Human reproduction open最新文献

{"title":"The declining efficiency of IVF in the USA.","authors":"Norbert Gleicher, Sonia Gayete-Lafuente, Lara Guijarro-Baude, Pasquale Patrizio, David F Albertini, David H Barad","doi":"10.1093/hropen/hoag004","DOIUrl":"https://doi.org/10.1093/hropen/hoag004","url":null,"abstract":"<p><strong>Study question: </strong>Has the efficiency of IVF cycles in the USA declined between 2012 and 2021?</p><p><strong>Summary answer: </strong>National U.S. data show a continuous linear decline in IVF cycle efficiency between 2012 and 2021.</p><p><strong>What is known already: </strong>Previous studies reported that live birth rates after IVF increased until 2010 but subsequently declined, potentially due to the introduction of IVF 'add-ons' and changes in clinical practice.</p><p><strong>Study design size duration: </strong>Retrospective cohort study, using publicly available national U.S. IVF outcome data reported annually to the Centers for Disease Control and Prevention (CDC) for the period 2012-2021.</p><p><strong>Participants/materials setting methods: </strong>CDC annual reports were used as a data source. Extracted variables included a number of IVF cycle starts, embryo transfers, embryo banking cycles, and live births. IVF 'treatment efficiency' was calculated as the proportion of live births per initiated cycle (intent-to-treat analysis).</p><p><strong>Main results and the role of chance: </strong>Over the study period, IVF cycle starts increased by 234.7% (176 274 to 413 776), embryo transfers by 150.3% (134 471 to 202 121), and embryo banking cycles by 902.3% (18 585 to 167 689). Live births increased by 179.2% (51 286 to 91 906). However, cycle efficiency declined from 29.1% in 2012 to 22.2% in 2021, a relative reduction of 23.4%, with an approximately linear decline across the decade.</p><p><strong>Limitations reasons for caution: </strong>The study is based on aggregate CDC data without patient-level granularity. Therefore, analyses could not control for confounding factors such as parity, infertility diagnosis, or detailed age subgroups. Embryo banking practices also complicate year-to-year comparisons of live birth rates.</p><p><strong>Wider implications of the findings: </strong>These findings suggest that despite substantial growth in IVF cycle numbers, treatment efficiency has progressively declined in the USA over the last decade. This decline coincided with a rapid increase in the use of embryo banking and other IVF 'add-ons'. The results raise concern about current clinical practices and highlight the need for critical re-evaluation of routine interventions in IVF.</p><p><strong>Study funding/competing interests: </strong>No external funding was received for this study. NG and DHB hold patents related to androgen treatment in females (DHEA) with numbers US8067400B2, US8501718B2, and US9375436B2 (listed in USPTO/public records and assigned to American Infertility of New York). They also receive royalties from Nutraceuticals LLC, which has helped commercialize DHEA as a nutritional supplement.</p><p><strong>Trial registration number: </strong>N/A.</p>","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 1","pages":"hoag004"},"PeriodicalIF":11.1,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12872396/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146144565","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":"Optimizing the protocol for modified natural cycle frozen embryo transfer (mNC-FET): a multicentre, single-blinded randomized controlled trial.","authors":"Marte Saupstad, Clara Colombo, Sara Johanna Bergenheim, Nina Pistoljevic-Kristiansen, Tine Vrist Dam, Jeanette Wulff Bogstad, Lisbeth Prætorius, Nina la Cour Freiesleben, Anna Klajnbard, Birgitte Oxlund-Mariegaard, Peter Humaidan, Ellen Christine Leth Løkkegaard, Merete Husth, Ulla Breth Knudsen, Anette Gabrielsen, Julie Lyng Forman, Morten Rønn Petersen, Kristine Løssl, Anja Pinborg","doi":"10.1093/hropen/hoag003","DOIUrl":"10.1093/hropen/hoag003","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Can the use of progesterone luteal phase support (LPS) and timing of blastocyst transfer, at 6 versus 7 days following hCG-trigger, improve the live birth rate (LBR) in modified natural cycle (mNC) frozen-thawed embryo transfer (FET)?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;Use of LPS and advanced timing of blastocyst transfer did not significantly improve the LBR in mNC-FET.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;Transfer of a frozen-thawed blastocyst in the mNC protocol is routinely conducted 7 days after the ovulation trigger, and progesterone LPS is commonly used despite limited evidence.