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Research Question: Is fertility affected in women with multiple sclerosis (MS), and what is their usage of assisted reproductive technology (ART)?, Design: Data regarding multiple sclerosis and ART usage among patients with multiple sclerosis were extracted from the Israeli health maintenance organization Clalit Health Service database. Data regarding the diagnosis and treatment of multiple sclerosis, cause of infertility and use of fertility treatments were collected for all female multiple sclerosis patients aged 18-45 years between 2005 and 2021. Each patient was matched by age in a 1:10 ratio with reference women from the general population. The prevalence of infertility was compared between the two groups. Univariate and multivariate statistical tests were used to analyse the association between multiple sclerosis and fertility treatments including IVF and ovarian stimulation., Results: During the study period, 1309 multiple sclerosis patients were compared with 13,090 controls from the general population matched for age. The mean age was 29 ± 7.8 years. The overall prevalence of infertility was 15.4% (202/1309) among the multiple sclerosis patients, similar to the general population (16.3%; 2129/13090) (P = 0.436). The prevalence of IVF and ovarian stimulation was similar among multiple sclerosis patients and matched controls from the general population (8.1% versus 7.2%, P = 0.240; 13.8% versus 14.3%; P = 0.624, respectively)., Conclusions: The results show similar rates of infertility and fertility treatments among multiple sclerosis patients and the general population. This provides reassurance that fertility among women with multiple sclerosis does not differ from that of women in the general population, and indicates there is no excessive usage of ART., (Copyright © 2024 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Research Question: Is there any association between pelvic pain and primary caesarean delivery for patients undergoing assisted reproductive technology (ART) treatment?, Design: Retrospective cohort study of nulliparous patients with singleton pregnancies who underwent ART treatment and achieved a live birth between 2012 and 2020. Cases included patients diagnosed with pelvic pain. A 3:1 ratio propensity-score-matched population of patients without a history of pelvic pain was included as the control group. Comparative statistics were performed using chi-squared test and Student's t-test. A multivariate regression analysis was conducted to evaluate the association between pelvic pain and mode of delivery., Results: One hundred and seventy-four patients with pelvic pain were compared with 575 controls. Patients with pelvic pain reported a significantly longer duration of infertility compared with controls (18.98 ± 20.2 months versus 14.06 ± 14.06 months; P = 0.003). Patients with pelvic pain had a significantly higher rate of anxiety disorders (115 ± 21.9 versus 55 ± 31.6; P = 0.009) and use of anxiolytics at embryo transfer (17 ± 3.2 versus 12 ± 6.9; P = 0.03) compared with controls. In addition, patients with pelvic pain had a higher rate of primary caesarean delivery compared with controls (59.8% versus 49.0%; P = 0.01). After adjusting for multiple variables, a significant association was found between pelvic pain and increased odds of primary caesarean delivery (adjusted OR 1.48, 95% CI 1.02-2.1)., Conclusion: Patients with pelvic pain have significantly higher odds of primary caesarean delivery compared with patients without a history of pelvic pain. The infertility outpatient setting may be uniquely positioned to identify patients at risk for undergoing primary caesarean delivery, and could facilitate earlier intervention for pelvic floor physical therapy during the preconception and antepartum periods., (Copyright © 2024 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Research Question: Is intra-abdominal fat obesity associated with infertility?, Design: This study analysed data from the 2013-2018 National Health and Nutrition Examination Survey, with a total of 3013 women enrolled. The participants were divided into two groups: infertility and non-infertility. Differences between the two groups were analysed using a weighted Student's t-test or Mann-Whitney U-test for continuous variables, or a weighted chi-squared test for categorical data. Visceral adipose tissue area (VATA) was assessed by dual-energy X-ray absorptiometry. The independent association between infertility and log VATA was assessed by weighted multivariate logistic regression models. Subgroup analyses were performed to assess the strength of the results. Interaction tests were used to examine whether covariates interacted with log VATA to influence infertility., Results: Log VATA was significantly higher in the infertility group compared with the non-infertility group (P < 0.001). After adjustment for potential confounders, the results of multivariate logistic regression analysis revealed that an increase in log VATA was associated with increased prevalence of female infertility (OR = 2.453, 95% CI 1.278-4.792). Subgroup analyses showed this association in individuals aged <35 years (P = 0.002), Mexican-Americans (P = 0.033), non-hypertensive individuals (P = 0.013) and non-diabetic individuals (P = 0.003)., Conclusions: An enlarged VATA is associated with increased risk of infertility. The direct effect of VATA on female infertility needs to be clarified further to provide a basis for future prevention and treatment of female infertility., (Copyright © 2024 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

