Human reproduction最新文献

{"title":"Evaluation of the association between self-reported pre-operative symptoms with surgically diagnosed endometriosis using the #ENZIAN classification in a multi-centre cohort.","authors":"Elisabeth Reiser,Georg Göbel,Alexandra Perricos-Hess,Olaf Buchweitz,Matthias Jaekel,Elisa Westphal,Stefan Rimbach,Monika Woelfler,Bernhard Kraemer,Thomas Kolben,Sara Dunja Pempelfort,Daria Pashkunova,Julian Metzler,Razvan Petru Derihaci,Petra Klein,Elisabeth Janschek,Philipp Guttenberg,Mathis Wuester,Angelika Wolfrum,Vanadin Seifert-Klauss,Simon-Hermann Enzelsberger,Joerg Keckstein,Rene Wenzl,Beata Seeber","doi":"10.1093/humrep/deaf120","DOIUrl":"https://doi.org/10.1093/humrep/deaf120","url":null,"abstract":"STUDY QUESTIONIs there an association between pre-operative symptoms and intraoperatively described localization and size of endometriosis lesions as assessed by the #ENZIAN classification system?SUMMARY ANSWERDyschezia is associated with any deep infiltrating endometriosis (DE) lesions; severe dyspareunia is associated with adenomyosis.WHAT IS KNOWN ALREADYPrevious attempts to correlate the common symptoms of endometriosis to the size and localization of lesions have been of moderate success.STUDY DESIGN, SIZE, DURATIONThis prospective, multicentre, non-interventional cross-sectional study was conducted between September 2022 and January 2024 at 18 endometriosis centres in Austria, Germany, and Switzerland, enrolling a total of 838 patients with endometriosis.PARTICIPANTS/MATERIALS, SETTING, METHODSThe study included 521 patients with complete information on pre-operative symptoms and intraoperatively diagnosed endometriosis classified by the #ENZIAN classification system. Associations between symptoms and localization of endometriosis lesions were analysed.MAIN RESULTS AND THE ROLE OF CHANCENearly all patients (n = 513) (98.5%) suffered from dysmenorrhea whereas 294 (56.4%), 208 (39.9%), and 102 (19.6%) patients reported dyspareunia, dyschezia, and dysuria, respectively. Dyspareunia rated as ≥8 on a visual analogue scale was reported 3.5-fold more often in patients with adenomyosis only (OR 3.56 [1.38-9.17]) than in those without, while dyschezia was almost twice as likely in those with any form of DE (OR 1.86 [1.3-2.65]).LIMITATIONS, REASONS FOR CAUTIONA larger study population is needed to clinically define relevant sub-groups based on localization of lesions.WIDER IMPLICATIONS OF THE FINDINGSThe findings of the present study identify adenomyosis as a strong driver of pain, especially dyspareunia, making awareness of its high prevalence of utmost importance. Few direct associations between symptoms and lesions were identified. Endometriosis-related symptoms, especially when chronic, are multi-factorial and cannot be readily correlated to specific lesion sites.STUDY FUNDING/COMPETING INTEREST(S)This study received no external funding and all the authors declare they have no conflicts of interest pertaining to this study.TRIAL REGISTRATION NUMBERClinical Trials NCT05624567.","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"73 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144664318","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":"Association of hepatitis B virus infection with oocyte quality, embryo development, and ART outcomes in couples with a freeze-all strategy at a single center.","authors":"Jiaying Lin,Qiuju Chen,Yining He,Mingru Yin,Qianqian Zhu","doi":"10.1093/humrep/deaf131","DOIUrl":"https://doi.org/10.1093/humrep/deaf131","url":null,"abstract":"STUDY QUESTIONDoes female or male hepatitis B virus (HBV) infection affect the oocyte and embryo quality, pregnancy outcomes, and neonatal outcomes in infertile couples undergoing ART treatment?SUMMARY ANSWERThe female or male HBV infection did not have a statistically significant negative impact on the development of oocytes and embryos, pregnancy outcomes, or neonatal outcomes of ART.WHAT IS KNOWN ALREADYOnly few studies assessing the effects of HBV infection on the reproductive outcomes among infertile population have been conducted with