicines Agency (EMA) conducts a review of liver injury risk with its use. The European Medicine Agency safety committee has advised that women should stop taking 5 mg UPA and that no new patients should commence treatment with the medicine until the ongoing review is completed. In this article, we review the rise of UPA as one of the emerging medical therapies for symptomatic uterine fibroids and the subsequent reports of adverse events leading to the suspension of its use.

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).Cross-sectional observational study.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).A self-reporting questionnaire was used to collect data on relationship and sexual experiences.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).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.

The apparent gender differences in favor of women in the risk of contracting and dying from coronavirus disease 2019 (COVID-19), and the fact that such trends have also been observed in recent epidemics including severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), have prompted the obvious question: Are the reasons life-style or biological? True, women generally make healthier lifestyle choices as compared to men. Women do not smoke or drink as much as men, and they have a lower burden of those diseases (heart disease, diabetes or chronic lung conditions) that are known to be significant factors in the higher death rates among men with COVID-19. But there is compelling evidence for a role for biological factors. Genes are likely to play an important role. The X chromosome, of which women possess two, contains the largest number of immune-related genes of the whole human genome, theoretically giving women double the advantage over men in mounting an efficient and rapid immune response. A fundamental difference between women and men is their hormonal milieu, and it is not unreasonable to suppose that the dominant female hormone estrogen could influence the response to infection. In this paper we evaluate the evidence and mechanisms by which estrogen could provide protection to women from a variety of viruses, perhaps including the coronavirus that causes COVID-19.

Study question What is the role of endocrine stimulation therapy prior to mTESE in men with hypogonadism and non obstructive azoospermia (NOA)? Summary answer In hypogonadal men there is a positive correlation between change of serum Testosterone (ΔT) before and after stimulation, and a successful mTESE. What is known already NOA is the most common cause of azoospermia and it is often associated with hypogonadism and testicular failure. It is common practice for endocrine stimulation therapies such as gonadotropines or selective estrogens receptor modulators to be used prior mTESE; however there is currently paucity of data regarding their efficacy. Study design, size, duration Retrospective analysis on infertile men with hypogonadism (defined as T Participants/materials, setting, methods Retrospective study on infertile men who underwent mTESE with or without prior endocrine stimulation therapy. Hypogonadism was defined as serum testosterone (T) level Main results and the role of chance One-hundred-sixty-eight men underwent mTESE out of which 59 men received endocrine stimulation therapy for NOA between 2015–2020. Among them, we selected men with hypogonadism defined as serum T Testosterone levels significantly increased after endocrine stimulation (6.3±3.3nm/L vs 11.7±7.4nm/L) with mean change in serum testosterone (ΔT) of 5.7 nm/L (–5.5–23.3, N35). In the stimulated group, pre-operative serum T levels were significantly higher (11.7±7.4 vs 7.8±3.0 p:0.007) as compared to unstimulated men but the success rate of mTESE did not differ significantly (16/40–40%) vs 13/31–42%). Men with Klinefelter syndrome demonstrated significant differences with regards to age, lower T levels, higher FSH and LH levels, lower Johnsen score and success rates compared to other causes of NOA. Comparing men who had successful mTESE vs unsuccessful mTESE - higher T and lower FSH and LH seemed to correlate with successful sperm retrieval. Among men who received endocrine stimulation therapy the ΔT before and after stimulation seemed to correlate with successful sperm retrieval (AUC:0.701, SE:0.089, p:0.043). In the stimulated group a ΔT>3.5nm/L showed a significant association with successful mTESE(p:0.041). Limitations, reasons for caution Retrospective study limitations. Wider implications of the findings: Our study shows a significant improvement of serum T following endocrine stimulation therapy. Overall, in hypogonadal men, the hormonal stimulation seems not to be related to a higher success rate of mTESE but our data do suggest a positive correlation between ΔT before and after stimulation, and a successful mTESE. Trial registration number Not applicable