In 15-30% of couples with infertility, no abnormalities are found after the initial diagnostic work-up. The aim of this study was to investigate the prevalence of endometriosis in patients with unexplained infertility undergoing diagnostic laparoscopy in the current era of improved imaging and assisted reproductive technology. A systematic search of PubMed, Embase and Cochrane Central was conducted to identify all studies reporting on pelvic pathologies found by laparoscopy in couples diagnosed with unexplained infertility. Normal ovulatory cycles, normal semen analysis and an infertility period of ≥12 months were the minimum requirements for a study population to be included. The prevalence of endometriosis was 44%, and most lesions were classified as minimal or mild (74%). The prevalence rates of tubal factors and adhesions were 20% and 16%, respectively. The detection rate for pelvic abnormalities was higher in women with prior fertility treatment (75%) compared with women without prior fertility treatment (53%). Despite the significant improvements in imaging for the diagnosis of endometriosis and tubal factors over the last decades, the prevalence rates of endometriosis and tubal abnormalities remain high in patients with unexplained infertility. The high prevalence of endometriosis in this population is important for decision-making in patients who also suffer from pain symptoms suggestive of endometriosis., (Copyright © 2024 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Globally, fertility awareness efforts include well-established risk factors for fertility problems. Risks disproportionately affecting women in the Global South, however, are neglected. To address this gap, we conducted a systematic review and meta-analyses of relevant risk factors to examine the association between risk factors and fertility problems. MEDLINE, Embase, Cochrane Library, regional databases and key organizational websites were used. Three authors screened and extracted data independently. Studies assessing exposure to risk (clinical, community-based samples) were included, and studies without control groups were excluded. Outcome of interest was fertility problems, e.g. inability to achieve pregnancy, live birth, neonatal death depending on study. The Newcastle-Ottawa Scale was used to assess study quality. A total of 3843 studies were identified, and 62 were included (58 in meta-analyses; n = 111,977). Results revealed the following: a ninefold risk of inability to become pregnant in genital tuberculosis (OR 8.91, 95% CI 1.89 to 42.12); an almost threefold risk in human immunodeficiency virus (OR 2.93, 95% CI 1.95 to 4.42) and bacterial vaginosis (OR 2.81, 95% CI 1.85 to 4.27); a twofold risk of tubal-factor infertility in female genital mutilation/cutting-Type II/III (OR 2.06, 95% CI 1.03 to 4.15); and postnatal mortality in consanguinity (stillbirth, OR 1.28, 95% CI 1.04 to 1.57; neonatal death, OR 1.57, 95% CI 1.22 to 2.02). It seems that risk factors affected reproductive processes through multiple pathways. Health promotion encompassing relevant health indicators could enhance prevention and early detection of fertility problems in the Global South and disproportionately affected populations. The multifactorial risk profile reinforces the need to place fertility within global health initiatives., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Research Question: What is the effect of letrozole use in patients undergoing frozen embryo transfer (FET) with normal ovulation? Although the number of FETs is increasing, an optimal protocol for FET (particularly vitrified-warmed embryo transfer) is yet to be determined. The aim of this study was to evaluate letrozole use on patients with normal menstrual cycles compared with hormone replacement therapy (HRT) cycles and natural cycles., Design: The study involved 2849 patients. Patients were divided into three groups: HRT cycle (n = 2115), letrozole cycle (n = 532) and natural cycle (n = 202). Inverse probability of treatment weighting aimed to equate each group according to measured baseline covariates to achieve a comparison with reduced selection bias and live birth rate as main pregnancy outcome was analysed., Results: In the crude analysis, the letrozole group had a higher live birth rate compared with the HRT cycle (OR 1.18, 95% CI 1.06 to 1.33) and natural cycle (OR 1.24, 95% CI 1.11 to 1.41); after adjusting for confounding factors, live birth rate was consistently higher in the letrozole group. Moreover, the biochemical pregnancy, clinical pregnancy, ongoing pregnancy and full-term delivery rates were higher in the letrozole group., Conclusion: For infertile women with normal menstrual cycle undergoing FET, mildly stimulated cycles with letrozole present a relatively large advantage compared with HRT cycle and natural cycle, with higher live birth pregnancy, indicating that letrozole administration could improve pregnancy outcomes in this population., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Research Question: Are there any associations between the variants of FSHR c.2039 G>A (p. Ser680Asn, rs6166) and LHCGR c.935A>G (p. Asn312Ser, rs2293275) and ovarian reserve, ovarian response, clinical pregnancy rate and POSEIDON group?, Design: A total of 210 infertile women were enrolled in this prospective study. The gene variants were analysed by the Sanger method. The clinical parameters were analysed based on genotypes., Results: The frequency of heterozygous and homozygous G allele for FSHR c.2039 G>A in the low prognosis group was significantly higher than that in other response groups (P = 0.034); there was no significant association between LHCGR c.935 