Human reproduction openPub Date : 2026-04-21eCollection Date: 2026-01-01DOI: 10.1093/hropen/hoag036
Huisheng Ge, Xiafei Wu, Dongni Huang, Li He, Dandan Liu, Lulu Wang, Liling Xiong, Dan Luo, Qiannan Hou, Hong Liu, Lunbo Tan, Yonghong Lin, Chang Chen, Xixi Wu
{"title":"Metabolic reprogramming in placenta and umbilical cord serum of polycystic ovary syndrome pregnancies: testosterone-associated alterations and interaction with obesity.","authors":"Huisheng Ge, Xiafei Wu, Dongni Huang, Li He, Dandan Liu, Lulu Wang, Liling Xiong, Dan Luo, Qiannan Hou, Hong Liu, Lunbo Tan, Yonghong Lin, Chang Chen, Xixi Wu","doi":"10.1093/hropen/hoag036","DOIUrl":"10.1093/hropen/hoag036","url":null,"abstract":"<p><strong>Study question: </strong>What are the specific metabolic and lipidomic alterations in placental tissue and umbilical cord serum of pregnancies complicated by PCOS, and how do maternal testosterone levels and obesity status interplay with these changes at the maternal-fetal interface?</p><p><strong>Summary answer: </strong>Pregnancies affected by PCOS exhibit distinct metabolomic and lipidomic reprogramming in both placental tissue and umbilical cord serum, characterized by alterations in key pathways such as tryptophan metabolism and fatty acid metabolism, with propionic and gluconic acids identified as central metabolic nodes; these changes are significantly associated with maternal testosterone levels and are differentially modulated by maternal obesity.</p><p><strong>What is known already: </strong>PCOS is known to adversely affect maternal and fetal metabolic health, carrying risks for intergenerational metabolic programming. However, the precise molecular nature of metabolic and lipidomic dysregulation at the maternal-fetal interface, particularly the specific drivers of hyperandrogenism and its complex interplay with maternal obesity, remains poorly characterized.</p><p><strong>Study design size duration: </strong>This prospective comparative study evaluated 48 pregnant women with PCOS and 50 healthy pregnant controls. All biological samples were collected at the time of term delivery.</p><p><strong>Participants/materials setting methods: </strong>Participants were recruited from a tertiary care center. To minimize labor-induced metabolic confounding, all subjects underwent elective term cesarean sections. Untargeted metabolomics and lipidomics analyses were performed on strictly standardized maternal-side placental tissue and umbilical cord serum using liquid chromatography-mass spectrometry. Statistical analyses included multivariable linear regression to adjust for confounders and LASSO regression for key feature selection. Participants were further stratified by pre-pregnancy BMI (obese: BMI ≥28 kg/m<sup>2</sup> vs non-obese: BMI <28 kg/m<sup>2</sup>) to assess the impact of maternal adiposity.</p><p><strong>Main results and the role of chance: </strong>PCOS pregnancies showed significantly distinct metabolomic and lipidomic profiles compared to controls in both placental tissue (407 differential metabolites, 186 differential lipids; FDR < 0.05) and umbilical cord serum (330 differential metabolites, 314 differential lipids; FDR < 0.05). Key enriched KEGG pathways included tryptophan metabolism, sphingolipid metabolism, and biosynthesis of unsaturated fatty acids. Maternal testosterone levels demonstrated strong and independent correlations with several key differential metabolites and lipids. Propionic acid and gluconic acid were identified as central metabolic nodes. Subgroup analysis revealed that maternal obesity exerts an additive metabolic burden that partially masks the intrinsic PCOS molecular phenotype. The role of c","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 3","pages":"hoag036"},"PeriodicalIF":8.6,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13186602/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147984717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Human reproduction openPub Date : 2026-04-16eCollection Date: 2026-01-01DOI: 10.1093/hropen/hoag033
Mahmoud Salama, Teresa K Woodruff
{"title":"Improving governance of IVF and oncofertility practice in the USA: a call to action.","authors":"Mahmoud Salama, Teresa K Woodruff","doi":"10.1093/hropen/hoag033","DOIUrl":"10.1093/hropen/hoag033","url":null,"abstract":"","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 2","pages":"hoag033"},"PeriodicalIF":8.6,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13151881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147870774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Human reproduction openPub Date : 2026-04-09eCollection Date: 2026-01-01DOI: 10.1093/hropen/hoag032
