Human reproduction openPub Date : 2026-06-03eCollection Date: 2026-01-01DOI: 10.1093/hropen/hoag055
Manuel Luque-Ramírez, Sara de Lope Quiñones, Alejandra Quintero-Tobar, María Ángeles Martínez-García, María Insenser, Lía Nattero-Chávez, María Garriga, Antonio Carlos Michael Fernández, Héctor Francisco Escobar-Morreale
{"title":"Evidence of early subclinical atherosclerosis in women with exercise-induced hypothalamic amenorrhea.","authors":"Manuel Luque-Ramírez, Sara de Lope Quiñones, Alejandra Quintero-Tobar, María Ángeles Martínez-García, María Insenser, Lía Nattero-Chávez, María Garriga, Antonio Carlos Michael Fernández, Héctor Francisco Escobar-Morreale","doi":"10.1093/hropen/hoag055","DOIUrl":"10.1093/hropen/hoag055","url":null,"abstract":"<p><strong>Study question: </strong>Do women with exercise-induced functional hypothalamic amenorrhea (Ex-FHA) have an increased risk of subclinical atherosclerosis, as measured by carotid intima-media thickness (cIMT)?</p><p><strong>Summary answer: </strong>Women with Ex-FHA appear to show greater cIMT than non-exercising control women (nonEx-control).</p><p><strong>What is known already: </strong>Long-term cardiovascular risk is a major concern in women with functional hypothalamic amenorrhea who exercise regularly. Although hypoestrogenic women with Ex-FHA consistently exhibit markers of risk, such as endothelial dysfunction, evidence of atherosclerosis is lacking.</p><p><strong>Study design size duration: </strong>From 2019 to 2025, we conducted a cross-sectional comparative study of five groups of premenopausal adult women (N = 50). According to our calculations, this sample size allowed us to detect a minimum difference of 0.019 mm in common cIMT between any pair of groups, setting α to 0.05 and power (1-β) to 0.80.</p><p><strong>Participants/materials setting methods: </strong>We included three groups of women with different mechanisms of ovulatory dysfunction: women with Ex-FHA, women with classic PCOS, and women with non-hyperandrogenic PCOS. Healthy exercising (Ex-control) and nonEx-control served as control groups. Smokers were excluded. All women received a comprehensive cardiometabolic phenotyping including anthropometrics, circulating sex steroids, carbohydrate metabolism and lipid profiles, office and 24-h ambulatory blood pressure monitoring, and cardioautonomic function studies. Ultrasound measurement of mean cIMT served as a marker of subclinical carotid atherosclerosis.</p><p><strong>Main results and the role of chance: </strong>Women with Ex-FHA were the only subgroup of study participants showing higher cIMT values than nonEx-controls [cIMT: 0.514 ± 0.057 vs 0.411 ± 0.054 mm, respectively; mean difference: 0.103 (95% CI: 0.031; 0.175); <i>P </i>= 0.002]. This difference remained after adjusting for BMI. Regarding carbohydrate and lipid metabolism, women with Ex-FHA showed a higher insulin sensitivity index than both subgroups of women with PCOS. Individuals with Ex-FHA had higher concentrations of HDL-cholesterol, HDL-triglycerides, and large- and medium-HDL particles than both subgroups of women with PCOS, Ex-controls, and nonEx-controls. Women with Ex-FHA presented with a lower resting heart rate than participants with classic PCOS, Ex-controls, and nonEx-controls. They also showed a lower diastolic blood pressure response to standing than nonEx-controls.</p><p><strong>Limitations reasons for caution: </strong>The limited sample size of our study population precluded us from identifying the main determinants of subclinical atherosclerosis in each subgroup of women. The cross-sectional observational design of this study does not allow causal inference regarding associations between independent variables and cIMT. Lastly, mul","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 3","pages":"hoag055"},"PeriodicalIF":8.6,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13293127/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148335002","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":"Vitrification with shortened equilibration across human embryonic developmental stages: a proof-of-concept study.","authors":"Noya Doolman, Eden Weinberg, Ettie Maman, Shmuel Inbar, Moran Shapira, Raoul Orvieto, Adva Aizer","doi":"10.1093/hropen/hoag053","DOIUrl":"10.1093/hropen/hoag053","url":null,"abstract":"<p><strong>Study question: </strong>Can vitrification with a shortened equilibration solution (ES) be safely applied to human embryos without compromising key embryological clinical outcomes?</p><p><strong>Summary answer: </strong>Vitrification with shortened equilibration was associated with comparable observed survival, developmental progression, and blastocyst re-expansion rates when compared to standard vitrification.