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BMJ Sexual & Reproductive Health

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Preprints posted in the last 30 days, ranked by how well they match BMJ Sexual & Reproductive Health's content profile, based on 10 papers previously published here. The average preprint has a 0.01% match score for this journal, so anything above that is already an above-average fit.

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How healthcare professionals manage uncertainty around hormone replacement therapy (dis-)continuation: the TAPER qualitative Study

Hillman, S.; Jones, L.; Kuypers, N.; Molloy, E.

2026-10-15 sexual and reproductive health 10.64898/2026.10.14.26365532 medRxiv
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Abstract Many women experience menopausal symptoms after stopping hormone replacement therapy (HRT). An evidence gap remains regarding how women and healthcare professionals (HCPs) make decisions about discontinuing and restarting HRT. Aim To explore experiences of HCPs that support women when they discontinue and restart HRT. Design and setting Qualitative study with HCPs working in NHS primary care. Method Semi-structured interviews with HCPs (n = 15) conducted between October 2025 and March 2026. A preliminary coding template was created using the discussion guide as a framework. Each interview was then coded inductively against the template which developed iteratively. Team based discussion helped refine codes into themes and sub-themes, and a subsequent conceptual model was created. Results The model describes HCPs experiences of supporting women to discontinue HRT as an iterative process characterised by uncertainty. Discussions about discontinuation were commonly prompted by changes in clinical risk or annual HRT review, but decisions about whether and when to stop also depended on womens symptoms, side effects, life stage and readiness. HCPs described agreeing an individualised discontinuation strategy, providing support during the process, and reviewing women after discontinuation to consider alternative treatments or, where appropriate, restarting HRT. Conclusion HCPs recognise the importance of readiness to discontinue and that decision making should be woman led, with HCP support, clear practice guidance and opportunities to revisit treatment. Further research is needed to support women weigh up their personalised risk and benefit of continuing/discontinuing and identify discontinuation strategies that limit resurgent symptoms.

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A modified Delphi study to determine Australian healthcare consumer priorities and consensus for the use of genomics and precision medicine approaches in pregnancy healthcare and research

Grace, T.; Hoskins, S.; Pringle, K.; Cruz, M.; Ludski, K.; Usher, L.; Ghafourniah, N.; Pennell, C. E.

2026-10-01 obstetrics and gynecology 10.64898/2026.09.29.26363624 medRxiv
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Background: Pregnancy is a uniquely complex ethical and clinical context in which precision medicine approaches, including genomics-driven risk prediction tools, biomarker-based stratification, and data-intensive analytics, are rapidly evolving. There is a need for community consultation on the ethical, social, and practical implications of precision medicine in pregnancy research and healthcare. Aim: The primary aim of this study was to engage healthcare consumers to build consensus on the acceptability of precision medicine approaches in pregnancy research and healthcare. We also sought to identify consumer priorities for future research. Methods: A two-round modified Delphi study was conducted to determine consumer opinions on the use of precision medicine approaches in pregnancy research and healthcare. Seven in-person workshops (round one) were held, with purposeful recruitment to ensure a representative group of healthcare consumers who engage with the healthcare system during pregnancy. These included first-time parents, culturally and linguistically diverse women, Aboriginal and Torres Strait Islander women, and women and their partners who had experienced previous pregnancy complications. Recruitment was conducted through established advocacy networks, and each workshop was facilitated by representatives from each organization. A second-round online survey, based on workshop content, was completed to assess the acceptability of precision medicine and to determine consumer priorities for future precision medicine research on pregnancy health. Results: Precision medicine research and the implementation of new technologies in clinical care were acceptable to participants; however, the need for transparency and trust between participants and researchers regarding the use and storage of genetic material was highlighted, particularly among Aboriginal and culturally and linguistically diverse participants. Outcomes related to survival and perinatal complications (stillbirth, preterm birth, and labor complications) were the highest-rated consumer research priorities, along with maternal mental health and breastfeeding. When asked whether participants would like to see PM available as part of routine pregnancy care for conditions with available treatments, complete consensus (100%) was reached. Conclusion: Healthcare consumers strongly support the use of precision medicine in pregnancy research and its translation into routine clinical care, particularly when effective interventions are available. However, implementation must be underpinned by transparency, trust, culturally appropriate governance, and clear communication about the collection, storage, and use of genetic material. These findings provide a consumer-informed framework for prioritizing future precision medicine research and guiding its responsible translation into pregnancy care.

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Trends in, and factors associated with, chemsex in a community sample of gay, bisexual, and other men who have sex with men in England, 2022-2025

Yuan, J.-M.; Viviani, L.; Mullen, D.; Ogaz, D.; Mohammed, H.

2026-10-21 sexual and reproductive health 10.64898/2026.10.19.26365930 medRxiv
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Background Chemsex, drug use before/during sex to facilitate and enhance the experience, is undertaken by a minority of gay, bisexual and other men who have sex with men (GBMSM), but evidence of chemsex prevalence in England is limited. This study describes trends in chemsex prevalence between 2022-2025 and identifies factors associated with chemsex amongst GBMSM in England. Methods Data from the RiiSH study (2022-2025), an annual online cross-sectional survey of GBMSM recruited through social networking/dating apps and community partners, were analysed. Trends in chemsex prevalence and adjusted prevalence were estimated using log-binomial regression models. The following seven variables were candidate factors associated with chemsex and were assessed through logistic regression: age, sexual orientation, education, employment, HIV status, HIV PrEP use, and sexual health service (SHS) use. Results 5728 GBMSM were included in this study. Adjusted chemsex prevalence varied from 6.1% in 2022 to 4.2% in 2023, 5.1% in 2024 and 6.8% in 2025. Chemsex was more likely in GBMSM who were: gay (aOR=1.57 versus other sexual orientations; 95%CI 1.11-2.29, p=0.01), unemployed (aOR=3.08 versus employed full-time; 95%CI 2.19-4.26, p<0.001); aged 35-59 versus 16-34 years (p<0.001), with recent HIV PrEP use (aOR=3.79 versus no recent use; 95%CI 2.63-5.56, p<0.001), SHS use (aOR=2.23 versus no recent use; 95%CI 1.76-2.83, p<0.001), and living with HIV (aOR=3.16 versus negative/unknown HIV status; 95%CI 2.43-4.09, p<0.001). Conclusions Chemsex prevalence was low and stable between 2022-2025. PrEP and SHS use were associated with chemsex, supporting integration of specialist support services within SHS.

