Human reproduction最新文献

{"title":"Road to in vitro maturation (IVM), from basic science to an informed clinical practice.","authors":"Sofia Makieva, Juan J Fraire-Zamora, Omar Farhan Ammar, George Liperis, Flor Sanchez, Christian C Kramme, Lan N Vuong, Robert B Gilchrist, Pietro Bortoletto, Claudia Massarotti","doi":"10.1093/humrep/deae182","DOIUrl":"10.1093/humrep/deae182","url":null,"abstract":"","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141901577","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":"A multicentre, randomized, double-blind, placebo-controlled trial of topical oestradiol gel for endometrial regeneration after induced abortion.","authors":"C Y Li, L R Teng, X X Jiang, L Shan, L Q Wang, X J Dong, Q F Li, C C Ren, Y Lin, J Jiang, X Y Gu, W Huang, Q Li, P Peng, Y Che, X Y Liu","doi":"10.1093/humrep/deae227","DOIUrl":"10.1093/humrep/deae227","url":null,"abstract":"<p><strong>Study question: </strong>Is topical oestradiol gel effective in promoting endometrial regeneration after a surgical abortion?</p><p><strong>Summary answer: </strong>Topical oestradiol gel is effective in promoting endometrial regeneration after a surgical abortion with few side-effects.</p><p><strong>What is known already: </strong>Oestrogen is effective in promoting endometrial regeneration. Transdermal oestrogen has been widely used in clinical practice for endometrial regeneration after induced abortion, but high-level evidence is limited.</p><p><strong>Study design, size, duration: </strong>We conducted a multicentre, superiority, randomized, double-blind, placebo-controlled trial. Between 9 March 2022 and 21 February 2023, 200 women were assigned in a 1:1 ratio to receive either oestradiol gel (treatment) and or oestradiol gel simulant (control) for 28 days. The participants were scheduled to have their endometrial thickness (mm) measured by ultrasonographic scan at 21-23 days post-abortion. The trial was blinded for participants, investigators, medical staff, and statistical analysts until final unblinding.</p><p><strong>Participants/materials, setting, methods: </strong>Participants were women undergoing induced abortion within 10 weeks of gestation. A total of 200 participants were enrolled, with 100 in each group. Eighty-eight (88%) in the treatment group and 82 (82%) in the control group completed the study as per the protocol and were included in the per-protocol set (PPS). The intent-to-treat (ITT) analysis included all participants randomized to the study groups and used inverse probability weighting to account for loss to follow-up.</p><p><strong>Main results and the role of chance: </strong>The ITT analysis showed revealed significantly greater endometrial thickness in the treatment group (mean 8.1 ± 2.5 mm) compared to the control group (mean 6.9 ± 2.1 mm) 21-23 days postabortion (mean difference 1.2 mm, 95% CI 0.7 to 1.9; P < 0.001). The median time to menstrual return was shorter in the treatment group (34 days, inter-quartile range [IQR] 30-38) than in the control group (35 days, IQR 32-42), with a difference of -1 day (95% CI -2.3 to -0.9; P = 0.036). No differences were observed in the timing or volume of bleeding in the first post-abortion cycle. The PPS analysis mirrored the ITT findings. Adverse events were minimal (6% versus 8%), and the blood profile, liver, kidney and coagulation test results were comparable between groups (all P > 0.05).</p><p><strong>Limitations, reasons for caution: </strong>Loss to follow-up was 11% in the treatment group and 15% of controls, with no significant difference (P > 0.05). Inconsistencies in the timing of the ultrasonographic scans may have affected the accuracy of endometrial thickness measurements.</p><p><strong>Wider implications of the findings: </strong>Our findings suggest that topical oestrogen supplementation immediately after abortion within the first 10 weeks of gest","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142345717","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":"CDC42 deficiency leads to endometrial stromal cell senescence in recurrent implantation failure.","authors":"Xinyi Tang, Yingchun Zhu, Zhiwen Cao, Xiaoying Wang, Xinyu Cai, Yurun Tang, Jidong Zhou, Min Wu, Xin Zhen, Lijun Ding, Guijun Yan, Haibin Wang, Haixiang Sun, Ruiwei Jiang","doi":"10.1093/humrep/deae246","DOIUrl":"https://doi.org/10.1093/humrep/deae246","url":null,"abstract":"<p><strong>Study question: </strong>Does the downregulation of cell division cycle 42 (CDC42) protein in endometrial stroma lead to endometrial senescence in patients with recurrent implantation failure (RIF), and what is the potential mechanism?</p><p><strong>Summary answer: </strong>CDC42 deficiency causes endometrial stromal senescence and decidualization defects, impairing uterine receptivity of RIF patients, via activation of Wnt signaling pathway.