Human reproduction最新文献

{"title":"L26/O-089 What drives cumulative live birth in IVF? Insights from a cohort study in LMIC","authors":"G. Abi Tayeh, K. Fares, J. Abi Hanna, E. Whaibeh, M. Mrad","doi":"10.1093/humrep/deag083.089","DOIUrl":"https://doi.org/10.1093/humrep/deag083.089","url":null,"abstract":"Study question Which demographic and clinical factors predict cumulative live birth rates among Lebanese patients undergoing assisted reproductive technology? Summary answer Maternal age, oocyte yield, and embryo transfer stage were key predictors of cumulative live birth rates in Lebanese ART patients. What is known already Cumulative live birth rate (CLBR) is a robust indicator of assisted reproductive technology success, capturing outcomes across multiple embryo transfers from a single ovarian stimulation cycle. Established predictors include maternal age, ovarian response, and embryo quality. However, most evidence originates from high-income countries, with limited data from low- and middle-income settings such as Lebanon. Context-specific evaluations of ART performance are essential for informing patient counseling and optimizing treatment strategies in diverse healthcare environments. Study design, size, duration This retrospective cohort study included 1,243 patients undergoing their first ART cycle at a fertility center in Beirut, Lebanon, between June 2020 and June 2024. Participants/materials, setting, methods Demographic, clinical, stimulation, and transfer strategy data were extracted from medical records. CLBRs were calculated using conservative and optimistic approaches across up to four embryo transfers. Logistic regression models identified independent predictors of live birth. Main results and the role of chance The overall live birth rate was 46.3%. Cumulative live birth rates were higher among patients undergoing freeze-all strategies compared to first fresh cycles (51.4% vs. 41.7% by the fourth transfer). Maternal age was inversely associated with success, with women aged ≥35 years exhibiting significantly reduced odds of live birth. Oocyte yield was a strong predictor of outcome, with retrieval of more than 15 oocytes resulting in CLBRs exceeding 60%. Embryo transfer stage was also a critical determinant: blastocyst-stage (Day 5) transfers were associated with substantially higher odds of live birth compared to cleavage-stage (Day 3) transfers (adjusted OR = 3.89, p < 0.001). These associations remained statistically significant after multivariable adjustment, indicating that the observed effects are unlikely to be attributable to chance alone. Limitations, reasons for caution The single-center, retrospective design may limit generalizability, and unmeasured confounding cannot be fully excluded. Wider implications of the findings These findings support optimizing transfer strategies and ovarian stimulation protocols to improve ART success in resource-constrained settings. Trial registration number Yes","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"10 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148401219","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":"L26/P-780 Natural cycles mitigate the adverse effects of thin endometrium on clinical outcomes following a frozen embryo transfer: A study of 23,221 single-blastocyst transfer cycles","authors":"L. Zha, L. Yu, Y. Guo, L. Jin","doi":"10.1093/humrep/deag083.1107","DOIUrl":"https://doi.org/10.1093/humrep/deag083.1107","url":null,"abstract":"Study question Does the association between endometrial thickness and clinical outcomes differ across three common endometrial preparation protocols in single-blastocyst frozen-thawed embryo transfer (FET) cycles? Summary answer Natural cycles (NC) appear to mitigate the adverse effects of thin endometrium on pregnancy and perinatal outcomes compared to hormone replacement therapy (HRT) -based protocols. What is known already Endometrial thickness is an established predictor of clinical outcomes in FET. Evidence suggests that the endometrial transcriptomic profiles of infertile patients during natural cycle FET demonstrate greater similarity to those of fertile controls than during hormone replacement therapy cycles. Nevertheless, it remains unclear whether the “optimal” EMT threshold remains consistent across