A>G and ovarian response. Moreover, the serum anti-Müllerian hormone (AMH) concentration, antral follicle count (AFC), oocytes retrieved, metaphase II (MII) oocytes and two-pronuclear (2PN) oocytes in patients with AG genotype for FSHR c.2039 G>A were significantly lower than those with AA genotype. The serum LH concentrations and clinical pregnancy rate of fresh embryo transfer in patients with GG genotype for LHCGR c.935 A>G were significantly higher than that of the AG genotype. In POSEIDON analysis, the low prognosis women with AA genotype for FSHR c.2039 G>A were more likely to appear in subgroup 1 (P = 0.038)., Conclusion: The FSHR c.2039 G>A variant has a significant beneficial influence on ovarian reserve and ovarian response. The LHCGR c.935 A>G variant is associated with increased clinical pregnancy rate of fresh embryo transfer in infertile women. In addition, the low prognosis women with AA genotype for FSHR c.2039 G>A tend to show better ovarian reserve and prognosis., (Copyright © 2021 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Research Question: What is the prevalence of disrupted markers of endometrial function among women experiencing recurrent implantation failure (RIF), and does the prevalence differ from a control cohort?, Design: Prospective controlled cohort study. In total, 86 women with a history of RIF and 37 women starting their first fertility treatment were recruited for this study. Endometrial and blood profiling were carried out in a hormone-substituted cycle using oestradiol and progesterone. Endometrial biopsies were analysed by histology, immune cell profiling, and the endometrial receptivity array (ERA®) test (Igenomix, Valencia, Spain). The vaginal microbiome was analysed using a NGS-based technology (ArtPRED, Amsterdam, the Netherlands). Blood tests included oestradiol, progesterone, prolactin, thyroid-stimulating hormone, vitamin D and anti-phospholipid antibody levels., Results: Patients who had experienced RIF produced a range of test abnormalities. Compared with controls, women with RIF had a higher prevalence of chronic endometritis (24% versus 6%), a lower vitamin D level and a borderline lower progesterone level. Women who had experienced RIF had a more favourable vaginal microbiome compared with controls. Although the RIF cohort was older than the controls (mean age 33.8 years versus 30.2 years), no differences between the groups were observed in immune cell profiling and the ERA test., Conclusion: These data demonstrate that a single test or treatment for the endometrial factor in RIF is unlikely to be clinically effective. Diagnosing the endometrium in women with RIF permits targeted rather than blind interventions. Relative vitamin D deficiency, lower mid-luteal progesterone and chronic endometritis are ready targets for treatment. Understanding the role and treatment of an unfavourable vaginal microbiome in RIF needs further investigation., (Copyright © 2020 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Research Question: Does the fertility-enhancing effect of tubal flushing during hysterosalpingography (HSG) with oil-based contrast change over time?, Design: This was a secondary analysis of the H2Oil (long-term follow-up) study, a multicentre randomized controlled trial evaluating the effectiveness of oil-based and water-based contrast during HSG. The main outcome was ongoing pregnancy. Cox proportional hazards models for time to ongoing pregnancy were fitted over 3 years of follow-up., Results: Data on 1107 couples were available; 550 couples had oil-based contrast and 557 water-based contrast at HSG. Ongoing pregnancy rates after 3 years were 77% and 71%, respectively. Median follow-up was 9-10 months (5th-95th percentile: <1 to 36). The hazard ratio for ongoing pregnancy for oil versus water over 3 years of follow-up was 1.26 (95% confidence interval [CI] 1.10-1.45). The scaled Schoenfeld residual plots showed a decrease in hazard ratio that was linear with log-transformed time. After including an interaction with log-transformed time, the hazard ratio immediately after HSG was 1.71 (95% CI 1.27-2.31) and reduced to no effect (hazard ratio of 1) at approximately 2 years. There was no evidence for a change in hazard ratio over time in a subgroup of women who experienced pain during HSG., Conclusions: The hazard ratio for ongoing pregnancy of oil-based versus water-based contrast was 1.71 immediately after HSG, gradually decreasing and plateauing towards a hazard ratio of 1 (indicating no effect) after approximately 2 years. This supports the hypothesis that oil-based contrast might dislodge debris or mucus plugs from the Fallopian tubes, but this has yet to be definitively proved., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Research Question: Adenomyosis has been reported in a high proportion (24.4%) of infertile women, but this may be over-representative. What is the exact prevalence of adenomyosis in an infertility clinic population?, Design: In this cross-sectional study, 320 infertile women ≤41 years of age attending the infertility clinic of a university teaching hospital were screened by two-dimensional transvaginal ultrasound (2D-TVS) to look for the sonographic markers of adenomyosis, with subsequent magnetic resonance imaging (MRI) if suspected. Additionally, the adenomyosis subtype (I-IV) was determined from MRI geography (Kishi classification). Comparisons between women with and without adenomyosis were carried out., Results: Adenomyosis was found by 2D-TVS in 24 cases (7.5%) and confirmed by MRI in 21 (6.6%). The mean age of the group was 29.2 ± 4.7 years. The most frequently observed sonographic finding (58.3% of cases) was asymmetrical myometrial thickening. The majority of MRI-confirmed cases (85.7%) had diffuse adenomyosis. A significantly higher prevalence was found in women ≥40 compared with women <40 years old (40.0% versus 4.9%, respectively; P < 0.0001). Adenomyotic women had significantly higher mean age (32.7 ± 3.0 versus 28.6 ± 4.4 years; P < 0.00001), body mass index (31.3 ± 2.7 versus 28.7 ± 3.3 kg/m 2 ; P < 0.0001), suffered more dysmenorrhoea (38% versus 17%; P = 0.02) and had more ovarian endometriomas (19% versus 6%; P = 0.03) than those without adenomyosis., Conclusion: The observed prevalence of adenomyosis detected de novo by 2D-TVS in a population of young infertile women (7.5%) should alert gynaecologists and ultrasonographers to look for the features of adenomyosis when scanning such patients., (Copyright © 2020 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Research Question: To investigate the association between anti-Müllerian hormone (AMH) concentration and maternal age with single euploid cryopreserved embryo transfer., Design: Retrospective cohort study from 2014 to 2018 at an academic medical centre, including 389 cycles of IVF with 24-chromosome Day 5/6 preimplantation genetic testing for aneuploidies (PGT-A). Multivariate logistic regression was used to study AMH and age in relation to IVF outcomes (positive beta human chorionic gonadotrophin [bHCG], ongoing pregnancy and pregnancy loss rates) for patients with at least one euploid embryo for transfer, controlling for patient and cycle confounders., Results: In this cohort the overall unadjusted positive bHCG rate was 69.2% and ongoing pregnancy rate was 52.7% per transfer, while the pregnancy loss rate was 23.4% per cycle with positive bHCG. Multivariate analysis found that compared with the reference group of AMH 1 to <5 ng/ml, AMH <1 and 5+ did not have any significant difference in positive bHCG (odds ratio, OR 0.65 [0.30-1.44] and 1.27 [0.61-2.65] for AMH <1 and AMH 5+, respectively) or ongoing pregnancy (OR 0.80 [0.43-1.50] and 1.41 [0.68-2.90]). However, AMH <1 had statistically significant lower euploid miscarriage rates compared with the reference group with OR 0.32 (0.12-0.85, P = 0.022); AMH 5+ did not have any statistical difference in miscarriage rate. Neither age at retrieval nor age at transfer were significantly associated with transfer outcomes., Conclusions: AMH concentration was not associated with positive bHCG or ongoing pregnancy for euploid embryo transfers after adjustment for potential confounders. Maternal age was not associated with euploid transfer outcomes. Further study is warranted in larger cohorts., (Copyright © 2019 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Research Question: Do ongoing pregnancy rates (OPR) differ between modified natural cycle IVF (MNC-IVF) and conventional high-dose ovarian stimulation (HDOS) in advanced-age Bologna poor responders?, Design: This was a retrospective cohort study including patients with poor ovarian response (POR) attending a tertiary referral university hospital from 1 January 2011 to 1 March 2017. All women who fulfilled the Bologna criteria for POR and aged ≥40 years who underwent their first intracytoplasmic sperm injection (ICSI) cycle in the study centre were included., Results: In total, 476 advanced-age Bologna poor responder patients were included in the study: 189 in the MNC-IVF group and 287 in the HDOS group. OPR per patient were significantly lower in the MNC-IVF group (5/189, 2.6%) compared with the HDOS group (29/287, 10.1%) (P = 0.002). However, after adjustment for relevant confounders (number of oocytes and presence of at least one top-quality embryo), the multivariate logistic regression analysis showed that the type of treatment strategy (HDOS versus MNC-IVF) was not significantly associated with OPR (odds ratio 2.56, 95% confidence interval 0.9-7.6)., Conclusions: In advanced-age Bologna poor responders, MNC-IVF, which is a more patient-friendly approach, could be a reasonable alternative in this difficult-to-treat group of women., (Copyright © 2019 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Research Question: Does the use of a levonorgestrel-releasing intrauterine system (LNG-IUS) improve the ongoing pregnancy rate of vitrified-warmed embryo transfer in women with adenomyosis undergoing IVF?, Design: This retrospective study included 358 women with adenomyosis undergoing IVF. Of these, 134 women were enrolled in the LNG-IUS group and another 224 women were in the control group. All women were screened for adenomyosis by transvaginal ultrasound and magnetic resonance imaging (MRI). There was no significant difference in the ages of women, FSH, cause of infertility, body mass index, total dose of gonadotrophin used and number of oocytes collected between the two groups. All comparisons performed were between patients undergoing vitrified-warmed embryo transfer., Results: Statistical differences were found in the ongoing pregnancy rates (41.8% vs 29.5%, P = 0.017) between the LNG-IUS group and control group. Logistic regression analysis showed that the odds ratio (OR) of ongoing pregnancy was significantly increased with LNG-IUS usage (adjusted OR = 1.628, 95% confidence interval 1.011-2.622). Also, differences were found in implantation rates (32.1% vs 22.1%, P = 0.005) and clinical pregnancy rates (44% versus 33.5%, P = 0.045) between the LNG-IUS group and control group., Conclusions: The results of this study offer some support for evaluating the effect of pretreatment with LNG-IUS in women with adenomyosis in future randomized controlled trials., (Copyright © 2019. Published by Elsevier Ltd.)

