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Manjunath Srinivas Kamath,1 Shiek SSJ Ahmed,2 M Dhanasekaran,3 S Winkins Santosh11Department of Biotechnology, School of Bioengineering, SRM University, 2Department of Biotechnology, Chettinad Hospital and Research Institute, 3Department of Stem Cells, Life Line Rigid Hospital Pvt Ltd, Kilpauk, Tamil Nadu, IndiaAbstract: Biomaterials-based three-dimensional scaffolds are being extensively investigated in bone tissue engineering. A potential scaffold should be osteoconductive, osteoinductive, and osteogenic for enhanced bone formation. In this study, a three-dimensional porous polycaprolactone (PCL) scaffold was engineered for prolonged release of resveratrol. Resveratrol-loaded albumin nanoparticles (RNP) were synthesized and entrapped into a PCL scaffold to form PCL-RNP by a solvent casting and leaching method. An X-ray diffraction study of RNP and PCL-RNP showed that resveratrol underwent amorphization, which is highly desired in drug delivery. Furthermore, Fourier transform infrared spectroscopy indicates that resveratrol was not chemically modified during the entrapment process. Release of resveratrol from PCL-RNP was sustained, with a cumulative release of 64% at the end of day 12. The scaffold was evaluated for its bone-forming potential in vitro using human bone marrow-derived mesenchymal stem cells for 16 days. Alkaline phosphatase activity assayed on days 8 and 12 showed a significant increase in activity (1.6-fold and 1.4-fold, respectively) induced by PCL-RNP compared with the PCL scaffold (the positive control). Moreover, von Kossa staining for calcium deposits on day 16 showed increased mineralization in PCL-RNP. These results suggest PCL-RNP significantly improves mineralization due to its controlled and prolonged release of resveratrol, thereby increasing the therapeutic potential in bone tissue engineering.Keywords: therapeutic scaffolds, polycaprolactone scaffolds, bone tissue engineering, resveratrol, albumin nanoparticles, mesenchymal stem cells

Objective: To evaluate the risk of monozygotic splitting with embryo biopsy during in vitro fertilisation (IVF).Design: A cohort study.Setting: Anonymised assisted reproductive technology national data from the Human Fertilisation and Embryology Authority, UK.Population: Women undergoing single-embryo transfer (SET) following either pre-implantation genetic testing (PGT) involving embryo biopsy or IVF without PGT.Methods: Data on women undergoing SET either following PGT and non-PGT IVF treatment in 2000-2016 were analysed to compare the risk of zygotic splitting and monozygotic twining. Logistic regression analysis was performed adjusting for potential confounders.Main Outcomes: Monozygotic spitting, monozygotic twin birth.Results: Data comprising a total of 207 697 SET cycles (4544 following PGT and 203 153 following non-PGT IVF) were analysed. The live birth rate per embryo transfer was 31.9% (95% confidence interval [CI] 30.5-33.2%) following PGT and 26.9% (95% CI 26.7-27.1%) following non-PGT IVF. The incidence of zygotic splitting following PGT was 2.4% (95% CI 1.7-3.3%) versus 1.5% (95% CI 1.4-1.6%) following non-PGT IVF. There was a significantly higher risk of zygotic splitting with PGT versus non-PGT IVF cycles (odds ratio [OR] 1.64, 95% CI 1.19-2.27). The higher risk of zygotic splitting with PGT cycles remained significant after adjusting for potential confounders (adjusted OR 1.51, 95% CI 1.06-2.15).Conclusions: The present study demonstrated an increased risk of monozygotic splitting with embryo biopsy. Given the current sparse literature, it is important to accumulate further evidence to validate the findings.Tweetable Abstract: A likely increased risk of monozygotic splitting following embryo biopsy. [ABSTRACT FROM AUTHOR]

The article presents a comment to the gold standard in reproductive medicine and advances in assisted reproductive technology (ART). It discusses the expensive cost for fertility treatments, the gap between clinical practice and evidence, and the challenges for evidence-based ART. It also examines the risk of informed patient choice.

To evaluate the effectiveness of Letrozole and Clomiphene (CC) combination versus Letrozole alone for ovulation induction in infertile women with PCOS. This was an open label randomized controlled trial conducted between September 2020 and March 2023 at a tertiary level hospital. Women with a diagnosis of infertility and PCOS were included. Participants were randomized in a 1:1 ratio, to either the combination of 2.5 mg letrozole and 50 mg Clomiphene Citrate (CC) daily or 2.5 mg letrozole alone from 2nd to 6 th day of menstrual cycle for up to three treatment cycles. The primary outcome was ovulation rate per cycle. The secondary outcomes included ovulation rate per woman randomised, cumulative pregnancy and live birth rates. A total of the 120 participants, 59 women in Letrozole and CC arm (intervention) and 61 women in the Letrozole alone arm (control) were recruited. The woman per cycle ovulation rate following Letrozole and CC combination versus Letrozole alone (71/92 (77.2%) vs. 52/83 (62.6%), RR 1.43, 95%CI 0.99 to 2.06) but was not statistically significant. A per ITT analysis, the clinical pregnancy rate per woman randomized (16/61(26.2%) vs. 13/59(22%), RR 1.12, 95%CI 0.76 to 1.64) and live birth rate per woman randomized (10/61(16.4%) vs 11/59(18.6%), RR 0.92, 095%CI 0.57 to 1.50) did not differ significantly between Letrozole and CC versus Letrozole group. There was no significant improvement in ovulation, clinical pregnancy, or live birth rates with a combination of letrozole and CC versus letrozole alone in per woman randomized with PCOS. Trial RegistrationThe trial was prospectively registered in the clinical trial registry of India (CTRI registration number CTRI/2020/07/026263), Registration dated: February 26, 2020., (© 2024. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

The purpose of the study is to explore the impact of dietary habits, including daily intake of nutrients and dietary patterns, on the semen characteristics of South-Asian men. This cross-sectional study included 162 South-Asian men aged 21-40 years who were undergoing infertility evaluation. Based on semen analysis, men were grouped into categories of normal and abnormal semen characteristics. The participants' dietary habits were captured using '24-hour dietary recall' and 'Food Frequency Questionnaire (FFQ)'. Daily dietary intake of various nutrients and adherence to prevalent dietary patterns were compared between men with normal and abnormal semen characteristics. Six dietary patterns were identified following factor analysis of FFQ data. Men with normal semen characteristics showed significantly higher consumption of "coastal diet" rich in seafood, fish, cereals, beans, and coconut oil than those with abnormal semen characteristics. Further, the multivariable-adjusted model, adjusted for clinically relevant confounders, like age, body mass index (BMI), physical activity, smoking and sexual abstinence, also showed a lower risk of abnormal semen characteristics among men consuming "coastal diet" (odds ratio [OR] = 0.56, 95% confidence interval [CI] 0.37-0.82). In terms of daily nutrient intake, men with normal semen characteristics showed significantly lower consumption of monounsaturated fatty acids (MUFA) compared to men with abnormal semen characteristics (p = 0.008). Our findings suggest that higher consumption of "coastal pattern diet" lowers the risk of abnormal semen characteristics. Additionally, a negative association of MUFA consumption with semen quality was also identified, which needs cautious interpretation until replicated in future studies with biochemical validations., (© 2024. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Objective: Recurrent pregnancy loss (RPL) has a multifactorial etiology, with a majority of cases remaining unexplained. To account for these unexplained cases, possible male factors are being explored. Conventional semen analysis lacks a qualitative assessment of sperms and information regarding sperm DNA integrity. Sperm DNA fragmentation (SDF) has diagnostic value in unexplained RPL, and it may account for a number of unexplained cases. Hence, we planned a study to explore and evaluate the impact of sperm DNA fragmentation in couples with unexplained recurrent pregnancy losses., Study Design: Analytical cross-sectional study was conducted at a tertiary-level referral facility in India between August 2021 and July 2023. Participants (n = 70) were divided into two groups-male partners of couples with unexplained RPL (following spontaneous conceptions) (n = 35) and men with at least one previous live birth (spontaneous or following fertility treatments for female factor infertility such as ovulation induction or intrauterine insemination) as controls (n = 35). Neither of the two groups of couples recruited for this study had undergone ART as fertility treatment. Primary outcome assessed was mean DNA fragmentation index (DFI). Secondary outcomes included differences in semen parameters such as sperm concentration, progressive sperm motility and morphology, proportion of men with high (≥30%) and low DFI in the two groups, and the association between various semen parameters and DFI., Results: Univariate logistic regression revealed that sperm DNA fragmentation was higher in men with unexplained RPL (30.0; IQR (interquartile range) 19.0, 46.0) as compared to controls (22.0; IQR 14.0, 30.0) although it was not statistically significant (OR, odds ratio, 1.02; 95% CI 1.0-1.1, p = 0.08). A higher proportion of men with unexplained RPL had DFI ≥30% compared to controls (54.2% vs. 25.7%; OR 3.43 (95% CI 1.2-9.4); p = 0.02). No statistically significant differences were observed in semen volume, sperm concentration, progressive motility, and morphology between the two groups. Sperm DNA fragmentation index also showed a weak but significant inverse relationship with sperm morphology (r = -0.336, p = 0.004)., Conclusion: The current study did not show any significant difference in the mean sperm DNA fragmentation levels in male partners of couples with unexplained RPL compared to controls. However, a higher proportion of men with DFI ≥30% were observed in unexplained RPL population when compared to controls., (© 2024 Japan Society of Obstetrics and Gynecology.)