different endometrial preparation protocols. Study design, size, duration This retrospective cohort study included 23,221 single-blastocyst transer cycles from 17,416 women at a single center between 2016 and August 2024. Endometrial preparation protocols included NC (1853 cycles), HRT (18086 cycles), or gonadotropin-releasing hormone agonist (GnRHa)-pretreated HRT (GnRHa+HRT; 3275 cycles). Participants/materials, setting, methods Generalized additive models were fitted to visualize EMT-outcome associations across the total cohort and specific cycles. EMT was stratified into five categories: ≤ 7, (7, 8], (8, 10], (10, 12], and >12 mm. Statistical associations were assessed using stabilized inverse probability of treatment weighting-weighted generalized linear mixed models (GLMMs), incorporating random intercepts to account for repeated cycles per patient. Primary outcomes included live birth and good perinatal outcome (GPO: singleton, ≥ 37 weeks, ≥ 2500g). Main results and the role of chance Substantial declines in LBRs were observed in HRT cycles at ≤ 7 mm (25.35%; aOR 0.40, 95% CI 0.33–0.48) and in GnRHa+HRT cycles at both ≤7 mm (18.18%; aOR 0.44, 95% CI 0.30–0.65) and (7, 8] mm (29.39%; aOR 0.70, 95% CI 0.53–0.93). A similar trend was manifested for GPO. Conversely, in NC cycles, an EMT ≤7 mm did not significantly impair LBR (aOR 0.88, 95% CI 0.54-1.46) or GPO (aOR 0.90, 95% CI 0.54-1.51), suggesting better resilience to thin endometrium. While clinical outcomes typically improved with increasing EMT across all strategies, the effect size was protocol-dependent. In GnRHa+HRT cycles, incremental increases in EMT up to 12 mm significantly enhanced both LBR and GPO. Conversely, NC cycles exhibited a minimal response to thickness variations; a significant benefit was observed only when reached (10, 12] mm, yielding peak odds for both live birth (aOR 1.37, 95% CI 1.08–1.74) and GPO (aOR 1.48, 95% CI 1.16–1.89). No detrimental effects were observed for EMT >12 mm. Sensitivity analyses controlling for oocyte retrieval age instead of age at transfer/pregnancy produced similar conclusions. Limitations, reasons for caution The retros","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"38 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148401351","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":"L26/O-186 Clinical and ultrasound andrological parameters predictive for a pregnancy with a live birth","authors":"F. Lotti, G. Bartolomei, B. Gasperetti, G. Asquino, V. Ciambrone, B. Batisti, F. Cioppi, E. Baldi, C. Krausz, M. Maggi","doi":"10.1093/humrep/deag083.184","DOIUrl":"https://doi.org/10.1093/humrep/deag083.184","url":null,"abstract":"Infertility affects 8%–12% of men. Clinical thresholds suggestive, but not predictive, of male infertility are commonly used, such as (i) seminal parameters < 5° centile of their distribution reported by the “WHO laboratory manual”, (ii) FSH > 8 U/L and low total or calculated free testosterone (with different cut-offs according to different scientific societies), (iii) mean testicular volume at Prader <15 mL and at ultrasound (US) < 12 mL. Conversely, only a few clinical cut-offs are available to predict male fertility, mainly related to semen parameters, usually defining “fertility” as the capacity to “induce a pregnancy” but not to “achieve a live birth”. This is a prospective, observational study with cross-sectional analysis of a first-time evaluation of clinical, seminal, hormonal, and male genital tract US characteristics of 604 males of infertile couples and 115 fertile men (derived from a spin-off of an US study on male fertility sponsored by the European Academy of Andrology) assessing differences between groups and investigating clinical and US predictors of a pregnancy with live birth. A total of 604 males (37.5 ± 7.0 years) of infertile couples and 115 males (36.6 ± 5.3 years) of fertile couples with live birth were evaluated in outpatient clinic and their parameters compared. For parameters with continuous distribution, iterative ROC curves identified thresholds predicting a pregnancy with live birth with the best sensitivity and specificity. These thresholds and other dichotomous parameters were used iteratively in binary logistic regression analyses adjusted for male and female partners age