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Use and Perceptions of Artificial Intelligence Among Respondents to a Self-Selected Survey of Obstetrician-Gynecologists in France

MARTINEAU, R.; COMBES, C.; YAUY, K.; DERUELLE, P.

2026-09-25 obstetrics and gynecology 10.64898/2026.09.23.26363805 medRxiv
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Background: Artificial intelligence (AI) is increasingly used in healthcare, but data on its real-world use and perceptions among obstetricians and gynecologists remain limited. Objectives: To assess familiarity, use, perceptions, and expectations regarding AI among physicians practicing obstetrics and gynecology in France. Study Design: We conducted a cross-sectional survey between June 2 and July 30, 2025, mainly distributed through professional organizations or associations and social media. Participation was voluntary and self-selected. AI use was defined as any use of an AI tool in routine clinical practice, regardless of type or frequency. Comparisons were made between AI users and non-users and between junior and senior physicians. Results: Among 469 respondents, representing approximately 5% of the target population, 199 of 466 (42.7%) reported AI use in practice; three respondents were excluded from this analysis because of discordant questionnaire responses. AI use was associated with male gender and professional status, with residents more represented among users. Junior physicians reported greater AI use than senior physicians and expressed greater concern regarding medical confidentiality. Current applications primarily involved administrative tasks, medical writing, literature retrieval, and translation; anticipated future uses centered on clinical decision support and medical data interpretation. Perceptions of several AI applications differed between groups. Conclusions: AI was reported to be used by a substantial proportion of respondents, primarily for supportive and informational tasks. These findings support further evaluation of training, validation, governance, and safe implementation of AI in obstetrics and gynecology.

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Barriers and incentives in the uptake of family planning services: Evidence from the Universal Access to Quality Contraception Project

Barman, K.; Gupta, I.; Roy, K. P.; Subbiah, R.

2026-09-22 sexual and reproductive health 10.64898/2026.09.20.26363531 medRxiv
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Population Services International (PSI) set out to demonstrate the engagement of the private sector in increasing access to modern contraceptives through innovative financing strategies, with a focus on marginalised populations, by implementing the SARAL or Universal Access to Quality Contraception (UAQ) project in the city of Agra, Uttar Pradesh. The objective of the UAQ program was to provide a full basket of choices of family planning methods to newly-married women, incentivising them to delay pregnancy for a specified period. A cross-sectional baseline survey was conducted in Agra during the month of June 2022, covering 1240 currently married women. Using baseline survey data, this paper examined the determinants of women's preference for an additional child, and whether supply-side family planning interventions alone are sufficient to drive adoption of family planning methods. Regression analysis was done to find the determinants of wanting more children and the determinants of the willingness to join the program. The results show that the two most significant variables in determining a womans preference for another child are the total number of children she already has, and not having any male children resulting in a strong son preference. The most significant variable in determining a womans preference for enrolling herself in the SARAL program is whether she has faced financial constraints in accessing family planning methods, with other determinants being inconvenience of using contraceptive methods, exposure to the governments outreach about family planning, and preference for a male child. The findings indicate that womens preferences for an additional child are mostly based on their own desires, and are generally determined by the number and gender of their existing children. However, when it comes to the use of family planning methods, the husbands views are a critical factor in making family planning decisions - this would imply that family planning programs need to reach out not just to women, but to their husbands as well. Raising awareness of, and increasing exposure to family planning services is much needed, and programs should incorporate a strong Information, Education and Communication (IEC) component.

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Uptake, reidentification and regret in pediatric gender care

Tollit, M. A.; Conabere, W.; Gray, K.; Sibley, C.; Ayub, I.; Pace, C. C.; Traill, A.; Russo-Batterham, T.; Cavve, B. S.; Ravipati, T.; Rayner, C.; Pang, K. C.

2026-09-24 pediatrics 10.64898/2026.09.17.26363359 medRxiv
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Background: Gender-affirming medical care (GAMC) for children and adolescents in Australia has become increasingly politicized, despite care being provided in accordance with latest evidence-based international guidelines. Critics of GAMC claim that current assessment and deliberation processes are insufficient, and that too many young people are accessing medical interventions, no longer identifying as trans, and expressing treatment regret. These claims have led to widespread bans on the provision of paediatric GAMC, despite growing evidence regarding harms caused by such bans. Aim: This study sought to describe the care journeys of the young people attending Australia's largest paediatric gender service, with a focus on reporting the rates at which young people commenced medical interventions, re-identified with their birth-assigned sex, and expressed regret about their treatment. Methods: The Royal Children's Hospital Gender Service (RCHGS) is a statewide service that provides individualised multidisciplinary care to trans and gender diverse young people in Victoria, Australia. An initial extended triage appointment explores the needs and goals of the young person and their family. Some proceed to receive individualised multidisciplinary care (MDC) at RCHGS which can include psychosocial assessment and management, family support, and medical interventions including pubertal suppression (PS) and gender-affirming hormonal therapy (GAHT). We undertook a retrospective file audit of all patients who had attended at least one RCHGS appointment and been discharged between 1/1/2017-31/12/2024. For each person, key data were extracted from their electronic medical record and recorded in REDCap. Results: 1,391 patients were discharged over the 8-year study period and many different care trajectories were observed. 814 (58.5%) did not access ongoing MDC. Of the remaining 577, 353 (25.4% of total cohort) started a medical intervention ((PS: n=64/1391 (4.6%); estradiol: n=97/1391 (7.0%); testosterone: n=244/1391 (17.5%)). For those who started these medical interventions, the median duration and number of sessions from first appointment until commencement of medications was 530 (IQR: 371-693) days and 9 (IQR: 7-13) sessions. 346 of these patients (98.0%) had data on gender identity at discharge and subsequent care pathways. 7 (2.0%) re-identified with their birth-registered sex and stopped treatment: 4 did so after commencing PS (4/61=6.6% of those starting PS), 2 did so after commencing testosterone, and 1 did so after commencing estradiol (3/341=0.9% of those starting GAHT). Just one of these patients, who had been on estradiol for 1 month, expressed treatment regret given concerns about initial breast budding and future fertility. Conclusion: This study highlights varied trajectories of those referred to paediatric gender services, directly challenges claims used to justify restrictions on paediatric GAMC and underscores the importance of a person-centred approach to care.