</p><p><strong>What is known already: </strong>Vitrification with shortened-equilibration exposure has been primarily evaluated in mouse models and in human oocytes at the germinal vesicle and metaphase II stages, where short exposure times have been shown to maintain post-warming survival and preserve mitochondrial integrity comparable to conventional vitrification. The European Commission (CE) approval exists for the use of shortened-equilibration vitrification protocols in human oocytes, although clinical experience remains limited. Conversely, evidence regarding the application of shortened-equilibration vitrification to human embryos is currently lacking, and there is currently no clinical regulatory approval for embryos or blastocyst vitrification using shortened-equilibration protocols.</p><p><strong>Study design size duration: </strong>Prospective proof-of-concept study performed in a single IVF laboratory from April 2025 to March 2026. It involved 45 human blastocysts, 49 cleavage-stage embryos, and 102 tripronuclear (3PN) zygotes. Blastocysts were allocated to standard, shortened-equilibration vitrification using full-volume (300 µl) or microdrop loading (50 µl) vitrification. 3PN zygotes were used as a model for early-stage embryo response and were vitrified immediately after fertilization or at the cleavage stage according to group allocation, using standard and shortened-equilibration protocols.</p><p><strong>Participants/materials setting methods: </strong>All blastocysts were identified as affected by preimplantation genetic testing for monogenic disorders (PGT-M) and used for research only; they were cryopreserved, then warmed using standard protocols, then re-vitrified per group using shortened-equilibration vitrification and subsequently warmed using one-step warming. 3PN zygotes were included as clinically relevant research material and assigned to standard vitrification or shortened-equilibration vitrification (300 µl, 2 min; microdrops 50 µl, 2-3 min). Outcomes included survival rate, day-3 development, blastocyst formation, iDAScore (morphokinetic assessment), and post-warming re-expansion.</p><p><strong>Main results and the role of chance: </strong>3PN zygotes were allocated to four groups: standard vitrification and shortened-equilibration vitrification using full-volume loading (300 µl, 2-min) or microdrop loading (50 µl, 2 or 3-min). Baseline characteristics were comparable between groups. Post-warming survival rates ranged from 89.2% to 100% (<i>P</i> = 0.408). Day-3 development ranged from 47% to 60% (","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 3","pages":"hoag053"},"PeriodicalIF":8.6,"publicationDate":"2026-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13283424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148304142","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 : 2026-06-02eCollection Date: 2026-01-01DOI: 10.1093/hropen/hoag052
David H Barad, Sarah Darmon, Sonia Gayete-Lafuente, Lara Guijarro-Baude, David F Albertini, Pasquale Patrizio, Cari Nicholas, Norbert Gleicher
{"title":"Association between ovarian reserve and utilization of preimplantation genetic testing for aneuploidy in autologous IVF cycles.","authors":"David H Barad, Sarah Darmon, Sonia Gayete-Lafuente, Lara Guijarro-Baude, David F Albertini, Pasquale Patrizio, Cari Nicholas, Norbert Gleicher","doi":"10.1093/hropen/hoag052","DOIUrl":"10.1093/hropen/hoag052","url":null,"abstract":"<p><strong>Study question: </strong>Does ovarian reserve, as measured by anti-Müllerian hormone (AMH), influence the utilization of preimplantation genetic testing for aneuploidy (PGT-A) in autologous IVF cycles across different age groups?</p><p><strong>Summary answer: </strong>Lower ovarian reserve, reflected by reduced AMH levels, was associated with a lower likelihood of undergoing PGT-A across all age strata.</p><p><strong>What is known already: </strong>PGT-A is widely used in IVF, particularly in older patients, but its utilization may be influenced not only by age but also by expected ovarian reserve and embryo yield. How ovarian reserve is associated with selection for PGT-A at a population level has not yet been well characterized.</p><p><strong>Study design size duration: </strong>This cross-sectional analysis of the US Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) database includes 258,532 patient-first autologous ovarian stimulation cycles performed between 2014 and 2021.