to evaluate the risk (odds ratio) to be men of a fertile couple. Comparing fertile and infertile couples, no difference in males or female partners age was observed. Evaluating clinical parameters, sperm concentration ≥ 40 × 106/mL, total count ≥ 128 × 106/ejaculate, progressive motility (PR) ≥ 52%, normal morphology ≥ 5%, FSH < 3.8 U/L, LH < 3.2 U/L, total and calculated free testosterone ≥17 and ≥0.335 nmol/L, respectively, mean testis volume (Prader) ≥ 20 mL, absence of epididymal dilation, and absence of cryptorchidism were predictive for a pregnancy with live birth. Evaluating US parameters, mean testis volume ≥ 16.5 mL, testis homogeneity, epididymis homogeneity, mean epididymal tail, and deferential ampulla <4.8 and 4.5 mm, respectively, prostate homogeneity and normal vascularization (defining absence of inflammation), absence of ejaculatory ducts dilation (defining absence of subobstruction), and seminal vesicles emptying > 2.8 mL (defining good seminal vesicles contraction) were predictive for a pregnancy with live birth. The absence of varicocele at US was not predictive of a pregnancy with live birth. Surprisingly, testis homogeneity at US showed the highest odds ratio for a pregnancy with live birth (OR = 33.7 [10.6–107.9]), followed by sperm concentration ≥ 40 × 106/mL and PR","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"65 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148401352","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":"L26/P-178 Are we done with overnight rescue IVM? Evidence from a five-year real-world sibling oocyte analysis integrating AI-derived oocyte quality assessment","authors":"M. Del Collado, D. Braga, A. Setti, B. Torrecillas, J. Fjeldstad, S. Corsac, L. Vanzella, A. Iaconelli Junior, E. Borges","doi":"10.1093/humrep/deag083.514","DOIUrl":"https://doi.org/10.1093/humrep/deag083.514","url":null,"abstract":"Study question Does overnight rescue IVM (R-IVM) remain biologically compromised, and can an AI-derived oocyte quality score reliably predict fertilization and blastocyst development across clinical contexts? Summary answer Overnight R-IVM remained biologically compromised despite preserved fertilization rates, whereas an AI-derived oocyte quality score was associated with blastocyst development across clinical contexts. What is known already The clinical utility of immature oocytes (GV and MI) retrieved during controlled ovarian stimulation remains debated. Short term R-IVM of MI oocytes within 6–8 hours has shown promising outcomes, particularly in poor-responder patients, although its laboratory cost effectiveness remains controversial. Consequently, many IVF laboratories preferentially perform overnight R-IVM of GV and MI oocytes to reduce workload and costs, despite awareness of suboptimal developmental outcomes. AI-based oocyte quality assessment has emerged as a promising tool to support clinical decision-making in IVF; nevertheless, data regarding its performance and biological relevance in R-IVM are currently lacking. Study design, size, duration This retrospective study analyzed data collected between 2020 and 2025 from 273 autologous ICSI cycles with overnight R-IVM at a university affiliated IVF center. The study included 505 rescue in vitro matured oocytes and 1,130 sibling in vivo-matured MII oocytes from the same cycles. Exploratory subanalyses were performed according to maternal age (<38 vs ≥ 38 years), ovarian response (≤5 vs > 5 retrieved oocytes), and number of in vivo matured MII oocytes (≤5 vs > 5). Participants/materials, setting, methods Analyses were conducted at the oocyte and embryo levels, comparing laboratory outcomes between maturation contexts within the same cycle. Outcomes included AI-derived oocyte and embryo quality scores, fertilization patterns and blastocyst development. To account for intra-cycle clustering, generalized estimating equations were applied. Predictive performance was evaluated using mixed-effects logistic regression, ROC analyses with cycle-level cluster bootstrap and exploratory analyses stratified R-IVM oocytes into oocyte score tertiles. Main results and the role of chance R-IVM oocytes exhibited lower oocyte scores compared with in vivo MII oocytes (2.79±2.36 vs 5.61±3.02; p < 0.001). 