inconsistent results. There is limited research that focuses on the oocyte and embryo development of HBV-infected females and males.STUDY DESIGN, SIZE, DURATIONA retrospective cohort study was performed among infertile couples undergoing the first frozen embryo transfer (FET) after the first ovarian stimulation with a freeze-all strategy during the period from 1 January 2011 to 31 March 2023.PARTICIPANTS/MATERIALS, SETTING, METHODSA total of 24 836 infertile couples, including 133 couples with female HBV-positive and male HBV-negative, 1471 couples with female HBV-negative and male HBV-positive, and 23 232 couples with both female and male HBV-negative underwent their first FET after the first ovarian stimulation with a freeze-all strategy. Propensity score matching (PSM) was used to balance the baseline parameters between the groups.MAIN RESULTS AND THE ROLE OF CHANCEAfter PSM, no statistically significant differences were observed regarding the comparison in the number of oocytes retrieved, MII oocytes, 1-2-3 PN-fertilized oocytes, 2PN-fertilized oocytes, embryo cleavages, available embryos, top-quality embryos, and available blastocysts between comparison groups (group with female HBV-positive and male HBV-negative and group with female HBV-negative and male HBV-positive) and the reference group. Consistently, the differences in the mature oocyte rate, fertilization rate, cleavage rate, as well as top-quality embryo rate and available embryo rate between comparison groups and the reference group were not statistically significant. The clinical pregnancy rate and the live birth rate showed a decreasing trend for couples with female HBV infection compared with the uninfected couples, although this did not reach statistical significance (clinical pregnancy: adjusted odds ratio, 0.69 [95% CI: 0.45-1.05] and live birth: 0.64 [0.41-1.00]). Couples with female HBV infection and couples with male HBV infection were not associated with increased risk of adverse neonatal outcomes including preterm birth, low birth weight, high birth weight, small for gestational age, and large for gestational age.LIMITATIONS, REASONS FOR CAUTIONThis was a retrospective cohort study in a single center, which limited the generalization of our results.WIDER IMPLICATIONS OF THE FINDINGSHBV infection was not statistically significantly associated with development of oocyte and embryo quality, pregnancy outcomes, and neonatal outcomes. The","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"95 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144645947","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":"Unveiling the molecular mechanisms of human platelet lysate in enhancing endometrial receptivity","authors":"Tina Tu-Thu Ngoc Nguyen, Yat Sze Sheila Kwok H, Carol Zhang, Stewart J Russell, Clifford L Librach","doi":"10.1093/humrep/deaf118","DOIUrl":"https://doi.org/10.1093/humrep/deaf118","url":null,"abstract":"STUDY QUESTION Which biological pathways are modulated by primary human endometrial cells in response to in vitro treatment with non-autologous human platelet lysate (HPL)? SUMMARY ANSWER HPL treatment stimulates endometrial growth and trophoblast attachment by activating cell proliferation, and modulating cell–cell signaling and extracellular matrix organization. WHAT IS KNOWN ALREADY There is currently no standard therapy for recurrent implantation failure (RIF), and existing treatments have variable effectiveness and do not consistently improve clinical pregnancy rates. Intrauterine infusion of autologous platelet-rich plasma (aPRP), before embryo transfer, promotes endometrial growth and may be the most effective immunomodulatory intervention to significantly improving pregnancy outcomes in RIF patients. HPL is a commercially available, pooled, and cell debris-cleared derivative of PRP suitable for cell culture. STUDY DESIGN, SIZE, DURATION Cross-sectional (control versus treatment) study including five non-RIF (control) patients and 18 RIF patients. The 18 RIF patients were categorized into two sub-groups: RIF and RIF including thin endometrium (TE). PARTICIPANTS/MATERIALS, SETTING, METHODS Endometrial tissue was collected from pre-menopausal women (32–47 years of age) during routine biopsy procedures at the CReATe Fertility Centre, Toronto. Primary endometrial epithelial (EECs) and stromal cells (ESCs) were enzymatically isolated, cultured separately, and treated for 48 h with either serum-free media (SFM) as the untreated control, or SFM supplemented with 1% HPL (EECs), or 10% HPL (ESCs). Cell proliferation was assessed by metabolic assay and immunocytochemistry for Ki-67 expression. Following 48-h treatment, total RNA was isolated from untreated and treated cells to prepare pooled RNA libraries, which were then subjected to RNA sequencing (150 cycles paired-end). Differential gene expression was performed using the DESeq2 package and RStudio/R. Significant differentially expressed genes were determined with the following cut-off values: log2FoldChange >|2| and Padj <0.05. Pathway enrichment analysis was then performed with Enrichr (Reactome 2022 database) to identify enriched pathways. After 48-h treatment with SFM or HPL, a trophoblast attachment assay was also performed with fluorescently labeled HTR-8/SVneo trophoblast spheroids, where spheroids were seeded on top of pre-treated EEC monolayers for a 1-h incubation to allow for attachment. Fluorescent microscopy and ImageJ software were used to image and quantify the total number of seeded and attached spheroids. MAIN RESULTS AND THE ROLE OF CHANCE Treatment with non-autologous HPL for 48 h significantly increased EEC proliferation by 1.24- to 1.49-fold (P < 0.05) in all groups. ESCs showed a significant proliferation increase of 1.29-fold in the proliferative phase RIF group and 1.92-fold in the secretory phase RIF+TE group (P < 0.05). HPL treatment upregula","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"16 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144639975","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":"Foundation models: the next level of AI in ART","authors":"Hugo L Hammer, Vajira Thambawita, Michael A Riegler","doi":"10.1093/humrep/deaf136","DOIUrl":"https://doi.org/10.1093/humrep/deaf136","url":null,"abstract":"Artificial intelligence (AI) in ART has traditionally employed narrow, task-specific models for procedures such as embryo selection and sperm analysis. Although effective, these systems depend on extensive manual annotation and address isolated tasks rather than integrating the diverse data generated in clinical practice. Recently, foundation models, pre-trained on vast, heterogeneous datasets via self-supervised learning, have emerged as promising tools for robust multimodal analysis and decision support. This Directions discusses the technical underpinnings of foundation models, explores their potential applications in ART, and integrates recent innovations that demonstrate how AI-driven methods can improve embryo selection, enable sperm epigenetics diagnostics, and personalize treatment protocols. Key challenges, including data quality, computational infrastructure, and regulatory issues, are also addressed.","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"7 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144639970","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":"Carboplatin and paclitaxel induced-gonadotoxicity on the ovarian reserve of young breast cancer patients with BRCA1 mutation","authors":"Joana Dias Nunes, Elissavet Ntemou, Géraldine Van den Steen, Necati Findikli, Maxime Fastrez, Anne Delbaere, Matteo Lambertini, Melody Devos, Isabelle Demeestere","doi":"10.1093/humrep/deaf133","DOIUrl":"https://doi.org/10.1093/humrep/deaf133","url":null,"abstract":"STUDY QUESTION Are ovarian tissue fragments from patients with BReast CAncer gene 1 (BRCA1)-mutated breast cancer (BC) more sensitive to carboplatin and/or paclitaxel exposure compared to those from non-mutated patients with BC? SUMMARY ANSWER Carboplatin and paclitaxel treatment showed similar gonadotoxicity, irrespective of the genetic background. WHAT IS KNOWN ALREADY Studies have shown that mutations of