</p><p><strong>Participants/materials setting methods: </strong>The study included the first autologous IVF cycles of women aged 21-46 years. Donor oocyte, donor embryo, and gestational carrier cycles were excluded, as were cycles using <150 IU/day of gonadotropins or with missing key data. Cycles were classified according to PGT-A use. Ovarian reserve was primarily assessed using the most recent AMH value measured within 1 year of treatment. Multivariable logistic regression models evaluated the association between AMH and PGT-A utilization, adjusting for age, calendar year, race, total gonadotropin dose, gravidity, and prior ART, with prespecified testing for the age-AMH interaction.</p><p><strong>Main results and the role of chance: </strong>Across the study population, higher AMH levels were associated with significantly increased odds of undergoing PGT-A. This association persisted after multivariable adjustment and within each age group. AMH modelled as both a continuous variable and dichotomized at 1 ng/ml showed consistent results, indicating an independent relationship between ovarian reserve and PGT-A utilization that was unlikely due to chance.</p><p><strong>Limitations reasons for caution: </strong>The observational, cross-sectional design limits causal inference. Residual confounding is possible, and registry data do not capture treatment intent or all of the clinical reasons underlying use or non-use of PGT-A. Embryo-level genetic outcomes and clinical outcomes such as live birth were not evaluated.</p><p><strong>Wider implications of the findings: </strong>These findings suggest a systematic selection pattern in IVF practice, whereby patients with diminished ovarian reserve are less likely to undergo PGT-A. This population imbalance should be considered when interpreting observational studies of PGT-A and when counselling patients about the clinical context in which PGT-A is most commonly used.</p><p><strong>S","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 3","pages":"hoag052"},"PeriodicalIF":8.6,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13274540/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148280298","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 : 2026-05-29eCollection Date: 2026-01-01DOI: 10.1093/hropen/hoag051
Jeffrey Pea, Yiru Zhu, Hoi Chang Lee, Lauren R Haky, John Proudfoot, Richard Nelson, Francesca E Duncan
{"title":"A phenotypic <i>in vitro</i> assay of mouse oocyte maturation identifies reversible blockers of meiotic progression for non-hormonal contraceptive discovery.","authors":"Jeffrey Pea, Yiru Zhu, Hoi Chang Lee, Lauren R Haky, John Proudfoot, Richard Nelson, Francesca E Duncan","doi":"10.1093/hropen/hoag051","DOIUrl":"10.1093/hropen/hoag051","url":null,"abstract":"<p><strong>Study question: </strong>Can oocyte maturation be adapted to a phenotypic assay within a drug screening pipeline to identify compounds that block meiotic progression for female non-hormonal contraceptive drug discovery?</p><p><strong>Summary answer: </strong>A complex phenotypic assay of mouse oocyte maturation identifies potent compounds that reversibly block meiotic progression at specific stages.</p><p><strong>What is known already: </strong>During oocyte maturation, prophase I-arrested oocytes resume meiosis, undergo germinal vesicle (GV) breakdown, and complete meiosis I with extrusion of the first polar body. Oocyte maturation is critical for generating a fertilizable gamete, and thus, blocking meiotic progression is a promising target for non-hormonal contraception. Moreover, this process can be recapitulated <i>in vitro</i>, providing a powerful phenotypic assay for drug screening.</p><p><strong>Study design size duration: </strong>Oocytes were collected from CD-1 mice following hyperstimulation and <i>in vitro</i> matured for 14-16 h in the presence of a single dose (10 µM) of compounds from a bioactive compound library. Incubation in dimethyl sulfoxide (DMSO) only or 10 µM milrinone, a known phosphodiesterase 3A (PDE3A) inhibitor, was used as vehicle and positive control, respectively. Primary screening and subsequent concentration-response testing were performed in duplicate.</p><p><strong>Participants/materials setting methods: </strong>Oocytes were incubated with compounds during IVM to identify compounds with inhibitory effects on meiotic progression. We were specifically interested in compounds that maintained arrest at prophase of meiosis I (GV-intact) or prevented extrusion of the first polar body. Brightfield images were taken before and after IVM to assess maturation status based on morphological criteria. Using this platform, we screened a subset of 818 compounds from the compound library based on annotated target and structural diversity. A hit was defined as a compound that inhibited meiotic progression by ≥80%. Hits were validated through an independent source of compound and concentration responsiveness. Hit compounds were also tested in a prolonged culture treatment to confirm maintenance of meiotic arrest. A counterscreen assay was performed on compounds that maintained arrest at prophase of meiosis I to rule out phenotypes due to inhibition of PDE3A activity.