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A community-based structured birth planning intervention to increase skilled delivery and decrease neonatal mortality: a cluster randomised controlled trial in Pakistan

Khan, M. A.; Walley, J. D.; Javed, W.; Khan, N.; Ahmad, M.; Khan, S. E.; Hicks, J. P.; King, R.; West, R.

2026-09-30 sexual and reproductive health 10.64898/2026.09.29.26364292 medRxiv
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Abstract Background: We developed and evaluated a behaviour change intervention to improve health outcomes for pregnant women and neonates in rural Pakistan. Methods: We used a parallel, three-arm, unblinded, cluster randomised controlled trial design. Eligible clusters were upgraded health facilities plus all associated community health workers (CHWs) and catchment populations. Randomisation was by computer program (1:1:1 ratio). All pregnant women were eligible. Control CHWs provided usual care to pregnant women. Arm 1 CHWs provided structured birth planning, including birth preparedness and complication readiness planning, and a voucher allowing free travel to access emergency obstetric/neonatal care. Arm 2 CHWs provided structured planning alone. Co-primary outcomes were skilled (doctors and midwifery-trained cadres) birth attendance and neonatal mortality (NNM) at 28 days. Findings: Between November 2011 to May 2012, respectively in arms 1, 2 and the control 21,317, 19,267 and 18,867 women were recruited, and 21,214, 19,125 and 18,812 were followed-up and analysed. Vouchers were almost never used to reclaim travel costs. Skilled attendance was 64% (12,045/18,812) in the control arm, 72.3% (15,335/21,214) (adjusted odds ratio [aOR] 1.56 [95% CI: 0.93, 2.62; p = 0.21]) in arm 1 and 78.1% (14,944/19,125) (aOR 2.16 [95% CI: 1.29, 3.62; p = 0.007]) in arm 2. NNM was 13.4 (per 1,000 live births) in the control arm, 45 (aOR 2.32 [95% CI: 1.48, 3.63; p < 0.001]) in arm 1 and 16.2 (aOR 1.36 [95% CI: 0.84, 2.21; p = 0.21]) in arm 2. Conclusions: Birth planning had inconsistent effects on skilled attendance and NNM, including apparently negative effects on NNM, with concerns about the quality of midwifery care. However, the control arm and arm 2 NNM was improbably low for this setting, and bias in the outcome may explain the observed differences. The travel voucher was little used.

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Can we Generate and Validate a Pregnancy Register for Research in the UK Greater Manchester Care Record Database Using Routine Primary Care Records

Cornett, C.; Tilston, G.; Martin, G.; Palin, V.

2026-10-02 obstetrics and gynecology 10.64898/2026.09.30.26364393 medRxiv
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Background: The Greater Manchester Care Record (GMCR) integrates health and social care data for 2.8 million individuals. While it contains maternity information, identifying individual pregnancies, including timing and outcomes, is complex due to variations in healthcare interactions and recording practices. This study develops open-source code to create a pregnancy register within the GMCR using diagnosis- and procedure-based algorithm established in other databases. Methods: 1,448 maternity SNOMED clinical codes identified pregnancy-related primary care records among women aged 14-49 years between March 2012 and August 2023. Codes were grouped by pregnancy outcome, with a hierarchical ruling approach where multiple outcomes appeared within one episode. Pregnancy start dates were derived from hierarchical coded events or imputed using biologically plausible duration based on outcome type. Internal validation compared GMCR register episodes against Hospital Episode Statistics (HES) hospital maternity admissions; external validation compared outcome rates against published UK estimates. Results: The algorithm was developed across 379,832 women, identifying 880,926 pregnancies. Internal validation showed nearly half of register deliveries had a corresponding HES record, with a positive predictive value (PPV) of 48.1%and a median date difference of 17 days (IQR 1-30). External comparison revealed live birth (927.8 vs. 995.6 per 1,000 deliveries) and stillbirth (2.12 vs. 3.9 per 1,000 births) rates close to national estimates but a notable discrepancy for miscarriage (8.00 vs. 15.3 per 100 pregnancies) and termination of pregnancy (5.36 vs. 25.1 per 1,000 women). Demographic alignment was strong for maternal age (31 vs. 29.8 years) and deprivation (IMD10 median: 3 vs. 2.6), though ethnic minority representation was expectedly higher in the GMCR (37.0% vs. 28.7%). Conclusions: This pregnancy register enriches the GMCR for maternal health research, enabling more comprehensive and regionally tailored studies to inform healthcare delivery and policy. This work represents an important first step in developing a scalable, open-source algorithmic tool to support pregnancy research across diverse populations. By making the code openly available, it can be adapted for use in federated data environments, enhancing reproducibility and collaboration.

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Effectiveness of a Community-Based Cervical Cancer Stigma Reduction Intervention on Cancer Stigma and Cervical Cancer Screening Uptake in Nepal: A Cluster-Randomized Controlled Trial

Timsina, P.; Paneru, B.; Shrestha, M.; Ghemosu, A.; Lee, S.; Poudel, L.; Ranjit, Y. S.; Spiegelman, D.; Sheth, S. S.; Stangl, A.; Shrestha, A.