Rikke B Uggerhøj, Andrea R Skaaning, Frederik N Kyhl, Lone Schmidt, Ditte Vassard
{"title":"Socioeconomic disparities in achieving a live birth after initiating ART treatment: a national register-based study among women in Denmark.","authors":"Rikke B Uggerhøj, Andrea R Skaaning, Frederik N Kyhl, Lone Schmidt, Ditte Vassard","doi":"10.1093/hropen/hoag032","DOIUrl":"10.1093/hropen/hoag032","url":null,"abstract":"<p><strong>Study question: </strong>How are educational level, labour market attachment, and income associated with achieving a live birth following ART treatment initiation among women in Denmark?</p><p><strong>Summary answer: </strong>Higher educational level, labour market attachment, and higher income were strongly associated with achieving a live birth after initiating ART treatment among women in Denmark.</p><p><strong>What is known already: </strong>During the study period 1994-2017, three 'fresh' IVF or ICSI treatments with hormonal stimulation were offered free of charge in public healthcare in Denmark, while additional ART treatments were self-financed in the private healthcare sector. Earlier research indicates that higher socioeconomic position (SEP) increases the probability of initiating ART treatment; however, knowledge about SEP and its relation to outcomes after ART treatment is limited.</p><p><strong>Study design size duration: </strong>This is a national, register-based cohort study based on the Danish National ART-Couple (DANAC II) Cohort. Women initiating ART treatment during 1994-2017 were identified in the Danish IVF register and individually linked with data from sociodemographic registries and the Medical Birth Registry using the Danish Personal Identification number. The study population comprised 68 738 women who initiated ART. The women were followed until achieving a live birth, death, migration, or end of study (31/12/2017). The median follow-up time was between 1.3 and 1.9 years.</p><p><strong>Participants/materials settings methods: </strong>Women included in the analyses were aged 18-45 years. Overall associations between achieving a live birth after initiating ART treatment and educational level, labour market attachment, and income were examined and further stratified by nulliparity at baseline and age group. Hazard ratios (HRs) with confidence intervals (CIs) were estimated by Cox proportional hazards regression, and with adjustment for potential confounders including age and ethnicity. Live births refer to both treatment and non-treatment-related births.</p><p><strong>Main results and the role of chance: </strong>Adjusted results showed that educational level, labour market attachment, and income significantly determined the probability of achieving a live birth after initiating ART treatment. HRs of achieving a live birth after initiating ART treatment increased stepwise with higher education and income level, respectively. Compared with primary school education, the highest HR was found among women with a research education (adjusted HR (aHR) = 3.02 [95% CI, 2.71; 3.35]). Unemployed women had the lowest HR of achieving a live birth after initiating ART treatment (aHR = 0.67 [95% CI, 0.64; 0.69]) compared to employed women. Women at the highest income level had two times higher HR (aHR = 2.00 [1.94; 2.06] of achieving a live birth after initiating ART compared to women at the lowest income level. Analyses of ","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 3","pages":"hoag032"},"PeriodicalIF":8.6,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13198383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148019116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Human reproduction openPub Date : 2026-04-08eCollection Date: 2026-01-01DOI: 10.1093/hropen/hoag031
Thomas M D'Hooghe
{"title":"Effectiveness of 12-month GnRH antagonist treatment for endometriosis-associated pain: driven by reduction in uterine bleeding?","authors":"Thomas M D'Hooghe","doi":"10.1093/hropen/hoag031","DOIUrl":"10.1093/hropen/hoag031","url":null,"abstract":"","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 2","pages":"hoag031"},"PeriodicalIF":8.6,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13135357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147824369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Human reproduction openPub Date : 2026-04-08eCollection Date: 2026-01-01DOI: 10.1093/hropen/hoag030
Jacques Donnez, Christian M Becker, Felice Petraglia, Andrew W Horne, Sven Becker, Stefan P Renner, Francisco Carmona Herrera, Hugh S Taylor, Maciej Paszkowski, Elke Bestel, Satoshi Hori, Marie-Madeleine Dolmans