2PN fertilization rates were comparable between groups (71.1% vs 70.9%; p > 0.05). Blastocyst formation was reduced following R-IVM compared with in vivo–matured MII oocytes (18.6% vs 59.5%; p < 0.001), and embryo quality assessed by AI was lower in R-IVM blastocysts (3.57±1.91 vs 5.62±2.17; p < 0.001). These differences were observed across subanalyses by maternal age, ovarian response, and number of in vivo-matured oocytes. Higher oocyte scores were associated with fertilization and blastocyst development in in vivo MII oocytes (2PN: OR = 1.39; blastocyst: OR ","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"38 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148401566","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":"L26/P-290 How long should ovum pickup (OPU) take? An analysis of 48,557 procedures across clinics and world regions","authors":"C. Lynch, A. Giovannini, R. Vassena","doi":"10.1093/humrep/deag083.626","DOIUrl":"https://doi.org/10.1093/humrep/deag083.626","url":null,"abstract":"Study question How much inter- and intra-clinic variability is there in the duration of ovum pick-up (OPU) procedures? Summary answer OPU length varies significantly across clinics and world regions, highlighting the opportunity for standardization and clinical need-based OPU length allocation. What is known already Ovum pick-up (OPU) length, i.e. the time from follicular puncture to the end of oocyte collection, is influenced by factors like ovarian reserve, response to ovarian stimulation and pelvic anatomy. Further, clinician and embryologist experience, and structural and operational constraints can affect the time allocated to OPU. As a critical step in a patient’s cycle, OPU length must balance the efficient retrieval of as many MII oocytes as possible, while preserving patient health and oocyte developmental competence. However, professional guidelines do not define optimal OPU length. Electronic witnessing systems can help in tracking process timings, providing an opportunity for standardization. Study design, size, duration We investigated variations in OPU length across years and geographical location through an electronic witnessing system (RI Witness®, CooperSurgical) and its digital platform (RI Witness IQ®, CooperSurgical). Electronic witnessing points of 48,557 OPUs across 36 clinics in 4 world regions (Europe, North America, Asia Pacific, and ‘Other’ regions combined due to sparse clinic presence in the database) were included. Records were collected for one month twice a year (March and September) between 2020-2025. Participants/materials, setting, methods Records were analysed using mixed-effects models with OPU length as main outcome and fixed effects for timepoint and world region, accounting for clustering by clinic. Differences between regions and clinics were tested via pairwise comparisons of estimated marginal means with multiplicity adjustment. Longitudinal trends were assessed with clinic-level random slopes. Clinic variability was quantified using coefficients of variation (CV) with bootstrap confidence intervals and BH-adjusted bootstrap pairwise comparisons. OPU lengths >60min and <10min were excluded. Main results and the role of chance The average length of OPU across clinics, regions and years was 20,38 min (SD: 8.5; Range: 10-60 min). Significant differences were observed among clinics (p < 0.0001), with the fastest one taking on average 15,51 min (SD: 5,54; IQR: 9,57-21,51) and the slowest one averaging 35,35 min (SD: 11,30; IQR: 19,05-52,05). Substantial variability was also observed within the same clinic, with 5/36 displaying a coefficient of variation (CV) > 0.40 (Range: 0.411-0424), while the 2 most consistent clinics displayed a CV < 0.30 (Range: 0.281-0.293). Regionally, OPUs averaged 19,52 min (SD: 7,58; IQR: 10,05-29,39) in Asia Pacific; 21,04 min (SD: 9,00; IQR: 10,09-31,59) in Europe; 26,41 min (SD: 10,57; IQR: 11,39-41,43) in North America; and 16,53 min (SD: 6,37, ","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"24 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148400929","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":"L26/P-769 GnRH-a downregulation plus controlled ovarian stimulation for FET endometrial preparation in women ≥35: comparison with four standard