2026-09-25 sexual and reproductive health 10.64898/2026.09.24.26363856 medRxiv
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Background Cancer stigma contributes to low cervical cancer screening rates among Nepali women. However, no stigma reduction interventions have been implemented thus far in Nepal. This study assessed the effectiveness of a muticomponent cervical cancer stigma reduction intervention on cancer stigma scores and cervical cancer screening uptake rates among urban Nepali women. Methods A two-arm, parallel cluster-randomized trial was conducted in Budhanilkantha Municipality, Kathmandu District, Nepal. Twelve administrative wards were randomized in a 1:1 ratio to the intervention or control group, with wards serving as the unit of randomization and individual women as the unit of analysis. A total of 310 women aged 30-60 years who had not undergone cervical cancer screening during the previous five years were enrolled. The three-hour intervention included cervical cancer education, a video featuring cervical cancer survivors, participatory group discussions, and myth-versus-fact activities addressing cancer stigma. Cancer stigma was assessed two months after the intervention using the Nepali version of the Cancer Stigma Scale. Cervical cancer screening uptake was assessed six months after the intervention. Data were analyzed using intent-to-treat and as treated approaches with a generalized estimation equation with logistic regression. Results From June 2022 to February 2023, 310 women were enrolled. At 2 months, stigma data were available for 248 participants (120 intervention, 128 control). In the intention-to-treat analysis, the odds of cancer stigma were lower in the intervention group than in the control group (OR 0.25, 95% CI 0.08 to 0.8; p=0.022). Odds were also lower for the severity domain (OR 0.31, 95% CI 0.10 to 0.90; p=0.048) and awkwardness domain (OR 0.21, 95% CI 0.08 to 0.56; p=0.001) with no differences in other subdomains. At 6 months, the odds of cervical cancer screening was 3.9 times greater in the intervention group than in the control group (95% CI: 1.1-13.20, p=0.028). As treated analysis reinforced these findings, with lower odds of stigma (AOR:0.09, 95% CI: 0.01-0.53, p=0.007), severity (AOR:0.16, 95% CI: 0.06-0.42, p<0.001), and awkwardness (AOR:0.1, 95% CI: 0.02-0.44, p=0.02). Cervical cancer screening odds was 4.02 times higher in the intervention group (95% CI:1.1-13.7, p=0.026). Conclusions Compared with the control condition, participants allocated to a community-based multicomponent intervention designed to reduce cancer stigma had lower odds of elevated cancer stigma two months after the intervention and higher odds of cervical cancer screening by six months. Larger cluster-randomized trials with more clusters and longer follow-up are needed to assess the reproducibility, durability, and generalizability of these findings.

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An insight into birthing and EmONC service utilisation for making birthing safe: a qualitative study in underdeveloped districts of Punjab, Pakistan.

Khan, S. E.; Khan, M. A.; Khan, N.; Walley, J.

2026-10-05 sexual and reproductive health 10.64898/2026.09.29.26364296 medRxiv
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Abstract Background: The qualitative study was conducted to understand the socio-cultural factors (challenges and enabling factors) those influence the decisions and ability of the pregnant women and their families to make better use of the available safe birthing and EmONC services in two districts (Khanewal and Jhang) of Punjab, Pakistan. Objectives: To explore the key social, personal and professional considerations (factors) that influence the women (and family) decision and ability to utilise various birthing and EMONC services and to understand care providers interest and ability to offer these safe birthing services in the districts of Jhang and Khanewal in Pakistan. Study Design: The qualitative study was conducted, during the year 2013/14, on three rural health centers and two district headquarter hospitals in Kanewal and Jhang districts in Punjab. Through purposive sampling, 42 registered clients were interviewed to explain the different birthing experience along with 15 service providers, 2 district level programme managers and 2 transport vendors. The collected qualitative data from interviews were transcribed, and key emerging concepts/ themes were identified. A range and continuum of coded responses/ comments were compiled and discussed under each theme. Results: Main themes were structured birth planning; antenatal at health centres; skilled birth attendance; emergency obstetric and neonatal care (EmONC); and EmONC travel. The study found that pregnant women consult their husbands and mother in laws for taking birthing decisions; consult the skilled birth attendant for management of complication; private clinics are preferred for various social and logistic reasons; many private clinics doing caesarean are not adequately equipped; male reluctance (for cultural reasons) to make in-advance transport arrangement for possible EmONC; travel voucher utilisation remained low because of limited coverage and less-friendly procedures. Conclusion: Safe birthing decisions could be complex; and influenced by multiple social, cultural, economic, service access and quality considerations. Safe birthing practices can be improved if interventions remain sensitive to these preferences and realities. Keywords: Skilled birth attendance, social determinants, lady health workers, birth planning

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Safety & Effectiveness of Mifepristone for Medication Abortion in a National Claims Cohort, 2017-2023

Woskie, L. R.; Strasser, J.; Griffin, R.; Luo, Q.; Rodriguez, M. I.; Upadhyay, U.

2026-10-05 obstetrics and gynecology 10.64898/2026.10.02.26364611 medRxiv
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BACKGROUND Extensive research has documented medication abortion safety. Large-scale insurance claims data offer an important complement to clinical studies by assessing real-world outcomes in routine practice. In claims data, researchers must infer mifepristone use, clinical outcomes, and event severity from diagnosis, treatment, and utilization codes. Understanding how these analytic choices influence safety and effectiveness estimates is important for interpreting evidence used to inform care delivery and medication policy. METHODS We conducted a retrospective cohort study of mifepristone use with national multipayer claims data, both medical and pharmacy, from 2017 through 2023. We identified both a broad cohort and a more specific medication-abortion cohort after excluding evidence of other indications. We classified potential safety events, effectiveness outcomes, and health care utilization within 45 days of mifepristone use. Serious adverse events required claims-observable consequences consistent with FDA seriousness criteria. RESULTS The broad cohort included 869,409 mifepristone uses among 698,780 unique patients for medication abortion or other indications. After restriction to uses with additional evidence of medication abortion, 775,931 uses among 626,443 unique patients remained. In the medication-abortion cohort, 3,306 uses were followed by at least one serious adverse event, resulting in an absolute 45-day risk of 0.43%. Serious bleeding or hemorrhage occurred after 0.24% of uses, serious infection or sepsis after 0.05%, serious hypersensitivity or anaphylaxis after 0.01%, and serious ectopic-pregnancy outcomes after 0.05%. CONCLUSIONS Serious adverse events after mifepristone use were rare in this national study. Applying established, clinically grounded criteria markedly reduced the number of events classified as serious.