</p><p><strong>What is known already: </strong>Uterine aging is unique due to the cyclic remodeling and decidualization of endometrial tissue. Several transcriptomic studies have reported increased senescence in the endometrium in young patients with RIF. Our previous transcriptomic sequencing study discovered that endometrium from women with RIF showed downregulation of CDC42, which is an essential molecule affected by various senescence-related diseases.</p><p><strong>Study design, size, duration: </strong>The endometrial samples of a total of 71 fertile control patients and 37 RIF patients were collected to verify the association between CDC42 expression and endometrial senescence of RIF patients. Primary endometrial stromal cells (EnSCs) were isolated from endometrial biopsies taken from patients without any endometrial complications and planning to undergo IVF, then subjected to adenovirus-mediated CDC42 knockdown and decidualization induction to explore the detailed mechanism by which CDC42 governs stromal senescence and decidualization. Wnt inhibitor XAV-939 was used to correct the endometrial senescence and decidualization defect.</p><p><strong>Participants/materials, setting, methods: </strong>Senescence was determined by cell cycle arrest markers (e.g. P16, P21, and P53), SASP molecules (e.g. IL6 and CXCL8), and SA-β-gal staining. Masson's staining and Sirius Red staining were used to detect the endometrial fibrosis. Decidualization was evaluated by the mRNA expression and protein secretion of PRL and IGFBP1, F-actin immunostaining, and the BeWo spheroids 'in vitro implantation' model. Methods used to assess cell function included adenovirus transduction, RNA-sequencing, bioinformatic analysis, western blotting, RT-qPCR, ELISA, and immunofluorescence.</p><p><strong>Main results and the role of chance: </strong>Here, we observed remarkably increased levels of stromal senescence and fibrosis, along with stromal CDC42 deficiency, in the endometrium of patients with RIF (P < 0.001). Knockdown of CDC42 effectively induced premature senescence in EnSCs, leading to aberrant accumulation of senescent EnSCs and collagen deposition during decidualization. CDC42 deficiency in EnSCs restrained the decidualization differentiation and receptivity to trophoblast cells. Transcriptomic analysis revealed Wnt signaling activation as a critical downstream alteration in CDC42-deficient EnSCs. Mechanistically, CDC42 interacted with AKT competitively to impede the binding of GSK3β to AKT. Knockdown of CDC42 inc","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564371","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":"Do we need placebo-controlled studies to validate new medical treatments of severe pain associated with endometriosis?","authors":"Michel Canis","doi":"10.1093/humrep/deae222","DOIUrl":"10.1093/humrep/deae222","url":null,"abstract":"","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142345718","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":"Do sperm factors influence embryonic aneuploidy? Long live the oocyte.","authors":"Yuval Fouks, Denis Vaughan, Veda Sripada, Alan S Penzias, Pietro Bortoletto, Denny Sakkas","doi":"10.1093/humrep/deae224","DOIUrl":"10.1093/humrep/deae224","url":null,"abstract":"<p><strong>Study question: </strong>What is the impact of male age- and sperm-related factors on embryonic aneuploidy?</p><p><strong>Summary answer: </strong>Using a 3-fold analysis framework encompassing patient-level, embryo-level, and matching analysis, we found no clinically significant interactions between male age and sperm quality with embryo ploidy.</p><p><strong>What is known already: </strong>While the effect of maternal age on embryo chromosomal aneuploidy is well-established, the impact of male age and sperm quality on ploidy is less well-defined.</p><p><strong>Study design, size, duration: </strong>This retrospective cohort study analyzed autologous preimplantation genetic testing for aneuploidy (PGT-A) and frozen embryo transfer cycles from December 2014 to June 2021. The study involved 11 087 cycles from 8484 patients, with a total of 35 797 embryos.</p><p><strong>Participants/materials, setting, methods: </strong>The aneuploidy rate, calculated as the ratio of aneuploid blastocysts to the total number of blastocysts biopsied in a single treatment cycle, was evaluated. In the embryo-level analysis, the main outcome measure was the ploidy state of the embryos. The study employed a multifaceted analytical approach that included a patient-level analysis using generalized linear mixed models, an embryo-level analysis focusing on chromosomal ploidy, and a propensity score matching analysis contrasting groups with distinct ploidy rates (0% and 100%). There were no interventions as this was an observational study of PGT-A cycles.