protocols","authors":"J. Zhou, H. Huang, L. Jiang, Y. Li, K. Qian","doi":"10.1093/humrep/deag083.1096","DOIUrl":"https://doi.org/10.1093/humrep/deag083.1096","url":null,"abstract":"Study question In women aged ≥35 undergoing FET, how does a GnRH-a+COS protocol compare with HRT, GnRH-a+HRT, COS, and natural cycle for live birth and perinatal outcomes? Summary answer After adjustment, live-birth odds were similar across protocols; COS showed lower clinical pregnancy versus GnRH-a+COS. Perinatal outcomes were largely comparable, except macrosomia. What is known already Endometrial preparation for frozen embryo transfer (FET) is commonly achieved with hormone replacement therapy (HRT), natural cycles, or stimulation-based regimens, with or without GnRH agonist suppression. These approaches generate distinct endocrine environments and may influence implantation as well as obstetric and neonatal risks, particularly in older women. However, head-to-head comparisons across multiple protocols are limited, and perinatal outcomes are inconsistently reported. We evaluated a GnRH-a downregulation plus controlled ovarian stimulation (COS) protocol against four widely used regimens in women aged ≥35. Study design, size, duration This retrospective cohort study included women aged ≥35 who underwent FET in 2023–2024. In total, 5,448 FET cycles were analyzed across five endometrial preparation protocols. Pregnancy outcomes were assessed per transfer, and obstetric and neonatal outcomes were evaluated among live births. Participants/materials, setting, methods Women aged ≥35 who underwent FET after IVF/ICSI in 2023–2024 were included if infertility lasted ≥12 months and baseline FSH was ≤15 IU/L. We excluded endometriosis, donor gametes, PGT/abnormal karyotype, recurrent miscarriage, uterine malformations, untreated hydrosalpinx or intrauterine disease, major immune/coagulation/endocrine disorders, and missing follow-up. Protocols were HRT, GnRH-a+HRT, COS, GnRH-a+COS, and NC. Multivariable logistic regression adjusted for age, BMI, AFC, endometrial thickness, embryos transferred, and embryo type. Main results and the role of chance Live birth rates were 30.3% (909/2,998) in HRT, 28.8% (336/1,168) in GnRH-a+HRT, 27.2% (77/283) in COS, 38.0% (54/142) in GnRH-a+COS, and 28.4% (243/857) in NC (P = 0.119). Clinical pregnancy rates differed: 41.4%, 41.4%, 34.6%, 48.6%, and 37.9%, respectively (P = 0.020). Biochemical pregnancy loss (7.6%, 10.4%, 7.8%, 8.5%, 5.3%) and multiple pregnancy (2.3%, 3.9%, 3.2%, 7.7%, 2.1%) also differed (both P < 0.001); ectopic pregnancy was uncommon (P = 0.424). With GnRH-a+COS as reference, adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for live birth were 0.787 (0.542–1.141) for HRT, 0.694 (0.473–1.018) for GnRH-a+HRT, 0.692 (0.440–1.088) for COS, and 0.716 (0.482–1.062) for NC. For clinical pregnancy, adjusted ORs were 0.852 (0.584–1.222), 0.804 (0.555–1.164), 0.638 (0.413–0.986), and 0.738 (0.505–1.080), respectively. Among live births, macrosomia differed across protocols (P = 0.015), while preterm birth (P = 0.085) and gestational hypertension (P = 0.079) were not statistically different. L","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"35 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148400942","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":"L26/P-648 Outcomes following PGT-A: an age-stratified emulated trial analysis using 110,403 UK IVF cycles","authors":"Y. Beebeejaun, T. Copeland, S. Sunkara","doi":"10.1093/humrep/deag083.978","DOIUrl":"https://doi.org/10.1093/humrep/deag083.978","url":null,"abstract":"Study question Does use of PGT-A in IVF cycles associate with improved clinical pregnancy and live birth rates, and do associations vary by female age? Summary answer Use of PGT-A was associated with higher clinical pregnancy and live birth rates, with stronger associations observed with advancing female age. What is known already Embryo selection in IVF is traditionally based on morphology, yet many morphologically high-quality embryos fail to implant. PGT-A, most commonly performed using next-generation sequencing, has been proposed to improve embryo selection by identifying euploid embryos. However, evidence for clinical benefit remains inconsistent. Conventional observational studies are vulnerable to selection and immortal time bias, while