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Transcriptomic Reproducibility in Endometrial Biopsies: Evidence Across Cycles and Tissue Regions in Hormonal Replacement Therapy Endometrial Preparation Protocols

Martinez-Martinez, A.; Sebastian-Leon, P.; Parraga-Leo, A.; Alama, P.; Caracena, L.; Sanz, F. J.; Diaz-Gimeno, P.

2026-09-25 sexual and reproductive health 10.64898/2026.09.23.26363653 medRxiv
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Study question. Are endometrial gene expression profiles reproducible across hormone replacement therapy (HRT) cycles and across different regions of the same endometrial biopsy? Summary answer. Endometrial transcriptomic profiles were highly reproducible across HRT cycles and across non-adjacent and adjacent regions of the same biopsy. What is known already. Endometrial transcriptomic analyses are increasingly used to understand endometrial physiology and to evaluate endometrial reproductive potential. However, this approach requires an endometrial biopsy in a prior endometrial cycle to the embryo transfer cycle in the IVF treatment. Therefore, endometrial transcriptomic analyses rely on the assumption that the gene expression profile is representative of subsequent endometrial cycles and of the whole biopsy specimen. However, inter-cycle and intra-biopsy reproducibility remain insufficiently characterized. Study design, size, duration. This was a prospective, single-center, observational clinical study including 20 participants recruited between June 2024 and March 2025. Participants/materials, setting, methods. Participants underwent two different endometrial preparation cycles under the same HRT conditions at a private fertility clinic, and an endometrial biopsy was collected during both cycles, with the same duration of progesterone exposure, in the mid-secretory phase by the same clinician. RNA was processed for whole endometrial transcriptome analysis using RNA sequencing. Three paired comparisons were performed: biopsies from the same participant collected in different cycles, non-adjacent regions of the same biopsy, and adjacent regions of the same biopsy. Gene expression reproducibility was assessed using Pearson correlation, hierarchical clustering, principal component analysis, and paired differential gene expression analysis. The reproducibility of estimated cell-type proportions was also assessed by deconvolution to observe potential differences in cellular composition. Main results and the role of chance. In the inter-cycle endometrial gene expression comparison, the mean {+/-} standard deviation (SD) gene expression correlation coefficient within participant pairs was 0.974 {+/-} 0.012, significantly higher than that observed between participant pairs (p = 1.56 x 10-6), the mean {+/-} SD Euclidean distance was significantly lower within than between participant pairs (p = 2.24 x 10-6), and no differentially expressed genes were identified within participant pairs. Principal component analysis and hierarchical clustering further supported the similarity of most paired samples. Intra-biopsy comparisons showed even higher reproducibility, with both non-adjacent and adjacent biopsy regions showing mean {+/-} SD correlation coefficients of 0.986 {+/-} 0.003 and 0.986 {+/-} 0.002, respectively. The correlation coefficients were significantly higher than those observed between biopsy pairs (p = 9.91 x 10-12 and p = 2.14 x 10-12, respectively). No differentially expressed genes were detected within intra-biopsy pairs, all paired regions clustered together by hierarchical clustering and principal component analysis, and intra-biopsy pairs showed lower Euclidean distances than inter-biopsy pairs (p = 9.91 x 10-12 and p = 2.14 x 10-12 in non-adjacent and adjacent regions, respectively). Estimated cell-type proportions did not differ significantly between paired samples in any of the three comparisons. Limitations, reasons for caution. The findings are specific to samples analyzed using the AmpliSeq Transcriptome Human Gene Expression Panel protocol. Although other transcriptomic platforms should be tested, we are expecting the same reproducibility due to the consistency of RNA seq platforms. All biopsies were collected by the same clinician, so operator-related variability could not be directly assessed. These findings can be extrapolated only to HRT cycles. Wider implications of the findings. These findings support the reproducibility of endometrial gene expression profiles under controlled HRT conditions from biopsies collected by the same clinician and suggest that a single biopsy region can provide a representative molecular profile of the whole biopsy specimen. These findings strengthen the methodological basis for bulk endometrial RNA sequencing studies and support the reliability of transcriptomic-based tools for endometrial evaluation in an endometrial cycle prior to an embryo transfer cycle for reproductive medicine.

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Antibiotic treatment of asymptomatic urogenital infections in infertile couples is associated with improved sperm quality including sperm apoptosis parameters

Novak, J.; Vik, V.; Drahos, M.; Langerova, A.; Thon, V.; Kratka, Z.

