Human reproduction最新文献

{"title":"A de novo C-terminal truncation mutation in NUP205 as a key factor in premature ovarian insufficiency.","authors":"Siying Cai,Huiying Li,Xinlei Ma,Qingchuan Chen,Shan Li,Qiaojuan Mei,Li Huang,Ling Zhang,Huaibiao Li,Kai Zhao,Wenpei Xiang","doi":"10.1093/humrep/deag068","DOIUrl":"https://doi.org/10.1093/humrep/deag068","url":null,"abstract":"STUDY QUESTIONDoes nucleoporin 205 (NUP205) deficiency caused by a novel de novo truncation mutation underlie the pathogenesis of premature ovarian insufficiency (POI)?SUMMARY ANSWERNUP205 plays a critical role in ovarian development, and mutations in NUP205 represent a key factor in the pathogenesis of POI.WHAT IS KNOWN ALREADYPOI is a highly heterogeneous disorder with a significant genetic basis. The nuclear pore complex (NPC) is a fundamental channel mediating nucleocytoplasmic transport, with NUP205 serving as a key scaffold component of the NPC.STUDY DESIGN, SIZE, DURATIONThis study employed a multilevel genetic and functional investigation, starting with whole-exome sequencing (WES) of a POI pedigree. Clinical significance was further assessed through a large-scale cohort involving 1030 POI cases. Functional validation was performed using the in vitro human cell line COV434 and an in vivo zebrafish model.PARTICIPANTS/MATERIALS, SETTING, METHODSA Chinese family with idiopathic POI was recruited. To evaluate the clinical prevalence of NUP205 variants, WES data from a previously published cohort of 1030 POI cases were rescreened. Candidate variants were prioritized based on American College of Medical Genetics and Genomics guidelines and the functional impact of the identified mutation was further evaluated through protein structural modeling. The expression of NUP205 in follicles was determined by reanalyzing public ovarian single-cell RNA sequencing datasets and confirmed via immunofluorescence on human ovarian tissues. Functional assays were performed through siRNA-mediated knockdown in COV434 cells, complementing phenotypic and ultrastructural analyses of a CRISPR/Cas9-generated nup205 (p.R1057*) truncation zebrafish model.MAIN RESULTS AND THE ROLE OF CHANCEA novel heterozygous nonsense mutation in NUP205 c.3160C>T (p.R1054*) was identified in the index pedigree, which was absent in public genomic databases. Expanded screening of the cohort identified five additional families carrying NUP205 variants (three heterozygous and two compound heterozygous) affecting highly conserved residues. In vitro, NUP205 knockdown in COV434 cells impaired the protein stability of NUP93 and NUP62, ultimately leading to NPC structural defects. In vivo, a zebrafish model carrying the equivalent nup205 (p.R1057*) mutation exhibited impaired oogenesis, compromised fertility, and lower fertilization rates. Transmission electron microscopy revealed abnormal NPC morphology in the theca cells of the mutant follicles. These findings demonstrate that NUP205 is essential for ovarian development and suggest that its deficiency is a key factor in POI pathogenesis, indicating that the observed association is unlikely to be due to chance.LIMITATIONS, REASONS FOR CAUTIONAlthough we identified additional NUP205 variants in a large POI cohort, the detailed molecular mechanisms of these specific variants remain to be further investigated.WIDER IMPLICATIONS OF THE FINDINGSThes","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"71 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147754547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sperm DNA fragmentation: how to test, when to test, and what to do with abnormal results-a pragmatic mini-review for clinical practice.","authors":"Sandro C Esteves,Peter Humaidan","doi":"10.1093/humrep/deag056","DOIUrl":"https://doi.org/10.1093/humrep/deag056","url":null,"abstract":"Sperm DNA fragmentation (SDF) represents strand breaks that may compromise embryo development, reproductive outcomes, and offspring health, particularly when the oocyte's repair capacity is limited. This mini-review provides a clinically pragmatic framework addressing how to test, when to test, and whom to test for SDF, translating biological and laboratory insights into actionable andrology practice. The mechanistic basis of SDF is summarized, including the two-step hypothesis linking defective chromatin packaging to oxidative stress, and the combined influence of paternal and maternal aging on the creation