BRCA1 gene negatively impact the ovarian reserve due to defects in DNA repair mechanisms. As a result, patients with BRCA germline mutations might be more vulnerable to chemotherapy-induced gonadotoxicity. Carboplatin and paclitaxel are known moderately gonadotoxic drugs, but the impact of their combination on fertility remains unclear, particularly in BRCA-mutated patients. STUDY DESIGN, SIZE, DURATION Cryopreserved ovarian tissue fragments from patients with BC, either carrying a BRCA1 germline mutation (n = 4) or not (n = 4), were exposed to chemotherapy using two models: (i) in vitro culture or (ii) in vivo xenotransplantation model. First, thawed ovarian tissue fragments were cultured for 3 days with carboplatin (10 µg/ml), paclitaxel (1 µM), carboplatin, and paclitaxel or vehicle (dimethyl sulfoxide). Next, ovarian tissue fragments from the same patients were xenografted into the peritoneum of immunodeficient mice, followed by 3-week injections with either carboplatin (50 mg/kg/week) and paclitaxel (10 mg/kg/every 3 days) or saline solution as a control. PARTICIPANTS/MATERIALS, SETTING, METHODS Ovarian cortex was processed for histological analyses to assess follicle activation and survival in both experimental models. Follicle counting and morphological assessment were performed to evaluate the rates of follicles at different developmental stages, as well as the rate of atretic follicles. Immunostainings were performed for follicle activation (KL and p-RPS6), apoptosis (Terminal deoxynucleotidyl transferase dUTP Nick-End Labeling (TUNEL) assay), and DNA repair mechanisms (γH2AX, RAD51, and DNA PKcs). MAIN RESULTS AND THE ROLE OF CHANCE While chemotherapy exposure did not significantly affect the proportion of primordial follicles in vitro, an increase in the proportion of quiescent follicles was observed after xenografting in the treated conditions compared to their respective controls, regardless of the presence of a BRCA mutation (BRCA+: 79.6 ± 5.07% versus 35.4 ± 8.26%, P = 0.0003; BRCA−: 81.8 ± 10.50% versus 17.9 ± 21.93%, P = 0.0014), reflecting the massive destruction of the pool of growing follicles. No difference was observed in the rate of atretic follicles, but the TUNEL assay revealed that chemotherapy, alone or in combination, increased DNA fragmentation rates (BRCA+: 37–49%; BRCA−: 43–55%) compared to the control conditions (BRCA+: 13–19%; BRCA−: 17–23%) both in vitro and in vivo. DNA repair mechanisms were affected following chemotherapy exposure, as evidenced by a significant increase in γH2AX-stained follicles in vitro (","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"37 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144611135","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":"Serum progesterone levels on fresh blastocyst transfer day: a key determinant of live birth rates","authors":"Chloé Maignien, Gianfranco Fornelli, Mathilde Bourdon, Léa Melka, Louis Marcellin, Christelle Laguillier-Morizot, Julie Firmin, Catherine Patrat, Pietro Santulli","doi":"10.1093/humrep/deaf138","DOIUrl":"https://doi.org/10.1093/humrep/deaf138","url":null,"abstract":"STUDY QUESTION Is there an association between mid-luteal serum progesterone (P) levels on the day of fresh embryo transfer (ET) at the blastocyst stage and the live birth rate (LBR)? SUMMARY ANSWER Serum P levels between 46.6 and 72.3 ng/ml on the day of fresh ET are associated with the highest LBR. WHAT IS KNOWN ALREADY Luteal phase monitoring is a standard practice in frozen ET cycles to personalize luteal phase support. However, the role of serum P levels in fresh ET cycles remains underexplored and inconsistent, with some studies suggesting a link to outcomes while others show no association. STUDY DESIGN, SIZE, DURATION This retrospective, single-center cohort study included all single autologous Day-5 blastocyst fresh ETs performed between June 2020 and March 2023. Serum P levels were measured on the day of ET. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 874 patients underwent ovarian stimulation according to standardized protocols, with ovulation triggered by human chorionic gonadotropin. All patients received the same luteal phase support regimen of vaginal micronized P (800 mg/day). Serum P levels were measured on the morning of ET in a single laboratory, with clinicians blinded to the results. Patients were divided into four quartiles based on their serum P levels: Q1 (10.2–46.5 ng/ml), Q2 (46.6–72.3 ng/ml), Q3 (72.4–106.9 ng/ml), and Q4 (107.0–364.8 ng/ml). The primary outcome was the LBR, with secondary outcomes including clinical pregnancy rates, early miscarriage rates, and neonatal outcomes (birth weight and gestational age at delivery). Univariate and multivariate logistic regression analyses were performed to identify factors associated with LBR. MAIN RESULTS AND THE ROLE OF CHANCE The median serum P level on ET day for the entire study population was 72.3 ng/ml (range: 46.5–106.9), with a minimum value of 10.2 ng/ml and a maximum value of 364.8 ng/ml. The overall LBR was 29.4% (260/874), ranging from 21.0% in Q1 to 38.1% in Q2, 29.5% in Q3, and 30.3% in Q4. A significant association between serum P levels and LBR was observed, with Q1 showing the lowest LBR and Q2 the highest (P < 0.001). Multivariate logistic regression indicated that serum P levels in Q1, Q3, and Q4 were associated with significantly lower LBRs compared to Q2, with adjusted odds ratios of 0.52 (95% CI: 0.32–0.82, P = 0.005), 0.55 (95% CI: 0.36–0.86, P = 0.010), and 0.54 (95% CI: 0.34–0.85, P = 0.010), respectively. For secondary outcomes, clinical pregnancy rates were significantly lower in Q1 (29.2% vs 44.1%, P < 0.001). Early miscarriage rates were higher in Q3 (38.5%) and Q4 (35.6%) compared to Q2 (12.3%, P < 0.001). Preterm birth was significantly more frequent in Q1 than in Q2 (15.2% vs 3.6%, P = 0.010). LIMITATIONS, REASONS FOR CAUTION The study’s retrospective design is a key limitation, introducing potential selection and confounding biases, despite efforts to mitigate these using multivariable analysis. WIDER IMPLICATIONS","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"13 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144603393","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 contribution of medically assisted reproduction to total, age-, and parity-specific fertility in Italy","authors":"Alessandra Burgio, Cinzia Castagnaro, Daniele Vignoli, Agnese Vitali","doi":"10.1093/humrep/deaf137","DOIUrl":"https://doi.org/10.1093/humrep/deaf137","url":null,"abstract":"STUDY QUESTION What is the contribution of medically assisted reproduction (MAR) to total, age-, and parity-specific fertility in Italy? SUMMARY ANSWER MAR contributed 3.7% to Italy’s total fertility rate in 2022 and 5.9% to fertility of first order; MAR’s contribution to fertility reached 16% among women aged 40 + and 31% among women aged 40 + at first birth. WHAT IS KNOWN ALREADY Demography, particularly via postponement of the age at childbearing for both women and men, plays a role in the diffusion of MAR techniques, and the diffusion of MAR techniques may contribute to postpone the age at childbearing. Recent studies found that the contribution of MAR to fertility rates is remarkable and increases over time in countries such as Czech Republic, Denmark, Australia, and the USA. Italy is a country distinguished by one of the lowest average number of children per woman globally, as well as the highest maternal age at first birth and among the highest shares of births to mothers aged 40 years and over in Europe. No prior study has focused on Italy. STUDY DESIGN, SIZE, DURATION This study relies on a unique combination of administrative data sources: the Certificate of Delivery Care Registry dataset based on the entire population of live birth deliveries in Italy in 2022 (N = 393 997), administered by the Ministry of Health; the Register of Live Births to the Resident Population in 2022 (N = 393 333), administered by the Italian National Institute of Statistics; and the resident population by age and sex to identify the female population at risk of having a(n additional) child by age (N = 17 006 665) provided