Digital health interventions for improving access to primary care in India: A scoping review.

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/.

Technologies that empower women for better access to healthcare in India - A scoping review.

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.

Use of modern technologies for promoting health at the population level 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.

In vitro fertilisation for unexplained subfertility.

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; I2 = 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; I2 = 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; I2 = 0%; low-quality evidence; 1 IVF to 1 IUI cycle: OR 1.63, 95% CI 0.91 to 2.92; 2 RCTs; 221 women; I2 = 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; I2 = 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; I2 = 0%; low-quality evidence; 1 IVF to 1 IUI cycle: OR 0.76, 95% CI 0.36 to 1.58; 2 RCTs; 221 women; I2 = 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; I2 = 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.

Individualized lifestyle intervention in PCOS women (IPOS): a study protocol for a multicentric randomized controlled trial for evaluating the effectiveness of an individualized lifestyle intervention in PCOS women who wish to conceive.

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/m2 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.

Endometrial scratching in women undergoing IVF/ICSI: an individual participant data meta-analysis.

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.

Impact of tubal patency test selection on the live birth rate following intrauterine insemination in couples with unexplained infertility: a retrospective cohort study.

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.

Effectiveness of GnRH Agonist Short Protocol Versus GnRH Antagonist Protocol in POSEIDON Groups 3 and 4: a Retrospective Cohort Study.

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.

Effect of female body mass index on intrauterine insemination outcomes: a systematic review and meta-analysis.

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/m2 were compared with a second cohort of women with a BMI category ≥ 25 kg/m2. 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.

A meta-analysis of 11 studies found that having a raised female BMI did not change IUI treatment outcomes.

The role of timing in frozen embryo transfer.

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.

Peri-implantation glucocorticoid administration for assisted reproductive technology cycles.

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; I2 = 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; I2 = 53%; very low-certainty evidence). The I2 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; I2 = 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; I2 = 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; I2 = 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; I2 = 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; I2 = 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.

Endometriosis and oocyte quality: an analysis of 13 614 donor oocyte recipient and autologous IVF cycles.

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.

Protocol for developing a core outcome set for male infertility research: an international consensus development study.

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.

Single nucleotide polymorphism array versus karyotype for prenatal diagnosis in fetuses with abnormal ultrasound: A systematic review and meta-analysis.

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.

Effectiveness of music therapy as an adjuvant to conscious sedation in women undergoing transvaginal oocyte retrieval: A randomized controlled trial.

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.

Non-invasive Prenatal Testing in Pregnancies Following Assisted Reproduction.

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.

The burden of scrub typhus in India: A systematic review.

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.

Risk of breast cancer in women treated with ovarian stimulation drugs for infertility: a systematic review and meta-analysis.

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, I2 = 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.