randomised trials are limited by sample size and generalisability. Emulated trial frameworks using large registries may provide complementary real-world evidence. Study design, size, duration A population-based emulated target trial was conducted using anonymised cycle-level data from the UK Human Fertilisation and Embryology Authority registry. A total of 110,403 autologous IVF/ICSI cycles meeting eligibility criteria were included. Cycles were analysed across the study period covered by the registry. Donor cycles, PGT-M cycles, and cycles with two or more embryos transferred were excluded. Participants/materials, setting, methods Eligible participants included women undergoing autologous IVF/ICSI cycles. Exclusions were donor oocyte cycles, PGT-M cycles, and cycles with two or more embryos transferred. Cycles without embryo transfer were retained and contributed zero events, consistent with an intention-to-treat estimand. Baseline confounding was addressed using propensity score–based overlap weighting to improve balance in the region of clinical equipoise; weighted Poisson regression estimated risk ratios in age-stratified analyses performed in Stata. Main results and the role of chance Overall, clinical pregnancy rates were higher in the PGT-A group (RR 1.64; 95% CI 1.55–1.73), as were live birth rates (RR 1.71; 95% CI 1.61–1.83), with a modest reduction in miscarriage risk (RR 0.83; 95% CI 0.70–0.99). Age-stratified analyses demonstrated a clear gradient in associations according to female age. In women aged <35 years, PGT-A use was associated with moderate increases in clinical pregnancy (RR 1.38; 95% CI 1.22–1.56) and live birth rates (RR 1.43; 95% CI 1.24–1.64), with no statistically significant difference in miscarriage rates (RR 0.83; 95% CI 0.52–1.32). In women aged ≥35 years, larger relative differences were observed, with higher clinical pregnancy (RR 1.99; 95% CI 1.86–2.13) and live birth rates (RR 2.19; 95% CI 2.02–2.37), alongside lower miscarriage rates (RR 0.69; 95% CI 0.56–0.85). Associations strengthened with advancing age, with progressively larger relative differences in live birth rates observed in women aged ≥38 and ≥40 years. Associations strengthened with advancing age, wit","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"37 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148400984","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":"L26/P-489 Pregnancy outcomes after up to six embryo transfers without preimplantation genetic testing in women aged <40 years managed under the OPTIMUM protocol","authors":"K. Kuroda, A. Moriyama, R. Tsutsumi, S. Ohgi, R. Hobo, R. Nakagawa, M. Nakata, H. Motoyama, Y. Kuribayashi, R. Sugiyama","doi":"10.1093/humrep/deag083.822","DOIUrl":"https://doi.org/10.1093/humrep/deag083.822","url":null,"abstract":"Study question What are pregnancy outcomes within six embryo transfers (ETs) without preimplantation genetic testing for aneuploidy (PGT-A) in women aged &amp;lt;40 years under the OPTIMUM protocol? Summary answer The cumulative ongoing pregnancy rate reached 99.4% within six ETs when women with ≥2 miscarriages or ≥ 3 failed ETs were managed under the OPTIMUM protocol. What is known already In Japan, public health insurance covers up to six ET cycles for women aged &amp;lt;40 years and has thus decreased the financial burden of assisted reproductive technology (ART). However, several add-on tests and treatments, including PGT-A, are generally not covered, and their clinical effectiveness remains controversial, particularly in young women with recurrent implantation failure (RIF) or recurrent pregnancy loss (RPL). Study design, size, duration This retrospective cohort study included 1,777 women aged &amp;lt;40 years who underwent ART treatment under the national health insurance system at a single clinic between April 2022 and September 2025. Women with ≥2 miscarriages or ≥ 3 failed ETs were managed using the OPTIMUM (OPtimization of Thyroid function, Thrombophilia, IMmunity, and Uterine Milieu) protocol. Cumulative pregnancy outcomes during up to six ET cycles were analyzed using vivola-Analytics, an ART-specific data analysis platform. Participants/materials, setting, methods The patients generally underwent single frozen-thawed blastocyst transfer. Under the OPTIMUM