2026-10-02 sexual and reproductive health 10.64898/2026.09.30.26364433 medRxiv
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Background: European Association of Urology (EAU) Guidelines identify urogenital infections as a possible treatable cause of infertility, yet the current recommendation for antibiotic treatment remains weak due to a lack of high-quality evidence. We evaluated the effect of antibiotic treatment of asymptomatic urogenital infections on both conventional and apoptosis-related (flow cytometry sperm apoptosis test, FACS-APO) sperm parameters, as well as on pregnancy outcomes, in infertile couples. Methods: In this retrospective, single-centre study, we analysed 265 couples with an asymptomatic urogenital infection (Ureaplasma urealyticum, Mycoplasma hominis, Mycoplasma genitalium, and Chlamydia trachomatis) confirmed in at least one partner by first-void urine testing, who received simultaneous antibiotic treatment. Paired conventional semen analysis and FACS-APO were performed before and 0-9 months after treatment completion. Partner infection concordance, the effect of follow-up timing on treatment response, and pregnancy outcomes within 12 months were also assessed. Results: Sperm concentration, total sperm count, total and progressive motility, and the proportion of viable sperm increased significantly after treatment, while the proportion of late apoptotic / necrotic sperm and calculated sperm DNA fragmentation decreased significantly (all p<0.05); the proportion of early apoptotic sperm remained unchanged, and semen volume did not change. Among 244 couples with complete bilateral microbiological testing, Ureaplasma urealyticum was by far the most prevalent pathogen (57.8% of men, 87.7% of women), and female partner positivity given male positivity was 83.0%. The improvement in sperm concentration and total sperm count was most pronounced within 3 months after treatment and diminished, or reversed, beyond 6 months. Pregnancy was achieved in 127 of 265 couples (47.9%; per-protocol rate 53.4%) within 12 months, most commonly following in vitro fertilization (72/127) or spontaneously (21/127). Conclusions: Antibiotic treatment of asymptomatic urogenital infections in infertile couples was associated with significant improvement in conventional semen parameters and a reduction in sperm apoptosis and calculated DNA fragmentation. Given the retrospective, uncontrolled design, these findings should be regarded as hypothesis-generating rather than definitive proof of a causal, fertility-enhancing effect, and warrant confirmation in prospective controlled studies.

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When Prescribing Diverges From Published Lactation Compatibility Guidance: A National Claims Analysis

Krutsch, K.; Appiah, D.

2026-10-21 epidemiology 10.64898/2026.10.19.26365940 medRxiv
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Purpose Prescribing to lactating women is constrained by limited evidence. Published compatibility classifications provide clinical guidance and a discrete research comparator. How often prescribing diverges from that guidance, and what characteristics are associated with divergence, is unknown at national scale. Methods Retrospective analysis of prescriptions filled during lactation, identified in the 2012-2014 MarketScan Commercial Claims Database. Prescriptions were classified as concordant (Hale's lactation risk category L1-L3) or discordant (L4-L5). Multivariable logistic regression identified factors associated with concordance. Results Of 96,484 new prescriptions, 95,710 (99.2%) were concordant and 774 (0.8%) were discordant. Discordant prescriptions were filled later after delivery (median 59 vs 33 days) and had a day supply three times longer (30 vs 10 days). In multivariable analysis (N=28,732), concordant prescriptions were associated with maternal age under 35 (adjusted odds ratio (aOR)=1.34, 95% confidence interval (CI): 1.02-1.75) and chronic-condition medications (aOR=10.94, 95% CI: 6.47-18.50), and were less likely within 14 days of delivery (aOR=0.53, 95% CI: 0.38-0.73) and with each additional day of supply (aOR=0.96, 95% CI: 0.96-0.96). Compared with family practice, concordance did not differ for obstetric, internal medicine, or emergency medicine prescriptions, but prescriptions from other provider types had lower odds of concordance (aOR=0.57, 95% CI: 0.41-0.79). Conclusions Prescribing during lactation was overwhelmingly concordant with published compatibility guidance; the rare divergence was patterned by prescription and prescriber characteristics. Because the categories are an expert classification rather than consensus guidance, divergence should not be read as inappropriate prescribing.

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Caregiver knowledge and Attitudes toward Human Papillomavirus Vaccination among adolescent girls living with HIV in Sierra Leone: A health facility-based cross-sectional study

Jiba, D. F.; Baldeh, M.; Turay, P.; Kanu, S.; Kamara, M. N.; Farma-Grant, L. M. L.; Barrie, U.; Awonuga, W. O.; Baio, M. M.; Sesay, D.; Shehab, D.; Sinnah, R.; Namanga, E. S.; Johnson, P. M. D.; Lakoh, S.; Dykens, J. A.

2026-09-23 sexual and reproductive health 10.64898/2026.09.21.26363609 medRxiv
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ObjectiveTo assess the knowledge, willingness and barriers to human papillomavirus (HPV) vaccination among caregivers of adolescent girls living with HIV in Sierra Leone. MethodsThis cross-sectional study examined HPV vaccine knowledge, willingness, and barriers among 249 caregivers of adolescent girls living with HIV in Sierra Leone. Data were collected through structured questionnaires at public tertiary hospitals and high-volume HIV clinics, and associations were assessed using chi-square tests, logistic regression, and Kruskal-Wallis analyses. ResultsOnly 32.1% (80/249) of caregivers had heard of HPV, with even fewer aware of its link to cervical cancer (24.4%, 60/246) or prevention methods of cervical cancer (31.9%, 79/248). Misconceptions were prevalent; 16.3% (36/221) erroneously linked oral contraceptives to cervical cancer, and 61.1% (44/72) of caregivers unwilling to vaccinate cited distrust in vaccine efficacy. While tertiary-educated caregivers exhibited the highest level of knowledge (45.5%, p < 0.001), their willingness to vaccinate (50%, 33/66) was comparable to that of less-educated groups, highlighting a knowledge-action gap. Structural barriers dominated, with 66.1% (154/233) citing unawareness of the vaccine and 10.3% (24/233) missing school-based vaccination days. Relationship dynamics significantly influenced willingness: extended family members showed the highest willingness (69.4%, p = 0.029), whereas grandparents were least willing (31%, 9/29). Although systemic gaps such as disrupted vaccination services, vaccine supplies and cold chain limited uptake, healthcare workers emerged as the most effective information source (rank sum = 889.5, p = 0.039). ConclusionThe study highlights the need for culturally tailored education to dispel myths and community-driven strategies engaging trusted actors like healthcare workers and extended families. This study justifies the need for integration of HPV vaccination and cervical cancer screening into HIV care services.

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Strategies to improve uptake of adolescent family planning and post-abortion care services in Northern Uganda: a qualitative descriptive study

Anyolitho, M. K.; Omech, B.; Kigongo, E.; Acheka, E.; Akello, J. A.; Ongom, M. C.; Udho, S.; Odette, M.; Acup, W.