{"title":"Linzagolix, with and without add-back therapy, in women with endometriosis-associated pain: results from EDELWEISS 6, a double-blind randomized extension and withdrawal study.","authors":"Jacques Donnez, Christian M Becker, Felice Petraglia, Andrew W Horne, Sven Becker, Stefan P Renner, Francisco Carmona Herrera, Hugh S Taylor, Maciej Paszkowski, Elke Bestel, Satoshi Hori, Marie-Madeleine Dolmans","doi":"10.1093/hropen/hoag030","DOIUrl":"10.1093/hropen/hoag030","url":null,"abstract":"<p><strong>Study question: </strong>Was the efficacy of linzagolix, observed at 6 months in women with endometriosis-associated pain, maintained when administered for an additional 6 months?</p><p><strong>Summary answer: </strong>Efficacy from this extension study complements the results of the main trial, by showing that linzagolix is effective at reducing endometriosis-associated pain for a majority of women.</p><p><strong>What is known already: </strong>In the pivotal EDELWEISS 3 randomized controlled trial, the efficacy and safety of 24 weeks of once-daily oral linzagolix (a GnRH antagonist) were reported in women with endometriosis-related pain. Risks of bone mineral density (BMD) loss and vasomotor symptoms were minimized in both groups.</p><p><strong>Study design size duration: </strong>EDELWEISS 3 was a prospective, randomized, double-blind study. Subjects completing the 6-month treatment period in EDELWEISS 3 were invited to participate in the present extension study: EDELWEISS 6. Only subjects who had completed the full 6-month treatment course in the main study and who met the inclusion criteria were eligible for entry into the extension study. Among 486 patients who completed the 6-month study, 353 participated in the extension study from March 2020 to February 2023. The current extension study started at Month 6 of the main EDELWEISS 3 phase-3 trial. Upon the end of treatment in the extension study (6-month treatment period from Month 6 to Month 12), subjects entered a post-treatment follow-up period of 6 months. The current report describes outcomes from the extension treatment period (up to 12 months) and subsequent follow-up of 6 months with no investigational medicinal product. The co-primary endpoints were the reduction in dysmenorrhea and non-menstrual pelvic pain at Month 12.</p><p><strong>Participants/materials setting methods: </strong>Premenopausal women with moderate-to-severe endometriosis who previously completed the full 6-month treatment period in the main study and met the inclusion criteria were eligible for the extension study. All subjects (n = 353), whether given placebo or not in the main study, received either 75 mg linzagolix alone or 200 mg combined with hormonal add-back therapy (ABT) once daily for the additional 6 months, i.e. those who were given a placebo during the main study were randomized to either group and those who had received active treatment continued with the same treatment (placebo/75 mg linzagolix [n = 57], placebo/200 mg linzagolix plus ABT [n = 57], 75 mg linzagolix [n = 118], and 200 mg linzagolix plus ABT [n = 121]). Pain was measured daily on a verbal rating scale and recorded in an electronic diary. The trial was performed in clinics and university hospitals in the USA and Europe.</p><p><strong>Main results and the role of chance: </strong>By Month 12, of the 353 women who were treated and analyzed, the proportion of subjects with a significant reduction in dysmenorrhea and stable or de","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 2","pages":"hoag030"},"PeriodicalIF":8.6,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13135359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147824407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Human reproduction openPub Date : 2026-04-07eCollection Date: 2026-01-01DOI: 10.1093/hropen/hoag029
Tamara Tomanic, Dragana Samardzija Nenadov, Sava Radovic Pletikosic, Bojana Stanic, Darija Obradovic, Sasa Lazovic, Nebojsa Andric
{"title":"Perfluorooctane sulfonate (PFOS) in follicular fluid and human granulosa cell dysfunction: a physiologically based toxicokinetic model translation of long-term low-level <i>in vitro</i> exposure data.","authors":"Tamara Tomanic, Dragana Samardzija Nenadov, Sava Radovic Pletikosic, Bojana Stanic, Darija Obradovic, Sasa Lazovic, Nebojsa Andric","doi":"10.1093/hropen/hoag029","DOIUrl":"10.1093/hropen/hoag029","url":null,"abstract":"<p><strong>Study question: </strong>Are bioactive human-equivalent doses (HEDs) of perfluorooctane sulfonate (PFOS), derived from long-term low-level <i>in vitro</i> exposure of human granulosa cells comparable to HEDs inferred from follicular fluid PFOS concentrations in women undergoing ART and in occupationally exposed women?