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;This multicentre, single-blinded, randomized controlled superiority trial investigated the effect of LPS and timing of blastocyst transfer on live birth rates following mNC-FET conducted from January 2019 to February 2024. Using an online randomization programme, patients were randomized 1:1:1:1 to: (A) transfer day 6 following ovulation trigger (Day 0) with LPS; (B) transfer day 7 with LPS; (C) transfer day 6 without LPS; (D) transfer day 7 without LPS. Use of LPS was masked from treating clinicians. The sample size calculation required 604 women to participate to detect an increase in live birth rate from 21% in control groups (LPS: C + D, timing: B + D) to 31% in intervention groups (LPS: A + B, timing: A + C). In total, 679 women were enrolled, and 610 women were randomized. Ultimately, 602 women (A: n = 151; B: n = 150; C: n = 149; D: n = 152) were included in the per-transfer analyses.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;Participants were women aged 18-41 years undergoing mNC-FET with a single autologous good-quality blastocyst, from eight public fertility clinics at tertiary care centres across Denmark.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;Our study found that use of LPS did not significantly affect the LBR compared with no LPS: 34.9% (105/301) versus 31.9% (96/301) (adjusted risk difference (aRD) 3.18, 95% CI: -4.13 to 10.49; &lt;i&gt;P&lt;/i&gt; = 0.39). Comparing blastocyst transfer on Day 6 versus Day 7, there was again no significant difference in LBR: 33.8% (99/300) versus 33.0% (99/302) (aRD -0.62, 95% CI: -7.99 to 6.75; &lt;i&gt;P&lt;/i&gt; = 0.87).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Limitations reasons for caution: &lt;/strong&gt;The sample size calculation was based on LBRs of studies using transfer of slow-frozen and cleavage stage embryos, but today's LBRs are higher. Consequently, the sample size might not have been sufficient to detect discrete differences in reproductive outcomes under present conditions. Further, despite using liberal inclusion criteria, most women participating were young (≤35 years) and lean, and had a good quality embryo available for transfer, giving them an &lt;i&gt;a priori&lt;/i&gt; good treatment prognosis. Hence, our findings might not apply to all women undergoing mNC-FET.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Wider implications of the findings: &lt;/strong","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 1","pages":"hoag003"},"PeriodicalIF":11.1,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12867578/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146121430","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":"Frozen versus fresh embryo transfer on perinatal outcomes-do endometrial preparation methods matter?","authors":"Haowen Zou, Deirdre Zander-Fox, Nicole Au, Yanhe Liu, Beverley Vollenhoven, Mark P Green, Rui Wang","doi":"10.1093/hropen/hoag002","DOIUrl":"10.1093/hropen/hoag002","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Are there differences between perinatal outcomes following frozen versus fresh embryo transfer in IVF, and do endometrium preparation methods contribute to the differences?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;Compared with fresh embryo transfers, frozen transfers, regardless of hormone replacement treatment or natural treatment cycles, were associated with lower chances of preterm birth, low birth weight, and small for gestational age, but higher chances of caesarean section, high birth weight, and large for gestational age.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;Frozen embryo transfer has been increasing over the past two decades, but its associated perinatal risks and underlying reasons remain controversial. Most existing observational studies have not accounted for multiple cycles from the same couple or known patients' characteristics or treatment protocols, such as endometrial preparation methods, in the analysis. Existing birthweight centile charts are likely to underestimate intra-uterine growth restriction due to the inclusion of deliveries following obstetric interventions.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;This multicentre retrospective cohort study used routinely collected clinical data of 8081 women undergoing IVF who gave birth to 9243 babies (6125 from the frozen and 3118 from fresh transfer cycles) in 12 IVF clinics across two states in Australia between 2015 and 2021, with follow-up data up to 2023.