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Objective: To determine the proportion of pregnancies resulting in birth that were conceived with the use of clomiphene citrate (CC) and the frequency of multiple pregnancy., Design: Whole-of-population cohort study, constructed through data linkage. Comprehensive Australian Government records of dispensed medications were linked to state Perinatal Registry records for all births of at least 20 weeks' gestation., Setting: The state of South Australia., Patient(s): Women who maintained pregnancy for at least 20 weeks and gave birth between July 2003 and December 2015, a total of 150,713 women with 241,561 pregnancies., Intervention(s): Not applicable., Main Outcome Measure(s): Ongoing pregnancy occurring in proximity to CC, defined as dispensing from 90 days before to the end of a conception window derived from newborn date of birth and gestational age., Result(s): Linkage to dispensed prescription records was achieved for 97.9% of women. Women who conceived with CC tended to be older and socioeconomically advantaged and more likely than other women to have a history of miscarriage. Ongoing pregnancies associated with CC comprised 1.6% of the total; 5.7% were multiple births (mostly twins, 94.6%) compared with 1.5% in the remainder (98.5% twins)., Conclusion(s): In South Australia, 1.6% of pregnancies (1 in 60) of at least 20 weeks' gestation were conceived proximal to CC dispensing. Of these, 5.7% were multiple pregnancies. This takes the proportion of women who achieved an ongoing pregnancy with medical assistance from 4.4%, based on reports from assisted reproductive technology clinics, to 6% in total., (Copyright © 2021 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: In Australia, fertility treatment is partly or wholly reimbursable under federal benefits schemes, without restrictions on age, number of treatment cycles or existing family size. In this study, we aimed to characterize the potential need for and use of fertility treatments in a population-based cohort of young Australian women., Methods: We conducted structured interviews with 974 members of a cohort constructed by tracing all female infants born at a single general hospital in Adelaide between 1973 and 1975. The main outcome measures were pregnancy history, difficulty becoming pregnant and assistance sought to become pregnant., Results: Of 657 women aged 30-32 who had sought pregnancy, 24% reported difficulty becoming pregnant and 26% had lost at least one pregnancy. Ovulatory problems (16%) and male fertility problems (13%) were common among those with difficulty. Over half of the women who had difficulty conceiving (58%) sought assistance, largely from specialists (53%). Consultations, tests and education only were common (22%), as were IVF/ICSI (17%). Close to a third (28%) of those seeking assistance were treated only with clomiphene, as were two-thirds (67%) of women with ovulatory problems., Conclusions: In this study, almost a quarter of women in their early 30s reported difficulty conceiving, and over a quarter reported pregnancy loss. This suggests that a significant proportion of young women experience substantial difficulties becoming pregnant. Our findings highlight the need to continue to document the range of women's reproductive experiences and to monitor fertility and treatment-seeking trends.

Study Question: Are reproductive, metabolic or psychological health profiles of women with clinically diagnosed polycystic ovary syndrome (PCOS) different from those with undiagnosed PCOS?Summary Answer: Obtaining a clinical diagnosis of PCOS is strongly linked to the experience of fertility problems, but not clinical depression or poor metabolic health, although these were highly prevalent in women with PCOS irrespective of when they were diagnosed.What Is Known Already: PCOS is an endocrine disorder that is relative common, but heterogeneous in presentation. This may impact on the pathways to diagnosis and timely treatment.Study Design, Size, Duration: A cross-sectional analysis of a community-based cohort of 974 women, established retrospectively when women were around 30 years of age.Participants/materials, Setting, Methods: In this cohort of women born in Adelaide, South Australia, half of women who met the Rotterdam criteria for PCOS were previously undiagnosed. We compared women with prior clinical diagnosis of PCOS, those diagnosed through participation in this research, and the remainder in the cohort. Sociodemographic characteristics, reproductive, metabolic and psychological health, including medical conditions and medications were considered. Logistic regression was undertaken to identify independent predictors of prior clinical diagnosis.Main Results and the Role Of Chance: There were 56 women with a prior clinical diagnosis of PCOS (5.7%) and a further 64 (6.6%) were undiagnosed until study entry. The great majority of women with a prior diagnosis of PCOS reported having had problems with periods (95%) and excess body hair (63%). Corresponding proportions for women undiagnosed until study participation were slightly lower (81% and 45%, respectively). Although the proportion of women attempting or achieving pregnancy was similar across all groups, those with a prior diagnosis of PCOS were four times more likely to have reported difficulties becoming pregnant than those undiagnosed (odds ratio = 4.05, 95% CI 1.74-9.45) and frequently sought medical assistance. Metabolic problems were higher in both PCOS groups compared to women without PCOS. In both PCOS groups, the prevalence of clinical depression was 50% higher than in those with no PCOS (P = 0.021).Limitations, Reasons For Caution: The number of women who were diagnosed with PCOS both prior to and during the study limited statistical power available to detect modest differences between the PCOS groups. Some women in the group classified as not having PCOS may have remained undiagnosed, but any bias from this source would contribute to more conservative findings.Wider Implications Of the Findings: Findings reinforce the need for early detection of PCOS symptoms from adolescence, ensuring timely diagnosis and appropriate health care. The high prevalence of depression among clinically diagnosed and undiagnosed women with PCOS suggests this is a feature of the condition and supports recent recommendations in the international PCOS guidelines to screen all women with PCOS for depression and anxiety.Study Funding/competing Interest(s): This work was supported by a project grant (2017) from the National Health and Medical Research Council of Australia (NHMRC) Centre for Research Excellence in Polycystic Ovary Syndrome (Grant ID APP1078444). R.C.F. and J.C.A. were supported by Robinson Research Institute Lloyd Cox Career Development Fellowships (2018). Establishment of the cohort was funded by an NHMRC Strategic Award No. 465455, a Career Development Award in Population Health (No. 349548) and the Australian Research Council (Future Fellowship FT100101018) awarded to M.J.D. All authors declared no conflict of interest.Trial Registration Number: N/A. [ABSTRACT FROM AUTHOR]

Introduction: Women with polycystic ovary syndrome are susceptible to depression and anxiety and so may also be at risk for postnatal depression. This study investigates whether women with polycystic ovary syndrome have an elevated risk of postnatal depression.Material and Methods: Cross-sectional data for parous women (n = 566) were available from a birth cohort. Polycystic ovary syndrome was diagnosed using the Rotterdam criteria. Details of reproductive history, pregnancy, birth, and postnatal depression were obtained through structured interview. Comparisons were made between women with and without polycystic ovary syndrome using logistic regression analysis, including the investigation of interactions.Results: A positive but statistically non-significant association was found between polycystic ovary syndrome and postnatal depression (odds ratio 1.6, 95% confidence interval 0.9-2.9). Compared with their counterparts, women with polycystic ovary syndrome were substantially more likely: to have difficulty conceiving (odds ratio 5.2, 95% confidence interval 2.9-9.4), to have conceived with medical assistance (odds ratio 11.6, 95% confidence interval 5.5-24.4), and to have pregnancy complications (gestational diabetes, pregnancy-induced hypertension, or preeclampsia; odds ratio 2.0, 95% confidence interval 1.1-3.5). Where women with polycystic ovary syndrome had a history of miscarriage or conceived with medical assistance, the combination interacted (p = 0.06 and p < 0.05, respectively), with over half of such women having postnatal depression.Conclusions: Although women with polycystic ovary syndrome may not have an excess risk of postnatal depression overall, those who had suffered a miscarriage or required medical assistance to conceive were at substantially elevated risk. Findings point to vulnerability inherent in polycystic ovary syndrome being amplified, either by stressful experiences on the pathway to pregnancy/childbirth or by specific fertility treatment regimens. [ABSTRACT FROM AUTHOR]

Study Question: Does fertility treatment influence cognitive ability in school aged children, and does the impact vary with the type of treatment?Summary Answer: The available high-quality evidence indicates that specific treatments may give rise to different effects on cognitive development, with certain treatments, including ICSI, associated with cognitive impairment.What Is Known Already: Previous reviews of the literature concerning cognitive outcomes among children conceived with medical assistance have concluded that study findings are generally 'reassuring', but limited attention has been paid to the quality of this research. In addition, no review has separately assessed the range of treatment modalities available, which vary in invasiveness, and thus, potentially, in their effects on developmental outcomes.Study