</p><p><strong>Summary answer: </strong>The bioactive HEDs overlapped with and, in some cases, were lower than the median HEDs inferred from follicular fluid PFOS concentrations.</p><p><strong>What is known already: </strong>PFOS exposure is a growing public health concern, with evidence suggesting adverse female reproductive effects. However, the relevance of current human exposure levels to granulosa cell function remains unclear.</p><p><strong>Study design size duration: </strong>Four independent vials of human granulosa cells (HGrC1 cells) were thawed and expanded into separate flasks (biological replicates). Cells were allocated to four experimental groups and exposed to PFOS (0.01, 0.1, or 1 µM) or vehicle control (0.05% DMSO) for up to 12 weeks, with re-dosing at each passage. Different apical endpoints, along with transcriptomic changes, were evaluated at designated time points. Clinical relevance of PFOS risk to human granulosa cells was assessed by integrating experimental data with physiologically based toxicokinetic (PBTK) modeling.</p><p><strong>Participants/materials setting methods: </strong>Viability of HGrC1 cells was assessed using the Alamar Blue assay. Estradiol and progesterone secretion were quantified by enzyme-linked immunosorbent assay. Flow cytometry was used to determine the proportions of live, apoptotic and necrotic cells, as well as cell cycle distribution. Global mRNA expression was assessed by DNA nanoball sequencing technology (DNBSEQ), whereas pathway-level molecular functions were derived using bioinformatic tools. Benchmark concentrations (BMCs) were calculated from key endpoints with concentration-dependent responses and used to estimate HEDs via PBTK modeling. These HEDs were compared with HEDs inferred from follicular fluid PFOS levels reported in the literature to derive bioactivity exposure ratios (BERs) and assess relevance to human exposure.</p><p><strong>Main results and the role of chance: </strong>In HGrC1 cells, long-term PFOS exposure altered steroidogenesis, apoptosis/necrosis, cell cycle distribution (<i>P</i> < 0.05), and gene expression (at least 2-fold change, <i>Q</i>-value ≤ 0.05). Median transcriptomic HEDs were 18.1 (95% CI: 1.1-35.1) and 17.5 ng/kg bw/day (95% CI: 8-27.1) for 6- and 12-week exposures, respectively, with corresponding 5th percentile HEDs of 3.7 ng/kg bw/day (95% CI: 0.4-9.3) and 1.4 ng/kg bw/day (95% CI: 0.5-3.5). Pathway-level HEDs ranged from 2.8 to 24.1 ng/kg bw/day, with eicosanoid synthesis showing the greatest sensitivity. HEDs for apical endpoints ranged from 0.4 to 203 ng/kg bw/day, with the sub-G<sub>1</sub> cell cycle phase being most sensi","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 2","pages":"hoag029"},"PeriodicalIF":8.6,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13110862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147791245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Reproductive fluids, commercial media, and organoids: bridging the gap in IVF culture systems.","authors":"Nathaly Hernández-Díaz, Sergio Navarro-Serna, Pilar Coy, Vicente Pérez-García","doi":"10.1093/hropen/hoag028","DOIUrl":"10.1093/hropen/hoag028","url":null,"abstract":"<p><strong>Background: </strong>Although assisted reproductive technologies have enabled millions of births worldwide, <i>in vitro</i> embryo culture systems remain a simplified and static approximation of the highly dynamic environment of the female reproductive tract. Commercial culture media lack many of the biochemical, biophysical, and temporal features of oviductal and uterine fluids, including hormonally regulated secretions, extracellular vesicles, and epithelial-derived signaling cues. These limitations are increasingly linked to altered embryonic programming, suboptimal implantation, and subtle but persistent effects on perinatal and long-term health outcomes.</p><p><strong>Objective and rationale: </strong>This review critically examines how reproductive tract-derived factors and advanced three-dimensional (3D) <i>in vitro</i> models can improve the physiological relevance of embryo culture systems in human ART. We focus on the biological roles of native reproductive fluids and extracellular vesicles and the emerging contribution of reproductive tract organoids and assembloids as sources of defined, stage-specific secretomes capable of bridging the gap between artificial and <i>in vivo</i>-like conditions.</p><p><strong>Search methods: </strong>A comprehensive literature search was conducted in PubMed, Scopus, and Web of Science for studies published up to March 2026 using terms related to embryo culture media, reproductive fluids, extracellular vesicles, organoids, implantation, and human IVF. Evidence from human studies and relevant animal models was included to provide mechanistic insight and translational context, with emphasis on experimental approaches directly informing ART practice.