by the Italian National Institute of Statistics. Comparisons are made with the year 2013. PARTICIPANTS/MATERIALS, SETTING, METHODS We calculate the age-specific fertility rates (total and by parity) for births conceived via MAR and those conceived naturally. These rates are then utilized to assess the contribution of MAR to total and parity-specific fertility, as well as to the mean maternal age at childbearing. This study is the first estimation of its kind for Italy. MAIN RESULTS AND THE ROLE OF CHANCE The contribution of MAR to the total fertility rate (for women aged 15–59 years) in Italy increased from 2.1% in 2013 to 3.7% in 2022. Among women aged 40 + , the contribution of MAR to the total fertility rate increases to 16.2% in 2022, up from 8.6% in 2013. The contribution of MAR to first-order fertility rate increases to 5.9% and it reaches 30.9% among women aged 40–59 years in 2022. The mean age at first childbirth among women who conceived via MAR equals to 37.8, up from 36.0 in 2013, compared to those who conceived naturally at a mean age at first birth of 30.4 in 2013 and of 31.3 in 2022. LIMITATIONS, REASONS FOR CAUTION Our approach may underestimate MAR’s contribution to the total fertility rate in Italy: mothers in Italy may be more likely to under-report of MAR-births than in other countries, due to social norms that are more res","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"11 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144603157","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":"Pathogenic variants in DLGAP5 cause female infertility characterized by oocyte maturation arrest and embryonic arrest","authors":"Ronggui Qu, Fan Liang, Li Fan, Rong Shi, Zhixian Chen, Biaobang Chen, Hao Gu, Xingzhu Du, Tianyu Wu, Huizhen Fan, Ran Yu, Yuxi Luo, Jian Mu, Weijie Wang, Qiaoli Li, Juanzi Shi, Lei Wang, Xiaoxi Sun, Zhihua Zhang, Qing Sang","doi":"10.1093/humrep/deaf139","DOIUrl":"https://doi.org/10.1093/humrep/deaf139","url":null,"abstract":"STUDY QUESTION Can new genetic factors responsible for oocyte defects be identified in infertile women, especially for those with spindle assembly defects? SUMMARY ANSWER We identified homozygous and compound heterozygous variants of DLGAP5 in three infertile individuals from two independent families. WHAT IS KNOWN ALREADY Some genes have been found to be responsible for female infertility with oocyte maturation defects. During mitosis, DLGAP5 is involved in promoting microtubule polymerization and spindle formation. STUDY DESIGN, SIZE, DURATION The DLGAP5 variants were identified by whole-exome sequencing in a cohort of 3627 female infertility patients diagnosed with oocyte maturation defects or embryonic development problems, and all participants were recruited from 2015 to 2023. Thirty-six hours after cell transfection, the expression levels of wild-type (WT) and mutant DLGAP5 were evaluated by western blot (n = 3 biological replicates). Human germinal vesicle (GV) oocytes retrieved from assisted reproductive procedure were introduced for cRNA (n = 3–5 oocytes per group) and antibody injection (n = 10–15 oocytes per group). Knock-in (KI) mouse model was generated by CRISPR-Cas9 and genotyping was performed at postnatal Days 10–15. Sexually mature females (6–10 weeks old) were used for fertility test (n = 6 mice per group, lasts 6–8 months), western blot (n = 3 biological replicates), IVF (n = 3 biological replicates), embryos collection (n = 3 biological replicates), immunofluorescence (n = 3 biological replicates), RNA-sequencing (RNA-seq, n = 3 biological replicates), and other functional assays between 2019 and 2023. PARTICIPANTS/MATERIALS, SETTING, METHODS The DLGAP5 variants were identified by whole-exome sequencing and further confirmed by Sanger sequencing. Western blot was used to detect the expression of mutant DLGAP5 in HEK-293T cells after transfection. cRNA injection and immunofluorescence were performed to view the location of DLGAP5 in human oocytes. Knockdown of DLGAP5 by Trim-Away in human oocytes was conducted to observe the effect of DLGAP5 on spindle assembly