Study question Is there a difference in treatment outcome between gonadotrophin releasing hormone (GnRH) pump or hMG for women with Type 1 anovulation undergoing ovulation induction? Summary answer Treatment with GnRH was more efficient compared to hMG, with fewer number of cycles to pregnancy, fewer days of stimulation and fewer cycle cancellations. What is known already Whilst there is a lot of information on ovulation induction in WHO type II anovulation (PCOS), type 1 anovulation is under-represented in research. WHO type 1 anovulation is characterised by low pituitary gonadotrophins and oestradiol. Treatment options used to include induction of ovulation using gonadotrophins (hMG) or the Gonadotrophin hormone releasing hormone (GnRH) pump delivering pulsatile GnRH. Since the withdrawal of GnRH pump, options have become limited. One study reveals that monofollicular cycles are lower and cycle cancellation higher in women with Type 1 anovulation women treated with gonadotrophins. Study design, size, duration: This is a single centre retrospective cohort study. All women with a diagnosis of WHO type 1 anovulation attending the Reproductive Medicine Unit at the University College London Hospital who received ovulation induction treatment using either hMG or GnRH pump between 1993 and 2020 were included in the study Participants/materials, setting, methods 147 women with WHO type 1 anovulation were included in the study. Diagnosis was based on the presence of primary or secondary amenorrhoea in combination with low gonadotrophins and oestradiol. Demographic and clinical data were obtained by reviewing medical records stored within an electronic database. A total of 599 treatment cycles were identified. Statistical analysis between the groups was performed using the independent T test and chi squared test. Main results and the role of chance 147 women with WHO type 1 anovulation underwent ovulation induction. hMG was used in 500 cycles (83.5%) and the GnRH pump in 99 cycles (16.5%). Per cycle started the pregnancy rate in the hMG cycles was 107/500 (21.4%) and in the GnRH pump cycles was 19/99 (19.2%) p = 0.36. Cycle cancellation was significantly greater in hMG than GnRH pump cycles (hMG 137/ 500 27.4% vs GnRH pump 17/99 17.2% p = 0.02). Over response was more common in hMG cycles than GnRH pump cycles (66/130 50.8% vs 3/16 18.8% p = 0.01). A total of 363/500 (72.5%) cycles in the hMG and 82/99 (82.8%) cycles in the GnRH pump group reached ovulation. There was no difference in the pregnancy rate after ovulation (hMG 107/363 29.5% vs GnRH pump 19/82 23.2% p = 0.15). The mean number of treatment cycles to achieve pregnancy was significantly fewer with the GnRH pump compared to hMG (1.8 (min 1 – max 3) vs 2.4 ( min 1 – max 8) p = 0.03).The mean days of stimulation required to reach ovulation was also significantly less with the GnRH pump compared to hMG (16.7 (min 8 – max 34) vs 23.4 (min 7 – max 72) p = Limitations, reasons for caution This is a retrospective cohort study and is reliant on the quality and quantity of the data entry at the time of clinical treatment. Wider implications of the findings: Ovulation induction for women with type 1 anovulation is now restricted to a single treatment, namely hMG. hMG is not as effective or optimal as GnRH. Reinstating GnRH in routine clinical practice should be promoted to allow more individualised treatment options and prevent the premature need for in vitro fertilisation.. Trial registration number NA

Combined (estrogen and a progestogen) hormone replacement therapy (cHRT) is associated with an increased risk of breast cancer, while estrogen replacement therapy is not. Whatever the underlying mechanism, it is the progestogen in cHRT that seems to increase the risk. Fear of breast cancer is a major limiting factor in the use of hormone replacement therapy, and when women discontinue cHRT because of side effects, the latter are often attributable to the progestogen component. cHRT is given to women with an intact uterus to protect against the effects of un-opposed estrogen such as an increased risk of endometrial cancer. Estrogen replacement therapy suffices for women with a prior hysterectomy. There is a clear distinction in risk and side effect profile between cHRT and estrogen replacement therapy. Apart from being the most effective treatment for menopausal symptoms, estrogen prevents osteoporosis, and may also have a potential role in prevention of Alzheimer’s Dementia, now the biggest killer of women in the United Kingdom. Evidence also suggests that progestogens could compromise the dementia-preventative effect of estrogen. Given the immense therapeutic and preventative potential of estrogen, the use of progestogens in cHRT needs re-appraisal. The levonorgestrel intrauterine system (LNg-IUS) could reduce breast cancer risk while protecting the endometrium. Other approaches to the safe use of progestogens await research.

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.

Context Clinical practice guidelines (CPGs) are key instruments to implement the practice of evidence-based medicine. We aimed to evaluate the methodological quality and variations in CPGs recommendations on the diagnosis and management of polycystic ovary syndrome (PCOS). Evidence Acquisition We searched MEDLINE, EMBASE, and CENTRAL until December 2020 for all evidence-based CPGs and consensus statements on PCOS. We extracted data in duplicate to map clinical recommendations across prespecified disease domains and assessed CPGs methodological quality of using the Appraisal of Guidelines, Research & Evaluation II tool. Evidence Synthesis We included 13 PCOS CPGs published between 2007 and 2018. CPGs recommendations were mostly focused on screening for and managing metabolic disease (12/13, 92%), followed by cardiovascular risk assessment (10/13, 77%). Mental health (8/13, 62%) and diagnosis in adolescents (7/13, 54%) were the least reported domains. Most CPGs had a high quality for scope and purpose description (12/13, 92%) while stakeholder’s involvement and applicability of recommendations to clinical practice were appropriate in only 2 CPGs (2/13, 15%). We identified inconsistency in recommendations on PCOS diagnosis in adolescents, optimal lifestyle interventions, hirsutism and acne treatments, interventions to reduce the risk of ovarian hyperstimulation syndrome, the frequency and screening criteria for metabolic and cardiovascular disease, and optimal screening tools for mental health illness in women with PCOS. Conclusion Current CPGs on the diagnosis and management of PCOS vary in their scope and methodological quality, which may hinder evidence translation into clinical practice. We identified disease domains with existing evidence gap to guide future research and guideline updates.