</p><p><strong>Main results and the role of chance: </strong>From our primary screen, 29 hits were identified that blocked meiotic maturation. Following hit validation via independent sources and concentration-response, 18 compounds were confirmed. Five compounds resulted in arrest at prophase of meiosis I, but only one was not based on PDE3A inhibition. Thirteen compounds enabled resumption of meiosis but not polar body extrusion, and 12 of these maintained arrest during prolonged culture. Thus, using this screening pipeline, we identified a total of 13 ","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 3","pages":"hoag051"},"PeriodicalIF":8.6,"publicationDate":"2026-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13290471/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148334965","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 : 2026-05-28eCollection Date: 2026-01-01DOI: 10.1093/hropen/hoag050
Sofia Makieva, Mara D Saenz-de-Juano, Carmen Almiñana, Stefan Bauersachs, Sandra Bernal-Ulloa, Min Xie, Ana G Velasco, Natalia Cervantes, Maike Sachs, Susanne E Ulbrich, Brigitte Leeners
{"title":"Reply: Extracellular vesicle-mediated signalling in human rescue <i>in vitro</i> maturation: methodological and mechanistic considerations.","authors":"Sofia Makieva, Mara D Saenz-de-Juano, Carmen Almiñana, Stefan Bauersachs, Sandra Bernal-Ulloa, Min Xie, Ana G Velasco, Natalia Cervantes, Maike Sachs, Susanne E Ulbrich, Brigitte Leeners","doi":"10.1093/hropen/hoag050","DOIUrl":"10.1093/hropen/hoag050","url":null,"abstract":"","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 3","pages":"hoag050"},"PeriodicalIF":8.6,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13269643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148273966","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 : 2026-05-25eCollection Date: 2026-01-01DOI: 10.1093/hropen/hoag041
Tekla Lind, Hanna P Nilsson, Mikael Andersson Franko, Kenny A Rodriguez-Wallberg
{"title":"Likelihood of childbirth in women with one versus two ovaries: a Swedish population-based study of women treated with unilateral oophorectomy for benign indications.","authors":"Tekla Lind, Hanna P Nilsson, Mikael Andersson Franko, Kenny A Rodriguez-Wallberg","doi":"10.1093/hropen/hoag041","DOIUrl":"10.1093/hropen/hoag041","url":null,"abstract":"<p><strong>Study question: </strong>What is the likelihood of future childbirth in women undergoing unilateral oophorectomy (UO) for benign indications, when compared to age-matched women with intact ovaries?</p><p><strong>Summary answer: </strong>A significantly reduced likelihood of future childbirth was observed in women with a history of UO, when compared to women with intact ovaries.</p><p><strong>What is known already: </strong>At the time of this study, the prevailing view is that a single ovary is sufficient to maintain fertility. This is the first large-scale observational study reporting an association between UO for benign indications and a decreased chance of future childbirth in a population-based cohort that was followed until the end of reproductive age.</p><p><strong>Study design size duration: </strong>This population-based register study included all Swedish women born 1955-1966, followed until the end of female reproductive age. We identified 17 856 women who underwent UO (exposed) and 171 731 age-matched controls. After exclusions, the exposed cohort consisted of 10 469 women of fertile age with a benign indication for UO and 101 753 age-matched controls.</p><p><strong>Participants/materials setting methods: </strong>All cases of UO were identified by surgery codes and diagnosis of benign diseases, and up to 10 controls per case, matched by age and county, were used in the analysis. Childbirth data were collected from the Swedish Medical Birth Register, and childbirth rates were compared between exposed cases and age-matched controls.</p><p><strong>Main results and the role of chance: </strong>The childbirth rate post-surgery was lower in women with UO compared to age-matched controls having intact ovaries: 25.5% versus 28.7%, respectively (risk ratio (RR) 0.89; confidence interval (95% CI) 0.86-0.91). Subgroup analysis of women who were nulliparous at the time of UO (N = 4083) versus their age-matched controls (N = 18 770) also indicated a lower childbirth rate: 41.3% vs 66%, respectively (RR 0.63; 95% CI 0.61-0.65). Additionally, an interaction analysis among the nulliparous women indicated that the reduced likelihood of having children was associated with older age at the time of UO.