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;Individuals undergoing autologous-oocyte IVF cycles who had singleton live births were included. An individual could have multiple treatment cycles included. Perinatal outcomes included preterm birth, low/high birth weight, small-/large-for-gestational-age, and caesarean section. The birthweight percentiles were calculated based on the New Australian birthweight centiles, where interventions-initiated births were excluded. Multivariable Poisson regression with robust variance was used to analyse all outcomes. Generalized estimating equations (GEEs) were used to account for the cluster effects of multiple embryo transfer cycles of the same individual. Adjusted risk ratios with 95% confidence intervals (CIs) were reported for each outcome. The adjusted model accounted for potential confounding factors, including female age, parity, semen source, ovulatory disorders, preimplantation genetic testing for aneuploidy, blastocyst transfer, number of embryos transferred, and site. In subgroup analysis, frozen transfers with different endometrial preparation methods (hormone replacement and natural cycles) were compared to the fresh transfers.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;Compared with births in the fresh group, births in the frozen transfer group were less likely to be preterm (8.9% vs 13.7%, adjusted risk ratio (aRR) 0.66 0.58-0.76), low birth weight (5.3% vs 8.5%, aRR 0.66, 0.55-0.78), an","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 1","pages":"hoag002"},"PeriodicalIF":11.1,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12848820/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146088345","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":"Comprehensive 16S rRNA gene sequencing and meta-transcriptomic analyses of the female reproductive tract microbiota: two molecular profiles with different messages.","authors":"Alberto Sola-Leyva, Inmaculada Pérez-Prieto, Analuce Canha-Gouveia, Eduardo Salas-Espejo, Nerea M Molina, Eva Vargas, Apostol Apostolov, Amruta D S Pathare, Sergio Vela-Moreno, Susana Ruiz-Durán, Bárbara Romero, Rocío Sánchez, José Antonio Castilla-Alcalá, Merli Saare, Ganesh Acharya, Andres Salumets, Signe Altmäe","doi":"10.1093/hropen/hoag001","DOIUrl":"10.1093/hropen/hoag001","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Does the analysis of endometrial microbes provide the same information when using DNA or RNA sequencing-based techniques?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;DNA vs RNA-based microbial analysis techniques demonstrated significant microbial compositional differences and lack of transcriptionally active lactobacilli in the endometrium.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;Our understanding of the endometrial microbiome is primarily based on DNA-based 16S rRNA gene profiling, but DNA detection does not imply the presence of living microbes. While this method is cost-effective and widely used, it has notable limitations, including the underestimation of microbial diversity, abundance, and functionality, as well as limited species-level resolution. While the microbiome reflects DNA-based characterization, the microbiota more precisely captures metabolically active communities. In this context, meta-transcriptomic analysis, an RNA-based approach, addresses these shortcomings by capturing functional transcripts that are actively expressed in living microbes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;This cross-sectional study consisted of 49 reproductive-aged women (27-42 years old) who were receiving ART. By simultaneously analysing the microbial composition and gene expression within female reproductive tract samples, we sought to provide a more comprehensive understanding of the microbiota and functional potential of these samples.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;Vaginal swabs, endometrial brushing, and endometrial biopsy samples were collected from 49 participants during the mid-secretory phase of their menstrual cycle, 6-9 days after the luteinizing hormone surge for parallel 16S rRNA gene sequencing and meta-transcriptome analyses. For DNA-based analysis, the 16S rRNA gene V4 region was sequenced. For RNA-based analysis, total RNA was extracted followed by ribosomal RNA depletion. Strand-specific total RNA sequencing libraries were prepared and sequenced. Taxonomy was assigned by using Kraken2 (v2.2.1), and Bracken (v2.7).