The global increase in life expectancy to 74 years for women, while the median age of the menopause remains at 51 years, means that an increasing number of women will live a significant portion of their adult lives in the menopause. The WHI publications in 2003/4 reported on the dangers of hormone replacement therapy, in particular with respect to breast cancer and dementia risk. This resulted in a dramatic reduction in hormone replacement therapy prescription and use. However, the findings from the WHI studies have been re-appraised, and the new perspective is reflected in the guidance published by NICE in 2015 in which they recommended that more women be offered hormone replacement therapy as the benefits are now perceived to outweigh the risks for most women. However, controversy continues to surround hormone replacement therapy, and there are probably few areas in medicine where the misuse of terminology causes quite as much confusion as in hormone replacement therapy. Commonly used terms such as ‘menopausal hormone therapy’ and ‘hormone replacement therapy’ lack specificity and there is an urgent need for correct terminology to accurately describe the hormones replaced.

Complications of early pregnancy, including pregnancy loss and threatened miscarriage, are common. Miscarriage affects almost one in five pregnancies and accounts for utilization of a significant proportion of healthcare resources. Women presenting with miscarriage should ideally be assessed, diagnosed, and managed in early pregnancy assessment units. They should be provided with comprehensive information about expectant, medical, and surgical management options, and helped to make informed decisions about their care. Early pregnancy loss can be a source of considerable distress to women and they should be provided with appropriate support and counselling. Recurrent miscarriage (RM) remains a challenge to patients and clinicians alike. Recognition of the psychosocial impact should prompt involvement of mental health specialists, counsellors, and social workers in patient management. Inconsistencies in definition (two or three consecutive miscarriages) confound research in RM. Although endocrinological, thrombotic, autoimmune, and uterine structural perturbations have been described in association with RM, antiphospholipid syndrome and embryonic karyotype abnormalities remain the two closest conditions for which a reasonable explanation can be offered to patients along with prognostication for future pregnancies. A diagnosis of RM has additional implications, not only for previable pregnancy loss, but an association with adverse obstetric and future maternal health outcomes. A global consensus on the definition of RM, along with phenotypic characterization of this heterogeneous condition would improve interpretation of available data and future research. A thorough understanding of the underlying molecular pathophysiological mechanisms in specific phenotypic categories of RM is the fundamental requisite for the advancement of this field.

As the epidemic of obesity spreads, increasing numbers of overweight or obese women are seeking fertility treatments as high body mass index (BMI) appears to be associated with delayed conception. Weight loss is recommended for women with high BMI before attempting natural conception or starting infertility treatment to improve fertility outcomes. Lifestyle interventions consisting of increased physical activity and caloric restriction have been shown to improve both metabolic and reproductive outcomes and remain the first-line therapy. Pharmacotherapy and bariatric surgery may be considered in resistant metabolic disease to other medical interventions.

Caesarean section (CS) rates continue to evoke worldwide concern because of their steady increase. The national caesarean section (CS) rate in the UK is almost 25%, having increased by 5.7% in the last 10 years. A rising primary CS rate is a significant contributor to this trend. The latest available data show that almost 1 in 5 women in the world now give birth by CS. The World Health Organisation states that, when medically justified, a caesarean section can effectively prevent maternal and perinatal mortality and morbidity . However, there is no evidence showing the benefits of caesarean delivery for women or infants who do not require the procedure. As with any surgery, caesarean sections are associated with short and long-term risk which can extend many years beyond the current delivery and affect the health of the woman, her child, and future pregnancies. These risks are higher in women with limited access to comprehensive obstetric care . There are two standard care pathways for women having childbirth following previous CS – Vaginal Birth After Caesarean (VBAC) or Elective Repeat CS (ERCS). Attempting a VBAC is a safe and appropriate choice that must be offered to most women who have had a prior caesarean delivery. Approximately 70–75% of women who attempt VBAC will have a successful vaginal delivery . Focused antenatal counselling sessions highlighting the risks and benefits of VBAC vs ERCS may impact upon the pathway a woman chooses. Continued counselling and discussion of relative risks versus benefits will also encourage patient choice and help support the woman throughout antenatal and intrapartum periods.