and oocyte maturation. Then, Dlgap5 KI mice were constructed to mimic the phenotype of the affected individuals. After phenotypic assessment, western blot, IVF, assessment of embryonic development, chromosome counting, RNA-seq, and quantitative real-time PCR were performed to elucidate the pathological mechanism of DLGAP5 variants. MAIN RESULTS AND THE ROLE OF CHANCE We identified homozygous nonsense DLGAP5 variant (NM_014750.5, c.431delA (p.Lys144Argfs*55)) in two affected sisters from family 1 and compound heterozygous variants (c.C847G (p.Pro283Ala) and c. C1202G (p.Thr401Ser)) in one infertile individual in family 2. p. Lys144Argfs*55 led to protein degradation (P < 0.0001) and p. Pro283Ala resulted in a significant decrease in protein level (P = 0.0021). DLGAP5 was located on the spindle and mutant did not alter its location. Knockdown of DLGAP5 in human ooc","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"109 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144603156","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":"Does endometrial thickness impact live birth rate following a frozen embryo transfer: outcomes of 30 676 euploid single embryo transfers.","authors":"Haley Genovese,Carlos Alonso Mayo,Erkan Kalafat,Human Fatemi,Baris Ata,Juan Garcia-Velasco,Emre Seli","doi":"10.1093/humrep/deaf129","DOIUrl":"https://doi.org/10.1093/humrep/deaf129","url":null,"abstract":"STUDY QUESTIONDoes endometrial thickness (ET) impact live birth rate (LBR) in patients undergoing single euploid frozen embryo transfer (FET)?SUMMARY ANSWERPatients with the thinnest endometrial lining exhibit a decline in LBR at all centers, but the magnitude of the decline and the ET threshold at which it is identified is variable by center and cycle type.WHAT IS KNOWN ALREADYThin endometrium is thought to be an impediment to FET cycle success, and it is widely believed that pregnancy and LBRs are improved when the ET is >6-8 mm. However, evidence for this is limited and some studies report contradictory findings which indicate that ET does not significantly impact LBR.STUDY DESIGN, SIZE, DURATIONThis is an international multicenter retrospective cohort study conducted between January 2017 and December 2022 at 25 different IVF centers in 3 countries and including a total of 30 676 cycles.PARTICIPANTS/MATERIALS, SETTING, METHODSAll FET cycles involved a single euploid blastocyst created with autologous oocytes. Endometrial preparation protocols were selected at the discretion of the physicians and the patients, and included programmed cycles, natural, and modified natural cycles (NC and mNC). The primary outcome was the LBR stratified by ET and cycle type. The distribution of ET measurements was assessed with histograms and quantile-quantile plots. Conditional density plots (CDPs) were utilized to determine the associations between ET measurement and LBR. Adjusted effect estimates of ET on LBR were assessed with multivariable logistic regression analyses, and receiver operating characteristics curves (ROC) were used to assess the performance of ET for predicting live birth.MAIN RESULTS AND THE ROLE OF CHANCEThere were 24 097 (78.6%) programmed cycles, 759 (2.5%) NCs, and 5820 (19.0%) mNCs included in the analyses. The median ET among all cycle types at all centers was 8.9 mm (9.0 mm in the USA, 8.7 mm in Spain, 8.0 mm in the UAE). When cycles from all centers were grouped together, CDPs showed a decline in LBR for ET <7 mm in both programmed and mNCs. Regression analyses demonstrated that in cycles with a lining <7 mm undergoing programmed cycles and mNC, odds of LBR were reduced by 22% [aOR 0.78 (95% CI 0.70-0.87), P ≤ 0.001] and 41% [aOR 0.59 (95% CI 0.49-0.72), P < 0.001], respectively. In patients undergoing NC, there was no ET threshold at which LBR was impacted and regression analysis demonstrated that LBR is not significantly impacted by ET <7 mm in patients undergoing NC [aOR 0.85 (95% CI 0.58-1.25), P = 0.41]. Sensitivity analyses were consistent with the overall analysis, Q-Q plots demonstrated that the distribution of ET measurements varied