</p><p><strong>Limitations reasons for caution: </strong>In this register-based study, the desire for pregnancy could not be captured, and it was unknown if it was similar among cases and controls. Although malignant indications of UO could be excluded in the study, the histopathology of the removed ovaries was not available; thus, it was not possible to adjust for specific diseases potentially affecting fertility, and therefore, residual confounding is a limitation. Additional limitations included the lack of adjustment for lifestyle factors, as such data was only available from the medical birth register, and thus only accessible for the women who had given birth.</p><p><strong>Wider implications of the findings: </strong>This large population","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 3","pages":"hoag041"},"PeriodicalIF":8.6,"publicationDate":"2026-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13234452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148201234","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 : 2026-05-22eCollection Date: 2026-01-01DOI: 10.1093/hropen/hoag048
Johnny S Younis, Liana Glick, Pietro Santulli, Ido Izhaki, Nora Shapso
{"title":"Does endometrioma diameter impact serum anti-Müllerian hormone levels? A systematic review and meta-analysis.","authors":"Johnny S Younis, Liana Glick, Pietro Santulli, Ido Izhaki, Nora Shapso","doi":"10.1093/hropen/hoag048","DOIUrl":"10.1093/hropen/hoag048","url":null,"abstract":"<p><strong>Study question: </strong>Is endometrioma diameter associated with ovarian reserve, as reflected by serum anti-Müllerian hormone (AMH) levels, in women of reproductive age with no history of ovarian surgery?</p><p><strong>Summary answer: </strong>Across 30 independent cohorts, endometrioma diameter showed no independent association with serum AMH levels when modeled either continuously or categorically, indicating that cyst size is unlikely to be a principal determinant of diminished ovarian reserve in non-operated endometrioma.</p><p><strong>What is known already: </strong>The extent to which endometrioma diameter contributes to ovarian reserve impairment remains uncertain and has historically informed size-based thresholds for surgical intervention. Whether larger cysts exert a greater deleterious effect on ovarian reserve remains debated. Observational studies in women without prior ovarian surgery have reported inconsistent and often contradictory findings.</p><p><strong>Study design size duration: </strong>Systematic review and meta-analysis of studies published in English between 1 January 2000 and 30 June 2025. Searches were conducted in PubMed, ClinicalTrials.gov, the Cochrane Library, Web of Science, and EBSCOhost.</p><p><strong>Participants/materials setting methods: </strong>Eligible studies compared serum AMH across different endometrioma diameters within the same population and setting in reproductive-age women with non-operated endometrioma. Two reviewers independently screened studies, extracted data, and assessed risk of bias using ROBINS-I. The primary inferential analysis was a cohort-level multivariable random-effects meta-regression based on 30 independent, non-overlapping cohorts derived from 16 studies, adjusting for age. Diameter was modeled both as a continuous predictor and as prespecified strata (<4 cm, 4-5 cm, 5-6 cm, >6 cm). Supportive exploratory threshold and subgroup analyses (predefined cut-offs 3-8 cm) were interpreted with multiplicity control using the Holm-Bonferroni sequentially rejective procedure.</p><p><strong>Main results and the role of chance: </strong>Sixteen studies, including 1484 women, met the inclusion criteria, and 30 independent cohorts were used in the primary analysis. Endometrioma diameter was not a significant predictor of serum AMH when modeled continuously (<i>β</i> = 0.122, SE = 0.128, <i>P </i>= 0.35) or categorically across diameter strata (<i>β</i> = 0.245, SE = 0.220, <i>P </i>= 0.28). In contrast, age accounted for most of the between-cohort heterogeneity (<i>R</i> <sup>2</sup> = 58.2%). Supportive subgroup and threshold analyses did not materially alter the primary inference after multiplicity adjustment. Of the 16 eligible studies, 2 were judged to be at low risk and 14 at moderate risk of bias, suggesting overall moderate certainty of the evidence.</p><p><strong>Limitations reasons for caution: </strong>The analysis was restricted to non-operated endometriomas; therefore,","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 3","pages":"hoag048"},"PeriodicalIF":8.6,"publicationDate":"2026-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13283431/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148304140","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 : 2026-05-19eCollection Date: 2026-01-01DOI: 10.1093/hropen/hoag045