</p><p><strong>Outcomes: </strong>Reproductive tract fluids contain complex mixtures of proteins, metabolites, lipids, and extracellular vesicles that regulate fertilization, early embryonic development, epigenetic programming, and maternal-embryo communication. While supplementation of embryo culture media with native fluids improves embryo quality and developmental competence in multiple species, clinical translation is constrained by donor variability, biosafety concerns, and limited standardization. Reproductive tract 3D cell cultures represent a promising complementary approach, as they can recapitulate key aspects of epithelial architecture, hormonal responsiveness, and secretory activity under controlled conditions. Organoid-derived secretomes, including extracellular vesicle cargo, have been shown to support reproductive processes such as sperm viability, trophoblast function, immune modulation, and endometrial receptivity. Moreover, advances in epithelial-stromal assembloids and microengineered platforms further enhance physiological fidelity by partially restoring multicellular interactions relevant to implantation-related signaling. However, these systems also present important limitations, including variability between lines, incomplete c","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 2","pages":"hoag028"},"PeriodicalIF":8.6,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13117623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147791186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Human reproduction openPub Date : 2026-03-27eCollection Date: 2026-01-01DOI: 10.1093/hropen/hoag027
Jonas Vibert, Eliane Maalouf, Jean-Marie Wenger, Antonio Mercorio, Giuseppe Benagiano, Nicola Pluchino
{"title":"IVF in endometriosis: emerging evidence of exacerbation of pelvic pain and potential predictors.","authors":"Jonas Vibert, Eliane Maalouf, Jean-Marie Wenger, Antonio Mercorio, Giuseppe Benagiano, Nicola Pluchino","doi":"10.1093/hropen/hoag027","DOIUrl":"10.1093/hropen/hoag027","url":null,"abstract":"<p><strong>Study question: </strong>Does IVF worsen pelvic pain in women with endometriosis?</p><p><strong>Summary answer: </strong>Nearly half of women with endometriosis reported perceived worsening of pelvic pain after IVF.</p><p><strong>What is known already: </strong>Prior studies generally suggested no IVF-related pain worsening, but few assessed delayed flares or longer-term trajectories.</p><p><strong>Study design size duration: </strong>International cross-sectional study based on an online survey conducted between September 2024 and April 2025 including 546 respondents.</p><p><strong>Participants/materials setting methods: </strong>Women aged ≥18 years with surgically or imaging-confirmed endometriosis and at least one completed IVF cycle. A 25-item questionnaire captured demographics, reproductive history, comorbidities, and patient-reported pain trajectories before, during, and after IVF. The primary outcome was perceived worsening of pelvic pain after IVF (patient-reported outcome measure; PROM). Secondary outcomes were worsening of dysmenorrhoea and dyspareunia. Group comparisons and exploratory multivariable logistic regressions were performed. Predictor analyses were exploratory.</p><p><strong>Main results and the role of chance: </strong>Among 546 respondents, 48.9% reported worsening pelvic pain after IVF, 49.1% reported worsening dysmenorrhoea, and 35.5% worsening dyspareunia. Current pain scores were significantly higher in women reporting worsening versus no worsening (all <i>P</i> < 0.001). In multivariable analyses, immediate post-cycle pain flare emerged as the strongest and most consistent predictor across all pain outcomes, independently associated with worsening of pelvic pain (adjusted odds ratio [aOR] 5.91, 95% CI 3.88-9.14), dysmenorrhoea (aOR 4.03, 95% CI 2.08-8.05), and dyspareunia (aOR 3.17, 95% CI 2.07-4.90) (all <i>P</i> < 0.001). For the primary outcome, reporting oocyte retrieval as the most painful IVF step (aOR 0.53, 95% CI 0.31-0.88; <i>P</i> = 0.016) and achieving a live birth after IVF (aOR 0.63, 95% CI 0.42-0.92; <i>P</i> = 0.020) were independently associated with lower odds of pelvic pain worsening. In secondary outcome models, live birth was associated with lower odds of dysmenorrhoea worsening, while bladder pain syndrome/interstitial cystitis independently predicted worsening of dyspareunia. A formal response rate could not be calculated due to open online dissemination without a known denominator.