The mucopolysaccharide diseases are a group of heterogeneous, inherited conditions that are characterized by the deficiency of specific lysosomal enzymes. These lysosomal enzymes are responsible for the breakdown of glycosaminoglycans (GAGs), which are a key component of connective tissue. When lysosomal enzymes are deficient, the resultant build-up of GAGs impacts on cellular functioning. The resultant clinical manifestations are multisystemic, progressive, and life-limiting. Although each condition is characterized by its own constellation of symptoms; there is a great deal of heterogeneity and overlap in the clinical manifestations (both within and between mucopolysaccharidosis [MPS] subtypes). Increasing understanding of the genetic and biochemical basis of the MPS diseases has paved the way for a wave of exciting developments in their treatment and management. New treatments have changed the face of many of the MPS diseases; and as a result, management has moved beyond the pediatric clinic into the adult clinic. For the first time, individuals with MPS are living into adulthood with fewer limitations than the natural course of their disease would predict. It is essential that in this new age of MPS disease management, early diagnosis achieved and those at risk of having a child affected by one of these conditions are appropriately counseled in relation to their reproductive options. It is also important that individuals with MPS are counseled independently, at an appropriate age (or when they have capacity) about the basis of their disease and what this means for them. Here we discuss the diagnosis and inheritance of the MPS conditions; specifically focusing on genetic counseling requirements. We also discuss the outcomes of a research study, undertaken by the UK Mucopolysaccharide Disease Society, into the experiences of women with MPS who have had successful pregnancies.

Summary In spite of the significant increase in obstetric and neonatal interventions aimed at reducing asphyxia there is no reduction in the rate of cerebral palsy (CP). Metabolic acidosis occurs in 2% of all births and over 90% of such infants do not develop CP. About 10% of cases of CP are due to pathological events that occur after birth, 10–20% of cases are related to intrapartum events, and identifying the cause of the remaining 70% is an ongoing challenge for obstetricians and paediatricians. The original aim of continuous electronic fetal monitoring (EFM) was to prevent harm by detection of fetal hypoxia before it led to disability or death. It was soon realised that EFM had a high false-positive rate and there were no significant differences in outcome measures when compared with intermittent auscultation. The increased operative intervention rates associated with EFM were reduced if fetal scalp blood sampling (FBS) was performed to measure the pH. However, fetal blood sampling used for the diagnosis of intrapartum fetal hypoxia is time consuming and may be associated with equipment failure or inability to obtain a sample. As it is a single measurement it needs to be repeated, with consequent inconvenience to the woman and the staff. Additional or alternative methods are needed to help mothers and babies who, despite abnormal fetal heart rate patterns and clinical findings during labour and delivery, would not benefit from intervention. New methods of pulse oximetry and fetal ECG waveform analysis explore the possibility of continuous surveillance as an adjunct to EFM. Recent studies suggest that maternal pyrexia is associated with increased adverse fetal outcome. Monitoring of maternal temperature and its normalisation should be part of intrapartum care, to avoid fetal neurological injuries.

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.This is a single-centre, retrospective, cross-sectional study of women who underwent pubertal induction compared with a reference group.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.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.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 FCR1, 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.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.

Antral follicle count (AFC) variation was examined across the menstural cycle and its effect on clinical management assessed. In 79 women, AFC was documented in early (iAFC) and late follicular phase (sAFC). Absolute agreement between iAFC and sAFC and agreement for classification into categories of risk of extremes of ovarian response were examined. Ovarian stimulation protocols designed with iAFC and sAFC, and the predictive value of iAFC and sAFC for extremes of ovarian response, were compared in women undergoing ovarian stimulation. Significant differences were found between iAFC and sAFC (16 [IQR 9-24] versus 13 [IQR 7- 21]; P = 0.001), with moderate agreement for the classification into at risk of extremes of response (k = 0.525). Agreement for protocol selection based on either AFC (k = 0.750) and starting gonadotrophin dose was good (concordance correlation coefficient 0.970 [95% CI 0.951 to 0.982]). Predictive value for iAFC and sAFC was maintained for poor ovarian response and risk of ovarian hyperstimulation syndrome (OR 0.634 [0.427 to 0.920], 0.467 [0.233 to 0.935]) and (OR 1.049 [0.974 to 1.131], 1.140 [1.011 to 1.285]). Across the cycle, AFC varies but does not significantly affect ovarian stimulation protocol design and prediction of extreme ovarian response.

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.

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 antimullerian hormone levels. There was no correlation between baseline antimullerian 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.

