Human reproduction最新文献

{"title":"Bacterial vaginosis toxins impair sperm capacitation and fertilization.","authors":"Shweta Bhagwat, Leila Asadi, Ronald McCarthy, Juan Ferreira, Ping Li, Ethan Li, Sariela Spivak, Ariana Gaydon, Vaka Reddy, Christy Armstrong, Sydney R Morrill, Hillary Zhou, Amanda L Lewis, Warren G Lewis, Celia M Santi","doi":"10.1093/humrep/deaf132","DOIUrl":"https://doi.org/10.1093/humrep/deaf132","url":null,"abstract":"<p><strong>Study question: </strong>What effect do toxins produced by bacterial vaginosis (BV) bacteria have on sperm function?</p><p><strong>Summary answer: </strong>BV toxins dysregulate sperm capacitation and intracellular calcium homeostasis, and impair the ability of sperm to fertilize oocytes.</p><p><strong>What is known already: </strong>In BV, which is linked to infertility, overgrowth of Prevotella and Gardnerella in the vagina is accompanied by elevated concentrations of the toxins lipopolysaccharide (LPS) and vaginolysin (VLY).</p><p><strong>Study design, size, duration: </strong>This was a laboratory study in which human semen samples were collected from consenting healthy donors with normal semen parameters. Mouse sperm samples were obtained from the caudal epididymis.</p><p><strong>Participants/materials, setting, methods: </strong>Motile mouse and human sperm were isolated via swim-up and treated under non-capacitating or capacitating conditions. LPS from Escherichia coli was commercially available. VLY was produced by cloning the Gardnerella VLY protein in the ClearColi expression system. Mouse sperm were pre-incubated in IVF medium with LPS or VLY and then co-cultured with ovulated cumulus-oocyte complexes. The effects of LPS and VLY on sperm motility and hyperactivation were assessed with computer-assisted sperm analysis. Effects on viability were assessed by Hoechst staining. Acrosomal exocytosis was assessed in sperm from transgenic Acr-eGFP mice and in human sperm stained with Pisum sativum agglutinin FITC. Intracellular calcium concentration was measured by using the calcium-sensitive dye Fluo-4 AM and fluorescence microscopy. The effects of LPS on sperm from CatSper knockout mice were assessed. Additionally, sperm were treated with a Toll-like receptor 4 (TLR4) antagonist and further exposed to LPS.</p><p><strong>Main results and the role of chance: </strong>Exposure of mouse sperm to LPS or VLY significantly decreased IVF (P < 0.05). Under capacitating conditions, both toxins initially increased mouse (P < 0.001) and human (P < 0.05) sperm hyperactivation, then significantly decreased sperm motility (P < 0.05), hyperactivation (P < 0.05), and acrosomal exocytosis (P < 0.01). These changes were accompanied by a rapid and irreversible increase in sperm intracellular calcium concentration. Effects of LPS, but not VLY, were prevented by polymyxin B, which binds LPS. The LPS-induced intracellular calcium increase required external calcium, but not the calcium channel CatSper, and was inhibited by a TLR4 antagonist.</p><p><strong>Large scale data: </strong>N/A.</p><p><strong>Limitations, reasons for caution: </strong>First, the commercially available LPS we used was isolated from Escherichia coli, rather than from the BV-associated bacteria Prevotella bivia. Second, we did not quantify the absolute sperm intracellular calcium concentration before or after LPS or VLY treatment. Third, all of our experiments were in vitro.</p><p><","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144617392","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}

{"title":"Association between weight loss and reproductive outcomes among women with overweight or obesity: a cohort study using UK real-world data","authors":"Maximiliane Lara Verfürden, Volker Schnecke, Eva Winning Lehmann, Adriana Rendón Guillén, Adam H Balen","doi":"10.1093/humrep/deaf122","DOIUrl":"https://doi.org/10.1093/humrep/deaf122","url":null,"abstract":"STUDY QUESTION In women with BMI ≥25 kg/m2, does a 10–25% weight loss versus stable weight increase the chance of pregnancy? SUMMARY ANSWER In women with overweight or obesity, weight loss was associated with an increase in the chance of pregnancy. WHAT IS KNOWN ALREADY Weight loss has been shown to improve conception rates among women with overweight or obesity and concomitant polycystic ovary syndrome (PCOS). However, evidence on the effect of weight loss on conception rates among the general population of women with overweight or obesity, irrespective of PCOS status, is lacking. STUDY DESIGN, SIZE, DURATION A large cohort study of patient data collected from primary-care practices linked to hospital records in England between January 2000 and May 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS Women were included if they were aged 18–40 years with BMI ≥25 kg/m2. Patient data were extracted from the UK Clinical Practice Research Datalink Aurum database of electronic medical records. The primary outcome was the first pregnancy recorded during a 3-year follow-up period. Key secondary outcomes were the occurrence of miscarriage, gestational diabetes, and pregnancy-induced hypertension, as well as emergency caesarean section, and risk of babies being born large for gestational age (LGA). MAIN RESULTS AND THE ROLE OF CHANCE The final cohort of 246 670 women comprised 195 666 who kept a stable weight and 51 004 who lost weight. Pregnancy occurred in 22 756/246 670 (9.2%) women. On average, a 10–25% weight loss (median 14%) was associated with a 5.2% increase in the chance of pregnancy over the following 3 years (hazard ratio 1.05; 95% CI 1.02, 1.09; P = 0.003) compared with stable weight. Gestational diabetes was reported for 950/11 825 (8.0%) women, and weight loss reduced the risk of gestational diabetes by 42% (odds ratio [OR] 0.58; 95% CI 0.48, 0.70; P < 0.001). Emergency caesarean section was performed in 1453/11 558 (12.6%) pregnancies. This intervention was significantly reduced in the weight-loss cohort (OR 0.82; 95% CI 0.71, 0.95; P = 0.008). Pregnancy-induced hypertension was reported in a few women (244/11 740 [2.1%]) and one-tenth of women (791/7988 [9.9%]) gave birth to babies who were LGA. Weight loss prior to pregnancy resulted in non-significant reductions in pregnancy-induced hypertension (OR 0.77; 95% CI 0.55, 1.07; P = 0.121) and risk of babies being born LGA (OR 0.86; 95% CI 0.72, 1.04; P = 0.117). Rates of miscarriages, preterm births, live births, or babies born small for gestational age were not impacted by weight loss. LIMITATIONS, REASONS FOR CAUTION In our study, the intention of pregnancy was unknown. Women who intend to conceive are more likely to attempt weight loss. The inclusion of women who do not intend to conceive may therefore underestimate the true relationship between weight loss and chance of pregnancy. Also, we assessed women aged between 18 and 40 years, but due to the requirement of having two BMI record","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"27 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144565798","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":"Stakeholders' experiences and perspectives of reproductive genetic carrier screening in gamete donation: a scoping review.","authors":"Diya Porwal, Giselle Newton, Julia Mansour, Lisa Dive","doi":"10.1093/humrep/deaf128","DOIUrl":"https://doi.org/10.1093/humrep/deaf128","url":null,"abstract":"<p><strong>Study question: </strong>What is known about stakeholders' experiences and perspectives with reproductive genetic carrier screening (RGCS) in gamete donation?</p><p><strong>Summary answer: </strong>RGCS has impacted donors' autonomy, recipients' decision-making, healthcare professionals' confidence, and third-party service providers' management of the donor pool.</p><p><strong>What is known already: </strong>Growing acceptance of diverse family structures and advances in RGCS technology have driven demand for RGCS in gamete donation, yet its clinical, social, and ethical implications remain poorly understood.</p><p><strong>Study design, size, duration: </strong>A scoping review of four databases (Medline, Embase, CINAHL, and Scopus) with citation searching was conducted to identify original research, position statements, and conference abstracts published in English with an unrestricted date range.</p><p><strong>Participants/materials, setting, methods: </strong>Of the 470 studies identified, 427 were excluded during title and abstract screening and 14 during full-text review based on inclusion and exclusion criteria. For the 29 studies included, data were extracted in excel, and NVivo was used to code data and derive themes.</p><p><strong>Main results and the role of chance: </strong>Four themes regarding stakeholders' experiences and perspectives with RGCS in gamete donation were derived: (i) RGCS presented new challenges regarding donor autonomy, informed consent, and result disclosure; (ii) recipients valued RGCS but decision-making was also shaped by cost, time constraints, and genetic literacy; (iii) healthcare professionals supported donors and recipients with RGCS, yet felt unskilled and inexperienced; and (iv) third-party service providers managed donor availability challenges from increased carrier detection through RGCS.