Access to quality healthcare remains a challenge in low-and middle-income countries. Vulnerable populations with unmet needs face the greatest challenge in accessing primary care for appropriate and timely healthcare. The use of digital technologies can not only strengthen health systems but also improve access to health care, particularly for the vulnerable. This scoping review aims to assess the various digital health technologies and interventions available for improving access to primary care for the vulnerable in India. This scoping review employed the Joanna Brigg Institute's (JBI) guidelines and Arksey and O'Malley's methodological framework. The literature search was conducted in Medline/PubMed, Embase, Web of Science-Core Collection, Scopus, AgeLine, PsycINFO, CINAHL, ERIC, Cochrane CENTRAL, and Cochrane Effective Practice and Organisation of Care (EPOC) Group Specialised Register databases, using the keywords, such as 'Access', 'Healthcare', 'Assistive technology', 'Digital health' 'Vulnerable', 'India' and 'Healthcare technology'. A two-staged screening of titles and abstracts, followed by full-text was conducted independently by two reviewers, using the Rayyan software. Subsequently, the data was extracted from selected studies using a pre-designed and approved extraction form. The data was then synthesised and analysed narratively. The protocol for this review has been registered with open science forum (OSF) registries (https://osf.io/63pjw/). The search yielded about 3840 records, 3544 records were eligible for screening of titles and abstracts. We included seven studies after a two-round screening and identified seven different technological innovations developed to bridge gaps in access to primary care. The commonly used digital health interventions for improving access to primary care were virtual tele-health systems and mHealth applications in-built within an android smartphone or a tablet. Digital health interventions was either used as a standalone tele-health aid or a collaborative system for community workers, primary care physicians as well as the health service users. The purpose of these innovations was to increase awareness and knowledge to access support for specific aspects of healthcare. Virtual primary health care with the specialist in the hub supporting general physicians at the primary health centres in blocks and districts was another such model used for improving access to primary care. Digital health interventions was also used for mass community screening of disabilities, such as persons with hearing disability. To re-imagine a digitally empowered health systems in India, also inclusive of the vulnerable, it is important to inclusively conceptualise, systematically develop and rigorously evaluate any public health interventions including those that are enabled by digital health interventions to bridge the gaps in access to primary care in India. Such a strategy could address the paucity of evidence in public health interventions and provide sustainable strategies to strengthen health systems in India. Trial registration: Open Science Framework-Registration Link: https://osf.io/63pjw/., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Vasanthan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Women from low- and middle-income countries face challenges in accessing and utilising quality healthcare. Technologies can aid in overcoming these challenges and the present scoping review is aimed at summarising the range of technologies used by women and assessing their role in enabling Indian women to learn about and access healthcare services. We conducted a comprehensive search from the date of inception of database till 2022 in PubMed and Google Scholar. Data was extracted from 43 studies and were thematically analysed. The range of technologies used by Indian women included integrated voice response system, short message services, audio-visual aids, telephone calls and mobile applications operated by health workers. Majority of the studies were community-based (79.1%), from five states (60.5%), done in rural settings (58.1%) and with interventional design (48.8%). Maternal and child health has been the major focus of studies, with lesser representation in domains of non-communicable and communicable diseases. The review also summarised barriers related to using technology - from health system and participant perspective. Technology-based interventions are enabling women to improve awareness about and accessibility to healthcare in India. Imparting digital literacy and scaling up technology use are potential solutions to scale-up healthcare access among women in India.

India, with a population of 1.4 billion, faces health equity challenges due to inaccessible public health systems, particularly in rural areas. Modern technologies like the internet and mobile phones are being used to bridge this gap, enhancing health equity by disseminating vital health information. Health Technology Assessment (HTA) evaluates these technologies, influencing healthcare policy and improving health outcomes. Key strategies include digital health hubs, mobile health units, public-private partnerships, and digital tools for community health workers. To scale these interventions, capacity building, infrastructure development, community engagement, and monitoring are required. Policymakers are urged to prioritize investments in health technologies based on evidence, considering cost-effectiveness, health outcomes, and health equity. Addressing data privacy and security is crucial. Future research should focus on technology-based interventions for maternal and child health., Competing Interests: No conflicts of interest to declare., (© 2023 The Authors.)

The prevalence of women with a raised body mass index (BMI) seeking assisted conception treatment is increasing. Findings of existing studies evaluating the effect of female BMI on intrauterine insemination (IUI) treatment outcomes remain inconsistent. This systematic review and meta-analysis evaluate the effect of female BMI on IUI treatment outcomes. Two authors independently conducted data extraction and assessed study quality. Risk ratios (RR) and 95% confidence intervals were calculated using the Mantel-Haenszel approach for dichotomous outcomes. 11 studies involving 23,145 IUI treatment events, comprising 21,211 cycles from 8 studies, and 1,934 participants in three studies, met the inclusion criteria for the meta-analysis. Two cohorts of women undergoing IUI treatment were compared - women with normal BMI < 25 kg/m 2 were compared with a second cohort of women with a BMI category ≥ 25 kg/m 2 . There was no statistically significant difference in live birth rate (LBR) (RR 1.06, 95% CI 0.86-1.307); clinical pregnancy rate (CPR) (RR 0.94, 95% CI 0.78-1.13); miscarriage (RR 0.92, 95% CI 0.31-2.74) or ectopic pregnancy rate (RR 2.20, 95% CI 0.78-6.23). Our meta-analysis showed that a raised female BMI did not affect IUI treatment outcomes. Nevertheless, weight loss counselling should be offered to women with a raised BMI undergoing IUI, to reduce the associated obstetric morbidity.

Background: In IVF/ICSI treatment, the process of embryo implantation is the success rate-limiting step. Endometrial scratching has been suggested to improve this process, but it is unclear if this procedure increases the chance of implantation and live birth (LB) and, if so, for whom, and how the scratch should be performed., Objective and Rationale: This individual participant data meta-analysis (IPD-MA) aims to answer the question of whether endometrial scratching in women undergoing IVF/ICSI influences the chance of a LB, and whether this effect is different in specific subgroups of women. After its incidental discovery in 2000, endometrial scratching has been suggested to improve embryo implantation. Numerous randomized controlled trials (RCTs) have been conducted, showing contradicting results. Conventional meta-analyses were limited by high within- and between-study heterogeneity, small study samples, and a high risk of bias for many of the trials. Also, the data integrity of several trials have been questioned. Thus, despite numerous RCTs and a multitude of conventional meta-analyses, no conclusion on the clinical effectiveness of endometrial scratching could be drawn. An IPD-MA approach is able to overcome many of these problems because it allows for increased uniformity of outcome definitions, can filter out studies with data integrity concerns, enables a more precise estimation of the true treatment effect thanks to adjustment for participant characteristics and not having to make the assumptions necessary in conventional meta-analyses, and because it allows for subgroup analysis., Search Methods: A systematic literature search identified RCTs on endometrial scratching in women undergoing IVF/ICSI. Authors of eligible studies were invited to share original data for this IPD-MA. Studies were assessed for risk of bias (RoB) and integrity checks were performed. The primary outcome was LB, with a one-stage intention to treat (ITT) as the primary analysis. Secondary analyses included as treated (AT), and the subset of women that underwent an embryo transfer (AT+ET). Treatment-covariate interaction for specific participant characteristics was analyzed in AT+ET., Outcomes: Out of 37 published and 15 unpublished RCTs (7690 participants), 15 RCTs (14 published, one unpublished) shared data. After data integrity checks, we included 13 RCTs (12 published, one unpublished) representing 4112 participants. RoB was evaluated as 'low' for 10/13 RCTs. The one-stage ITT analysis for scratch versus no scratch/sham showed an improvement of LB rates (odds ratio (OR) 1.29 [95% CI 1.02-1.64]). AT, AT+ET, and low-RoB-sensitivity analyses yielded similar results (OR 1.22 [95% CI 0.96-1.54]; OR 1.25 [95% CI 0.99-1.57]; OR 1.26 [95% CI 1.03-1.55], respectively). Treatment-covariate interaction analysis showed no evidence of interaction with age, number of previous failed embryo transfers, treatment type, or infertility cause., Wider Implications: This is the first meta-analysis based on IPD of more than 4000 participants, and it demonstrates that endometrial scratching may improve LB rates in women undergoing IVF/ICSI. Subgroup analysis for age, number of previous failed embryo transfers, treatment type, and infertility cause could not identify subgroups in which endometrial scratching performed better or worse. The timing of endometrial scratching may play a role in its effectiveness. The use of endometrial scratching in clinical practice should be considered with caution, meaning that patients should be properly counseled on the level of evidence and the uncertainties., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Competing Interests: The authors declare no conflict of interest.