Although spontaneous fertility and successful pregnancies have been reported in well-chelated and transfused women with beta thalassaemia major (BTM), majority of women are subfertile due to hypogonadotropic hypogonadism (HH). Little is known about the effect of iron overload on ovarian follicles and whether ovarian reserve is affected by the disease or treatment status. This study compares the markers of ovarian reserve in women with transfusion-dependent BTM over a period of ten years with healthy women from a control population.We performed a 10-year mixed (retrospective and prospective) longitudinal study in 17 women with transfusion-dependent BTM from our thalassaemia clinic between July 2007 to June 2017. The results were compared with 52 age-matched healthy women without any medical conditions (control population) attending our fertility clinic. Patient demographics, medical history, menstrual history, hormonal parameters (serum levels of FSH, estradiol, TSH and AMH) and antral follicle count were recorded in all women from both groups. Serum levels of ferritin, cardiac T2*, liver iron concentration, thyroid function (TSH) and liver function test results were also recorded at three different time points.Serum AMH levels, estradiol levels and antral follicle count were significantly lower in women with BTM compared with the control group (p 0.05 for all). Low AMH levels were noted in both groups of women (with and without HH) with a background of BTM. Serum AMH levels positively correlated with AFC in women with BTM.Serum AMH level and AFC were significantly lower in women with transfusion dependent BTM as compared to age-matched healthy controls suggesting a direct impact of the disease activity or iron overload on the ovary.

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.

Caesarean section (CS) has evolved from a procedure with considerable morbidity and mortality risks into one that is safe enough to be considered as a matter of maternal choice in high resource countries. Improvements in operative techniques, anaesthesia, intensive care, blood transfusion services and availability of antibiotics have all contributed to improved safety of the procedure for pregnant women. Rates of CS are rising all over the world and so are the rates of vaginal birth after caesarean (VBAC). Attempting a VBAC is a safe and appropriate choice that must be offered to most women who have had a prior caesarean delivery. Approximately 70–75% of women who attempt VBAC will have a successful vaginal delivery. However VBAC is associated with risks for both mother and the baby. The possibility of uterine rupture in labour ranges from 3 to 7 per 1000 pregnancies while the risk of perinatal death or severe morbidity should uterine rupture occur is higher with trial of vaginal delivery than with repeat caesarean delivery. These risks and the associated medico-legal sequelae have resulted in revised national and international guidelines with focus on antenatal counselling, individualised risk assessment as well as stringent facility and personnel requirements to conduct VBAC.

Uterine fibroids are the most common benign tumours in women of reproductive age group and are a cause of significant healthcare burden. Although surgical treatments have been the traditional gold standard for symptomatic uterine fibroids, several medical therapeutic approaches have been used to achieve symptom suppression in women who wish to preserve their uterus or are at elevated risk of complications during surgery. Medical therapies used for uterine fibroids include tranexamic acid, NSAIDs, contraceptive steroids, progesterone coil, GnRH analogues, aromatase inhibitors, SERMs and progesterone receptor modulators. The levonorgestrel containing intrauterine system reduces menstrual blood loss associated with fibroids, but drawbacks include the possibility of device expulsion and fitting difficulties. The use of GnRH agonists for 3-4 months prior to fibroid surgery can achieve reduction in uterine volume and fibroid size. They are beneficial in the correction of preoperative iron deficiency anaemia, if present, and reduce intra-operative blood loss. Although medical treatments provide effective symptom relief, women resorting to these therapies should be made aware of the high rates of future re-intervention. It is important for clinicians to recognise limitations of these therapies and that appropriate patient selection is of utmost importance.

The last two decades have witnessed tremendous advances in the field of reproductive medicine, especially assisted reproductive technology and stem cell research. As research continues in future, it is vital to ensure that individuals from all ethnic backgrounds are represented in the study populations so that the findings of the research can be generalised for the benefit of all. Many studies, however, have noted a trend of low participation rates amongst Asian women in reproductive research. Inequalities in the ethnicity of research participants can be a source of substantial bias, and have major ethical and scientific ramifications. Several factors such as educational status, fear of wrong-doing, communication barriers, and socio-cultural beliefs have been suggested to play a role. There is a need for further exploration of the factors influencing Asian women's decision to accept or decline participation in reproductive research and for development of effective targeted strategies for research recruitment with the aim of encouraging research participation as well as donation of cryopreserved embryos or other reproductive tissues.