and repair of DNA lesions. Contemporary methods for detecting both single- and double-strand breaks (DSBs), as well as DSB-specific platforms, are reviewed with emphasis on assay-specific cut-offs and clinical indications. Management strategies are outlined, prioritizing andrological optimization through lifestyle modification, antioxidant supplementation, treatment of genital tract infection, varicocele repair, and selected hormonal therapy, followed by retesting after one spermatogenic cycle. For persistently high SDF, selective use of testicular sperm for ICSI (Testi-ICSI) and laboratory adjuncts is discussed, supported by evidence of lower miscarriage and higher live-birth rates in defined high-SDF phenotypes. The limitations of the existing observational evidence base-particularly the paucity of phenotype-targeted randomized controlled trials-are highlighted. The review also underscores the value of embedding SDF testing within quality-managed programs and incorporating systematic audits of indications, treatment effects, and ART outcomes. Beyond ART, SDF assessment is positioned within preconception care, recognizing sperm chromatin integrity as a determinant of reproductive and intergenerational health. Future priorities include randomized trials comparing testicular and ejaculated sperm for ICSI in high-SDF cohorts, validation of DSB-specific assays, and longitudinal offspring follow-up to clarify intergenerational effects. This integrative approach promotes precision rather than proliferation of testing, aligning molecular insight with clinical prudence to improve reproductive and generational outcomes.","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"22 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147754546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Once, twice, three times frozen: viability and post-transfer outcomes of fresh and vitrified-warmed mouse embryos.","authors":"Tong Li,Darren J X Chow,Shan Li,Ryan D Rose,Tiffany C Y Tan,Kylie R Dunning","doi":"10.1093/humrep/deag065","DOIUrl":"https://doi.org/10.1093/humrep/deag065","url":null,"abstract":"STUDY QUESTIONWhat is the impact of one, two, or three vitrification-warming cycles on embryo viability, implantation potential, and post-transfer development compared with fresh transfer?SUMMARY ANSWERRepeated vitrification-warming cycles progressively impaired embryo cryosurvival, blastocyst quality, and foetal growth after two or more cycles.WHAT IS KNOWN ALREADYCryopreservation is central to embryo storage and preimplantation genetic testing, where embryos are biopsied and frozen while awaiting results. However, the impact of repeated vitrification-warming cycles remains unclear due to confounding factors including biopsy effects, prior implantation failure, the absence of a true non-cryopreserved control, and fresh transfer comparisons confounded by supraphysiological hormonal exposure.STUDY DESIGN, SIZE, DURATIONTo overcome the constraints of clinical studies, this study used the mouse as a controlled preclinical model. This allowed precise experimental control over embryo stage at cryopreservation and vitrification protocol and enabled direct comparison with a non-vitrified (fresh) control group without the confounding effects of supraphysiologic hormone exposure or biopsy. While species differences are recognized, this model enables focused assessment of cryopreservation-specific effects. Outcomes included post-warming survival, cell lineage allocation, as well as post embryo transfer outcomes on Day 18.5 of development (pregnancy and implantation rates, foetal and placental weights). Post-warming survival was assessed after one, two, or three freeze-warm cycles (3035, 1465, and 447 blastocysts, respectively; 23 independent experimental replicates). Inner cell mass (ICM) and trophectoderm (TE) cell numbers were quantified following one, two, or three freeze-warm cycles and compared to a fresh (non-vitrified) control (35, 36, 33, and 28 blastocysts, respectively; four independent experimental replicates). Post-transfer outcomes were evaluated after one, two, or three freeze-warm cycles and compared to a fresh (non-vitrified) control (30, 33, 39, and 22 pseudo-pregnant recipients, respectively). Sample size calculations were performed to ensure the study was appropriately powered.PARTICIPANTS/MATERIALS, SETTING, METHODSMurine embryos were generated following IVF and cultured to the