Background: In vitro fertilisation (IVF) is a treatment for unexplained subfertility but is invasive, expensive, and associated with risks., Objectives: To evaluate the effectiveness and safety of IVF versus expectant management, unstimulated intrauterine insemination (IUI), and IUI with ovarian stimulation using gonadotropins, clomiphene citrate (CC), or letrozole in improving pregnancy outcomes., Search Methods: We searched following databases from inception to November 2021, with no language restriction: Cochrane Gynaecology and Fertility Register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL. We searched reference lists of articles and conference abstracts., Selection Criteria: Randomised controlled trials (RCTs) comparing effectiveness of IVF for unexplained subfertility with expectant management, unstimulated IUI, and stimulated IUI., Data Collection and Analysis: We followed standard Cochrane methods., Main Results: IVF versus expectant management (two RCTs) We are uncertain whether IVF improves live birth rate (LBR) and clinical pregnancy rate (CPR) compared to expectant management (odds ratio (OR) 22.0, 95% confidence interval (CI) 2.56 to 189.37; 1 RCT; 51 women; very low-quality evidence; OR 3.24, 95% CI 1.07 to 9.8; 2 RCTs; 86 women; I 2 = 80%; very low-quality evidence). Adverse effects were not reported. Assuming 4% LBR and 12% CPR with expectant management, these would be 8.8% to 9% and 13% to 58% with IVF. IVF versus unstimulated IUI (two RCTs) IVF may improve LBR compared to unstimulated IUI (OR 2.47, 95% CI 1.19 to 5.12; 2 RCTs; 156 women; I 2 = 60%; low-quality evidence). We are uncertain whether there is a difference between IVF and IUI for multiple pregnancy rate (MPR) (OR 1.03, 95% CI 0.04 to 27.29; 1 RCT; 43 women; very low-quality evidence) and miscarriage rate (OR 1.72, 95% CI 0.14 to 21.25; 1 RCT; 43 women; very low-quality evidence). No study reported ovarian hyperstimulation syndrome (OHSS). Assuming 16% LBR, 3% MPR, and 6% miscarriage rate with unstimulated IUI, these outcomes would be 18.5% to 49%, 0.1% to 46%, and 0.9% to 58% with IVF. IVF versus IUI + ovarian stimulation with gonadotropins (6 RCTs), CC (1 RCT), or letrozole (no RCTs) Stratified analysis was based on pretreatment status. Treatment-naive women There may be little or no difference in LBR between IVF and IUI + gonadotropins (1 IVF to 2 to 3 IUI cycles: OR 1.19, 95% CI 0.87 to 1.61; 3 RCTs; 731 women; I 2 = 0%; low-quality evidence; 1 IVF to 1 IUI cycle: OR 1.63, 95% CI 0.91 to 2.92; 2 RCTs; 221 women; I 2 = 54%; low-quality evidence); or between IVF and IUI + CC (OR 2.51, 95% CI 0.96 to 6.55; 1 RCT; 103 women; low-quality evidence). Assuming 42% LBR with IUI + gonadotropins (1 IVF to 2 to 3 IUI cycles) and 26% LBR with IUI + gonadotropins (1 IVF to 1 IUI cycle), LBR would be 39% to 54% and 24% to 51% with IVF. Assuming 15% LBR with IUI + CC, LBR would be 15% to 54% with IVF. There may be little or no difference in CPR between IVF and IUI + gonadotropins (1 IVF to 2 to 3 IUI cycles: OR 1.17, 95% CI 0.85 to 1.59; 3 RCTs; 731 women; I 2 = 0%; low-quality evidence; 1 IVF to 1 IUI cycle: OR 4.59, 95% CI 1.86 to 11.35; 1 RCT; 103 women; low-quality evidence); or between IVF and IUI + CC (OR 3.58, 95% CI 1.51 to 8.49; 1 RCT; 103 women; low-quality evidence). Assuming 48% CPR with IUI + gonadotropins (1 IVF to 2 to 3 IUI cycles) and 17% with IUI + gonadotropins (1 IVF to 1 IUI cycle), CPR would be 44% to 60% and 28% to 70% with IVF. Assuming 21% CPR with IUI + CC, CPR would be 29% to 69% with IVF. There may be little or no difference in multiple pregnancy rate (MPR) between IVF and IUI + gonadotropins (1 IVF to 2 to 3 IUI cycles: OR 0.82, 95% CI 0.38 to 1.77; 3 RCTs; 731 women; I 2 = 0%; low-quality evidence; 1 IVF to 1 IUI cycle: OR 0.76, 95% CI 0.36 to 1.58; 2 RCTs; 221 women; I 2 = 0%; low-quality evidence); or between IVF and IUI + CC (OR 0.64, 95% CI 0.17 to 2.41; 1 RCT; 102 women; low-quality evidence). We are uncertain if there is a difference in OHSS between IVF and IUI + gonadotropins with 1 IVF to 2 to 3 IUI cycles (OR 6.86, 95% CI 0.35 to 134.59; 1 RCT; 207 women; very low-quality evidence); and there may be little or no difference in OHSS with 1 IVF to 1 IUI cycle (OR 1.22, 95% CI 0.36 to 4.16; 2 RCTs; 221 women; I 2 = 0%; low-quality evidence). There may be little or no difference between IVF and IUI + CC (OR 1.53, 95% CI 0.24 to 9.57; 1 RCT; 102 women; low-quality evidence). We are uncertain if there is a difference in miscarriage rate between IVF and IUI + gonadotropins with 1 IVF to 2 to 3 IUI cycles (OR 0.31, 95% CI 0.03 to 3.04; 1 RCT; 207 women; very low-quality evidence); and there may be little or no difference with 1 IVF to 1 IUI cycle (OR 1.16, 95% CI 0.44 to 3.02; 1 RCT; 103 women; low-quality evidence). There may be little or no difference between IVF and IUI + CC (OR 1.48, 95% CI 0.54 to 4.05; 1 RCT; 102 women; low-quality evidence). In women pretreated with IUI + CC IVF may improve LBR compared with IUI + gonadotropins (OR 3.90, 95% CI 2.32 to 6.57; 1 RCT; 280 women; low-quality evidence). Assuming 22% LBR with IUI + gonadotropins, LBR would be 39% to 65% with IVF. IVF may improve CPR compared with IUI + gonadotropins (OR 14.13, 95% CI 7.57 to 26.38; 1 RCT; 280 women; low-quality evidence). Assuming 30% CPR with IUI + gonadotropins, CPR would be 76% to 92% with IVF., Authors' Conclusions: IVF may improve LBR over unstimulated IUI. Data should be interpreted with caution as overall evidence quality was low., (Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Objective: We planned a study to evaluate the impact of selecting hysterosalpingography (HSG) over diagnostic laparoscopy during initial fertility evaluation on IUI treatment outcomes in couples diagnosed with unexplained infertility., Methods: The study comprised a retrospective cohort and included couples evaluated for infertility at our tertiary level hospital between January 2008 and December 2019. Couples diagnosed with unexplained infertility based on tubal patency tests (either HSG or diagnostic laparoscopy) were included. We compared outcomes following ovarian stimulation (OS) and intrauterine insemination (IUI) between women who underwent HSG versus laparoscopy for up to three treatment cycles., Results: A total of 7413 women were screened, out of which 1002 women were diagnosed with unexplained infertility. We did not find a significant statistical difference in the clinical pregnancy (16.7% vs. 11.7%; OR (odds ratio) 1.51; 95% CI (confidence interval) 0.90-2.5) or live birth rate per IUI cycle (15.1% vs. 10.7%; OR 1.51, 95% CI 0.9-2.6) in women who underwent HSG for tubal evaluation as compared to laparoscopy. After adjustment for potential confounders through multivariate analysis, we found that outcomes were comparable between the HSG and laparoscopy., Conclusion: The current study did not find any significant difference in treatment outcomes following OS and IUI in women with unexplained infertility who underwent HSG compared to laparoscopy for the assessment of the tubal patency during the initial fertility workup. The finding suggests minimal or no impact of selecting HSG over diagnostic laparoscopy as a tubal patency test on the subsequent IUI outcomes., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The aim of this study is to compare the ART (assisted reproductive technology) outcomes and cancellation rates between GnRH antagonist protocol and GnRH agonist short protocol in POSEIDON (Patient-Oriented Strategy Encompassing IndividualizeD Oocyte Number) groups 3 and 4. It is a retrospective cohort study conducted in the Department of Reproductive Medicine and Surgery of a tertiary-level hospital. Women who underwent ART treatment with either GnRH antagonist or GnRH agonist short protocol with fresh embryo transfer, between January 2012 and December 2019 belonging to POSEIDON 3 and 4 groups, were included. Among the 295 women who belonged to the POSEIDON groups 3 or 4, 138 women received GnRH antagonist and 157 women received GnRH agonist short protocol. The median total dose of gonadotropin in the GnRH antagonist protocol was not significantly different from GnRH agonist short protocol [3000, IQR (2481-3675) vs. 3175, IQR (2643-3993), p = 0.370]. There was a significant difference in the duration of stimulation between the GnRH antagonist and GnRH agonist short protocol [10, IQR (9-12) vs. 10, IQR (8-11), p = 0.002]. The median number of mature oocytes retrieved was significantly different in the cohort of women receiving GnRH antagonist protocol compared to GnRH agonist short protocol [3, IQR (2-5) vs. 3, IQR (2-4), p = 0.029]. There was no significant difference in the clinical pregnancy rate (24% vs. 20%, p = 0.503) and cycle cancellation rate (29.7% vs. 36.3%, p = 0.290) between the GnRH antagonist and agonist short protocols respectively. Live birth rate was not significantly different between the GnRH antagonist protocol (16.7%) and GnRH agonist short protocol (14.0%) [OR 1.23, 95% CI (0.56-2.68), p = 0.604]. After adjusting for the significant confounding factors, the live birth rate was not significantly associated with the antagonist protocol compared with the short protocol [aOR 1.08, 95% CI (0.44-2.63), p = 0.870]. Though GnRH antagonist protocol results in higher mature oocyte yield when compared with GnRH agonist short protocol, it does not translate into an increase in live birth in POSEIDON groups 3 and 4., (© 2023. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Background: Polycystic ovary syndrome (PCOS) is a common endocrine condition which affects women in the reproductive age group. South Asian women with PCOS have a higher risk of insulin resistance and metabolic disorder compared to women from other ethnic backgrounds. Lifestyle interventions such as dietary advice and physical exercise are recommended as a first-line management option for infertile women with PCOS. Most of the randomized controlled trials evaluating the role of lifestyle interventions in infertile PCOS women were characterized by methodological issues. The uptake of lifestyle modifications as a treatment strategy in the South Asian population is complicated by a difficult-to-change conventional high-carbohydrate diet and limited availability of space for physical activity in the region., Methods: The study is designed as an open-label, multicentre, randomized controlled trial in South Asian women with PCOS. Women attending the fertility clinic will be screened for eligibility, and women aged between 19 and 37 years who have been diagnosed with PCOS and wishing to conceive will be invited to participate in the trial. We will include women with body mass index (BMI) between ≥ 23 and ≤ 35 kg/m 2 and duration of infertility ≤ 3 years. We plan to randomize women with PCOS into two groups: group A will receive the intervention which will consist of individualized advice on diet and physical exercise along with a telephonic reminder system and follow-up visits, and group B (control) will receive one-time advice on diet and physical exercise. Both groups will receive up to three cycles of ovulation induction with letrozole after 3 months of randomization during the 6-month treatment period. The primary outcome of the trial will be the live birth following conception during the intervention period. The secondary outcomes include clinical pregnancy rate, ongoing pregnancy rate, miscarriage rate, ectopic pregnancy rate, stillbirth, time to pregnancy, mean weight loss, differences in anthropometric parameters, improvement in menstrual regularity and quality of life score., Discussion: The IPOS trial results could help clarify and provide more robust evidence for advocating an individualized lifestyle intervention in PCOS women who wish to conceive., Trial Registration: Clinical Trial Registry of India CTRI/2023/04/051620. Registered on 13 April 2023., (© 2023. The Author(s).)

Background: While elective single-embryo transfer (eSET) has been advocated in select countries, the global acceptance of the eSET policy has been undermined due to various issues. It is imperative to understand the couples' perspectives regarding the number of embryos transferred., Aims: We planned a study to evaluate the knowledge and attitude of infertile couples undergoing assisted reproductive technology towards eSET in self-funded treatment cycles in a low-resource setting., Settings and Design: We conducted a cross-sectional study at a tertiary-level referral facility between February 2020 and September 2022., Materials and Methods: This was an interviewer-administered questionnaire-based survey in two stages. The first stage involved the assessment of the knowledge of the participants. Following this, participants were given an information pamphlet and the second stage of the interview was conducted to assess the attitude and change in preference for embryo transfer number., Statistical Analysis Used: The Chi-square and Fisher's exact test were applied to find an association between categorical variables. Logistic regression was used to assess the association between factors and outcomes., Results: eSET was the preferred choice for only 5.8% of the participants. Following our educational intervention using an information leaflet, there was a statistically significant increase in the preference for eSET ( P = 0.01). Univariate logistic regression analysis revealed that participants with a monthly income of ≤50,000 INR had a significantly higher preference for eSET., Conclusion: Continued emphasis on the risks of double-embryo transfer coupled with individualised selection criteria for eSET may help to achieve reasonable congruency between the clinician and couples' decision., Competing Interests: Dr. Mohan Shashikant Kamath is the Associate Editor of JHRS. He has had no role in peer-review process or editorial decisions., (Copyright: © 2023 Journal of Human Reproductive Sciences.)