Background Uterine-sparing surgical interventions have long been practiced as an alternative to hysterectomy in the management of severe postpartum haemorrhage (PPH); however, the risks of impairment of subsequent fertility from such procedures are unclear. Objective To evaluate the menstrual and fertility outcomes following radiological or conservative surgical interventions for severe PPH. Search strategy A systematic review of English and non-English articles using the Cochrane Library 2012, PubMed (1950–2012), Embase (1980–2012), and the National Research Register. The keywords used for our search included ‘fertility’, ‘reproductive outcome’, ‘postpartum haemorrhage’, ‘embolisation’, ‘hypogastric artery ligation’, ‘B-Lynch suture’, ‘stepwise uterine devascularisation’, ‘tamponade’, and ‘uterine compression sutures’. Selection criteria Studies including human female subjects with at least five cases. Data collection and analysis Independent extraction of articles by two authors using predefined data fields, including study quality indicators. Main results We identified 402 publications and after exclusions, 28 studies were included in the systematic review. Seventeen studies (675 women) reported on the fertility outcomes after uterine artery embolisation, five studies (195 women) reported on the fertility outcomes after uterine devascularisation, and six studies (125 women) reported on the fertility outcomes following uterine compression sutures. Overall, 553 out of 606 (91.25%) women resumed menstruation within 6 months of delivery. One hundred and eighty-three out of 235 (77.87%) women who desired another pregnancy achieved conception. Author's conclusions Uterine-sparing radiological and surgical techniques for the management of severe PPH do not appear to adversely affect the menstrual and fertility outcomes in most women; however, the number of studies and the quality of the available evidence is of concern.

AIM: The human embryo-maternal interface in the first trimester of pregnancy is an area of extensive tissue remodeling. Because collagen is the most abundant constituent of the extracellular matrix of the placental bed, successful invasion must involve its rapid turnover. We compared the nature and distribution of collagen fibrils in decidua basalis and parietalis. METHODS: We used a direct-vision hysteroscopic technique to obtain biopsies of the decidua basalis and parietalis from 11 women undergoing pregnancy termination in the first trimester. The biopsies were subjected to light, transmission and scanning electron microscopy, and immunohistochemical studies using mouse monoclonal antibodies against cytokeratin 7 and collagen types I, III and V. RESULTS: Collagen fibrils in the stroma of decidua basalis were significantly thicker when compared to those in decidua parietalis (56.48 ± 1.37 nm vs 45.64 ± 0.85 nm; P < 0.0001 [mean ± standard error]) between 9 and 12 weeks gestation, but this difference in thickness was not observed at gestations below 9 weeks. In basalis, the fibrils appeared disrupted at most places surrounding the decidual/trophoblast cells while a uniform regular arrangement was preserved throughout most of parietalis. CONCLUSION: There are differences in the ultrastructure of collagen fibrils between basalis and parietalis, with thicker and disrupted fibrils within abundant amorphous tissue in basalis, and thinner uniform fibrils in parietalis. These differences may reflect an adaptive response by decidua or a direct consequence of the invading trophoblast cells.

Metformin, an oral antihyperglycemic drug, acts as an insulin sensitizer in the treatment of type 2 diabetes mellitus. It has also been widely used in the treatment of polycystic ovary syndrome (PCOS) and gestational diabetes mellitus. Although randomized clinical trials have failed to establish its superiority over other forms of treatment, metformin continues to be a treatment option in specific subgroups of women either alone or as an adjunct with other therapies in management of PCOS.This narrative review was conducted to assess the present role of metformin in management of clinical conditions related to women's health. A PubMed search was conducted using the following terms: "metformin," "polycystic," "ovary," "Women's," "health," "gestational," "diabetes," "cancer," and "fertility," and all relevant studies were evaluated for accumulation of evidence.Metformin is used as a second-line drug for ovulation induction in women with PCOS who are resistant to clomiphene citrate. Metformin also forms one of the management options in women who need antiandrogen therapy without the need for contraception at the same time. Women with PCOS undergoing in vitro fertilization are likely to benefit from metformin therapy to reduce their risk of ovarian hyperstimulation syndrome. Metformin alone or in combination with insulin has been reported to have similar safety and efficacy to insulin for the treatment of GDM. There is growing evidence that metformin may be associated with a decreased risk of developing cancers and improved response to chemotherapy.

The last three decades have witnessed a dramatic increase in the use of assisted reproductive technology (ART) so that now, in developed countries, 1.7% to 4.0% of all children are born after ART. Although absolute risks appear small, data from prospective and retrospective studies indicate increased risks of adverse maternal and perinatal outcomes after ART as compared with spontaneous conception. Recent studies suggest that underlying maternal factors and subfertility play an important role in some of these outcomes rather than the ART procedure itself. A significant risk of assisted conception is multiple pregnancies, but even singleton pregnancies achieved by ART are at a higher risk of hypertensive disease, diabetes, prematurity, low birth weight, and perinatal mortality even after adjusting for confounders. Couples undergoing ART procedures should be counseled in advance regarding increased risks of pregnancy complications and higher rates of obstetric interventions. Although conflicting data exist, studies of children born from ART suggest increased rates of congenital malformations, imprinting disorders (Beckwith-Wiedemann syndrome and Angelman syndrome), and marginally increased risk of cancer. However, the current evidence is inadequate, and prospective long-term studies are needed to eliminate the effect of confounders and draw definite conclusions about the long-term outcomes after ART. The absolute risk of imprinting disorders remains small, and routine screening is not recommended at present. The long-term outcomes after ART are difficult to evaluate because of the variability in ART methods and data reporting, and there is a need for standardized methodology for follow-up after ART.