blastocyst stage, and underwent zero (fresh), one, two, or three repeated vitrification-warming cycles. Post-warming survival was assessed morphologically, and immunohistochemistry for OCT-3/4 (ICM) and CDX2 (TE) was used to assess cell lineage allocation. Embryo transfers were used to further evaluate developmental competence with pregnancy rate, implantation outcomes (implantation rate, viable implantation rate, resorption rate), foetal and placental outcomes (foetal weight, placental weight, and the foetal-to-placental weight ratio) measured on Day 18.5 of development.MAIN RESULTS AND THE ROLE OF CHANCEEmbryo cryosurvival declined significantly with increasing","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"100 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147751275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fertility preservation trends, perspectives, and reflections in gender diverse adults across the life course.","authors":"Karen N Dsouza,Minerva A Orellana,Dzhuliyan V Vasilev,Yeonsoo Lee,Madeline Whitney,Danielle Aase,Jensen Reckhow,Eliza Nguyen,Felicity T Enders,Laura Pacheco-Spann,Salym J Winter,Alice Y Chang,Caroline J Davidge-Pitts,Cesar A Gonzalez,Jacob Eleazer,Alessandra Ainsworth,Zaraq Khan","doi":"10.1093/humrep/deag070","DOIUrl":"https://doi.org/10.1093/humrep/deag070","url":null,"abstract":"STUDY QUESTIONWhat is the fertility preservation (FP) utilization rate among transgender and gender diverse (TGD) patients at the Transgender and Intersex Specialty Care Clinic (TISCC) within the Mayo Clinic?SUMMARY ANSWERThe rate of utilization of FP services by TGD patients at Mayo Clinic's TISCC was determined to be 6.62%.WHAT IS KNOWN ALREADYTGD patients encounter several barriers when pursuing FP, which may contribute to a lower utilization rate of these services. These barriers include financial constraints and lack of insurance coverage, as well as societal and healthcare provider attitudes; TGD individuals face discrimination or lack of understanding, making it uncomfortable or difficult to discuss FP options. Additionally, there continues to be a lack of inclusive policies and support within healthcare systems that can further impede access to FP services for TGD individuals.STUDY DESIGN, SIZE, DURATIONThe study was executed in two phases. In the first phase, a retrospective cohort study was completed with TGD patients who provided electronic health record (EHR) research authorization from Mayo Clinic's TISCC in Rochester, MN between 1 January 2015 and 30 July 2021. Search terms related to FP were used to determine the FP utilization rate among this patient population. In the second phase of the study, two sets of patients, (i) patients who were included in the cohort study in Phase 1, and (ii) members of JASMYN, a community organization specializing in care and wellness coordination for Lesbian, Gay, Bisexual, and Transgender (LGBT) teens and young adults in North Florida. Individuals were invited to participate in a qualitative interview exploring their cumulative healthcare experiences accessing gender-affirming care. Interviews were conducted from January 2023 to June 2023. Interviews examined participants' perceptions of FP options, motivations for pursuing FP, and barriers to accessing both gender and fertility care. When applicable, participants also discussed their experiences pursuing FP and reflected on their satisfaction with their fertility and family planning decisions.PARTICIPANTS/MATERIALS, SETTING, METHODSIn phase 1, a total of N = 1189 patients sought care from Mayo Clinic's TISCC in Rochester, MN. Out of these patients, N = 589 patients provided research authorization and were included in the retrospective cohort study. The study team assessed whether FP terms were mentioned in each patient's EHR, and whether patients scheduled and attended appointments with either the Department of Reproductive Endocrinology or the Department of Urology. FP search terms included sperm cryopreservation, sperm extraction, sperm aspiration, testicular tissue cryopreservation, oocyte cryopreservation, embryo cryopreservation, and ovarian tissue cryopreservation. In phase 2, N = 36 participants were interviewed, with N = 25 participants recruited from Mayo Clinic's TISCC in Rochester, MN, and N = 11 participants recruited from JASMYN in Jac","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"6 