</p><p><strong>Main results and the role of chance: </strong>No clinically relevant factors influencing ploidy rate related to male and sperm quality were revealed. In contrast, female age (coefficient = -0.053), BMI (coefficient = 0.003), prior ART cycle (coefficient = -0.066), and number of oocytes retrieved (coefficient = -0.018) were identified at the patient level. Embryo analysis identified age (coefficient = -0.1244) and ICSI usage (coefficient = -0.0129) as significant factors. Despite these, no significant interactions between male and female assessed factors on the ploidy rate emerged. Propensity score matching between maximal (100% vs 0%) euploid rates did not reveal significant differences of influence by male age and sperm quality.</p><p><strong>Limitations, reasons for caution: </strong>The focus on patients having blastocyst biopsy for PGT-A may not reflect the broader IVF population. Other semen quality parameters like DNA fragmentation were not included. Exclusion of embryo mosaicism from the analysis could affect aneuploidy rate interpretations. There may also be unmeasured influences like lifestyle or environmental factors.</p><p><strong>Wider implications of the findings: </strong>Male age and sperm quality parameters were consistent across both maximal and minimal ploidy rate comparisons. No significant clinical characteristics related to the factors assessed for the male-influenced blastocyst","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365082","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":"Prenatal phthalate exposure and pubertal development in 16-year-old daughters: reproductive hormones and number of ovarian follicles.","authors":"Maria Assens, Hanne Frederiksen, Anette Tønnes Pedersen, Jørgen Holm Petersen, Anna-Maria Andersson, Karin Sundberg, Lisa Neerup Jensen, Paul Curtin, Niels E Skakkebæk, Shanna H Swan, Katharina M Main","doi":"10.1093/humrep/deae229","DOIUrl":"10.1093/humrep/deae229","url":null,"abstract":"<p><strong>Study question: </strong>Is there a possible association between prenatal phthalate exposure and late effects in teenage daughters with respect to reproductive hormone levels, uterine volume, and number of ovarian follicles?</p><p><strong>Summary answer: </strong>Our study showed subtle associations between phthalate metabolite concentrations in maternal serum from pregnancy or cord blood and LH and insulin-like growth factor 1 (IGF-1) levels as well as uterine volume in their daughters 16 years later.</p><p><strong>What is known already: </strong>Endocrine-disrupting environmental chemicals may adversely affect human reproductive health, and many societies have experienced a trend toward earlier puberty and an increasing prevalence of infertility in young couples. The scientific evidence of adverse effects of foetal exposure to a large range of chemicals, including phthalates, on male reproductive health is growing, but very few studies have explored effects on female reproduction.</p><p><strong>Study design, size, duration: </strong>This follow-up study included 317 teenage daughters who were part of the Copenhagen Mother-Child Cohort, a population-based longitudinal birth cohort of 1210 females born between 1997 and 2002.</p><p><strong>Participants/materials, setting, methods: </strong>A total of 317 female participants (median age 16 years) were examined for weight, height, and menstrual pattern. A serum sample was analysed for concentrations of reproductive hormones, and trans-abdominal 3D ultrasonography was performed to obtain the number of ovarian follicles, ovarian and uterine size. Prenatal maternal serum samples were available for 115 females, and cord blood samples were available for 118 females. These were analysed for concentrations of 32 phthalate metabolites. Weighted quantile sum regression was used for modelling associations of combined prenatal phthalate exposure with the reproductive outcomes in post-menarcheal females.</p><p><strong>Main results and the role of chance: </strong>In bivariate correlation analyses, negative significant associations were found between several prenatal phthalate metabolite concentrations and serum hormone concentrations (testosterone, 17-OH-progesterone, and IGF-1) as well as number of ovarian follicles in puberty. Positive significant correlations were found between prenatal phthalate exposure and FSH and sex hormone-binding globulin concentrations. Combined analyses of phthalate exposure (weighted quantile sums) showed significant negative associations with IGF-1 concentration and uterine volume as well as a significant positive association with LH concentration.