Fibroids, the most common tumor in women of reproductive age, impact negatively on women's health and quality of life, and have significant cost implications for their management. The current mainstay treatments are surgical (myomectomy and hysterectomy) and more recently radiological (UAE and focused ultrasound surgery). Hysterectomy is curative but precludes future fertility, whereas the impact of the other treatments on reproduction is uncertain. With women in Western societies deferring childbearing to their 30s and 40s, when fibroids are most symptomatic, there is a pressing need for a uterus-sparing medical therapy that is cheap, effective, and enhances reproductive potential. Serendipity and meticulous translational research has shown that progesterone augments fibroid proliferation, raising the possibility that progesterone receptor modulators could inhibit fibroid growth; this research has culminated in the emergence of ulipristal acetate (UA), a first-in-class, oral selective progesterone receptor modulator (SPRM) that has successfully completed phase III clinical trials. It has been licensed in Western Europe for short-term clinical use prior to surgery, and has shown efficacy with a significant reduction in uterine bleeding, fibroid volume, and improved quality of life, without the side effects associated with other medications such as gonadotropin-releasing hormone (GnRH) agonists. As with all new medicines, there are concerns surrounding UA, not least its effect on the endometrium and the long-term impact on general health and reproduction. Research to date has tended to be industry led, and therefore, there is a need for researcher/clinician-led studies to address the wider issues concerning SPRMs. UA may not turn out to be the "Holy Grail" of medical therapy in the treatment of symptomatic uterine fibroids, but it has rightly given cause for a huge optimism. Further laboratory and clinical research into PRMs and related compounds will no doubt lead to more refined medications.

Background: Discrepancies in the results from studies of early events in human trophoblast invasion of decidua have been acknowledged and are attributed largely to deficiencies in the accuracy of sampling of the decidual tissue used in the research. We describe a novel technique of biopsy of decidua parietalis and basalis that overcomes the issue of accuracy of site of the biopsy. Methods & results: :The technique is applicable to pregnancies undergoing first trimester surgical termination. Following cervical dilatation, a rigid hysteroscope is introduced into the cervical canal. The pressure of the saline distending medium shears the membranes of the gestation sac away from the decidua parietalis, leaving the pregnancy suspended at the site of the early placenta (the decidual basalis). Under direct vision a biopsy forceps is used to sample the decidua parietalis, and then the forceps is introduced beneath the gestation sac to sample the decidua basalis. Morphological and immunohistochemical studies have confirmed the accuracyof site and adequacy of the samples, with a 40% myometrial spiral artery success rate. Conclusion: This is a simple novel technique of decidual biopsy under direct vision which allows for high accuracy of the site of biopsy material, and therefore has the potential to revolutionize research on trophoblastedecidua interactions during the critical early stages of human pregnancy.

In normal labour, the fetal head presents with the occiput in lateral position in early stages of labour followed by anterior rotation in advanced labour. Malpositions of fetal head result when the occiput persists in a lateral or posterior position while malpresentations occur due to extension of the fetal head causing brow or face to present. Malpresentations of fetal head are usually diagnosed in labour and are associated with difficult labour and increased risk of operative intervention. Regular systematic clinical examinations to monitor progress of labour and fetal wellbeing are necessary once the diagnosis is confirmed. Although vaginal delivery is possible in many cases, caesarean section becomes necessary when the malposition or malpresentation persists and labour fails to progress.

Aim: Oxidative stress is thought to play a central role in the pathophysiology of various conditions affecting women's health, including cancer, preeclampsia and osteoporosis. On the back of animal experimentation, we sought to establish whether the oral administration of vitamin C at high doses to postmenopausal women would achieve the plasma antioxidant activity that could prevent osteoporosis. Methods: In our pilot study, we administered vitamin C at a dose of 10 grams daily to eight healthy postmenopausal women over a period of four weeks and measured their serum levels of vitamin C and crosslaps (markers of bone turnover) at baseline and then on a weekly basis. Results: We found an initial rise in the plasma levels of vitamin C, but these rapidly fell over four weeks and could not be sustained despite continued therapy, presumably due to limited absorption and possibly even augmented excretion. We found no discernable change in the serum levels of crosslaps in association with the consumption of high doses of vitamin C. Conclusion: Although vitamin C has antioxidant properties, when given orally, even at a high dose, the serum levels required for it to exhibit antioxidant activity cannot be attained. This approach holds no potential for the use of vitamin C in the prevention of osteoporosis, although other routes of administration could overcome this.