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;Our findings suggest that in low-microbial-biomass environments such as the endometrium, the correlation between 16S rRNA gene sequencing and meta-transcriptomics is relatively weak. This highlights the limitations of microbial analysis of low-microbial-biomass samples. Alternatively, microbial functions and genome activity may be tissue-specific and dependent on the host tissue environment. Moreover, RNA-based analysis provides higher resolution in detecting certain pathogens, even within the endometrium.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Large scale data: &lt;/strong&gt;The data presented in the study are deposited in the NCBI SRA Database, accession number PRJNA1247240.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Limitations reasons for caution: &lt;/strong&gt;High levels of host RNA and the low abundance of microbial reads in the endometriu","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 1","pages":"hoag001"},"PeriodicalIF":11.1,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12866996/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146121363","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":"Correction to: Ovarian ferroptosis induced by androgen is involved in pathogenesis of PCOS.","authors":"","doi":"10.1093/hropen/hoaf078","DOIUrl":"https://doi.org/10.1093/hropen/hoaf078","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1093/hropen/hoae013.].</p>","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 4","pages":"hoaf078"},"PeriodicalIF":11.1,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12721862/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145822199","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":"Reply: Reassessing pre-existing comorbidity patterns in testicular cancer: controversies and future directions.","authors":"Marie Juul Ornstrup, Agnethe Berglund, Mads Agerbæk, Claus Højbjerg Gravholt","doi":"10.1093/hropen/hoaf080","DOIUrl":"10.1093/hropen/hoaf080","url":null,"abstract":"","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 1","pages":"hoaf080"},"PeriodicalIF":11.1,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12774466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145919145","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":"Reassessing pre-existing comorbidity patterns in testicular cancer: controversies and future directions.","authors":"Yinwei Chen, Yi Liu, Chang Liu","doi":"10.1093/hropen/hoaf079","DOIUrl":"10.1093/hropen/hoaf079","url":null,"abstract":"","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 1","pages":"hoaf079"},"PeriodicalIF":11.1,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12774460/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145919167","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":"Atopic dermatitis and fecundity: a Danish National Birth Cohort study.","authors":"Camilla L Kjersgaard, Anne Gaml-Sørensen, Pernille J Clemmensen, Linn H Arendt, Siri E Håberg, Onyebuchi A Arah, Mette Deleuran, Cecilia H Ramlau-Hansen","doi":"10.1093/hropen/hoaf077","DOIUrl":"10.1093/hropen/hoaf077","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Do women with atopic dermatitis have higher fecundity than those without?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;Pregnant women with a history of atopic dermatitis had a slightly shorter time-to-pregnancy (TTP) and a lower risk of conceiving using infertility treatment than those without.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;Atopic dermatitis has a characteristic T-helper-2-cell-skewed immune response that mirrors the immune shift in pregnancy, which is necessary for the pregnant woman's immune response to tolerate the fetus. Therefore, it has been hypothesized that atopic dermatitis may be advantageous for conception and pregnancy maintenance. However, this has not yet been investigated.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;This cohort study included 88 713 pregnant women from the population-based Danish National Birth Cohort (DNBC), who were enrolled between 1996 and 2002.