Research Question: Is active smoking among donors, recipients and male partners associated with oocyte donation cycle outcomes, in donors and recipients?, Design: Retrospective cohort over a 4-year period including 4747 oocyte recipients and partners, and 3101 oocyte donors. All oocyte donation cycles were carried out between 2010 and 2014, and for whom donor, recipient and male partner smoking status at the time of treatment were known., Results: Ovarian response was significantly reduced in oocyte donors who smoked compared with those who did not: 13.9 (SD 6.7) mature oocytes in heavy smokers versus 14.8 (SD 7.6) in non-smokers (P = 0.020). Nevertheless, biochemical, clinical and ongoing pregnancy rates and live birth rates were not affected by the degree of smoking among donors, recipients or recipients' partners., Conclusions: This study suggests that smoking is not associated with compromised oocyte quality or altered uterine receptivity in oocyte donation cycles., (Copyright © 2018 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

A total of 101 patients with one normal tube were compared with 117 patients with two normal tubes to assess the effect of unilateral tubal abnormalities on the results of intrauterine inseminations. The clinical pregnancy and live birth rates seemed to reduce by one-half in almost all types of abnormality, suggesting that these patients should be preferentially treated with IVF., (Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

In this review, the definition, incidence and possible causes of empty follicle syndrome (EFS), including molecular mechanisms that may underlie the syndrome, are discussed, along with prevention and treatment options. EFS is the complete failure to retrieve oocytes after ovarian stimulation, despite apparently normal follicle development and adequate follicular steroidogenesis. Two variants of EFS have been described: the 'genuine' form (gEFS), which occurs in the presence of adequate circulating HCG levels at the time of oocyte aspiration, and the 'false' form (f-EFS), which is associated with circulating HCG below a critical threshold. Heterogeneous HCG concentration thresholds, however, have been used to define gEFS, and to date no standardization exist. The situation is unclear when GnRH-analogues are used for ovulation trigger, as the threshold circulating LH and progesterone levels used to define EFS as 'genuine' are not established. The cause of fEFS has been clearly identified as an error in HCG administration at the time of ovulation trigger; in contrast, the cause of gEFS is still unclear, although some pathogenetic hypotheses have been proposed. Optimal treatment and prognosis of these patients are still poorly understood. Large, systematic multi-centre studies are needed to increase the understanding of EFS., (Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Data from 19,950 women were retrospectively analysed to determine the effect of chromosomal polymorphisms on female infertility and pregnancy outcome; fertile women were used as controls. Frequency of chromosomal polymorphisms and adverse pregnancy outcomes were compared between groups. A significantly higher incidence of chromosomal polymorphisms was found in total infertile patients, and patients with tubal infertility, ovulatory dysfunction, cervical and uterine abnormalities, and unexplained infertility compared with controls (5.53% [P < 0.001], 4.86% [P = 0.012] 5.40% [P < 0.001], 5.75% [P < 0.001] and 8.51% [P < 0.001], versus 3.74%, respectively). Infertile women had a higher incidence of 9qh+ and inv(9) compared with controls (P < 0.001 and P = 0.027). Logistic regression analysis showed an effect of chromosomal polymorphisms on female infertility (adjusted OR 1.662, 95% CI 1.551 to 1.796, P < 0.001). All couples reported a phenotypically normal baby. In control and tubal infertility groups, miscarriage rates were higher in women with chromosomal polymorphisms than in women with normal chromosomes (4.95% versus 0.96%, P = 0.001 and 6.17% versus 1.08%, P < 0.001). Preterm birth rate showed a similar trend. Chromosomal polymorphisms adversely affected spontaneous miscarriage rates (adjusted OR 1.625, 95% CI 1.514 to 1.769, P = 0.005)., (Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Obesity negatively affects reproductive functioning and psychological wellbeing. Distress experienced by infertile women with elevated body mass index (BMI) was investigated. Infertile women (n = 403) were stratified according to World Health Organization (2000) BMI categories (normal, overweight and obese) and infertility category (polycystic ovary syndrome [PCOS] or non-PCOS). Participants anonymously completed a Demographics Questionnaire, International Physical Activity Questionnaire, Depression, Anxiety and Stress Scale, Positive and Negative Affect Schedule, Rosenberg Self Esteem Scale, Fertility Problem Inventory, Clinical Perfectionism Questionnaire and the Eating Disorder Examination Questionnaire. Women in the obese BMI group were no more psychologically vulnerable to general mood (depression, anxiety and stress) or fertility-specific distress than normal or overweight BMI women. Independent of their PCOS status, obese women reported more frequent episodes of binge eating, shape concerns and low self-esteem symptoms associated with disordered eating. Women with PCOS had elevated shape concerns and anxiety independent of their BMI category compared with women who did not have PCOS. Obese infertile women presenting with the characteristics of binge eating, low self-esteem and body shape concerns may represent a vulnerable subgroup that could benefit from accessing targeted psychological interventions as do women with PCOS who have body shape concerns., (Copyright © 2015 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