protocol, after one or two failed ETs, hysteroscopy was performed, and intrauterine pathologies were treated. Further evaluations for RIF or RPL included endometrial CD138 immunostaining and assessments of thyroid, immunological, and thrombophilic factors. Targeted treatments comprised antibiotics for chronic endometritis, vitamin D or tacrolimus for elevated Th1/Th2 ratios, levothyroxine for hypothyroidism, and low-dose aspirin for thrombophilia. Main results and the role of chance The mean age of the recruited patients was 34.2 ± 3.3 years. Without the use of PGT-A, the cumulative pregnancy rate and ongoing pregnancy or live birth rate after three ETs were 88.6% and 79.9%, respectively. Women with ≥2 miscarriages or ≥ 3 failed ETs were managed using the OPTIMUM protocol. After four, five, and six ETs, they achieved cumulative pregnancy rates of 95.7%, 99.3%, and 99.9%, respectively, and cumulative ongoing pregnancy or live birth rates of 91.3%, 97.4%, and 99.4%, respectively. Most patients achieved live birth within the coverage of the national health insurance system. Limitations, reasons for caution This study is limited by its retrospective design and single-center setting, which may restrict the generalizability of the findings. Residual confounding factors and unmeasured variables cannot be fully excluded. Wider implications of the findings In Japan, the national health insurance system does not permit routine use of costly add-ons (e.g., PGT-A) with ART. Nevertheless, most w","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"69 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148401061","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":"L26/P-473 Lactobacillus-containing probiotics may enhance pregnancy rates in infertile women undergoing assisted reproductive technology: systematic review and meta-analysis","authors":"D. Hiratsuka, Y. Hirota","doi":"10.1093/humrep/deag083.806","DOIUrl":"https://doi.org/10.1093/humrep/deag083.806","url":null,"abstract":"Study question In infertile women undergoing assisted reproductive technology (ART), does Lactobacillus-containing probiotic supplementation improve clinical pregnancy rates versus placebo or no treatment? Summary answer Lactobacillus-containing probiotics were associated with higher clinical pregnancy rates (RR 1.49), with stronger effects when administered for &amp;gt;14 days (RR 1.99). What is known already Despite advances in ART, a subset of patients continues to experience implantation failure, and uterine/endometrial factors remain difficult to modify once embryo quality is optimised. Emerging evidence links endometrial microbiota composition to implantation, with non-Lactobacillus-dominant profiles more frequently observed in infertile women and associated with poorer reproductive outcomes; however, trials of Lactobacillus-containing probiotics in ART have shown inconsistent results, potentially due to heterogeneity in patient selection, probiotic strains, administration routes, and treatment duration. Study design, size, duration Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-compliant systematic review and random-effects meta-analysis registered in PROSPERO (CRD420251149619). We searched PubMed, Embase, Web of Science, Cochrane CENTRAL, and ClinicalTrials.gov (January 2005–October 2025; English). The primary analysis synthesized randomised controlled trials (RCTs) in infertile women undergoing ART comparing Lactobacillus-containing probiotics with placebo/no treatment for clinical pregnancy. A secondary exploratory analysis pooled observational 16S rRNA studies assessing conversion to Lactobacillus-dominant endometrial microbiota. Participants/materials, setting, methods Infertile women undergoing ART were included. Lactobacillus-containing probiotics (vaginal/oral) were compared with placebo or no treatment. Two reviewers independently screened studies, extracted data, and assessed risk of bias (RoB 2; ROBINS-I). Random-effects models pooled risk ratios for clinical pregnancy, with a prespecified subgroup by treatment duration (&amp;gt;14 vs ≤ 14 days). Exploratory observational data were synthesized by pooling the proportion of women converting from non-Lactobacillus-dominant to Lactobacillus-dominant endometrial microbiota (defined as ≥ 90% Lactobacillus