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;The women were defined as having atopic dermatitis if, in a computer-assisted interview conducted around gestational week 17, they reported having ever been diagnosed with atopic dermatitis by a doctor. The women were also asked whether the pregnancy was planned or unplanned, to report their TTP within one of five prespecified categories, and whether they had conceived with the use of infertility treatment. We used multinomial logistic regression models to assess associations between atopic dermatitis and fecundity in seven categories: (TTP &lt;1 month, 1-2 months, 3-5 months, 6-12 months, &gt;12 months, pregnant after infertility treatment or unplanned). In addition, we modeled TTP as dichotomous outcomes using logistic regression: subfecundity (TTP ≥6 months vs &lt;6 months) and infertility (TTP &gt;12 months vs ≤12 months). We also assessed women with an atopic constitution (atopic dermatitis, allergic rhinitis, asthma, and food allergies), as this is associated with more severe atopic dermatitis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;Overall, 3641 (4.1%) women reported ever having had atopic dermatitis. Compared to women without atopic dermatitis, women with atopic dermatitis had a lower relative risk ratio (RRR) of having a TTP &gt;12 months: 0.83 (95% CI: 0.72; 0.96), and use of infertility treatment, RRR: 0.81 (95% CI: 0.69; 0.94). Moreover, women with atopic dermatitis had a lower odds ratio (OR) of subfecundity: 0.89 (95% CI: 0.82; 0.96) and infertility: 0.85 (95% CI: 0.77; 0.95) than women without in the logistic regression model. Results were robust across several sub-analyses.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Limitations reasons for caution: &lt;/strong&gt;The results can only be generalized to women who eventually conceive, since the DNBC consists only of women who successfully conceived.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Wider implications of the findings: &lt;/strong&gt;The findings support the hypothesis of an immunological benefit in conceiving when having atopic dermatitis. The res","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 1","pages":"hoaf077"},"PeriodicalIF":11.1,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12802894/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145991972","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":"Organoids simulating the bovine oviduct mediate the embryo-maternal interface via extracellular vesicle-transmitted signaling.","authors":"Nico G Menjivar, Ahmed Gad, Riley E Thompson, Mindy A Meyers, Soham Ghosh, Fiona K Hollinshead, Dawit Tesfaye","doi":"10.1093/hropen/hoaf076","DOIUrl":"10.1093/hropen/hoaf076","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Does the implementation of a three-dimensional (3D) organoid model system that stably emulates some key functional, structural, and biological complexities of the oviduct provide a favorable apical environment for the production of extracellular vesicles (EVs) that exert an influence on early embryo development &lt;i&gt;in vitro&lt;/i&gt;?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;Our findings show that &lt;i&gt;in vitro&lt;/i&gt;, epithelium dependably propagates highly differentiated oviductal organoids containing both networks of ciliated and secretory cells capable of producing &lt;i&gt;in vivo&lt;/i&gt;-like, cargo-specific oviductal extracellular vesicles (oEVs) with the capacity to improve the quality of &lt;i&gt;in vitro&lt;/i&gt;-produced embryos under conditions of heat stress (HS).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;Recapitulating the maternal contribution that persists during preimplantation embryonic development &lt;i&gt;in vitro&lt;/i&gt; is a substantial scientific challenge due to both technical limitations and the significant gaps in our scientific knowledge concerning the maternal-embryonic cellular and molecular dialogue. As a result of the limited access to suitable model systems and the inability to directly observe this process &lt;i&gt;in vivo&lt;/i&gt;, this early stage of embryonic development has often been described as particularly elusive and an enigmatic stage of development. Irrespectively, oEVs have recently been identified as key players in mediating the biological information transfer of the embryo-oviduct interactions, which beneficially contributes to the early development of embryos &lt;i&gt;in vitro&lt;/i&gt;.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;Over a 2-year period, resected ovaries from intact reproductive tracts (n = 10; a pool of two bovine animals per replicate) containing both complete contralateral and ipsilateral oviducts from assessed stage II, diestrus tracts were processed for the generation of oviductal organoids. Afterward, enriched oEVs from 3D organoids and &lt;i&gt;in vivo&lt;/i&gt;-collected oviductal fluid (OF) were co-cultured with bovine presumptive zygotes from Day 1 to Day 3 and continued until the blastocyst stage for further evaluation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;Organoids were characterized by light microscopy, gene expression, immunofluorescence, and 3D reconstruction, as