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147751276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Large-scale analysis of FMR1 CGG repeat length and risk of premature ovarian insufficiency in over 92 000 women.","authors":"Emily J Morbey,Felix R Day,Daniel J Wright,Jack R A Murzynowski,Sinead M McGlacken-Byrne,Anna Murray,Ken K Ong,John R B Perry","doi":"10.1093/humrep/deag061","DOIUrl":"https://doi.org/10.1093/humrep/deag061","url":null,"abstract":"STUDY QUESTIONDoes FMR1 repeat length confer clinically meaningful predictive value for premature ovarian insufficiency (POI)?SUMMARY ANSWERFMR1 repeat length increases POI risk from ∼36 repeats onward but has limited diagnostic utility compared with a polygenic score for menopause timing.WHAT IS KNOWN ALREADYFMR1 premutation carriers (≥55 repeats) are reported to have high risk of Fragile-X Associated Primary Ovarian Insufficiency (FXPOI), but prior studies were small and highly ascertained.STUDY DESIGN, SIZE, DURATIONCross-sectional analysis of ∼92 000 women from the UK Biobank with genetic and health data.PARTICIPANTS/MATERIALS, SETTING, METHODSFemale UK Biobank participants were genotyped for FMR1 repeat length. Associations with self-reported POI, age at menopause, and other reproductive phenotypes were analysed in women. FMR1 protein levels were measured, and genome-wide analyses were conducted to identify potential genetic modifiers.MAIN RESULTS AND THE ROLE OF CHANCEOf 518 female premutation carriers with available age at natural menopause, only 6.9% reported POI. Elevated POI risk was observed starting at 36 repeats, increasing continuously with repeat length, but no threshold showed strong predictive power (maximum AUC 0.60 vs AUC 0.64 for polygenic score). No association was found between repeat length and FMR1 protein levels, consistent with an RNA gain-of-function toxicity mechanism. RAD52 was identified as a potential genetic modifier.LARGE SCALE DATAUK Biobank resource (https://www.ukbiobank.ac.uk).LIMITATIONS, REASONS FOR CAUTIONPOI was self-reported rather than clinically confirmed. Analyses could not assess AGG interruptions, mosaicism, or X-inactivation. Genetic modifiers require replication. Findings are limited to a single population dataset.WIDER IMPLICATIONS OF THE FINDINGSThese results challenge the utility of the FXPOI disease category, suggest limited diagnostic value of clinical FMR1 premutation testing for POI, and highlight alternative mechanisms and potential modifiers such as RAD52.STUDY FUNDING/COMPETING INTEREST(S)This work was conducted using the UK Biobank resource (application 9905). This work was funded by the Medical Research Council (unit programs: MC_UU_12015/2, MC_UU_00006/2) and Wellcome (Discovery award 302536/Z/23/Z). The sponsors had no role in the study design, collection, analysis, or interpretation of the data, the writing of the manuscript or the decision to submit it for publication. J.R.B.P. and A.M. have engaged in paid consultancy for Ovartix Ltd.TRIAL REGISTRATION NUMBERN/A.","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"71 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147719564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histological and immunohistochemical characteristics of superficial peritoneal endometriotic lesions of clinical responders and non-responders to dienogest treatment.","authors":"Nicola Berlanda,Veronica Bandini,Giorgio Alberto Croci,Dhouha Dridi,Maria Vittoria Nobili,Sonia Cipriani,Paolo Vercellini","doi":"10.1093/humrep/deag059","DOIUrl":"https://doi.org/10.1093/humrep/deag059","url":null,"abstract":"STUDY QUESTIONAre there histological and immunohistochemical patterns of superficial peritoneal endometriotic lesions of symptomatic patients that characterize non-response to dienogest treatment and may suggest progesterone resistance?SUMMARY ANSWERNo significant histological or immunohistochemical differences were observed in superficial peritoneal endometriotic lesions between clinical responders and non-responders to dienogest treatment.WHAT IS KNOWN ALREADYProgestogens are effective in reducing pelvic pain symptoms in approximately two-thirds of patients with endometriosis. Treatment failure can be reasonably explained by progesterone resistance, but the available evidence is not definitive.STUDY DESIGN, SIZE, DURATIONA prospective, single-centre, single-arm, observational study was conducted between January 2023 and January 2024 in 55 women