The potential reproductive benefits of metformin, a drug endowed with the capacity to ameliorate insulin resistance in polycystic ovary syndrome (PCOS), has garnered much interest over the past 2 decades. In this review, randomized-controlled trials (RCT) and meta-analyses of RCT comparing metformin are critically appraised and summarized. PubMed and CENTRAL databases were consulted. Evidence is insufficient to favour the use of metformin or metformin plus clomiphene citrate instead of clomiphene citrate for ovulation induction in women with newly diagnosed PCOS. Evidence is also insufficient to recommend metformin as a primary treatment for non-obese women with PCOS. Metformin plus clomiphene citrate should be considered as an effective option in clomiphene citrate-resistant PCOS. In women with PCOS undergoing gonadotrophin ovulation induction, metformin significantly increased pregnancy and live birth rates (P < 0.0001 and P = 0.020, respectively) with reduced risk of cancelled cycles. A beneficial effect of metformin co-treatment in increasing clinical pregnancy rates and reducing the risk of OHSS in PCOS patients undergoing assisted reproduction techniques has been shown. No evidence was found of reduced risk of spontaneous abortion or increased risk of major anomalies in women with PCOS taking metformin during the first trimester., (Copyright © 2015 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Women with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome may reproduce after uterine transplantation or IVF using a gestational surrogate. As uterine transplantation is still an experimental procedure, data on their clinical outcome using assisted reproduction techniques are imperative to allow evidence-based counselling. For this purpose, a systematic non-restricted electronic literature search was conducted. The 14 studies included in this review were published between 1988 and 2011. From a cohort of 140 patients with MRKH syndrome, mostly from the the USA and Israel, only four studies contained data on more than 10 patients; the others were case reports or small series. In the studies reviewed, 125 patients underwent 369 cycles of IVF with gestational surrogacy, and delivered 71 newborns. The reporting of outcome of patients with MRKH syndrome undergoing assisted reproduction techniques in the available literature is less than optimal and is characterized by bias of publication, inconsistent reports, including few patients, treated over a long time span, and lacking systematic reports from large IVF centres. None of the national registries contain specific outcome data on patients with MRKH syndrome. The paucity of data limits the possibility to draw firm conclusions but substantiates the need for a systematic multicentre reporting system., (Copyright © 2015 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

A retrospective matched-control study to evaluate the effect of uterine anomalies on pregnancy rates after 2481 embryo transfers in conventionally stimulated IVF/intracytoplasmic sperm injection (ICSI) cycles. The study group of 289 embryo transfers before and 538 embryo transfers following hysteroscopic resection of a uterine septum was compared with two consecutive embryo transfers in the control group. Groups were matched for age, body mass index, ovarian stimulation, embryo quality, IVF or ICSI and infertility aetiologies. Number of embryos transferred, embryo quality and absence of uterine anomalies significantly predicted the pregnancy rates in the study group: odds ratios (OR) 1.7, 2.6 and 2.5, respectively (P<0.001). Pregnancy rates after embryo transfer before hysteroscopic metroplasty were significantly lower, both in women with subseptate and septate uterus and in women with arcuate uterus compared with controls. If two or three embryos with at least one best-quality embryo were transferred, the differences were 9.6% versus 43.6%, OR 7.3 (P<0.001) and 20.9% versus 35.5%, OR 2.1 (P<0.03), respectively. Differences in terms of live birth rates were even more evident: 1.9% versus 38.6%, OR 32 (P<0.001) and 3.0% versus 30.4%, OR 14 (P<0.001). After surgery, the differences disappeared. This retrospective matched control study evaluated the influence of septate, subseptate and arcuate uterus on pregnancy and live birth rates after 2481 in conventionally