Sandro C Esteves, Peter Humaidan
{"title":"Reconsidering the interpretation of sperm DNA fragmentation testing in ART decision-making.","authors":"Sandro C Esteves, Peter Humaidan","doi":"10.1093/hropen/hoag045","DOIUrl":"10.1093/hropen/hoag045","url":null,"abstract":"","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 3","pages":"hoag045"},"PeriodicalIF":8.6,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13236097/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148201210","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 : 2026-05-19eCollection Date: 2026-01-01DOI: 10.1093/hropen/hoag044
Ying Li, Matthew Hoi Kin Chau, Ying Xin Zhang, Bao Heng Gui, Wai Ting Lui, Ching Man Vivian Lam, Ye Cao, Teresa Cheuk Yan Chung, Chong Cong Wu, Patricia Nga Ping Ip, David Yiu Leung Chan, Yvonne Ka Yin Kwok, Jacqueline Pui Wah Chung, Kwong Wai Choy
{"title":"Underrecognized triploidy and genome-wide uniparental disomy in human blastocysts revealed by a concurrent preimplantation genetic testing approach.","authors":"Ying Li, Matthew Hoi Kin Chau, Ying Xin Zhang, Bao Heng Gui, Wai Ting Lui, Ching Man Vivian Lam, Ye Cao, Teresa Cheuk Yan Chung, Chong Cong Wu, Patricia Nga Ping Ip, David Yiu Leung Chan, Yvonne Ka Yin Kwok, Jacqueline Pui Wah Chung, Kwong Wai Choy","doi":"10.1093/hropen/hoag044","DOIUrl":"10.1093/hropen/hoag044","url":null,"abstract":"<p><strong>Study question: </strong>What is the incidence of triploidy and genome-wide uniparental disomy (gwUPD) in human embryos currently undetected by conventional preimplantation genetic testing (PGT)?</p><p><strong>Summary answer: </strong>Triploidy and gwUPD were detected in 0.8% (8/1049) and 1.4% (15/1049) of blastocysts, respectively.</p><p><strong>What is known already: </strong>Concurrent PGT enhances embryo selection by simultaneously detecting monogenic disorders (PGT-M) or structural rearrangements (PGT-SR) and aneuploidy (PGT-A). However, triploidy and gwUPD, two genome-wide abnormalities causative of severe pregnancy outcomes, are not routinely detected by conventional PGT platforms and thus remain under-recognized at the preimplantation stage.</p><p><strong>Study design size duration: </strong>This study consisted of three phases: Phase I validated the detection capability of PGT-Plus on cell lines with previously ascertained genetic abnormalities; Phase II performed retrospective clinical validation on leftover trophectoderm biopsy whole-genome amplification (WGA) samples, including 65 for PGT-M, 67 for PGT-SR, and 130 for PGT-A received during January 2019 and July 2023; and Phase III was prospective implementation of PGT-Plus under a diagnostic setting on 529 blastocysts received from August 2023 to June 2024. Additionally, a cohort consisting of 258 embryo transfers, previously ascertained as euploid by conventional PGT-A methods but associated with unfavorable outcomes, was retested by PGT-Plus, which identified previously undetected cases of gwUPD or triploidy.</p><p><strong>Participants/materials setting methods: </strong>In Phase I, cell lines with ascertained genetic abnormalities were tested using at least one of the following methods, including G-banded Karyotyping, quantitative fluorescence PCR (QF-PCR), chromosomal microarray analysis (CMA), and mate-pair sequencing. The previous results were compared with those from PGT-Plus. In Phase II, results from conventional PGT platforms were compared in parallel with PGT-Plus to evaluate its accuracy. Cell lines or real trophoblast biopsy samples from blastocysts were amplified by the multiple displacement amplification (MDA) method. PGT-Plus data analysis was performed in various dimensions. For PGT-A analysis, except for canonical read-count analysis to assess the genome dosage, single nucleotide polymorphism (SNP) analysis was also performed to identify triploidy and gwUPD. Furthermore, for families requesting PGT-M and PGT-SR, linkage analysis was carried out for haplotype construction in addition to read-count analysis and SNP analysis. In addition to prospective cohort of Phase III, a unique cohort with adverse reproductive outcomes after transfer of a 'euploid' embryo, as determined by conventional PGT-A platforms, was retested to identify any triploidy and UPD among these copy-number neutral embryos. The unfavorable outcomes included no pregnancy, biochemical pregnan","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 3","pages":"hoag044"},"PeriodicalIF":8.6,"publicationDate":"2026-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13262742/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148254788","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}