treated with dienogest, 2 mg/day, before laparoscopic surgery for endometriosis.PARTICIPANTS/MATERIALS, SETTING, METHODSAll the participants had histologically confirmed endometriosis. Patients were classified as clinical responders (n = 36) or non-responders (n = 19) based on the self-reported 7-point Patient Global Impression of Change scale. In addition, pain severity was dichotomized as either 'absent/mild' (0-3 points) or 'moderate/severe' (4-10 points) across individual pain domains, using a 0-10-point numerical rating scale. The histological morphology and the immunohistochemical expression of progesterone receptors, oestrogen receptors, and CD15 were evaluated in the excised superficial peritoneal lesions. Tissue analyses were all performed by the same blinded pathologist.MAIN RESULTS AND THE ROLE OF CHANCEA histological morphological response to chronic progestogen treatment, defined by the presence of stromal atrophy and absence of active glands, was observed in 29/36 (80.5%) clinical responders and 16/19 (84.2%) non-responders. Furthermore, no statistically significant between-group differences were observed in progesterone receptor (PR), oestrogen receptor (ER), and CD15 expression. At univariate logistic regression analysis, no significant associations were identified between clinical response to dienogest therapy and several individual variables (i.e. body mass index, age at diagnosis, duration of therapy, histological morphological response, phenotypic subtypes of peritoneal endometriotic lesions, and presence of adenomyosis or deep endometriosis). Exploratory analyses based on pain severity categorization yielded results broadly consistent with the main findings. However, patients with moderate/severe deep dyspareunia showed a significantly lower proportion of high-intensity glandular ER expression in comparison to those with absent/mild deep dyspareunia. In addition, a significantly lower glandular PR expression was detected in patients with moderate/severe dyschezia symptoms compared with those with absent/mild dyschezia.LIMITATIONS, REASONS FOR CAUTIONOnly superficial peritoneal endome","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"45 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147708535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Variations in ovulation time and menstrual cycle characteristics: analysis of a prospective long-term cohort study.","authors":"Maria-Nefeli Malliou-Becher,Pia Maria Herrmann,Alexander Freis,Tanja Freundl-Schütt,Lisa-Maria Wallwiener,Siegfried Baur,Richard J Fehring,Christian Gnoth,Andreas Mallios,Thomas Strowitzki,Petra Frank-Herrmann","doi":"10.1093/humrep/deag057","DOIUrl":"https://doi.org/10.1093/humrep/deag057","url":null,"abstract":"STUDY QUESTIONWhat are the variations in ovulation time and menstrual cycle characteristics among and within various individuals over the course of 12 menstrual cycles?SUMMARY ANSWERThere are considerable variations in both cycle length and ovulation time, with pronounced intra-individual variability over a 12-cycle observation period.WHAT IS KNOWN ALREADYAlthough it is commonly believed that healthy women have regular cycles with a predictable mid-cycle ovulation, more recent research shows a significant variation in cycle length and ovulation time. Previous studies have focused only on cycle length, often excluding cycles outside the 25-35-day range, thus limiting the understanding of natural variation; they have also lacked precise ovulation diagnostics or included small sample sizes, making it difficult to capture the full scope of cycle and ovulation variability. Similarly, a recent big data study, while valuable, was limited by a self-selected group and the absence of accurate ovulation diagnostics, reducing its generalizability.STUDY DESIGN, SIZE, DURATIONThis study was designed as a prospective long-term observational study, which involved collecting data from 1923 women with a total of 43 999 menstrual cycles from January 1985 to July 2019. After fulfilling the inclusion criteria, the main group consisted of 1051 women, all of whom contributed data for 12 cycles (12 612 cycles), including 420 conception cycles.PARTICIPANTS/MATERIALS, SETTING, METHODSParticipants in the study were between 18 and 44 years of age at study entry and did not take any reproductive hormones. Women who were postpartum, breastfeeding, amenorrheic, or within a 3-month period after