stimulated IVF/intracytoplasmic sperm injection (ICSI) cycles. The study group included 827 embryo transfers (289 embryo transfers before and 538 embryo transfers following hysteroscopic resection of uterine septum ans was compared with two consecutive mebryo transfers in the control group. Both groups were matched by age, body mass index, stimulation protocol, quality of embryos, use of IVF or ICSI, and infertility aetiologies. Multivariate logistic regression analysis of the study group showed that the number of embryos, embryo quality and the absence of uterine anomalies significantly predicted the pregnancy rates: odds ratios (OR) 1.7, 2.6, and 2.5, respectively (P<0.001). The pregnancy and live birth rates before surgery were lower compared with controls, both in women with subseptate or septate uterus and in women with arcuate uterus. If two or three embryos with at least one best quality embryo were transferred, the differences in terms of pregnancy rates were 9.6% versus 43.6%, OR=7.3 (P<0.001) and 20.9% versus 35.5%, OR=2.1 (P<0.03), respectively. The differences in terms of live birth rates were even more evident: 1.9% versus 38.6%, OR=32 (P<0.001) and 3.0% versus 30.4%, OR=14 (P<0.001). After surgery, the differences disappeared. Negative impact of uterine anomalies on pregnancy and on live birth rates are two important arguments for treating uterine anomalies in infertile women., (Copyright © 2010 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

The aim of this retrospective cohort study was to evaluate clinical outcome after multidisciplinary laparoscopic excision of deep endometriosis. Patients (n = 56) were asked to complete questionnaires regarding quality of life (QOL), pain, fertility and sexuality to compare their status before and after surgery, and their medical files were analysed. Statistical analysis was performed with life table analysis, paired Wilcoxon and McNemar tests. Gynaecological pain, QOL and sexual activity improved significantly (P < 0.001; P < 0.0001 to P = 0.008 and P < 0.0001 to P = 0.0003 respectively) during a median follow-up 29 months after surgery. Post operative complications occurred in 11% but were directly related to surgery in only 5%. The cumulative recurrence rate of endometriosis was 2 and 7% at 1 and 4 years after surgery respectively. Cumulative pregnancy rate was 31 and 70% at 1 and 4 years after surgery respectively. In conclusion, multidisciplinary CO(2) laser laparoscopic excision of deep endometriosis with colorectal extension improves pain, QOL and sexuality with high fertility and low complication and recurrence rates.

Acquired immune deficiency syndrome (AIDS), caused by the human immunodeficiency virus (HIV), disproportionately affects Africa whereby the majority of new infections and deaths occur in sub-Saharan Africa. It is the leading cause of death in Africa and a major cause of maternal mortality. HIV/AIDS impacts on every aspect of reproductive health and presents considerable challenges to healthcare systems. Fertility is particularly valued in Africa and voluntary childlessness is unusual. AIDS results in a reduction in both fecundity and fertility, as well as compromising the outcome of pregnancy. The stigma of childlessness is quite profound and impacts both social life and social standing within the community, particularly of the women who are affected. Unfortunately, treatment for infertility is often inadequate and, because of limited resources, is frequently denied to HIV-positive couples. Undoubtedly the challenges in dealing with the HIV/AIDS pandemic in Africa are enormous; however, appropriate solutions are available and these need to be put in place. It is essential that the management of the HIV patient is holistic and takes all needs, including that of fertility, into account.

Rising Caesarean section (CS) rates have fuelled concerns about the effect of abdominal delivery on female fertility due to post-surgical complications affecting the Fallopian tubes. The association between exposure to CS and subsequent tubal infertility was explored by means of a case-control study. This study compared 220 women with secondary infertility due to tubal factor with 1244 women with secondary infertility due to non-tubal causes and 18,376 fertile women (women with a previous live birth followed by another live birth during the time period when the infertile cases were trying to conceive) in terms of exposure to CS. Exposure to CS in women with secondary tubal infertility was similar to other infertile women (21.4% versus 21.6%) but lower in fertile controls (14.5%). After adjusting for confounding factors, CS does not appear to be significantly associated with tubal infertility [adjusted odds ratio (95% confidence interval) for previous CS for infertile and fertile controls were 1.06 (0.73-1.52) and 1.2 (0.9-1.7), respectively]. However, other factors that were found to be predictive of secondary tubal infertility include history of intrauterine device use, pelvic inflammatory disease, ectopic pregnancy, endometriosis and previous pelvic surgery.