</p><p><strong>Limitations, reasons for caution: </strong>Phthalate metabolites were measured in serum from single prenatal maternal blood samples and cord blood samples. Potential concomitant exposure to other endocrine-disrupting environmental chemicals before or after birth was not controlled for. The study population size ","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390141","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":"Psychological characteristics and structural brain changes in women with endometriosis and endometriosis-independent chronic pelvic pain.","authors":"L Maulitz, S Nehls, E Stickeler, A Ignatov, T Kupec, A T Henn, N Chechko, S N Tchaikovski","doi":"10.1093/humrep/deae207","DOIUrl":"10.1093/humrep/deae207","url":null,"abstract":"<p><strong>Study question: </strong>Are there neurobiological changes induced by endometriosis?</p><p><strong>Summary answer: </strong>Women with endometriosis demonstrate specific neurobiological changes distinct from those in patients with chronic pelvic pain (CPP) in the absence of endometriosis.</p><p><strong>What is known already: </strong>Endometriosis is a chronic disease affecting women of reproductive age that presents with pain and infertility often accompanied by comorbid mental disorders. Only one study with a number of limitations has investigated changes in gray matter volumes and functional connectivity in a small group of patients with endometriosis.</p><p><strong>Study design, size, duration: </strong>This prospective study recruited 53 women undergoing a laparoscopy due to suspicion of symptomatic endometriosis and 25 healthy, pain-free women. Clinical and psychological characteristics, thermal pain perception, and voxel- and surface-based morphology were assessed in all study participants. Thereafter, the patients underwent a laparoscopy, where endometriosis was either histologically confirmed and removed, or ruled out. Correspondingly, patients were assigned into the group with endometriosis (n = 27) or with endometriosis-independent CPP (n = 26) and compared to the pain-free controls.</p><p><strong>Participants/materials, setting, methods: </strong>The study groups were generally representative for the population of women with endometriosis. Sociodemographic, medical, clinical, and psychological characteristics were collected using various questionnaires and a structured clinical interview. Thermal pain perception and voxel- and surface-based morphometry were assessed using thermode and MRI, respectively.</p><p><strong>Main results and the role of chance: </strong>Despite comparable pain intensity and burden of mental disorders, both patient groups demonstrated distinct neurobiological patterns. Women with endometriosis exhibited increased gray matter volume (GMV) in the left cerebellum, lingual gyrus and calcarine gyrus, compared to those with endometriosis-independent CPP. Patients with CPP had decreased GMV in the right cerebellum as compared to controls. Dysmenorrhoea severity correlated positively with GMV in the left inferior parietal lobule, whereas depressive symptoms were associated with decreased GMV in the right superior medial gyrus across patient groups. Dyspareunia correlated negatively with cortical thickness in the left inferior temporal gyrus and left middle temporal gyrus.</p><p><strong>Limitations, reasons for caution: </strong>The study groups differed in a few baseline-characteristics, including educational levels, smoking and BMI. While measuring pain perception thresholds, we did not attempt to mimic CPP by placement of the thermode on the abdominal wall.</p><p><strong>Wider implications of the findings: </strong>Changes in gray matter volume associated with endometriosis differ from those observed in w","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145580","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 uric acid and fructose levels in polycystic ovary syndrome.","authors":"Di Feng, Xiao Wang, Jiahui Song, Hongyue Yang, Yuanyuan Peng, Xinmei Wang, Wanting Chen, Peiyu Li, Yuanyuan Fang, Bei Shi, Da Li","doi":"10.1093/humrep/deae219","DOIUrl":"10.1093/humrep/deae219","url":null,"abstract":"<p><strong>Study question: </strong>Is there a relationship between serum uric acid and fructose levels in polycystic ovary syndrome (PCOS)?</p><p><strong>Summary answer: </strong>Elevated serum uric acid levels in women with PCOS positively correlate with serum fructose levels, and elevated serum fructose levels are an independent risk factor for hyperuricemia in women with PCOS.</p><p><strong>What is known already: </strong>Our previous study suggested a link between elevated serum fructose levels and PCOS. Fructose is unique as it generates uric acid during metabolism, and high uric acid levels are associated with metabolic disorders and an increased risk of anovulation. However, the relationship between serum uric acid and fructose levels in women with PCOS remains unclear.