In the decade since non-invasive prenatal testing (NIPT) was first implemented as a prenatal screening tool, it has gained recognition for its sensitivity and specificity in the detection of common aneuploidies. This review mainly focuses on the emerging role of NIPT in pregnancies following assisted reproductive technology (ART) in the light of current evidence and recommendations. It also deals with the challenges, shortcomings and interpretational difficulties related to NIPT in ART pregnancies, with particular emphasis on twin and vanishing twin pregnancies, which are widely regarded as the Achilles' heel of most pre-natal screening platforms. Future directions for exploration towards improving the performance and extending the scope of NIPT are also addressed., (© 2022 Bentham Science Publishers.)

The process of implantation is characterized by a complex cross-talk between the endometrium and the blastocyst, with the endometrium only being receptive to implantation during a transient window of implantation of approximately 2-3 days during the midsecretory phase. The timing of embryo transfer, including frozen embryo transfer, is therefore critical to the success of implantation. In this article, we discuss various elements that may guide the timing of frozen embryo transfer, including the role of endometrial characteristics such as thickness, days postovulation or length of progesterone administration, stage of the embryo, and the application of endometrial receptivity tests to guide personalized embryo transfer., (Copyright © 2022 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Infertility is a global health issue. The variation in the prevalence of unexplained infertility is attributed to the choice of investigation. There remains a knowledge gap on the impact of minimal and mild endometriosis on treatment outcomes following intrauterine insemination (IUI)., Aim: The aim of this study was to compare treatment outcomes following ovarian stimulation (OS) and intrauterine insemination (IUI) between minimal and mild endometriosis versus unexplained infertility., Settings and Design: A retrospective analysis of women undergoing OS with intrauterine insemination during the year 20142020 in the Department of Reproductive Medicine and Surgery, Christian Medical College, Vellore, was considered for the study., Materials and Methods: Women with minimal and mild endometriosis or unexplained infertility diagnosed by diagnostic hysterolaparoscopy were included for the analysis. Univariate and multivariate analysis was done. The primary outcome was live birth rate (LBR) per cycle. The secondary outcomes measured were clinical pregnancy rate (CPR) , cumulative LBR (CLBR) per women, cumulative CPR (CCPR) per women and miscarriage rate., Statistical Analysis Used: The baseline parameters were compared using a t-test for continuous data, and categorical data were compared using the Chi-square/Fisher's exact test as appropriate. The outcomes were assessed using logistic regression analysis and expressed as odds ratio (OR) with 95% confidence intervals (CI)., Results: There were no significant differences in CPR per cycle (14.28% vs. 18.8%, OR: 0.71; 95% CI: 0.401.28) and LBR per cycle (14.28% vs. 16.6%, OR: 0.84; 95% CI: 0.461.51) between the endometriosis and unexplained infertility groups. The cumulative LBR per woman and CCPR per woman also did not show any significant difference in between the two groups., Conclusion: The current study did not find any significant differences in cumulative LBR and CPR following OS-IUI in women with minimal or mild endometriosis and unexplained infertility., Competing Interests: Dr Mohan S Kamath is a deputy editor with the JHRS, but he has had no role in the blinded peer-review or editorial process pertaining to this manuscript., (Copyright: © 2022 Journal of Human Reproductive Sciences.)

Background: The use of peri-implantation glucocorticoids has been advocated to improve embryo implantation during assistive reproductive technology (ART) cycles such as in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI). It has been proposed that glucocorticoids may improve the intrauterine environment by acting as immunomodulators to reduce the uterine natural killer (NK) cell count and activity, normalising the cytokine expression profile in the endometrium and by suppression of endometrial inflammation., Objectives: To evaluate the effectiveness and safety of glucocorticoids versus no glucocorticoids administered around the time of anticipated implantation in women undergoing IVF or ICSI., Search Methods: We searched the Cochrane Gynaecology and Fertility (CGF) Group specialised register, CENTRAL (now also containing output from two trial registers and CINAHL), MEDLINE and Embase, on 20 December 2021, together with reference checking, contact with experts in the field and relevant conference proceedings to identify additional studies. This review is an update of the review first published in  2007 and last updated in 2012., Selection Criteria: Randomised controlled trials (RCTs) comparing the efficacy of supplementary systemic administration of glucocorticoids in the peri-implantation period with a placebo or no glucocorticoids in subfertile women undergoing IVF or ICSI were included., Data Collection and Analysis: We used standard methodological procedures recommended by Cochrane. The primary review outcomes were live birth rate and multiple pregnancy., Main Results: We included 16 RCTs (2232 couples analysed). We are uncertain whether glucocorticoids improved live birth rates (odds ratio (OR) 1.37, 95% confidence interval (CI) 0.69 to 2.71; 2 RCTs, n = 366; I 2 = 7%; very low-certainty evidence). This suggests that if the chance of live birth following no glucocorticoids/placebo is assumed to be 9%, the chance following glucocorticoids would be between 6% and 21%. We are also uncertain whether there was a difference between peri-implantation glucocorticoids on multiple pregnancy rates per couple (OR 0.86, 95% CI 0.33 to 2.20; 4 RCTs, n = 504; I 2 = 53%; very low-certainty evidence). The I 2 of 53% may represent moderate statistical heterogeneity and results have to be interpreted with caution. With regard to pregnancy rates, we are uncertain whether there was a difference between ongoing pregnancy rates after glucocorticoids versus no glucocorticoids/placebo (OR 1.19, 95% CI 0.80 to 1.76; 3 RCTs, n = 476; I 2 = 0%; very low-certainty evidence) and clinical pregnancy rates after glucocorticoids versus no glucocorticoids/placebo (OR 1.17, 95% CI 0.95 to 1.44; 13 RCTs, n = 1967; I 2 = 0%; low-certainty evidence). This suggests that if the chance of clinical pregnancy following no glucocorticoids/placebo is assumed to be 25%, the chance following glucocorticoids would be between 24% and 32%. Furthermore, we are also uncertain whether peri-implantation glucocorticoids influenced miscarriage rates per couple (OR 1.09, 95% CI 0.63 to 1.87; 6 RCTs, n = 821; I 2 = 0%; very low-certainty evidence), the incidence of ectopic pregnancies per couple (OR 2.28, 95% CI 0.33 to 15.62; 3 RCTs, n = 320; I 2 = 0%; very low-certainty evidence) and ovarian hyperstimulation syndrome (OHSS) per couple (OR 1.07, 95% CI 0.60 to 1.90; 3 RCTs, n = 370; I 2 = 0%; very low-certainty evidence) compared to no glucocorticoids/placebo. The evidence was very low to low certainty: the main limitations were serious risk of bias due to poor reporting of study methods, and serious imprecision., Authors' Conclusions: Overall, there was insufficient evidence that administration of peri-implantation glucocorticoids in IVF/ICSI cycles influenced clinical outcomes. These findings were limited to the routine use of glucocorticoids in subfertile women undergoing IVF or ICSI., (Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Study Question: Does endometriosis affect live birth following donor oocyte recipient versus autologous IVF?, Summary Answer: There was no significant difference in the live birth rate (LBR) in women with endometriosis undergoing donor oocyte recipient cycles versus autologous IVF cycles., What Is Known Already: For infertile women with endometriosis, IVF is often considered as a treatment option. Lower implantation and pregnancy rates have been observed following IVF in women with endometriosis. It has been debated whether the lower pregnancy rate is due to the effect on oocyte quality or the endometrium, thus affecting implantation. To delineate whether endometriosis affects oocyte quality or the endometrium, we planned a study, using a donor oocyte recipient model, where the recipients were women diagnosed with endometriosis and compared their outcomes with women who underwent autologous IVF, who had also been diagnosed with endometriosis., Study Design Size Duration: Human Fertilization and Embryology Authority (HFEA) anonymized data from 1996 to 2016 were analyzed. This comprised of a total of 758 donor oocyte recipients, where the recipients were women diagnosed with endometriosis, and 12 856 autologous IVF cycles where the women were diagnosed with endometriosis as the sole cause of infertility., Participants/materials Setting Methods: Data on all women with endometriosis undergoing donor oocyte recipient and autologous IVF cycles were analyzed to compare live birth outcomes. Logistic regression analysis was performed adjusting for number of previous IVF cycles, previous live birth, period of treatment, day of embryo transfer, number of embryos transferred and fresh or frozen embryo transfer cycle., Main Results and the Role of Chance: There was no significant difference in the LBR in women with endometriosis undergoing donor oocyte recipient fresh embryo transfer cycles compared to women undergoing autologous IVF fresh embryo transfer cycles (31.6% vs 31.0%; odds ratio (OR) 1.03, 99.5% CI 0.79-1.35). After adjusting for confounders, there was no significant difference in LBR in women with endometriosis undergoing donor oocyte recipient fresh embryo transfer cycles versus autologous fresh embryo transfer cycles (adjusted OR (aOR) 1.05, 99.5% CI 0.79-1.41).There was no significant difference in the LBR in women with endometriosis undergoing donor oocyte recipient frozen embryo transfer cycles compared to women undergoing autologous frozen embryo transfer cycles (19.6% vs 24.0%; OR 0.77, 99.5% CI 0.47-1.25). After adjusting for potential confounders, there was no significant difference in the LBR in women undergoing donor oocyte recipient frozen embryo transfer cycles compared with autologous frozen embryo transfer cycles (aOR 0.85, 99.5% CI 0.51-1.41)., Limitations Reasons for Caution: Although the analysis was adjusted for potential confounders, there was no information on the extent and classification of endometriosis as well as oocyte number. Furthermore, adenomyosis is thought to co-exist in women with endometriosis and may have independent pathophysiological mechanisms affecting fertility, for which there was no information., Wider Implications of the Findings: The study shows no difference in LBR between donor oocyte recipient cycles in which all recipients had endometriosis compared to autologous IVF cycles in women with endometriosis. Therefore, this study finding suggests that there may be a minimal or no effect of oocyte quality on IVF outcomes in women with endometriosis., Study Funding/competing Interests: No funding was obtained. M.S.K. is an associate editor with Human Reproduction Open . He was not involved in the editorial or peer review process for the manuscript., Trial Registration Number: N/A., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Aim: Assisted reproductive technique (ART) has emerged as the highest form of treatment for infertile couples. Transvaginal oocyte retrieval is currently performed under conscious sedation in most centers. Since it is a relatively painful procedure, a number of adjuvant therapies have been tried to improve pain relief during the procedure. Music therapy is a nonpharmacological technique that has been successfully used for pain relief in perioperative and chronic pain of malignancy. However, studies evaluating its usefulness in ART-related procedures are limited. We evaluated the effectiveness of music therapy as an adjuvant for pain relief during oocyte retrieval., Methods: This was a randomized controlled trial conducted at a tertiary level teaching hospital in South India from September 2020 to March 2021. All women undergoing transvaginal oocyte retrieval were randomized to receive either music therapy along with conscious sedation (Group A) or conscious sedation alone (Group B). The primary outcome was postprocedure pain score assessed by the visual analog scale. Secondary outcomes included anxiety score., Results: A total of 109 women were randomized into Group A (54 women) and Group B (55 women). The postprocedure pain score was comparable between the two study groups (6.0, interquartile range [IQR] 4 to 6 vs. 6.0, IQR 4 to 6; p = 0.69). However, anxiety levels were found to be significantly lower in women who were offered music therapy (3.0, IQR 1 to 5 vs. 4.0, IQR 3 to 6; p = 0.004)., Conclusion: The use of music therapy as an adjuvant to conscious sedation was found to have no significant benefit in pain relief during oocyte retrieval., (© 2022 Japan Society of Obstetrics and Gynecology.)

