Human reproduction最新文献

{"title":"Early menstrual cycle impacts of oestrogen and progesterone on the timing of the fertile window.","authors":"René Ecochard, Thomas Bouchard, Rene Leiva, Saman H Abdullah, Hans Boehringer","doi":"10.1093/humrep/deae236","DOIUrl":"10.1093/humrep/deae236","url":null,"abstract":"<p><strong>Study question: </strong>What is the effect of oestrogen and progesterone at the beginning of the menstrual cycle in delaying entry into the fertile window?</p><p><strong>Summary answer: </strong>Both oestrogen and progesterone contribute to a delay in the onset of the fertile window.</p><p><strong>What is known already: </strong>Oestrogen enhances cervical mucus secretion while progesterone inhibits it.</p><p><strong>Study design, size, duration: </strong>Observational study. Daily observation of 220 menstrual cycles contributed by 88 women with no known menstrual cycle disorder.</p><p><strong>Participants/materials, setting, methods: </strong>Women recorded cervical mucus daily and collected first-morning urine samples for analysis of oestrone-3-glucuronide, pregnanediol-3-alpha-glucuronide (PDG), FHS, and LH. They underwent serial ovarian ultrasound examinations. The main outcome measure was the timing within the cycle of the onset of the fertile window, as identified by the appearance of mucus felt or seen at the vulva.</p><p><strong>Main results and the role of chance: </strong>Low oestrogen secretion and persistent progesterone secretion during the first week of the menstrual cycle both negatively affect mucus secretion. Doubling oestrogen approximately doubled the odds of entering the fertile window (OR: 1.82 95% CI=1.23; 2.69). Increasing PDG from below 1.5 to 4 µg/mg creatinine was associated with a 2-fold decrease in the odds of entering the fertile window (OR: 0.51 95% CI=0.31; 0.82). Prolonged progesterone secretion during the first week of the menstrual cycle was also statistically significantly associated with higher LH secretion. Finally, the later onset of the fertile window was associated with statistically significant persistently elevated LH secretion during the luteal phase of the previous menstrual cycle.</p><p><strong>Limitations, reasons for caution: </strong>This post hoc study was conducted to assess the potential impact of residual progesterone secretion at the beginning of the menstrual cycle. It was conducted on an existing data set because of the scarcity of data available to answer the question. Analysis with other datasets with similar hormone results would be useful to confirm these findings.</p><p><strong>Wider implications of the findings: </strong>This study provides evidence for residual progesterone secretion in the early latency phase of some menstrual cycles, which may delay the onset of the fertile window. This progesterone secretion may be supported by subtly increased LH secretion during the few days before and after the onset of menses, which may relate to follicular waves in the luteal phase. Persistent progesterone secretion should be considered in predicting the onset of the fertile window and in assessing ovulatory dysfunction.</p><p><strong>Study funding/competing interest(s): </strong>The authors declare no conflicts of interest. No funding was provided for this secondary data analysis.<","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"2798-2805"},"PeriodicalIF":6.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375325","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":"In vitro growth of secondary follicles from cryopreserved-thawed ovarian cortex.","authors":"Hui Cheng, Fu Wei, Julieta S Del Valle, Tessa H R Stolk, Judith A Huirne, Joyce D Asseler, Gonneke S K Pilgram, Lucette A J Van Der Westerlaken, Norah M Van Mello, Susana M Chuva De Sousa Lopes","doi":"10.1093/humrep/deae240","DOIUrl":"10.1093/humrep/deae240","url":null,"abstract":"<p><strong>Study question: </strong>Can secondary follicles be obtained from cultured cryopreserved-thawed human ovarian cortical tissue?</p><p><strong>Summary answer: </strong>We obtained high-quality secondary follicles from cultured cryopreserved-thawed human ovarian cortical tissue from cis female donors (cOVA), but not from trans masculine donors (tOVA) in the same culture conditions.</p><p><strong>What is known already: </strong>The in vitro growth of oocytes present in unilaminar follicles into metaphase II stage (MII) oocytes has been previously achieved starting from freshly obtained ovarian cortical tissue from adult cis female donors. This involved a multi-step culture protocol and the first step included the transition from unilaminar follicles to multilayered secondary follicles. Given that the ovarian cortex (from both cis female and trans masculine donors) used for fertility preservation is cryopreserved, it is crucial to investigate the potential of unilaminar follicles from cryopreserved-thawed ovarian cortex to grow in culture.