</p><p><strong>Study design, size, duration: </strong>In a case-control study of 774 women (482 controls and 292 patients with PCOS) between May and October 2020 at the Shengjing Hospital of China Medical University, the relationship between uric acid and fructose levels in women with PCOS was examined. Participants were divided into subgroups based on various factors, including BMI, insulin resistance, dyslipidemia, metabolic syndrome, and hyperuricemia.</p><p><strong>Participants/materials, setting, methods: </strong>Serum uric acid concentrations were measured using enzymatic assays, and serum fructose levels were determined using a fluorescent enzyme immunoassay. Dietary fructose data were collected through a validated food-frequency questionnaire of 81 food items. We applied restricted cubic splines to a flexibly model and visualized the linear/nonlinear relationships between serum uric acid and fructose levels in PCOS. Multivariate logistic analysis was executed to assess the association between serum fructose levels and hyperuricemia in PCOS. Human granulosa cell and oocyte mRNA profile sequencing data were downloaded for mapping uric acid and fructose metabolism genes in PCOS. Further downstream analyses, including Gene Ontology, Kyoto Encyclopedia of Genes and Genomes analysis, and protein-protein interactions were then carried out on the differentially expressed genes (DEGs). The correlation between uric acid and fructose metabolism genes was calculated using the Pearson correlation coefficient. The GeneCards database was used to identify DEGs related to uric acid and fructose metabolism in PCOS, and then several DEGs were confirmed by quantitative real-time PCR.</p><p><strong>Main results and the role of chance: </strong>Both serum fructose and uric acid levels were significantly increased in women with PCOS compared with the control women (P  <  0.001), and there was no statistically significant difference in dietary fructose intake between PCOS and controls, regardless of metabolic status. There was a positive linear correlation between serum uric acid and fructose levels in women with PCOS (Poverall < 0.001, Pnon-linear = 0.30). In contrast, no correlation was","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390140","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":"Livebirth rates are influenced by an interaction between male and female partners' age: analysis of 59 951 fresh IVF/ICSI cycles with and without male infertility.","authors":"A K Datta, S Campbell, R Diaz-Fernandez, G Nargund","doi":"10.1093/humrep/deae198","DOIUrl":"10.1093/humrep/deae198","url":null,"abstract":"<p><strong>Study question: </strong>Does advanced male partner's age impact live birth rates (LBRs) in IVF treatment when female partner's age is factored in?</p><p><strong>Summary answer: </strong>In fresh IVF cycles LBRs decline with male partner's age ≥40 years when the female partner is aged 35-39 years, irrespective of the presence or absence of male factor; but not when the female partner is <35 years or ≥40 years of age; this decline is not observed in ICSI cycles.</p><p><strong>What is known already: </strong>Advanced paternal age is associated with declining sperm parameters, impaired embryo development, compromised pregnancy outcomes, and abnormalities in the offspring in IVF/ICSI cycles. However, data on the interaction between maternal and paternal age on IVF outcomes are very limited and inconsistent. No significant effect of male partner's age on pregnancy outcomes has been noted in donor oocyte cycles.</p><p><strong>Study design, size, duration: </strong>Retrospective analysis of all eligible autologous IVF/ICSI cycles with oocyte retrieval and intended fresh embryo transfer (ET) from the UK's national anonymized registry, published online by the Human Fertilisation and Embryology Authority (HFEA). There were 59 951 cycles that qualified the inclusion criteria in the study period: 1 January 2017 to 31 December 2018.</p><p><strong>Participants/materials, setting, methods: </strong>Couples underwent IVF (n = 27 226) or ICSI (n = 32 725) treatment with partner's sperm followed by fresh ET due to unexplained (n = 31 846), tubal (n = 6605), or male infertility (n = 22 905). Treatment cycles with endometriosis (n = 5563), ovulatory disorders (n = 9970), female partner aged >44 years (n = 636), and PGT (n = 280) were excluded. Women were stratified by age in the following groups: <35, 35-39, 40-42, and 43-44 years; male partner's age as <35 (reference group), 35-37, 38-39, 40-42, 43-44, 45-50, 51-55, 55-60, and >55 years as presented by the HFEA. Some age-groups were merged in the analysis to increase the population size. Chi-square test was used to compare binominal data; and multiple logistic regression to find any association between male and female age-groups on live birth adjusting for other confounders that had a significant effect on this outcome.