stopping hormonal contraception were excluded. Participants agreed to keep cycle records according to the symptothermal method, 'Sensiplan'. Ovulation time was determined using an evidence-based algorithm based on evaluating cervical mucus patterns and basal body temperature shifts, with ovulation time defined as the day before the temperature rise. Data analysis was descriptive, using absolute and relative frequencies, standard deviation, percentiles, and ranges. Age dependency was assessed using unpaired sample t-tests and one-way ANOVA. Linear regression was used to assess long-term trends.MAIN RESULTS AND THE ROLE OF CHANCEIn 62.4% of women, cycle lengths varied by 1 week or more within 12 cycles. Accordingly, the time of ovulation varied by 1 week or more within 12 cycles in 54.8% of women, with 96.5% experiencing fluctuations of 4 days or more over the 12 months. The median spontaneous cycle length was 28 days, with a mean of 29.66 days (SD = 7.55). Only 52.7% of women consistently had cycle lengths between 23 and 35 days across all 12 cycles. Ovulation occurred most frequently between Days 12 and 16, with almost half of conceptions (45.7%) occurring after Day 16. A one-way analysis of variance revealed a significant reduction in mean cycle length with increasing age (P < 0.001), s","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"21 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147663641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Live birth rates after natural cycle versus artificial cycle in women receiving donated oocytes and the impact of female age.","authors":"Filipa Rafael,Beatriz Nunes David,Juan Manuel Mascarós,Ana Neves,Elena Labarta,Nicolas Garrido,Sofia Nunes,Juan A Garcia-Velasco,Sérgio Reis-Soares,Samuel Santos-Ribeiro","doi":"10.1093/humrep/deag058","DOIUrl":"https://doi.org/10.1093/humrep/deag058","url":null,"abstract":"STUDY QUESTIONCan natural cycles (NC) be effectively utilized in advanced maternal age (AMA) undergoing oocyte donation, without compromising live birth rates (LBRs) and miscarriage outcomes, when compared to artificial cycles (ACs)?SUMMARY ANSWERIn donor oocyte embryo transfer cycles, NC demonstrated superior outcomes in reproductive efficacy and obstetrical safety compared to AC, independent of the recipient's age.WHAT IS KNOWN ALREADYPrevious studies have posited that NC may result in better outcomes when compared to AC embryo transfer, including a lower risk of miscarriage and hypertensive disorders of pregnancy. Recent studies support that NC-frozen embryo transfer (FET) decreases obstetrical and neonatal complications compared to AC-FET, even if LBR differences remain controversial in some general populations. There is limited research on the use of NCs in women of AMA.STUDY DESIGN, SIZE, DURATIONThis retrospective, multicentre, cohort study included all single blastocyst embryo transfers following oocyte donation performed between January 2010 and December 2023, subdivided according to the type of endometrial preparation performed (NC or AC). The oocyte donation model was chosen to minimize the potential confounding effect related to poor oocyte competence in older women and the influence of ovarian stimulation performed during autologous IVF on endometrial receptivity prior to a fresh embryo transfer.PARTICIPANTS/MATERIALS, SETTING, METHODSThe main objective of the study was to compare LBR. Secondary outcomes included hCG-positive pregnancy rate, clinical pregnancy rate, miscarriage rate, obstetric, and perinatal outcomes. Confounder-adjustment was performed using a multivariable generalized estimating equations model regression analysis, adjusting for multiple confounders. A sub-analysis compared results when the AC protocol was optimized with progesterone (P4) monitoring and rescue therapy. Additionally, an interaction variable was added to the final multivariable model to assess whether female recipient age may modify the effect of each type of endometrial preparation on LBRs.MAIN RESULTS AND THE ROLE OF CHANCEIn total, 67 048 embryo transfers were analysed, including NC (n = 6922) and AC (n = 60 126). The NC group demonstrated consistent superiority over AC after adjustment for confounders across all transfers. NC was associated with a higher LBR (aOR 1.38, 95% CI 1.29-1.47; P < 0.01) and significantly lower miscarriage rate per hCG-positive pregnancy (aOR 0.68, 95% CI 0.61-0.76; P < 0.01). This