Design, Size, Duration: A systematic review was undertaken. We searched PubMed, PsycINFO and the Educational Resources Information Centre database to identify English-language studies published up until 21 November 2016.Participants/materials, Setting, Methods: Two authors independently reviewed identified articles, extracted data and assessed study quality. Studies were eligible if they assessed cognitive development from age 4 years or more, among children conceived with fertility treatment compared with either children conceived naturally or children born from a different type of fertility treatment. Where available, data were extracted and reported separately according to the various components of treatment (e.g. mode of fertilization, embryo freezing, etc.). Risk of bias was assessed using the Newcastle-Ottawa Scale, with a score ≥7/9 indicative of high quality.Main Results and the Role Of Chance: The search identified 861 articles, of which 35 were included. Of these, seven were rated high quality. Most studies (n = 22) were subject to selection bias, due to the exclusion of children at increased risk of cognitive impairment. Among high-quality studies, there was no difference in cognitive outcomes among children conceived with conventional IVF and those conceived naturally. Findings among high-quality studies of children conceived with ICSI were inconsistent: when compared with children conceived naturally, one study reported lower intelligence quotient (IQ; 5-7 points, on average) among ICSI children whereas the remaining two high-quality studies reported no difference between groups. Furthermore, among the three high-quality studies comparing children conceived with ICSI compared with conventional IVF, one reported a significant increase in the risk of mental retardation, one reported a small difference in IQ (3 points lower, on average) and one no difference at all. There were scant studies examining exposure to embryo freezing, or less invasive treatments such as ovulation induction without IVF/ICSI.Limitation, Reasons For Caution: Most existing studies had methodological limitations including selection bias and/or failure to address confounding by family background. In addition, a meta-analysis could not be performed due to heterogeneity in the assessment of cognitive outcomes. These factors impeded our ability to synthesize the evidence and draw reliable conclusions.Wider Implications Of the Findings: The conflicting findings among studies of children conceived with ICSI require clarification, in light of the increasing use of this technique for reasons other than male-factor infertility. Further population-based studies are needed that utilize contemporary data to examine specific aspects of treatment and combinations of techniques (e.g. ICSI with frozen embryo cycles). Importantly, studies should include the complete group of children exposed to treatment.Study Funding/competing Interest(s): A.R.R. is supported by a Career Development Fellowship from the National Health and Medical Research Council of Australia. L.J.M. is funded by a fellowship from the Heart Foundation of Australia. The authors declare there are no competing interests.Trial Registration Number: Not applicable. [ABSTRACT FROM AUTHOR]

Monitoring the safety of intracytoplasmic sperm injection (ICSI) has been impeded by uncertainties regarding the extent to which offspring health is influenced by paternal characteristics linked to male infertility or the processes that ICSI treatment entails. Few studies examining long-term health and developmental outcomes in children conceived with ICSI have considered the influence of paternal infertility adequately. In the available literature, large population-based studies suggest underlying male factors, and the severity of male factor infertility, increase the risk of mental retardation and autism in offspring, as does the ICSI procedure itself, but these findings have not been replicated consistently. Robust evidence of the influence of male factors on other health outcomes is lacking, with many studies limited by sample size. Nevertheless, emerging evidence suggests children conceived with ICSI have increased adiposity, particularly girls. Further, young men conceived with ICSI may have impaired spermatogenesis; the mechanisms underlying this remain unclear, with inconclusive evidence of inheritance of Y chromosome microdeletions. The current inconsistent and often sparse literature concerning the long-term health of children conceived with ICSI, and the specific influence of male infertility factors, underscore the need for concerted monitoring of children conceived with this technique across the lifespan. With the rapid expansion of use of ICSI for non-male factors, sufficiently large studies that compare outcomes between groups conceived with this technique for male factors versus non-male factors will provide critical evidence to elucidate the intergenerational impact of male infertility. [ABSTRACT FROM AUTHOR]