The aim of this study was to review the existing literature on the effect of war on female and male fertility. A MEDLINE search for studies that included participants defined as infertile because they were unsuccessful in achieving a pregnancy after a year and studies that assessed the effect of war on semen parameters and menstrual dysfunction were performed. Twenty articles were included in this review. For female fertility, studies showed that women who were prisoners of war or who were living in areas exposed to bombardment had increased risk of menstrual abnormalities. For male fertility, the results were conflicting. The Vietnam War was not associated with difficulty in conception although one study revealed a decrease in sperm characteristics. Studies of male US and Danish 1990/91 Gulf war veterans showed no evidence of reduced fertility; however, studies of UK and Australian veterans reported increased risk of infertility. The Lebanese and Slovenian civil wars were associated with a decrease in sperm parameters. Exposure to mustard gas was also associated with abnormal semen parameters; however, exposure to depleted uranium had no effect on semen characteristics. Most of the studies examined had major limitations including recall bias and small number of cases included.

Magnetic resonance imaging (MRI) allows the diagnosis of adenomyosis in vivo with a high sensitivity and specificity. Usually the diagnosis of adenomyosis is obtained from women in their fourth to fifth decade of life. However, recent data suggest that adenomyosis may develop much sooner in life, particularly in women with endometriosis. In order to test these suggestions, MRI of the uterus in 227 women with and without endometriosis was performed and the results were related to the age of the subjects (age groups: 17-24, 25-29, 30-34 and >34 years). The study revealed that the process of the development of adenomyosis, represented by an increased diameter of the dorsal junctional zone of the uterus as the imaging correlative of the invasion of basal endometrium into the junctional zone, had already commenced early in the third decade of life and progressed steadily during the fourth decade in women with endometriosis. Women without endometriosis showed almost no signs of adenomyosis up to the age of 34 years. Surprisingly, parallel in both groups of women, a marked increase in the incidence of adenomyosis could be observed beyond the age of 34 years, thus representing a common phenomenon in the age-related pathophysiological continuum of adenomyosis.

Obese women are characterized by similar comorbidities to men, particularly type 2 diabetes mellitus and cardiovascular diseases. Moreover, they also develop some specific problems, including fertility-related disorders and some hormone-dependent forms of cancer. The relationship between excess body fat and reproductive disturbances appears to be stronger for early-onset obesity. Early onset of obesity, particularly during adolescence, favours the development of menses irregularities, chronic oligo-anovulation and infertility in adulthood. Moreover, obesity in women can increase the risk of miscarriage and impair the outcome of assisted reproductive technologies. The main factor implicated in the association between obesity and fertility-related disorders is insulin excess, which accompanies insulin resistance. Hyperinsulinaemia may be directly responsible for the development of androgen excess, through its effects in reducing sex hormone-binding globulin synthesis and circulating concentrations, and in stimulating ovarian androgen production rates. Androgen excess, in turn, represents one of the major factors leading to altered ovarian physiology and associated ovulatory disturbances. Obesity-associated hyperleptinaemia may represent an additional factor involved in anovulation, not only through the induction of insulin resistance, but also through a direct impairment of ovarian function.

Choosing the number of embryos to be transferred is a major problem in assisted reproductive technologies. This study aimed to establish and validate a score predicting implantation rates in order to help in the choice of the number of embryos to be transferred, allowing the best compromise between high pregnancy rate and low multiple pregnancy risk. Clinical and biological parameters influencing implantation rates were retrospectively analysed in 739 embryo transfers and an implantation score was established. This score was then prospectively validated in 521 embryo transfers. Three parameters (age, ovarian response to FSH stimulation and embryo morphology) appeared to be predictive of the implantation rates and were included in an implantation score (3-9). The prospective study confirmed the validity of the score since implantation rates were higher when the score increased (5.9% for score 3 versus 22.4% for score 9; P < 0.05). Therefore, success rates can be predicted by the implantation score, which is of clinical value in choosing the number of embryos to be transferred in order to decrease multiple pregnancies while keeping high pregnancy rates. However, choosing the right number of embryos to be transferred needs further studies, since the percentage of multiple pregnancies remained relatively high in this prospective study (27%).