</p><p><strong>Study design, size, duration: </strong>Cryopreserved-thawed ovarian cortical tissue from adult trans masculine donors (n = 3) and adult cis female donors (n = 3) was used for in vitro culture following the first culture step described in two published culture protocols (7-8 days and 21 days) and compared to freshly isolated ovarian cortex from trans masculine donors (n = 3) and to ovarian cortex prior to culture.</p><p><strong>Participants/materials, setting, methods: </strong>Ovarian cortical tissue was obtained from adult trans masculine donors undergoing gender-affirming surgery while using testosterone, and from adult cis female donors undergoing oophorectomy for fertility preservation purposes before chemotherapy. The ovarian cortex was fixed either prior (day 0) or after the culture period. Follicular survival, growth, and morphology were assessed through histology and immunofluorescence.</p><p><strong>Main results and the role of chance: </strong>We quantified the different stages of follicular development (primordial, primary, secondary, and atretic) after culture and observed an increase in the percentage of secondary follicles as well as an increase in COLIV deposition in the stromal compartment regardless of the culture media used. The quality of the secondary follicles obtained from cOVA was comparable to those prior to culture. However, in the same culture conditions, the secondary follicles from tOVA (fresh and cryo) showed low-quality secondary follicles, containing oocytes with small diameter, granulosa cells that expressed abnormal levels of KRT19 and steroidogenic-marker STAR and lacked ACTA2+ theca cells, when compared to tOVA secondary follicles prior to culture.</p><p><strong>Limitations, reasons for caution: </strong>The number of different donors used was limited.</p><p><strong>Wider implications of the findings: </strong>Our study revealed that cryopreserved-thawed cO","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"2743-2753"},"PeriodicalIF":6.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11630006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142464096","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":"Measuring non-events: infertility estimation using cross-sectional, population-based data from four countries in sub-Saharan Africa.","authors":"Suzanne O Bell, Caroline Moreau, Dana Sarnak, Simon P S Kibira, Philip Anglewicz, Peter Gichangi, Alexander C McLain, Marie Thoma","doi":"10.1093/humrep/deae218","DOIUrl":"10.1093/humrep/deae218","url":null,"abstract":"<p><strong>Study question: </strong>Does the prevalence of 12-month infertility in Burkina Faso, Côte d'Ivoire, Kenya, and Uganda differ between women trying to conceive and the broader population of women exposed to unprotected sex, and how are prevalence estimates affected by model assumptions and adjustments?</p><p><strong>Summary answer: </strong>Estimates of 12-month infertility among tryers ranged from 8% in Burkina Faso to 30% in Côte d'Ivoire, increasing substantially among a larger population of women exposed to unprotected intercourse.</p><p><strong>What is known already: </strong>While having a child is a fundamental human experience, the extent to which women and couples experience infertility is a neglected area of research, particularly in sub-Saharan Africa. Existing estimates of infertility in this region vary widely from 2% to 32%, however, potential impacts of variability in study populations and model assumptions have not been well-examined.</p><p><strong>Study design, size, duration: </strong>We used cross-sectional nationally representative survey data from Burkina Faso, Côte d'Ivoire, Kenya, and Uganda. We employed a multi-stage cluster random sampling design with probability proportional to the size selection of clusters within each country to produce representative samples of women aged 15-49. Samples ranged from 3864 in Côte d'Ivoire to 9489 in Kenya.</p><p><strong>Participants/materials, setting, methods: </strong>We created two analytic samples in each country-tryers and a broader sample of women exposed to unprotected sex-exploring differences in population characteristics and estimating the period prevalence of 12-month infertility using the current duration (CD) approach. We also examined the impact of several model assumptions within each of the two analytic samples, including adjustments for recent injectable contraceptive use, unrecognized pregnancy, infertility treatment, underreported contraceptive use, and sexual activity.