well as histological two-dimensional (2D) cross-sectioning. Enriched oEVs from conditioned organoid culture media and OF were characterized using transmission electron microscopy, nanoparticle tracking analysis, and western blotting. Following the establishment of a stable oEV production system, bovine zygotes were divided into five groups [38.5°C Control, 41°C Control, 41°C N-EVs (oEVs derived from organoids cultured under thermoneutral conditions), 41°C S-EVs (oEVs derived from organoids cultured HS conditions), 41°C Ovi-EVs (oEVs collected from diestrus OF)] and cultured until the blastocyst stage. Following the pr","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2026 1","pages":"hoaf076"},"PeriodicalIF":11.1,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12774516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145919190","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":"Parental and cell-division origin analysis to reduce false-positives in mosaic embryos for preimplantation genetic testing.","authors":"Qi Zhang, Guicen Liu, Yezhou Xiang, Yangyun Zou, Yulin Chen, Yingying Xia, Shun Xiong, Tao Fu, Jiang Wang, Yan Jiang, Jiaojiao Xiong, Xiaodong Zhang, Sijia Lu, Dongyun Liu, Guoning Huang, Tingting Lin","doi":"10.1093/hropen/hoaf075","DOIUrl":"10.1093/hropen/hoaf075","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Can parental and cell-division origin analysis identify the false-positive chromosomal aberrations in mosaic embryos detected during preimplantation genetic testing for aneuploidy (PGT-A)?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;Parental origin analysis reclassified over half of mosaic embryos as euploid to reduce diagnostic uncertainty, and cell-division origin analysis effectively differentiated mitotic from meiotic errors to guide evidence-based mosaic embryo transfer.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;Mosaic embryos pose significant challenges in PGT-A, with reported detection rates varying widely (2-35.6%) due to biological and technical factors, but current methods lack reliable approaches to distinguish true mosaicism from technical artifacts. Decisions regarding mosaic embryo transfer remain conservative and hampered by inadequate understanding of the origins of errors (mitotic vs meiotic) and limited data on long-term neonatal outcomes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;In this retrospective study, we analyzed 9062 PGT-A results and 8645 amniocentesis samples from 2021 to 2024 to investigate the difference in mosaicism rates between PGT treatment and prenatal diagnosis. An analysis of parental and cell-division origins was performed on 1221 consecutive results from PGT-A and PGT for monogenic disorders (PGT-M) from 259 patients across 304 treatment cycles in 2024. Multi-site re-biopsies of 36 donated embryos and the clinical outcomes of 19 mosaic embryo transfers were analyzed in 2024 and 2025.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;An innovative algorithm, termed parental haplotype trace (PH-trace), was developed to identify the genetic origin of chromosomal aberrations for mosaic verification. Briefly, biallelic homozygous single-nucleotide polymorphisms (SNPs) in the parental genome exhibit equal allelic frequencies in euploid embryos. When chromosomal aberrations occur, these SNPs show an allelic bias toward either the maternal or paternal genome. We defined the ratio of maternal-biased SNPs to paternal-biased SNPs as the uneven score to quantitatively assess the parental origin of chromosomal aberrations. Receiver operating characteristic (ROC) curve analysis based on uneven scores from euploid and aneuploid embryos was used to determine critical thresholds for identifying false-positive mosaic embryos. Additionally, heterozygous SNPs in the parental genome were used to determine the cell-division origin of chromosomal aberrations. To validate our findings, we performed multi-site re-biopsies of aneuploid and mosaic embryos.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;The prevalence of mosaicism differed significantly between PGT-A and prenatal diagnosis (12.2% vs 0.9%, &lt;i&gt;P &lt;/i&gt;&lt; 0.001). Parental origin analysis based on PH-trace reclassified 52.6% of mosaic embryos as euploid and increased the overall rate of usable embryos by 8","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 4","pages":"hoaf075"},"PeriodicalIF":11.1,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12714397/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145806685","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}