2026-09-27 sexual and reproductive health 10.64898/2026.09.24.26363969 medRxiv
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Introduction: Adolescents in low- and middle-income countries continue to face barriers to family planning (FP) and post-abortion care (PAC), including stigma, limited confidentiality, inadequate information, and health-system constraints. This study explored adolescents and key stakeholders perspectives on strategies to improve uptake of adolescent FP and PAC services in Lira District, Northern Uganda. Methods and Materials: An exploratory qualitative descriptive study was conducted using 13 focus group discussions (FGDs) with 65 adolescent citizen scientists aged 10-19 years and 13 key informant interviews (KIIs) with stakeholders involved in adolescent sexual and reproductive health and PAC. Data were collected using semi-structured guides, audio-recorded with consent, and supplemented by field notes, then analyzed thematically using Braun and Clarkes six-phase framework. Results: Five interconnected themes emerged, including strengthening school, community, and faith-based SRH education; strengthening the health system and service delivery; policy, legal, and institutional clarity; community engagement and trust building; and integration of FP and PAC. Participants prioritized accessible and accurate SRH education, supportive community engagement, confidential and respectful care, and reliable commodities, clear operational guidance, coordinated referrals, and integrated services. The findings indicate that uptake is shaped by interacting with individual, social, health-system, and policy conditions rather than knowledge alone. A participatory, multilevel approach that connects community-generated knowledge with adolescent-responsive health-system strengthening may offer a feasible pathway for improving FP and PAC uptake in Northern Uganda. Conclusion: Adolescents and key stakeholders identified interconnected community, health-system, policy, and service-delivery strategies for improving uptake of FP and PAC services. Priority actions included accessible SRH education, supportive community engagement, confidential and respectful care, reliable commodities, clear operational and legal guidance, and integrated FP and PAC delivery.

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Menstrual health, food insecurity, and protection vulnerability among adolescent girls in internally displaced persons camps in Benue State, Nigeria: A focused ethnographic study

Aja, P. M.; Ofor, O. C.; Roux, F.; Abanni, S.; Uzodimma, O. L.; Obiorah, C. M.; Uhundu, M. M.; Chidimma, O.; Olatunde, M. B.; Offor, C. U.; Akoshile, F. T.; Zainab, O.; Marycynthia, O. C.; Agatha, O. N.

2026-10-11 sexual and reproductive health 10.64898/2026.10.07.26365008 medRxiv
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Adolescent girls living in internally displaced persons (IDP) camps manage menstruation amid food insecurity, inadequate water, sanitation and hygiene (WASH), disrupted education, gendered social norms and protection systems. These challenges are often addressed through separate humanitarian programmes, obscuring how they interact in girls everyday lives. This study explored menstrual-health experiences and perceived nutritional deprivation among adolescent girls in five IDP camps in Benue State, Nigeria. We conducted a focused ethnographic qualitative study in the International Market, Mega, Ortese, Uikpam, and Abagana camps. Twenty-five in-depth interviews with menstruating adolescent girls aged 13-19 years were complemented by focus group discussions with adolescent girls, adult women, adult men, and camp leaders, and structured WASH and food observations. Interviews and discussions were conducted in English, Tiv or both, transcribed verbatim and translated where necessary. Data were managed in MAXQDA and analysed using reflexive thematic analysis. Frequencies describe the distribution of 435 coded excerpts and are not participant prevalence estimates. Six themes and 20 subthemes were generated. Menstrual-health management and material constraints accounted for 95 coded excerpts (21.8%), followed by knowledge and lived experience (80; 18.4%), food insecurity and perceived nutritional deprivation (70; 16.1%), coping and adaptive agency (70; 16.1%), sociocultural beliefs and taboos (65; 14.9%), and self-reported symptoms and participation restrictions (55; 12.6%). Girls described irregular access to commercial pads, reliance on improvised materials, limited water and soap, and toilets that were unsafe or inaccessible at night. Dietary monotony, meal skipping, and hunger were perceived to intensify pain, weakness, and fatigue. Fear of staining, menstrual silence, and household restrictions contributed to withdrawal from school, livelihood, and domestic activities. Peer support was protective, but some girls undertook informal work to obtain menstrual materials, raising safeguarding concerns. Menstrual health in prolonged displacement is not an isolated hygiene issue but an outcome of interacting material, nutritional, sociocultural, educational, and protection constraints. Humanitarian responses should combine predictable access to acceptable menstrual materials with safe WASH facilities, adolescent-responsive food and nutrition support, confidential health services, community education and safeguarding mechanisms. Reported symptoms and nutritional experiences were not clinically measured.

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Community-Delivered Antenatal Care to Address Access Barriers: Perspectives of Women and Healthcare Workers

Kabajaasi, O.; Nansozi, W. N.; Younger, A.; Kiconco, J.; Nankya, S.; Lukakamwa, D.; Kamwesigye, A.; Bwaga, I.; Odur, A.; Mukisa-Bisoborwa, R.; Ganzevoort, W.; Gordijn, S.; Klipstein-Grobusch, K.; Rijken, M.; Byamugisha, J.; Papageorghiou, A. T.; Ali, S.

2026-09-25 obstetrics and gynecology 10.64898/2026.09.23.26363848 medRxiv
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Stillbirth remains a major public health concern, particularly in resource-constrained settings. Barriers to timely, high-quality antenatal care may delay the recognition and management of pregnancy complications. We explored the perspectives of women, Village Health Team (VHT) members and healthcare workers on community-delivered approaches to improve pregnancy care, in particular prevention of stillbirth in Uganda. An exploratory qualitative study was conducted at four referral hospitals in Uganda. Data were collected through focus group discussions, in-depth interviews, and key informants interviews with women, Village Health Team members and healthcare workers. Audio-recordings were transcribed verbatim and translated into English where required. Data were analysed thematically using an iteratively developed codebook and NVivo software. In total, 56 participants took part, comprising women (n=27), Village Health Team members (n=11) and frontline healthcare workers (n=18). Participants highlighted the need for the adoption of simple and user-friendly wearable pregnancy monitoring tools for self-monitoring of early warning signs. Health education sessions focused on identifying early warning signs of pregnancy complications highlighted, emphasizing the importance of empowering women with information to seek care early through digital platforms. Limited follow-up support was also a critical concern, with the majority of the women advocating for better emotional and psychological care after a stillbirth, both at a facility and at home. Participants viewed community-delivered antenatal care as an acceptable approach to reducing access barriers. Implementation would require trained personnel, quality-assured tools, clear referral pathways and integration with facility-based care. Structured communication and psychosocial support after stillbirth were also identified as priorities. These findings should inform co-design and prospective evaluation of community-delivered models.