</p><p><strong>Main results and the role of chance: </strong>LBRs per oocyte retrieval as well as per ET were no different across the male partners' age-groups when the female partners were aged <35 years or in 40- to 44-year age-group, whether male-factor infertility was included or excluded and whether it was IVF or ICSI cycle. However, when IVF was the method of insemination in the female partner's age-group of 35-39 years, LBRs per oocyte retrieval dropped significantly from 27.0% in the male age-group of <35 years (reference group) to 22.9% (P = 0.002), 22.0% (P = 0.006), and 18.8% (P = 0.004) in 40-44, 45-50, and >50 years age-group, respectively in population that included male-fact","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11532605/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142143052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CALR3 defects disrupt sperm-zona pellucida binding in humans: new insights into male factor fertilization failure and relevant clinical therapeutic approaches.","authors":"Yang Gao, Rufeng Xue, Rui Guo, Fan Yang, Xuan Sha, Yuqian Li, Rong Hua, Guotong Li, Qunshan Shen, Kuokuo Li, Wenwen Liu, Yuping Xu, Ping Zhou, Zhaolian Wei, Zhiguo Zhang, Yunxia Cao, Xiaojin He, Huan Wu","doi":"10.1093/humrep/deae205","DOIUrl":"10.1093/humrep/deae205","url":null,"abstract":"<p><strong>Study question: </strong>Do biallelic deleterious variants of Calreticulin 3 (CALR3) cause fertilization failure (FF), resulting in male infertility in humans?</p><p><strong>Summary answer: </strong>Biallelic mutations in CALR3 were identified in two infertile men from unrelated families and were shown to cause FF associated with failed sperm-zona pellucida (ZP) binding.</p><p><strong>What is known already: </strong>In male mice, the Calr3-knockout has been reported to cause male infertility and FF. However, the mechanism behind this remains unclear in humans.</p><p><strong>Study design, size, duration: </strong>Sequencing studies were conducted in a research hospital on samples from Han Chinese families with primary infertility and sperm head deformations to identify the underlying genetic causes.</p><p><strong>Participants/materials, setting, methods: </strong>Data from two infertile probands characterized by sperm head deformation were collected through in silico analysis. Sperm cells from the probands were characterized using light and electron microscopy and used to verify the pathogenicity of genetic factors through functional assays. Subzonal insemination (SUZI) and IVF assays were performed to determine the exact pathogenesis of FF. ICSI were administered to overcome CALR3-affected male infertility.</p><p><strong>Main results and the role of chance: </strong>Novel biallelic deleterious mutations in CALR3 were identified in two infertile men from unrelated families. We found one homozygous frameshift CALR3 mutation (M1: c.17_27del, p.V6Gfs*34) and one compound heterozygous CALR3 mutation (M2: c.943A>G, p.N315D; M3: c.544T>C, p.Y182H). These mutations are rare in the general population and cause acrosomal ultrastructural defects in affected sperm. Furthermore, spermatozoa from patients harbouring the CALR3 mutations were unable to bind to the sperm-ZP or they disrupted gamete fusion or prevented oocyte activation. Molecular assays have revealed that CALR3 is crucial for the maturation of the ZP binding protein in humans. Notably, the successful fertilization via SUZI and ICSI attempts for two patients, as well as the normal expression of PLCζ in the mutant sperm, suggests that ICSI is an optimal treatment for CALR3-deficient FF.</p><p><strong>Limitations, reasons for caution: </strong>The results are based on sperm-related findings from two patients. Further studies are required to gain insight into the developmental stage and function of CALR3 in human testis.</p><p><strong>Wider implications of the findings: </strong>Our findings highlight the underlying risk of FF associated with sperm defects and provide a valuable reference for personalized genetic counselling and clinical treatment of these patients.</p><p><strong>Study funding/competing interest(s): </strong>This study was supported by the National Key R&D Program of China (2021YFC2700901), Hefei Comprehensive National Science Center Medical-Industrial Integration Medical ","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":null,"pages":null},"PeriodicalIF":6.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139889","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}