Epidemiological data suggest that diets rich in antioxidants protect against diseases associated with free radical damage, including cancer, cardiovascular disease and diabetes. Early observations also suggested that vitamin supplements with antioxidant properties, like vitamins C and E, could also prevent or ameliorate pre-eclampsia, but most large randomized clinical trials have failed to show any benefit. Vitamin C given orally, even at high doses, does not achieve sustained serum levels that might be required for effective antioxidant activity. This may explain the failure of the numerous clinical trials involving its use in pre-eclampsia, cancers, cardiovascular diseases, etc. Vitamin C supplementation to stave off pre-eclampsia, cancer and other diseases is a 'nutraceutical' industry-driven myth which should be abandoned. We do not dispute a role for oxidative stress in the pathophysiology of pre-eclampsia, nor the possibility of amelioration of the disease by an anti-oxidant given at the right time and in the correct dosage. We simply wish to make a case that the massive and expensive clinical trials of vitamins C and E should cease until further rigorous scientific research is undertaken.

Labor admission test (LAT) is performed at the onset of labor to establish fetal well-being in low-risk pregnancies and identify those fetuses who either may be hypoxic, needing delivery or at risk of developing hypoxia during labor so that additional measures of fetal surveillance can be instituted to prevent adverse outcomes. We searched the literature in Medline, Cochrane Library and PubMed using the words— cardiotocograph, cardiotocogram, nonstress test, vibroacoustic stimulus (VAS), amniotic fluid index (AFI), Doppler, labor admission test, labor admission cardiotocography (CTG) and reviewed four randomized controlled trials (RCTs) and three systematic reviews to summarize the current evidence regarding use of LAT. Although the existing RCTs and systematic reviews do not favor admission testing, we have critically reviewed the methodology used in some of these major studies. There is a need for robust RCTs with adequate sample size to evaluate the effectiveness of LAT. In clinical practice, while a normal admission CTG reassures the mother and the clinician about the health of the baby, an admission CTG with nonreassuring FHR pattern leads to careful review which may reveal a growth restricted or compromised fetus before onset of active labor when the risk of fetal hypoxia is higher with increasing frequency and duration of uterine contractions. Like in other obstetric interventions, the woman should be offered the choice of LAT after providing appropriate information and her informed decision should be respected.

The use of assisted reproductive techniques (ART) is on the rise throughout the world and the number of babies born as a result of ART has reached an estimated total of 5 million since the world's first, Louise Brown, was born in 1978. Data from many prospective and retrospective studies have suggested increased risks of adverse maternal, perinatal and long-term outcomes after ART compared to natural conception. Recent research suggests that underlying maternal factors rather than ART methods themselves play a significant role in causing such outcomes. Couples attempting ART need to be provided with accurate and reliable information on risks of adverse reproductive outcomes and reassured that absolute risks appear small. Clinicians need to remain vigilant about increased risk of pregnancy complications and formulate a plan of care for the woman, from periconception to the puerperium, which aims to prevent or minimise maternal and perinatal morbidity. This review attempts to summarise the available data on reproductive outcomes after ART and provide guidance to the obstetricians and primary care physicians about management of ART pregnancies.

The human embryo-maternal interface in the first trimester of pregnancy is an area of extensive tissue remodeling. Because collagen is the most abundant constituent of the extracellular matrix of the placental bed, successful invasion must involve its rapid turnover. We compared the nature and distribution of collagen fibrils in decidua basalis and parietalis.We used a direct-vision hysteroscopic technique to obtain biopsies of the decidua basalis and parietalis from 11 women undergoing pregnancy termination in the first trimester. The biopsies were subjected to light, transmission and scanning electron microscopy, and immunohistochemical studies using mouse monoclonal antibodies against cytokeratin 7 and collagen types I, III and V.Collagen fibrils in the stroma of decidua basalis were significantly thicker when compared to those in decidua parietalis (56.48 ± 1.37 nm vs 45.64 ± 0.85 nm; P0.0001 [mean ± standard error]) between 9 and 12 weeks gestation, but this difference in thickness was not observed at gestations below 9 weeks. In basalis, the fibrils appeared disrupted at most places surrounding the decidual/trophoblast cells while a uniform regular arrangement was preserved throughout most of parietalis.There are differences in the ultrastructure of collagen fibrils between basalis and parietalis, with thicker and disrupted fibrils within abundant amorphous tissue in basalis, and thinner uniform fibrils in parietalis. These differences may reflect an adaptive response by decidua or a direct consequence of the invading trophoblast cells.