Objective: To estimate the incremental yield of single nucleotide polymorphism (SNP) array over karyotype and to assess the diagnostic accuracy of SNP array as a stand-alone test versus SNP array with karyotype in detecting chromosomal abnormalities for prenatal diagnosis in women with an abnormal fetal ultrasound., Study Design: Studies in which SNP array and karyotype had been used for diagnosing chromosomal aberrations in fetuses with abnormal ultrasound findings were included. A systematic search of relevant studies published in the English language in EMBASE, PubMed, CENTRAL, CDSR (Cochrane database of systematic reviews), SCOPUS and Web of science between 1996 and May 2020 was performed. Primary outcome was incremental yield of SNP array over karyotype (number of patients with abnormalities detected by SNP array over number of patients with normal karyotype). Other outcomes included diagnostic accuracy of SNP array alone versus SNP array and karyotype for prenatal diagnosis. Pooled sensitivities, specificities, and their 95% confidence intervals (CI) were presented., Result(s): Seven studies were included. The incremental yield of SNP array over karyotype was 8% (95% Confidence interval, CI 4-12%) while incremental yield of karyotype over SNP array in foetus with abnormal ultrasound was 0% (95% CI 0-1%). The agreement between SNP array and karyotype was 92%. The variant of unknown significance rates ranged between 4 and 8 %. The pooled sensitivity and specificity of SNP array versus SNP array and karyotype was 0.97 (95% CI 0.92-0.99) and 1.00 (95% CI1.00-1.00), respectively., Conclusion(s): SNP array provides additional information on chromosomal abnormalities over and above conventional karyotype. When used as a stand-alone test, SNP array performs favourably as a diagnostic modality when compared against SNP array and karyotype for prenatal diagnosis with an abnormal fetal ultrasound., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Study Question: We aim to develop, disseminate and implement a minimum data set, known as a core outcome set, for future male infertility research., What Is Known Already: Research into male infertility can be challenging to design, conduct and report. Evidence from randomized trials can be difficult to interpret and of limited ability to inform clinical practice for numerous reasons. These may include complex issues, such as variation in outcome measures and outcome reporting bias, as well as failure to consider the perspectives of men and their partners with lived experience of fertility problems. Previously, the Core Outcome Measure for Infertility Trials (COMMIT) initiative, an international consortium of researchers, healthcare professionals and people with fertility problems, has developed a core outcome set for general infertility research. Now, a bespoke core outcome set for male infertility is required to address the unique challenges pertinent to male infertility research., Study Design Size Duration: Stakeholders, including healthcare professionals, allied healthcare professionals, scientists, researchers and people with fertility problems, will be invited to participate. Formal consensus science methods will be used, including the modified Delphi method, modified Nominal Group Technique and the National Institutes of Health's consensus development conference., Participants/materials Setting Methods: An international steering group, including the relevant stakeholders outlined above, has been established to guide the development of this core outcome set. Possible core outcomes will be identified by undertaking a systematic review of randomized controlled trials evaluating potential treatments for male factor infertility. These outcomes will be entered into a modified Delphi method. Repeated reflection and re-scoring should promote convergence towards consensus outcomes, which will be prioritized during a consensus development meeting to identify a final core outcome set. We will establish standardized definitions and recommend high-quality measurement instruments for individual core outcomes., Study Funding/competing Interests: This work has been supported by the Urology Foundation small project award, 2021. C.L.R.B. is the recipient of a BMGF grant and received consultancy fees from Exscentia and Exceed sperm testing, paid to the University of Dundee and speaking fees or honoraria paid personally by Ferring, Copper Surgical and RBMO. S.B. received royalties from Cambridge University Press, Speaker honoraria for Obstetrical and Gynaecological Society of Singapore, Merk SMART Masterclass and Merk FERRING Forum, paid to the University of Aberdeen. Payment for leadership roles within NHS Grampian, previously paid to self, now paid to University of Aberdeen. An Honorarium is received as Editor in Chief of Human Reproduction Open. M.L.E. is an advisor to the companies Hannah and Ro. B.W.M. received an investigator grant from the NHMRC, No: GNT1176437 is a paid consultant for ObsEva and has received research funding from Ferring and Merck. R.R.H. received royalties from Elsevier for a book, consultancy fees from Glyciome, and presentation fees from GryNumber Health and Aytu Bioscience. Aytu Bioscience also funded MiOXYS systems and sensors. Attendance at Fertility 2020 and Roadshow South Africa by Ralf Henkel was funded by LogixX Pharma Ltd. R.R.H. is also Editor in Chief of Andrologia and has been an employee of LogixX Pharma Ltd. since 2020. M.S.K. is an associate editor with Human Reproduction Open . K.Mc.E. received an honoraria for lectures from Bayer and Pharmasure in 2019 and payment for an ESHRE grant review in 2019. His attendance at ESHRE 2019 and AUA 2019 was sponsored by Pharmasure and Bayer, respectively. The remaining authors declare no competing interests., Trial Registration Number: Core Outcome Measures in Effectiveness Trials (COMET) initiative registration No: 1586. Available at www.comet-initiative.org/Studies/Details/1586., Trial Registration Date: N/A., Date of First Patient’s Enrolment: N/A., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Manual motor deficits are common in children with attention deficit/hyperactivity disorder (ADHD); however, it is unclear whether these impairments persist into adulthood. The aim of this study was to examine manual dexterity and strength in young adults with ADHD aged 18-25 years. Sixty-one individuals with confirmed ADHD and 56 adults without ADHD completed Purdue Pegboard tasks for manual dexterity and maximal hand- and pinch-grip tests for strength. In the Purdue Pegboard task, participants placed pins using the right, left, and both-hands, respectively. In addition, participants built assemblies using pins, washers, and collars with alternating hand movements. The results demonstrated that women without ADHD out-performed the other three groups in the right-hand, bimanual, and assembly PPB tasks. Both maximal hand strength tests demonstrated that men were stronger than women, but no differences were observed between adults with and without ADHD. The current findings suggest that adults with ADHD may have deficits in manual dexterity and tasks requiring bimanual coordination., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Study Question: What is the knowledge, anxiety levels and attitudes of infertile couples towards coronavirus disease 2019 (COVID-19) and its impact on undergoing self-funded treatment cycles?, Summary Answer: In spite of a high level of awareness about COVID-19, anxiety levels were low and many participants wanted to continue fertility treatment during the pandemic., What Is Known Already: The COVID-19 pandemic has strained the already overburdened public health infrastructure in many of the resource-limited settings across the world. After an initial decision to suspend fertility treatments, regulatory authorities advocated phased resumptions of treatment. Owing to limited healthcare resources and the detrimental impact of COVID-19 on the economy and job losses, fertility services have been disproportionately affected. It is important to understand the perceptions of infertile couples, who are the key stakeholders in shared decision-making, especially for self-funded treatments, on the continuation of fertility treatment during the current COVID-19 pandemic., Study Design Size Duration: This was a questionnaire-based cross-sectional study conducted among 502 participants (251 infertile couples) at a tertiary level infertility clinic between May 2020 and November 2020. The study recruitment period (6 months) coincided with the increase and peak of COVID-19 infection in India. The study included infertile couples who had attended the clinic either for assessment or fertility treatment., Participants/materials Setting Methods: An interviewer administered the questionnaire survey, which was conducted in two stages for each participant. In the first stage, knowledge about COVID-19 and anxiety levels caused by the ongoing pandemic were assessed using a validated Generalized Anxiety Disorder-7 (GAD-7) tool. Following this, all the participants were provided with a COVID-19 information pamphlet. Subsequently, in the second stage, participants were administered another questionnaire to assess their attitudes towards fertility treatment and pregnancy during the COVID-19 pandemic., Main Results and the Role of Chance: The results showed that the knowledge levels and awareness about COVID-19 was high among infertile couples attending the infertility clinic. The majority of the participants were aware of the mode of spread (87.6-93.4% correct answers to different questions), common symptoms (64.1-96.2%) and the importance of preventative measures (95.6-97.4%). Most of the participants (474/502; 94.4%) did not show anxiety when being assessed using GAD-7. A vast majority (96.5-99.2%) of the participants were in agreement with the need for following preventative measures for reducing the spread of COVID-19. About one-third of the participants wanted to delay the fertility treatment until the pandemic is over (166/502; 33.1%). Approximately 42.2% (212/502) of the participants did not feel the need to suspend fertility treatment during the pandemic. Further analysis revealed that participants' education levels significantly influenced the desire to continue fertility treatment: participants with lower levels of education (below graduate) were less likely to continue fertility treatment (adjusted odds ratio 0.34, 95% CI, 0.12-0.98)., Limitations Reasons for Caution: Questionnaire-based responses could have limited the ability of the interviewer to capture the entire range of thoughts and views of the participants on the COVID pandemic and their fertility treatments. Furthermore, a language barrier was encountered for some couples for which assistance from a translator was sought., Wider Implications of the Findings: Given the impact of infertility and the associated stigma, public health policy makers, regulatory authorities and fertility societies should consider a way to sustain the treatment options and develop appropriate guidelines to continue treatment, particularly when much of the world is experiencing the second and third waves of the COVID pandemic., Study Funding/competing Interests: This study has not received any specific grant from funding agencies in the public, commercial or not-for-profit sectors. M.S.K. is an associate editor with Human Reproduction Open . The other authors have no competing interests to declare., Trial Registration Number: N/A., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Objective: One in seven couples is infertile and ovulatory dysfunction accounts for 25% of the cases. Polycystic ovarian syndrome (PCOS) is the most common endocrinopathy associated with ovulatory dysfunction. Traditionally, clomiphene is considered the first-line drug for infertile PCOS women. Recently, letrozole was found to be an effective alternative ovulogen. The recent Cochrane review concluded that although live birth was higher with letrozole in unselected PCOS population, evidence was insufficient regarding effect of letrozole in treatment-naïve women., Materials and Methods: We conducted a cohort study that included treatment-naïve infertile PCOS women at a tertiary level infertility center in South India. Participants in the prospective arm were given letrozole 2.5 mg daily for 5 days and the retrospective arm included women who had undergone ovulation induction with clomiphene (100 mg) for up to five treatment cycles. The primary outcome was ovulation rate. Secondary outcomes were clinical pregnancy, live birth, multiple pregnancy, and miscarriage rate. The trial was registered under the Clinical Trials Registry, India (CTRI/2018/07/014704)., Results: A total of 135 women in the letrozole group and 127 women in the clomiphene group underwent treatment. The ovulation rate per woman was similar in both groups (84.4% vs. 77.2%; p = 0.13). Letrozole was associated with significantly higher clinical pregnancy (38.5% vs. 22.0%; p = 0.004) and live birth rate per woman (30.3% vs. 18.9%; p = 0.03)., Conclusion: The current study found letrozole to be a superior ovulation induction agent as compared to clomiphene in treatment-naïve infertile women with PCOS., (© 2021 Japan Society of Obstetrics and Gynecology.)