spp.). Main results and the role of chance Of 517 records screened, seven RCTs (n = 796; probiotics 399, control 397; published 2023–2025) were included. Lactobacillus-containing probiotics were associated with higher clinical pregnancy rates (41.98% vs 28.25%; RR 1.49, 95% CI 1.07–2.07; I²=29%). Effects were stronger with &amp;gt;14 days of treatment (RR 1.99, 95% CI 1.44–2.75; I²=0%) than with ≤14 days (RR 1.16, 95% CI 0.67–2.00). No adverse events were reported in the included trials, although adverse-event reporting was limited. RoB 2 judged no trial at high overall risk, but several had some concerns, mainly due to unclear blinding/allocation reporti","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"42 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148401062","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":"L26/P-022 High-resolution analysis of sperm mitochondrial DNA integrity using droplet digital PCR","authors":"J. Mela, S. Lacerenza, J. Farro, C. Peconi, G. Santosuosso, E. Rega, E. Giardina","doi":"10.1093/humrep/deag083.358","DOIUrl":"https://doi.org/10.1093/humrep/deag083.358","url":null,"abstract":"Study question How can sperm mitochondrial DNA integrity be assessed with high sensitivity and quantitative resolution? Summary answer A ddPCR-based tetraplex approach enables sensitive and quantitative assessment of mitochondrial DNA fragmentation and copy number in sperm with high analytical resolution. What is known already Sperm DNA integrity is a key determinant of sperm quality and reproductive potential. While nuclear DNA fragmentation is widely investigated and used in clinical practice, mitochondrial DNA (mtDNA) integrity remains comparatively less explored despite its higher susceptibility to oxidative stress. Previous studies have reported an association between nuclear and mitochondrial DNA damage, suggesting shared mechanisms underlying sperm dysfunction. In parallel, microfluidic sperm selection technologies are increasingly adopted in reproductive laboratories to better reproduce physiological conditions, highlighting the need for sensitive analytical methods to detect differences in sperm functional parameters under different experimental conditions. Study design, size, duration This laboratory-based experimental study was conducted on paired semen samples obtained from 35 men over a one-year period. All samples were analysed within the same experimental workflow to allow intra-sample comparison. Participants/materials, setting, methods Semen samples were processed using swim-up and microfluidic sperm selection techniques. DNA extracted from paired sample fractions was analysed using a tetraplex droplet digital PCR (ddPCR) assay combining three mitochondrial targets to enhance the sensitivity of mitochondrial DNA fragmentation detection and one nuclear target to enable accurate estimation of mitochondrial DNA copy number per sperm cell. Main results and the role of chance The ddPCR tetraplex assay successfully quantified mitochondrial DNA fragmentation and the mean mitochondrial DNA copy number per spermatozoon simultaneously in all analysed samples, demonstrating high analytical sensitivity and reproducibility. Paired analyses revealed significantly higher mitochondrial DNA fragmentation in sperm fractions obtained after swim-up compared with microfluidic sperm selection (p = 1.91 × 10−-6). Conversely, the mean mitochondrial DNA copy number was significantly higher in sperm fractions selected by microfluidics (p = 3.15 × 10−⁵). These differences were consistently observed across paired samples, indicating that the findings are unlikely to be attributable to random variation. Overall, the results demonstrate the ability of ddPCR to simultaneously assess mitochondrial DNA fragmentation and copy number through an integrated multiparametric approach. Limitations, reasons for caution The study is limited by the absence of direct clinical outcome correlations and by the moderate sample size. Further investigations are currently in progress to confirm the translational relevance of mitochondrial DNA integrity assessment and to better ch","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"6 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148401079","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}