</p><p><strong>Main results and the role of chance: </strong>Employing the CD approach among tryers produced an overall 12-month infertility prevalence of 7.9% (95% CI 6.6-12.7) in Burkina Faso, 29.6% (95% CI 15.3-100.0) in Côte d'Ivoire, 24.5% (95% CI 16.5-34.6) in Kenya, and 14.7% (95% CI 8.1-22.4) in Uganda. Results among women exposed to unprotected intercourse indicated much higher levels of infertility, ranging from 22.4% (95% CI 18.6-30.8) in Uganda to 63.7% (95% CI 48.8-87.9) in Côte d'Ivoire. Sensitivity analyses suggest infertility estimates are particularly sensitive to adjustments around pregnancy recognition timing and sexual activity, with little impact of adjustments for recent injectable contraceptive use, infertility treatment, and underreporting of traditional and coital dependent contraceptive use.</p><p><strong>Limitations, reasons for caution: </strong>There was substantial digit preference in responses at 12 months, particularly among the tryers, which could introduce bia","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"2848-2860"},"PeriodicalIF":6.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11629970/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142345720","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":"Time will tell: time-lapse technology and artificial intelligence to set time cut-offs indicating embryo incompetence.","authors":"Giovanni Coticchio, Alessandro Bartolacci, Valentino Cimadomo, Samuele Trio, Federica Innocenti, Andrea Borini, Alberto Vaiarelli, Laura Rienzi, Aisling Ahlström, Danilo Cimadomo","doi":"10.1093/humrep/deae239","DOIUrl":"10.1093/humrep/deae239","url":null,"abstract":"<p><strong>Study question: </strong>Can more reliable time cut-offs of embryo developmental incompetence be generated by combining time-lapse technology (TLT), artificial intelligence, and preimplantation genetics screening for aneuploidy (PGT-A)?</p><p><strong>Summary answer: </strong>Embryo developmental incompetence can be better predicted by time cut-offs at multiple developmental stages and for different ranges of maternal age.</p><p><strong>What is known already: </strong>TLT is instrumental for the continual and undisturbed observation of embryo development. It has produced morphokinetic algorithms aimed at selecting embryos able to generate a viable pregnancy, however, such efforts have had limited success. Regardless, the potential of this technology for improving multiple aspects of the IVF process remains considerable. Specifically, TLT could be harnessed to discriminate developmentally incompetent embryos: i.e. those unable to develop to the blastocyst stage or affected by full-chromosome meiotic aneuploidies. If proven valuable, this application would prevent the non-productive use of such embryos, thereby improving laboratory and clinical efficiency and reducing patient stress and costs due to unnecessary embryo transfer and cryopreservation.</p><p><strong>Study design, size, duration: </strong>The training dataset involved embryos of PGT-A cycles cultured in Embryoscope with a single media (836 euploid and 1179 aneuploid blastocysts and 1874 arrested embryos; 2013-2020). Selection criteria were ejaculated sperm, own (not donated) fresh oocytes, trophectoderm biopsy and comprehensive-chromosome-testing to diagnose uniform aneuploidies. Out-of-sample (30% of training), internal (299 euploid and 490 aneuploid blastocysts and 680 arrested embryos; 2021-2022) and external (97 euploid, 110 aneuploid and 603 untested blastocysts and 514 arrested embryos, 2018 to early 2022) validations were conducted.</p><p><strong>Participants/materials, setting, methods: </strong>A training dataset (70%) was used to define thresholds. Several models were generated by fitting outcomes to each timing (tPNa-t8) and maternal age. ROC curves pinpointed in-sample classification values associated with 95%, 99% and 99.99% true-positive rate for predicting incompetence. These values were integrated with upper limits of maternal age ranges (<35, 35-37, 38-40, 41-42, and >42 years) in logit functions to identify time cut-offs, whose accuracy was tested on the validation datasets through confusion matrices.</p><p><strong>Main results and the role of chance: </strong>For developmental (in)competence, the best performing (i) tPNa cut-offs were 27.8 hpi (error-rate: 0/743), 32.6 hpi (error rate: 0/934), 26.8 hpi (error rate: 0/1178), 22.9 hpi (error-rate: 1/654, 0.1%) and 17.2 hpi (error rate: 4/423, 0.9%) in the <35, 35-37, 38-40, 41-42, and >42 years groups, respectively; (ii) tPNf cut-offs were 36.7 hpi (error rate: 0/738), 47.9 hpi (error rate: 0/921), 45.6 hpi (e","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"2663-2673"},"PeriodicalIF":6.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499366","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":"Role, benefits, and risks of AMH testing for non-ART related indications.","authors":"Zoya Enakshi Ali, Claudia Massarotti, George Liperis, Mina Mincheva, Omar F Ammar, Julia Uraji, Antonio La Marca, Raj Mathur, Helen C O'Neill, Mariana Moura-Ramos, Juan J Fraire-Zamora","doi":"10.1093/humrep/deae234","DOIUrl":"10.1093/humrep/deae234","url":null,"abstract":"","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"2873-2877"},"PeriodicalIF":6.