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Opioid Analgesic Initiation During Pregnancy and the Risk of Adverse Maternal and Neonatal Outcomes: A Target Trial Emulation

Varney, B.; Gillies, M. B.; Huybrechts, K. F.; Hernandez-Diaz, S.; Pearson, S.-A.; Shand, A.; Tran, D.; Brett, J.; Camacho, X.; Bruno, C.; Zoega, H.; Havard, A.

2026-10-21 obstetrics and gynecology 10.64898/2026.10.19.26365967 medRxiv
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Summary Background We used sequential target trial emulation (TTE) to examine associations between opioid analgesic initiation and adverse maternal and neonatal outcomes while accounting for gestational timing, time at risk, and potential confounding. Methods Using the Early Life Course platform, comprising linked population-based data for births in New South Wales, Australia (2013-2019), we emulated a new trial at each gestational week, comparing women who initiated a prescribed opioid analgesic with eligible non-initiators. Baseline covariates were balanced using inverse probability weighting. Weighted logistic regression estimated odds ratios (ORs) for neonatal outcomes, postpartum haemorrhage, and severe maternal morbidity. Pooled logistic regression estimated hazard ratios (HRs) for other maternal outcomes, combined across gestational weeks using fixed-effects meta-analysis. Sensitivity analyses assessed unmeasured confounding, exposure misclassification, and potential reverse causation. Findings Among 511,357 pregnancies, over 80% of opioid initiators received only one dispensing. Opioid initiation was not associated with increased risks of placental abruption (HR 0.94, 95% CI 0.75-1.16), severe maternal morbidity (OR 1.05, 0.97-1.11), postpartum haemorrhage (OR 0.98, 0.95-1.02), low Apgar score (OR 0.99, 0.87-1.08), small for gestational age (OR 0.90, 0.85-0.95), or neonatal abstinence syndrome (OR 0.98, 0.72-1.30). Risks were elevated for PPROM (HR 1.10, 0.98-1.23), preterm birth (HR 1.26, 1.19-1.33), severe neonatal morbidity (OR 1.08, 1.02-1.17), and perinatal death (OR 1.29, 1.10-1.52). Perinatal death estimates attenuated in analyses addressing potential reverse causation. Interpretation Using a TTE approach that accounted for gestational timing and time at risk, we found no appreciable increase in most maternal or neonatal outcomes following predominantly short-term opioid initiation. Elevated risks of preterm birth, perinatal death, and third-trimester PPROM may reflect causal effects or confounding by pregnancy-related indications. Studies using time-appropriate designs and detailed information on prescribing indications and their timing are needed to clarify these associations.

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Effect of the WHO Labour Care Guide Implementation on Maternal and Newborn Outcomes in Selected Referral Hospitals of Zambia: A Difference-in-Differences Analysis

Makasa, M.; Benedictus, M.; Lambwe, K.; Bellington, V.

2026-10-08 obstetrics and gynecology 10.64898/2026.10.06.26364926 medRxiv
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Background Despite being originally developed to support labour monitoring in low-resource and rural settings, the partograph has remained the standard tool for labour management and continues to be used by obstetricians and midwives across diverse settings worldwide. However, inappropriate use and non-use of the partograph persist and have been associated with increased odds of adverse perinatal outcomes, including perinatal death. To address these limitations, the World Health Organization introduced the Labour Care Guide in 2020 as a comprehensive tool to standardise and improve the quality of care during childbirth. Henceforth, some countries such as Rwanda and Uganda have since implemented its use. This study aimed to assess the effect of WHO Labour Care Guide implementation, compared with the traditional partograph, on selected maternal and perinatal outcomes across participating facilities. Methods This was a quasi-experimental implementation study conducted in selected referral hospitals in Zambia, comparing maternal and perinatal outcomes before and after implementation of the WHO Labour Care Guide. Facilities were grouped into implementation and comparison sites. Routine HMIS/DHIS2 data were used to assess selected outcomes across the pre- and post-implementation periods. Descriptive statistics were used to summarise outcome trends, while a difference-in-differences analytical approach was applied using Stata version 18 to compare changes over time between implementation and comparison sites. Results The analysis included 12 hospitals, 192 facility-month observations, 89,122 total births, and 87,004 live births. Overall, the stillbirth rate was 23.8 per 1,000 total births, birth asphyxia rate was 40.1 per 1,000 live births, caesarean section rate was 34.6 per 100 live births, low-birthweight rate was 168.6 per 1,000 live births, and maternal mortality ratio was 313.8 per 100,000 live births. The implementation sites reporting higher birth asphyxia rates (42.7 versus 38.0 per 1,000 live births). Difference-in-differences analysis showed no statistically significant effect of LCG implementation on stillbirths, IRR 1.07 (95% CI: 0.69-1.67, p=0.752); fresh stillbirths, IRR 1.23 (95% CI: 0.74-2.05, p=0.431); birth asphyxia, IRR 0.65 (95% CI: 0.34-1.27, p=0.207); or caesarean section, IRR 1.02 (95% CI: 0.80-1.30, p=0.892). Conclusion Implementation of the WHO Labour Care Guide was not associated with statistically significant changes in stillbirths, fresh stillbirths, birth asphyxia, or caesarean section rates during the study period. Despite the higher birth asphyxia rates in the implementation sites the difference remained statistically not significant. Scale-up of the LCG should be accompanied by sustained training, mentorship, audit and feedback, and strengthening of emergency obstetric and newborn care systems.