Background: Women with abnormal hysterosalpingography (HSG) are anxious regarding the presence of tubal pathology. It is important to know the predictive value of HSG and the need for subsequent laparoscopy following an abnormal report. In the era of assisted reproductive technology, the role of invasive testing such as diagnostic laparoscopy is being increasingly questioned due to its invasiveness and associated risks. There is a need to explore the positive predictive value (PPV) of HSG in detecting bilateral tubal block in our population as PPV changes with the prevalence of disease., Aim: The aim of this study was to evaluate the diagnostic accuracy of HSG in identifying tubal blockage in subfertile women., Setting and Design: This was a prospective diagnostic study conducted in the department of reproductive medicine and surgery in a university-level hospital., Materials and Methods: The study included 199 subfertile women who had undergone HSG earlier and were planned for laparoscopy from April 2017 to January 2021. Findings of HSG and laparoscopy were compared with HSG as index test and laparoscopy as reference test, and the outcomes analysed were PPV of HSG for a bilateral tubal block, bilateral hydrosalpinx, abnormal HSG (unilateral or bilateral tubal block) and agreement between HSG and diagnostic laparoscopy in detecting normal and abnormal findings., Statistical Analysis: Kappa statistics, Stuart-Maxwell tests of marginal homogeneity and prevalence-adjusted bias-adjusted kappa (PABAK) statistics were used., Results: The PPV for a bilateral block with HSG was 20.9% (95% CI: 13.7-29.7). The PPV of HSG for bilateral hydrosalpinx was 50.0% (95% CI: 6.8-93.2). PABAK was estimated to be 0.42 (95% CI: 0.30-0.55), suggestive of moderate agreement between the tests. Findings of laparoscopy in women with at least one patent tube in HSG showed that in 12.3% of cases, the management was likely to change due to the operative findings., Conclusion: The current study showed low PPV for bilateral tubal block diagnosed with HSG which translates into a need for further confirmation by laparoscopy. In one out of every eight women with at least one patent tube on HSG, performing laparoscopy changed the management., Competing Interests: Dr. Mohan S Kamath is the Deputy Editor for Journal of Human Reproductive Sciences. However, for the current manuscript, he was not involved in the editorial decisions or blind peer review process. The other authors have no conflict of interest., (Copyright: © 2021 Journal of Human Reproductive Sciences.)

Background: Scrub typhus, a vector-borne zoonotic infection caused by the bacteria Orientia tsutsugamushi, is one of the most common and clinically important rickettsial infections worldwide. An estimated one million cases occur annually with a high case fatality rate. Although scrub typhus is a major public health threat in India, the burden and distribution remains unclear. We aimed to estimate the burden of scrub typhus in India., Methodology: We performed a systematic review of published literature on scrub typhus from India to extract information on epidemiology, morbidity, and mortality. Important databases were searched using keywords and appropriate combinations. We identified observational, interventional, and population-based studies and extracted the data to evaluate the number of cases diagnosed using serology or PCR and the number of deaths due to scrub typhus. We conducted a systematic narrative synthesis to summarize included studies., Principal Findings: In the last decade, there were 18,781 confirmed scrub typhus cases reported in 138 hospital-based studies and two community-based studies. IgM ELISA was used in 122 studies to confirm the cases in majority (89%). The proportion of scrub typhus among acute undifferentiated febrile illness (AUFI) studies was 25.3%, and community seroprevalence was 34.2%. Ninety studies had data published on multiple organ involvement out of which 17.4% of cases had multiple organ dysfunction syndromes, 20.4% patients required ICU admission, and 19.1% needed ventilation. The overall case-fatality rate was 6.3%, and the mortality among those with multi-organ dysfunction syndrome was as high as 38.9%., Conclusion/significance: Scrub typhus, a common acute febrile illness in India causing severe morbidity, accounts for a large number of deaths. The burden of the disease has been underappreciated. Early diagnosis and prompt treatment can significantly reduce complications and mortality. Establishing good surveillance and instituting appropriate control measures are urgently needed., Competing Interests: The authors have declared that no competing interests exist.

Background: It is well known that seasonal variations influence natural conception and birth rates variably in different populations. It has been hypothesised that similar seasonal influences may affect treatment outcomes following assisted reproductive technology (ART). However, most studies report conflicting results., Aim: The aim of the study is to elucidate whether seasonality had any impact on the treatment success of the ART program., Study Setting and Design: We conducted a retrospective cohort study at a university-level tertiary care hospital in South India., Materials and Methods: All couples who underwent ART between January 2012 and December 2016 were included in the study. We divided the study population into three groups based on the seasonal differences experienced in our region. The primary outcome was live birth rate (LBR)., Statistical Analysis: Univariate and multiple logistic regression models were used to compare outcomes and results reported as odds ratio (OR) and 95% confidence interval (CI)., Results: Univariate analysis revealed no significant difference in LBR in monsoon season (174/651, 26.7% vs. 83/319, 26.0%; OR 1.04, 95% CI 0.77,1.41; P = 0.81) as compared to summer. However, LBR was significantly higher in winter season (114/341, 33.4% vs. 83/319, 26.0%; OR 1.43; 95% CI: 1.02, 2.00; P = 0.04). Further, multivariate analysis following adjustment for various confounding factors revealed no significant statistical difference in LBR in monsoon (adjusted odds ratio [aOR], 0.92; 95% CI: 0.66, 1.26; P = 0.59) or winter (aOR 1.32; 95% CI: 0.92, 1.88; P = 0.13) as compared to summer season., Conclusion: The current study found no significant effect of seasonal variation on LBR following ART., Competing Interests: Dr. Mohan S Kamath is the Deputy Editor for Journal of Human Reproductive Sciences. However, for the current manuscript, he was not involved in the editorial decisions or blind peer review process., (Copyright: © 2021 Journal of Human Reproductive Sciences.)

Objective: To evaluate the evidence addressing the association between the use of ovarian stimulation drugs and the risk of breast cancer., Design: Systematic review and meta-analysis., Setting: Not applicable., Patient(s): Women without any previous history of breast cancer undergoing ovarian stimulation., Intervention(s): Electronic databases were searched from 1990 until January 2020. All cohort studies reporting new incidences of breast cancer in infertile women using ovarian stimulating drugs were included. Treated (exposed) infertile women were compared with the unexposed general population with unexposed infertile women as controls., Main Outcome Measure(s): New diagnosis of breast cancer within an infertile and general population after exposure to ovarian stimulation drugs., Result(s): Overall, the quality of evidence was very low because of the serious risk of bias and indirectness (nonrandomized studies). There was no significant increase in the risk of breast cancer among women treated with any ovarian stimulation drug for infertility compared with that in unexposed controls from the general population and the infertile population (pooled odds ratio 1.03, 95% Confidence interval 0.86 to 1.23, 20 studies, I 2 = 88.41%, very low quality of evidence). Furthermore, no significant increase in the risk of breast cancer was found with the use of clomiphene citrate or gonadotropins, alone or in combination., Conclusion(s): The current study found that the use of clomiphene citrate and gonadotropins in infertile women was not associated with an increased risk of breast cancer., (Crown Copyright © 2021. Published by Elsevier Inc. All rights reserved.)