between the centers and the percentage of programmed cycles with ET <7 mm was lowest in the USA (2.6%) and Spain (5.2%), compared with the UAE (12%). Two models were developed to determine the prognostic value of ET for predicting live birth. The performance of the model with endometrial thickness ","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"22 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144604027","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":"Ovarian stimulation with follitropin delta for in vitro fertilization: a multicentre, randomized, assessor-blind comparison with follitropin alfa using conventional dosing regimens (ADAPT-1 trial)","authors":"Andrea Bernabeu, Philipp Zajc, Marta García Sánchez, Rina Agrawal, Enrico Papaleo, Stefan Jirecek, Signe Møgelmose, Ida Engberg Jepsen, Rita Lobo","doi":"10.1093/humrep/deaf119","DOIUrl":"https://doi.org/10.1093/humrep/deaf119","url":null,"abstract":"STUDY QUESTION How do ovarian responses using conventional dosing for follitropin delta 15 µg/day compare with follitropin alfa 225 IU/day in women undergoing ovarian stimulation? SUMMARY ANSWER The ADAPT-1 trial demonstrates similar ovarian responses with follitropin delta 15 µg/day and follitropin alfa 225 IU/day starting doses in a conventional dosing regimen. WHAT IS KNOWN ALREADY Follitropin delta, a recombinant FSH (rFSH), is currently approved for ovarian stimulation using an individualized fixed daily dose based on serum anti-Müllerian hormone (AMH) and bodyweight (maximum 12 µg/day for first cycle and 24 µg/day in subsequent cycles). Other rFSHs, such as follitropin alfa, conventionally apply a starting dose of 150–225 IU, fixed for the initial days of stimulation, after which dose adjustments can be made (maximum 450 IU/day). Ovarian stimulation with follitropin delta 10 µg/day provides a similar ovarian response to follitropin alfa 150 IU/day for serum concentration and number of follicles ≥12 mm. STUDY DESIGN, SIZE, DURATION ADAPT-1 was a randomized, accessor-blinded, multicentre trial comparing efficacy and safety of a starting dose of follitropin delta 15 µg/day with follitropin alfa 225 IU/day in conventional dosing regimens. The primary endpoint was the number of oocytes retrieved; mean difference between treatment groups was estimated using a negative binomial regression model (treatment and serum AMH level as factors). During the follow-up period, clinical pregnancies resulting from the first fresh/frozen transfers within 3 months of the start of stimulation, and ovarian hyperstimulation syndrome (OHSS) rates were assessed. PARTICIPANTS/MATERIALS, SETTING, METHODS Participants, 18–40 years, undergoing IVF/ICSI could enrol at specialist reproductive clinics in Austria, France, Italy, Spain, and the United Kingdom for ovarian stimulation if they had no contraindications for treatment with a starting gonadotropin dose of 225 IU/day. Patients could enrol if they reported infertility for at least 1 year if ≤37 years and at least 6 months for those >37 years, and regular menstrual cycles (21–35 days). All cycles used a GnRH antagonist protocol. MAIN RESULTS AND THE ROLE OF CHANCE Between 1 August 2022 and 16 April 2024, 300 of 337 screened patients were randomized to, and received, follitropin delta (n = 200) or follitropin alfa (n = 100). The two treatment groups were comparable in terms of demographics, baseline characteristics, and duration of infertility. The mean duration of treatment was ∼9 days in both groups. The mean total dose of follitropin delta was 143.7 ± 33.6 µg and 154.3 ± 23.1 µg (2105 ± 315 IU) for follitropin alfa. Three-quarters (226/300) used an human Chorionic Gonadotropin trigger for final follicular maturation. A mean of 9.9 oocytes was retrieved for both groups (estimated difference: 0.0 oocytes; 95% CI −1.3, 1.2). The category of 8–14 oocytes retrieved was the most common ovarian response (follitropin ","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"109 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144594251","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}