</p><p><strong>Limitations reasons for caution: </strong>Self-reported, retrospective data are prone to recall and selection bias, and the cross-sectional design precludes causal inference. Recruitment via associations and social media without a denominator limits generalizability, absence of baseline pain scores impedes assessment of change, and incomplete capture of peri-IVF hormonal regimens may confound results.</p><p><strong>Wider implications of the findings: </strong>IVF may not be pain-neutral in e","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 2","pages":"hoag027"},"PeriodicalIF":8.6,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13091650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147724749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Human reproduction openPub Date : 2026-03-26eCollection Date: 2026-01-01DOI: 10.1093/hropen/hoag025
Shizuko Takahashi, Sonia Gayete-Lafuente, Elizabeth Choong, Lara Guijarro-Baude, David H Barad, Pasquale Patrizio, Michael Dunn, Julian Savulescu, Norbert Gleicher
{"title":"Reclaiming 'abnormal' embryos after preimplantation genetic testing for aneuploidy: patients' perspectives on transferring embryos against prior institutional advice.","authors":"Shizuko Takahashi, Sonia Gayete-Lafuente, Elizabeth Choong, Lara Guijarro-Baude, David H Barad, Pasquale Patrizio, Michael Dunn, Julian Savulescu, Norbert Gleicher","doi":"10.1093/hropen/hoag025","DOIUrl":"10.1093/hropen/hoag025","url":null,"abstract":"<p><strong>Study question: </strong>How do patients make sense of and justify the transfer of embryos labelled 'abnormal' by preimplantation genetic testing for aneuploidy (PGT-A)?</p><p><strong>Summary answer: </strong>Patients described a process of unlearning the authority of genetic testing and reframing their decisions as morally reasoned acts of reproductive agency-a reclaiming of possibility amid biomedical exclusion.</p><p><strong>What is known already: </strong>PGT-A is widely used in IVF, although its clinical utility and interpretation remain debated, and its claimed benefit on cumulative live birth rates unproven. Many clinics refuse transfer of embryos labelled 'abnormal', despite reports of healthy live births following transfer of selected embryos labelled 'mosaic' or 'aneuploid'.</p><p><strong>Study design size duration: </strong>Qualitative retrospective study of 21 participants (15 women and 6 men) conducted between 2019 and 2025 at a private fertility clinic associated with a research university in New York City, NY, USA.</p><p><strong>Participants/materials setting methods: </strong>Participants had previously been denied transfer of embryos labelled 'abnormal' by PGT-A at multiple clinics and sought care at the study site. Semi-structured interviews were conducted, audio-recorded, transcribed verbatim, and analysed using inductive, reflexive thematic analyses.</p><p><strong>Main results and the role of chance: </strong>Among 21 participants, transfer outcomes included 6 healthy births following transfers of embryos labelled 'abnormal', 1 ongoing, 4 first-trimester miscarriages, 1 chemical pregnancy, and 12 failed implantations. One overarching theme 'reclaiming possibility', spanning four interrelated phases, was identified: (i) reassessing scientific authority of PGT-A; (ii) navigating institutional and relational constraints; (iii) embracing moral responsibility to give, or withhold, embryos a chance; and (iv) retrospective/anticipatory validation through a no-regrets stance. Participants resisted exclusionary classifications, pursued transfer despite refusals, and made sense of known, unknown, or adverse outcomes without equating results with the test's predictive accuracy.</p><p><strong>Limitations reasons for caution: </strong>Participants were self-selected from a single clinic that was willing to consider such embryo transfers; therefore, the findings may have limited transferability to other settings or to patients who accepted an original institutional transfer refusal.</p><p><strong>Wider implications of the findings: </strong>Patients' narratives challenge assumptions that PGT-A results are determinative of embryo viability and highlight the ethical complexity of categorical transfer refusals by clinics. These findings support the need for transparent pre-test counselling, explicit institutional policies on embryo transfer, and patient-led pathways under robust informed consent. Integrating uncertainty-aware counse","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 2","pages":"hoag025"},"PeriodicalIF":8.6,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13070650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147678983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}