Study Question: Does the cause of infertility affect the perinatal outcomes preterm birth (PTB) and low birth weight (LBW) following IVF treatment?, Summary Answer: The risk of PTB and LBW was higher with female causes of infertility-ovulatory disorders, tubal disorders and endometriosis-compared to unexplained infertility but the absolute increase in risk was low., What Is Known Already: Infertility is associated with an increased risk of adverse perinatal outcomes. Risk of adverse perinatal outcomes is also higher following ART compared to spontaneous conceptions. Infertility can result from female and/or male factors or is unexplained when the cause cannot be delineated by standard investigations. Given that infertility and ART are contributory to the adverse perinatal outcomes, it is a matter of interest to delineate if the specific cause of infertility influences perinatal outcomes following IVF treatment., Study Design, Size, Duration: Anonymous data were obtained from the Human Fertilization and Embryology Authority (HFEA). The HFEA has collected data prospectively on all ART cycles performed in the UK since 1991. Data from 1991 to 2016 comprising a total of 117 401 singleton live births following IVF with or without ICSI (IVF ± ICSI) for sole causes of infertility were analysed for PTB and LBW. Cycles having more than one cause of infertility and/or multiple births were excluded., Participants/materials, Setting, Methods: Data on all women undergoing stimulated IVF ± ICSI treatment cycles were analysed to compare perinatal outcomes of PTB and LBW among singleton live births based on the cause of infertility (ovulatory disorders, tubal disorders, endometriosis, male factor, unexplained). Logistic regression analysis was performed, adjusting for female age category, period of treatment, previous live births, IVF or ICSI, number of embryos transferred and fresh or frozen embryo transfer cycles., Main Results and the Role of Chance: Compared to unexplained infertility, the risk of PTB was significantly higher with ovulatory disorders (adjusted odds ratio (aOR) 1.31, 99.5% CI 1.17 to 1.46); tubal disorders (aOR 1.25, 99.5% CI 1.14 to 1.38) and endometriosis (aOR 1.17, 99.5% CI 1.01 to 1.35). There was no significant difference in the risk of PTB with male factor causes compared to unexplained infertility (aOR 1.01, 99.5% CI 0.93, 1.10). The risk of LBW was significantly higher with ovulatory disorders (aOR 1. 29, 99.5% CI 1.16 to 1.44) and tubal disorders (aOR 1.12, 99.5% CI 1.02 to 1.23) and there was no increase in the risk of LBW with endometriosis (aOR 1.11, 99.5% CI 0.96 to 1.30) and male factor causes (aOR 0.94, 99.5% CI 0.87, 1.03), compared to unexplained infertility., Limitations, Reasons for Caution: Although the analysis was adjusted for several important confounders, there was no information on the medical history of women during pregnancy to allow adjustment. The limitations with observational data would apply to this study, including residual confounding., Wider Implications of the Findings: This is the largest study to address the causes of infertility affecting perinatal outcomes of PTB and LBW. The information is important for the management of pregnancies and the underlying reasons for the associations observed need to be further understood., Study Funding/competing Interest(s): No funding was obtained. There are no competing interests to declare., Trial Registration Number: N/A., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Study Question: Is there a difference in dietary patterns among subfertile South Asian women undergoing frozen embryo transfer (FET)?, Summary Answer: Significant regional differences in dietary pattern exist among subfertile South Asian women undergoing FET., What Is Known Already: Preconception consumption of certain food groups or adopting specific dietary patterns, such as the 'Mediterranean diet', and its level of adherence have been shown to enhance the odds of achieving a successful pregnancy in women undergoing ART. However, differences in geographic location, individual preference, cultural beliefs and local availability contribute to such dietary choices. There is also a predisposition to a vitamin B12 deficiency in those of South Asian ethnicity and a predominant pattern of vegetarian food intake. There is a paucity of studies analysing the type of dietary pattern followed by South Asian women, their vitamin B12 levels and the potential impact on ART treatment outcomes., Study Design Size Duration: This is a cross-sectional study of 159 South Asian women aged 21-37 years, belonging to the Eastern (n = 75) and Southern (n = 84) regions of India plus Bangladesh, and undergoing a FET cycle at a tertiary level infertility clinic between February 2019 and March 2020., Participants/materials Setting Methods: Women underwent dietary assessment using '24-hour dietary recall' to capture daily nutrient consumption. A 'Food Frequency Questionnaire' listing commonly consumed foods was used to record frequency of intake. The primary outcome was the characterisation of regional dietary patterns in the cohorts using principal component analysis (PCA). Secondary outcomes included association of vitamin B12 intake and serum levels with clinical and ongoing pregnancy., Main Results and the Role of Chance: Four components contributing to overall variance in dietary pattern were identified, namely: meat, poultry and seafood; green leafy vegetables and root tubers; fruits, dairy and sugar; nuts and oilseeds. PCA analysis showed a significantly higher consumption of two components in the East-meat, poultry and fish ( P  < 0.001); green leafy vegetables and root tubers ( P  < 0.001). All women reported taking preconception oral folic acid supplementation. The dietary intake of vitamin B12 and serum concentration correlated, showing a good validity of measured dietary intake ( r  = 0.398; P ≤ 0.001). Compared to the Southern region, participants from the East showed a higher daily median intake of vitamin B12 (1.11 versus 0.28 mcg, respectively; P  < 0.001) and a higher serum vitamin B12 levels (441 versus 239 pg/ml, respectively; P  < 0.001). Ongoing pregnancy showed no association with dietary vitamin B12 intake (relative risk 0.90; 95% CI, 0.68 to 1.19) or serum vitamin B12 levels (relative risk 0.99; 95% CI, 0.73 to 1.33) after adjustments for female age, body mass index (BMI) and geographic differences. Women belonging to different quartiles of serum vitamin B12 concentration had a similar likelihood of ongoing pregnancy., Limitations Reasons for Caution: Self-reported dietary assessment is prone to measurement errors owing to its subjective nature and recall bias. The study was not adequately powered to detect the impact of geographic differences in vitamin B12 intake and serum levels on FET treatment outcomes, the second objective. We adjusted for potential confounders, such as female age and BMI, but it is possible that residual confounders, such as physical activity, stress and use of dietary supplements, may have influenced the results. Extrapolation of the study findings to women undergoing ART in other populations should be made with caution., Wider Implications of the Findings: Our study findings suggest important differences in local dietary patterns within the South Asian region. Hence a personalised approach to dietary assessment and intervention when undergoing ART based on population dynamics is warranted. The geographic differences in the vitamin B12 intake or serum levels did not have an impact on the FET outcomes. There is also a need to further investigate the impact of such dietary differences on ART treatment outcomes in a large study population., Study Funding/competing Interests: No grant from funding agencies in the public, commercial, or not-for-profit sectors was obtained. The authors have nothing to disclose., Trial Registration Number: N/A., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Study Question: Do live birth outcomes differ when Patient-Oriented Strategy Encompassing IndividualizeD Oocyte Number (POSEIDON) stratified groups are compared with women with good prognosis (non-POSEIDON group) undergoing ART?, Summary Answer: The current study showed no significant difference in the live birth rates (LBRs) per embryo transfer between POSEIDON groups 1 and 2 when compared with women in the non-POSEIDON group undergoing ART., What Is Known Already: Recently, there has been a lot of focus on the POSEIDON classification for low prognosis women undergoing ART and various management options have been advocated. For POSEIDON groups 1 and 2, low starting dose and gonadotrophin receptor polymorphism have been suggested as possible reasons for a hyporesponse, and increasing the starting gonadotrophin dose, the addition of recombinant LH and dual stimulation have been suggested as treatment options. Most of these treatment options are hypothetical in nature and need validation., Study Design Size Duration: In the current cohort study, a total of 1425 cycles were analyzed retrospectively following a single cycle fresh embryo transfer. The study period was from January 2013 to June 2018., Participants/materials Setting Methods: Women undergoing ART at a tertiary level infertility clinic were included. Clinical and treatment-related details were obtained from the hospital's electronic medical records. The ART outcomes in a non-POSEIDON group (women with an adequate ovarian reserve and / or optimal ovarian response i.e. >9 oocytes retrieved in the previous ART cycle) and a low prognosis group stratified by POSEIDON criteria were compared. We also examined the effectiveness of the modifications made in the current ART treatment protocols among women with an adequate ovarian reserve who had a history of poor/suboptimal response (POSEIDON 1 and 2)., Main Results and the Role of Chance: There was no statistically significant difference in the LBR per embryo transfer in POSEIDON group 1 (32/109, 29%) and group 2 (17/58, 29%) when compared with the non-POSEIDON group (340/1041, 33%) (adjusted odds ratio (aOR) 0.69; 95% CI 0.37-1.27 and aOR 0.93, 95% CI 0.43-1.97, respectively), while significantly lower LBR were observed in POSEIDON groups 3 (17/97, 17.5%) and 4 (12/120, 10%) (aOR 0.49; 95% CI 0.28-0.89 and aOR 0.38, 95% CI 0.19-0.74, respectively). The gonadotrophin dose alone was increased in one-quarter of the cycles and in another 27% the dose was increased along with the protocol change among POSEIDON group 1. In POSEIDON group 2, a change in the dose alone and in combination with protocol change was performed in 5 and 41% of cycles, respectively., Limitations Reasons for Caution: A limitation of our study is the retrospective nature of the study with an inherent risk of unknown confounders influencing the outcomes. Other limitations are the lack of cumulative live birth data and the relatively small sample within POSEIDON group 2, which could lead to a type II error., Wider Implications of the Findings: The current study showed no significant difference in the LBR between the POSEIDON groups 1 and 2 when compared with the non-POSEIDON group of women, while groups 3 and 4 had significantly lower LBR. The simple gonadotrophin/protocol changes in groups 1 and 2 resulted in LBRs comparable to women with good prognosis. These findings call for revisiting the proposed treatment strategies for POSEIDON groups 1 and 2., Study Funding/competing Interests: No funding was obtained. There are no competing interests to declare., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Background: Men with azoospermia undergoing a surgical sperm retrieval are anxious about the well-being of the baby. It is therefore important to study the perinatal outcomes in this group compared to the ejaculate sample group., Aim: The aim of the study was to compare the perinatal outcomes between ejaculate and surgical sperm retrieval (SSR) groups in couples undergoing intracytoplasmic sperm injection for male factor., Study Setting and Design: This was a retrospective cohort study conducted in a university-level infertility unit., Materials and Methods: It is a retrospective cohort study analysis of 628 assisted reproductive technique (ART) cycles with male factor and combined (male and female) factor infertility over a period of 5 years (January 2011-December 2015). All women who underwent a fresh embryo ART cycle were followed up. The study population included the ejaculate and SSR groups. The perinatal outcomes of these two groups were compared. The congenital anomaly risks among the two groups were also analyzed., Statistical Analysis: Chi-square test, Fisher's exact test and Logistic regression., Results: A total of 628 ART cycles were included in the current study, of which 478 cycles used ejaculate sperm, while SSR was done in 150 cycles. The analysis was restricted to singletons, and the risk of preterm birth was 22.9% in the ejaculate group, 5.9% in the epididymal group, and 12% in the testicular group (epididymal vs. ejaculate odds ratio [OR], 0.21; 95% confidence interval [CI]: 0.02-1.66) (testicular vs. ejaculate OR, 0.46; 95% CI: 0.12-1.65). The risk of low birth weight was 23.7% in the ejaculate group, 11.8% in the epididymal group, and 20.0% in the testicular group (epididymal vs. ejaculate OR, 0.42; 95% CI: 0.09-1.9) (testicular vs. ejaculate OR, 0.80; 95% CI: 0.27-2.3). The incidence of congenital anomalies was 7.3% in the ejaculate group, 0 in the epididymal group, and 3.5% in the testicular group (epididymal vs. ejaculate OR, 0.28; 95% CI: 0.01-5.2) (testicular vs. ejaculate OR, 0.63; 95% CI: 0.10-3.7) which was not significantly different., Conclusion: The current study showed no significant differences in the risk of adverse perinatal outcomes in the ejaculate group versus the surgically retrieved sperm groups., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Journal of Human Reproductive Sciences.)