</p><p><strong>Limitations, reasons for caution: </strong>This review was restricted to articles published in English. A range of terms were used to describe RGCS; thus, it is possible that not all relevant articles were identified in the search. Most included studies were conducted in the USA within a private medical system that permits compensation for gamete donors, which may shape the results and relevance to other countries with differing healthcare systems.</p><p><strong>Wider implications of the findings: </strong>Our findings suggest that the growing demand for RGCS technology may impact donors' willingness to donate and the availability of donor gametes. Third-party service providers may refine their exclusion criteria to include donors with a positive carrier status in the donor pool or increase the involvement of recipients in donor selection. Healthcare professionals working in gamete donation require more guidance and training on RGCS. Further research is required to establish a more robust evidence base regarding how RGCS impacts stakeholders and to establish clearer guidelines regarding RGCS in","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560006","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 between markers of female adiposity and live birth among patients undergoing fertility treatment or attempting unassisted conception","authors":"Iris T Lee, Kurt T Barnhart, Wei-Ting Hwang, Stefanie N Hinkle, Erica Johnstone, James L Mills, Ellen C Caniglia, Enrique F Schisterman, Pauline Mendola, Ginny L Ryan, Jim Hotaling, C Matthew Peterson, Bradley J Van Voorhis, Sunni L Mumford","doi":"10.1093/humrep/deaf124","DOIUrl":"https://doi.org/10.1093/humrep/deaf124","url":null,"abstract":"STUDY QUESTION Beyond BMI, are there better predictors of the impact of high female adiposity on reproductive outcomes in patients undergoing fertility treatment or attempting unassisted conception? SUMMARY ANSWER Though BMI remains a predictor of fertility outcomes, alternative markers of adiposity, such as percent body fat, provide distinct information and may be more strongly associated with outcomes than BMI. WHAT IS KNOWN ALREADY Elevated BMI is associated with a lower probability of live birth, though randomized trials have not consistently demonstrated the efficacy of weight loss for increasing live birth among patients utilizing infertility treatment. STUDY DESIGN, SIZE, DURATION This was a secondary analysis of data gathered from 2013 to 2017 during the Folic Acid and Zinc Supplementation Trial (FAZST). Participants in FAZST included 2370 heterosexual couples seeking infertility care at four US fertility centers. Couples were followed for 9 months while undergoing fertility treatments or attempting unassisted conception, with up to 9 additional months of follow-up if pregnancy occurred. PARTICIPANTS/MATERIALS, SETTING, METHODS For inclusion in the present study, female participants must have had at least one marker of adiposity measured at their baseline visit for FAZST. The primary exposure was high adiposity (defined by commonly used cutoffs in the literature) by each of five markers: BMI, percent body fat measured by dual-energy X-ray absorptiometry (DXA), serum leptin, serum adiponectin/leptin ratio, and waist circumference. Of the participants in FAZST, BMI was available for 99.6%, percent body fat for 7.3% (DXA only offered to 218 participants at two study sites between 2016 and 2017), leptin for 89.7%, adiponectin/leptin ratio for 89.7%, and waist circumference for 90.9%. Generalized linear models including age, race, parity, education, physical activity, male partner BMI ≥30 kg/m2, and Healthy Eating Index were used to estimate the relative risk of live birth. MAIN RESULTS AND THE ROLE OF CHANCE High adiposity by BMI was associated with decreased probability of live birth (adjusted relative risk [aRR] 0.85, 95% CI 0.74–0.98). The other markers demonstrated similar associations, though a stronger effect size was seen with percent body fat (aRR 0.34, 95% CI 0.22–0.55). In an analysis by tertile, even moderately elevated percent body fat was associated with a decrease in live birth. When stratifying by infertility treatment status, associations were attenuated for most markers in the group utilizing infertility treatment, though percent body fat remained significantly associated with live birth. However, this marker was only available in a subset of participants. LIMITATIONS, REASONS FOR CAUTION Only a subset of participants underwent DXA scans and had data on percent body fat, limiting the generalizability of the finding that this marker was most strongly associated with live birth. There were few participants with low BMIs, limiti","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"7 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144547224","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}