superiority persisted even in optimized AC cycles with P4 monitoring and rescue therapy (LBR aOR 1.42, 95% CI 1.31-1.54; P < 0.01). Furthermore, NC was associated with significantly lower obstetrical risks in singleton pregnancies, including hypertensive disorders of pregnancy (aOR 0.72, 95% CI 0.56-0.94; P = 0.01), Caesarean delivery (aOR 0.86, 95% CI 0.77-0.96; P < 0.01), and large for gestational age (aOR 0.77, 95% CI 0.67-0.89; P < 0.01). ","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"67 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147663947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of preimplantation genetic testing for aneuploidy (PGT-A) on obstetric and neonatal outcomes: a systematic review and meta-analysis.","authors":"C B Hyttel,K Løssl,N F Wang,A Pinborg","doi":"10.1093/humrep/deag049","DOIUrl":"https://doi.org/10.1093/humrep/deag049","url":null,"abstract":"STUDY QUESTIONAre pregnancies after preimplantation genetic testing for aneuploidy (PGT-A) with trophectoderm (TE) biopsy and preferable elective freeze-all procedure associated with an increased risk of adverse obstetric and neonatal outcomes compared to pregnancies after IVF/ICSI without PGT-A?SUMMARY ANSWERIn this systematic review and meta-analysis specifically focusing on comparing a homogenous infertile population treated with IVF/ICSI, PGT-A was not associated with any adverse obstetric or neonatal outcomes.WHAT IS KNOWN ALREADYAn increased risk of hypertensive disorders of pregnancy (HDP) following IVF/ICSI with PGT in general as compared to IVF/ICSI without PGT has been reported. However, people undergoing PGT for monogenic diseases or structural rearrangements are often fertile in contrast to infertile people undergoing general IVF/ICSI treatment.STUDY DESIGN, SIZE DURATIONA systematic literature search was performed in PubMed, Embase, and Cochrane Library on 15 November 2024 and the search was updated on 11 June 2025. Inclusion criteria were: (i) randomized clinical trials or cohort studies comparing IVF/ICSI with or without PGT-A, (ii) embryo cultivation until the blastocyst stage, (iii) TE biopsy, and (iv) vitrification as cryopreservation method. Exclusion criteria were: (i) case series and case reports, (ii) polar body- or cleavage-stage biopsy, (iii) slow freeze, (iv) use of donor oocytes, or (v) natural conception controls. The main outcomes were HDP, preterm delivery, abnormal placentation, low birth weight, very low birth weight, and small for gestational age.PARTICIPANTS/MATERIALS, SETTING, METHODSMeta-analyses were performed for outcomes reported in ≥3 of the included studies. Frozen embryo transfer (FET)-cycles only subgroup-analyses were performed if the data were available in ≥3 of the included studies. Newcastle-Ottawa quality assessment score and Risk-of-Bias 2 were used to assess potential bias in the individual studies, and the GRADE approach was used to assess the certainty of evidence.MAIN RESULTS AND THE ROLE OF CHANCEA total of 2260 records were screened, and 12 studies comprising 56 113 live births were included, of which 17 254 resulted from PGT-A and 38 859 resulted from IVF/ICSI without PGT-A. No outcomes differed significantly between the PGT-A and non-PGT-A group in the main analyses or the subgroup-analyses on FET-cycles.LIMITATIONS, REASONS FOR CAUTIONThe included studies were mainly retrospective, and the number of cases was low for some outcomes.WIDER IMPLICATIONS OF THE FINDINGSCurrent evidence does not suggest adverse obstetric or neonatal effects of PGT-A, though further research is needed, particularly for rare outcomes.STUDY FUNDING/COMPETING INTERTEST(S)This study was not funded. A.P. has received independent research grants and lecture fees from Abbott, IBSA, Gedeon Richter, Ferring, and Merck A/S. A.P. is part of research advisory boards for Gedeon Richter and Ferring Pharmaceuticals A/S. K.L. has","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"21 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147655751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Intracytoplasmic sperm injection: a paradigm shift in reproductive medicine.","authors":"","doi":"10.1093/humrep/deag052","DOIUrl":"https://doi.org/10.1093/humrep/deag052","url":null,"abstract":"","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"18 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147641709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}