Study Question: Are systematic reviews published within a 3-year period on interventions in ART concordant in their conclusions?, Summary Answer: The majority of the systematic reviews published within a 3-year period in the field of assisted reproduction on the same topic had discordant conclusions., What Is Known Already: Systematic reviews and meta-analyses have now replaced individual randomized controlled trials (RCTs) at the top of the evidence pyramid. There has been a proliferation of systematic reviews and meta-analyses, many of which suffer from methodological issues and provide varying conclusions., Study Design Size Duration: We assessed nine interventions in women undergoing ART with at least three systematic reviews each, published from January 2015 to December 2017., Participants/materials Setting Methods: The systematic reviews which included RCTs were considered eligible for inclusion. The primary outcome was extent of concordance between systematic reviews on the same topic. Secondary outcomes included assessment of quality of systematic reviews, differences in included studies in meta-analyses covering the same search period, selective reporting and reporting the quality of evidence., Main Results and the Role of Chance: Concordant results and conclusions were found in only one topic, with reviews in the remaining eight topics displaying partial discordance. The AMSTAR grading for the majority of the non-Cochrane reviews was critically low whilst it was categorized as high for all of the Cochrane reviews. For three of the nine topics, none of the included systematic reviews assessed the quality of evidence. We were unable to assess selective reporting as most of the reviews did not have a pre-specified published protocol., Limitations Reasons for Caution: We were limited by the high proportion of reviews lacking a pre-specified protocol, which made it impossible to assess for selective reporting. Furthermore, many reviews did not specify primary and secondary outcomes which made it difficult to assess reporting bias. All the authors of this review were Cochrane review authors which may introduce some assessment bias. The categorization of the review's conclusions as beneficial, harmful or neutral was subjective, depending on the tone and wording of the conclusion section of the review., Wider Implications of the Findings: The majority of the systematic reviews published within a 3-year period on the same topic in the field of assisted reproduction revealed discordant conclusions and suffered from serious methodological issues, hindering the process of informed healthcare decision-making., Study Funding/competing Interests: All the authors are Cochrane authors. M.S.K. is an editorial board member of Cochrane Gynaecology and Fertility group. No grant from funding agencies in the public, commercial or not-for-profit sectors was obtained., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Study Question: Can consensus definitions for the core outcome set for infertility be identified in order to recommend a standardized approach to reporting?, Summary Answer: Consensus definitions for individual core outcomes, contextual statements and a standardized reporting table have been developed., What Is Known Already: Different definitions exist for individual core outcomes for infertility. This variation increases the opportunities for researchers to engage with selective outcome reporting, which undermines secondary research and compromises clinical practice guideline development., Study Design, Size, Duration: Potential definitions were identified by a systematic review of definition development initiatives and clinical practice guidelines and by reviewing Cochrane Gynaecology and Fertility Group guidelines. These definitions were discussed in a face-to-face consensus development meeting, which agreed consensus definitions. A standardized approach to reporting was also developed as part of the process., Participants/materials, Setting, Methods: Healthcare professionals, researchers and people with fertility problems were brought together in an open and transparent process using formal consensus development methods., Main Results and the Role of Chance: Forty-four potential definitions were inventoried across four definition development initiatives, including the Harbin Consensus Conference Workshop Group and International Committee for Monitoring Assisted Reproductive Technologies, 12 clinical practice guidelines and Cochrane Gynaecology and Fertility Group guidelines. Twenty-seven participants, from 11 countries, contributed to the consensus development meeting. Consensus definitions were successfully developed for all core outcomes. Specific recommendations were made to improve reporting., Limitations, Reasons for Caution: We used consensus development methods, which have inherent limitations. There was limited representation from low- and middle-income countries., Wider Implications of the Findings: A minimum data set should assist researchers in populating protocols, case report forms and other data collection tools. The generic reporting table should provide clear guidance to researchers and improve the reporting of their results within journal publications and conference presentations. Research funding bodies, the Standard Protocol Items: Recommendations for Interventional Trials statement, and over 80 specialty journals have committed to implementing this core outcome set., Study Funding/competing Interest(s): This research was funded by the Catalyst Fund, Royal Society of New Zealand, Auckland Medical Research Fund and Maurice and Phyllis Paykel Trust. Siladitya Bhattacharya reports being the Editor-in-Chief of Human Reproduction Open and an editor of the Cochrane Gynaecology and Fertility Group. J.L.H.E. reports being the Editor Emeritus of Human Reproduction. R.S.L. reports consultancy fees from Abbvie, Bayer, Ferring, Fractyl, Insud Pharma and Kindex and research sponsorship from Guerbet and Hass Avocado Board. B.W.M. reports consultancy fees from Guerbet, iGenomix, Merck, Merck KGaA and ObsEva. C.N. reports being the Editor-in-Chief of Fertility and Sterility and Section Editor of the Journal of Urology, research sponsorship from Ferring, and a financial interest in NexHand. E.H.Y.N. reports research sponsorship from Merck. A.S. reports consultancy fees from Guerbet. J.W. reports being a statistical editor for the Cochrane Gynaecology and Fertility Group. A.V. reports that he is a Statistical Editor of the Cochrane Gynaecology & Fertility Review Group and of the journal Reproduction. His employing institution has received payment from Human Fertilisation and Embryology Authority for his advice on review of research evidence to inform their 'traffic light' system for infertility treatment 'add-ons'. N.L.V. reports consultancy and conference fees from Ferring, Merck and Merck Sharp and Dohme. The remaining authors declare no competing interests in relation to the work presented. All authors have completed the disclosure form., Trial Registration Number: Core Outcome Measures in Effectiveness Trials Initiative: 1023., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Study Question: Does oral antioxidant pretreatment for the male partner improve clinical pregnancy rate in couples undergoing ART for male factor subfertility?, Summary Answer: There was no significant difference in clinical pregnancy rate following oral antioxidant pretreatment for male partner in couples undergoing ART for male factor subfertility compared to no pretreatment., What Is Known Already: Damage to sperm mediated by reactive oxygen species (ROS) contributes significantly to male factor infertility. The ROS-related injury reduces fertilization potential and adversely affects the sperm DNA integrity. Antioxidants act as free radical scavengers to protect spermatozoa against ROS induced damage. During ART, use of sperms which have been exposed to ROS-mediated damage may affect the treatment outcome. Pretreatment with antioxidants may reduce the ROS-mediated sperm DNA damage. Currently, antioxidants are commonly prescribed to men who require ART for male factor subfertility but there is ambiguity regarding their role., Study Design Size Duration: This was an open label, randomized controlled trial conducted at a tertiary level infertility clinic between February 2013 and October 2019. The trial included 200 subfertile couples who were undergoing ART treatment for male factor subfertility., Participants/materials Setting Methods: Couples were randomized into treatment arm (n = 100) and control arm (n = 100). In the treatment arm, the male partner received oral antioxidants (Vitamin C, Vitamin E and Zinc) for 3 months just prior to the ART cycle. In the control arm, no antioxidant was given to the male partner. The primary outcome was clinical pregnancy rate, while live birth rate (LBR), miscarriage rate and changes in semen parameters were the secondary outcomes., Main Results and the Role of Chance: Out of 200 women randomized, 135 underwent embryo transfer as per protocol. Following intention to treat analysis, no significant difference was noted in clinical pregnancy (36/100, 36% vs 26/100, 26%; odds ratio (OR) 1.60, 95% CI 0.87 to 2.93) and LBR (25/100, 25% vs 22/100, 22%; OR 1.18, 95% CI 0.61 to 2.27) between antioxidant and no pretreatment arms. The clinical pregnancy rate per embryo transfer was significantly higher following antioxidant pretreatment (35/64, 54.7% vs 26/71, 36.6%; OR 2.09, 95% CI 1.05 to 4.16) compared to no pretreatment. There was no significant difference in LBR per embryo transfer (25/64, 39.1%, vs 22/71, 31.0%; OR 1.43, 95% CI 0.70 to 2.91) after antioxidant pretreatment versus no pretreatment. The semen parameters of sperm concentration (median, interquartile range, IQR) (18.2, 8.6 to 37.5 vs 20.5, 8.0 to 52.5, million/ml; P  =   0.97), motility (median, IQR) (34, 20 to 45 vs 31, 18 to 45%; P  =   0.38) and morphology (mean ± SD) (2.0 ± 1.4 vs 2.2 ± 1.5%; P  =   0.69) did not show any significant improvement after intake of antioxidant compared to no treatment, respectively., Limitations Reasons for Caution: The objective assessment of sperm DNA damage was not carried out before and after the antioxidant pretreatment. Since the clinicians were aware of the group allotment, performance bias cannot be ruled out., Wider Implications of the Findings: The current study did not show any significant difference in clinical pregnancy and LBR following antioxidant pretreatment for the male partner in couples undergoing ART for male subfertility. The findings need further validation in a larger placebo-controlled randomized trial., Study Funding/competing Interests: This trial has been funded by Fluid Research grant of Christian Medical College, Vellore (internal funding). The authors have no conflicts of interest to declare., Trial Registration Number: CTRI/2013/02/003431., Trial Registration Date: 26 February 2013., Date of First Patient’s Enrolment: 11 February 2013., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)