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371736","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 composition of commercially available human embryo culture media","authors":"M S Zagers, M Laverde, M Goddijn, J J de Groot, F A P Schrauwen, F M Vaz, S Mastenbroek","doi":"10.1093/humrep/deae248","DOIUrl":"https://doi.org/10.1093/humrep/deae248","url":null,"abstract":"STUDY QUESTION What is the composition of currently available commercial human embryo culture media provided by seven suppliers, for each stage of human preimplantation embryo development? SUMMARY ANSWER While common trends existed across brands, distinct differences in composition underlined the absence of a clear standard for human embryo culture medium formulation. WHAT IS KNOWN ALREADY The reluctance of manufacturers to fully disclose the composition of their human embryo culture media generates uncertainty regarding the culture conditions that are used for human preimplantation embryo culture. The critical role of the embryo culture environment is well-recognized, with proven effects on IVF success rates and child outcomes, such as birth weight. The lack of comprehensive composition details restricts research efforts crucial for enhancing our understanding of its impacts on these outcomes. The ongoing demand for greater transparency remains unmet, highlighting a significant barrier in embryo culture medium optimization. STUDY DESIGN, SIZE, DURATION For this study, 47 different human embryo culture media and protein supplements were purchased between December 2019 and June 2020; they comprise complete media (n = 23), unsupplemented media (n = 14), and supplements (n = 10). Unsupplemented media were supplemented with each available supplement from the same brand (n = 33 combinations). All samples were directly frozen in liquid nitrogen and stored at −80°C until composition analysis. PARTICIPANTS/MATERIALS, SETTING, METHODS We determined the concentrations of 40 components in all samples collected (n = 80). Seven electrolytes (calcium, chloride, iron, magnesium, phosphate, potassium, sodium), glucose, immunoglobulins A, G, and M (IgA, IgG, IgM), uric acid, alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT), and albumin, as well as the total protein concentration, were determined in each sample using a Cobas 8000 Analyser (Roche Diagnostics). Analysis of pyruvate, lactate, carnitine, and 21 amino acids was achieved with Ultra-High Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS/MS). MAIN RESULTS AND THE ROLE OF CHANCE Our analysis showed that generally, the concentrations of components of ready-to-use human embryo culture media align with established assumptions about the changing needs of an embryo during early development. For instance, glucose concentrations displayed a high-low-high pattern in sequential media systems from all brands: 2.5–3 mM in most fertilization media, 0.5 mM or below in all cleavage stage media, and 2.5–3.3 mM in most blastocyst stage media. Continuous media generally resembled glucose concentrations of cleavage stage media. However, for other components, such as lactate, glycine, and potassium, we observed clear differences in medium composition across different brands. No two embryo culture media compositions were the same. Remarkably, even embryo culture media from brands that belong to th","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"59 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142712534","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":"Upregulated let-7 expression in the follicular fluid of patients with endometriomas leads to dysfunction of granulosa cells through targeting of IGF1R","authors":"Libing Shi, Hanqi Ying, Yongdong Dai, Yan Rong, Jianmin Chen, Feng Zhou, Shasha Wang, Shiqian Xu, Xiaomei Tong, Songying Zhang","doi":"10.1093/humrep/deae247","DOIUrl":"https://doi.org/10.1093/humrep/deae247","url":null,"abstract":"STUDY QUESTION What molecular mechanisms underlie the decline in ovarian reserve as the number and quality of oocytes decrease in patients with ovarian endometriomas (OEM)? SUMMARY ANSWER Elevated expression of the let-7 micro(mi)RNAs in the follicular microenvironment of OEM-affected ovaries targets the expression of type 1 insulin-like growth factor receptor (IGF1R) in granulosa cell (GC) and disrupts their proliferation, steroid hormone secretion levels, adenosine triphosphate (ATP) energy metabolism, and reactive oxygen species (ROS) oxidative stress levels. WHAT IS KNOWN ALREADY Patients with OEM exhibit diminished ovarian reserve, characterized by reduced oocyte quantity and quality. Fibrotic changes in the ovarian tissue surrounding the OEM create a disruptive microenvironment for follicular growth and development. STUDY DESIGN, SIZE, DURATION This is a cross-sectional study aimed to elucidate the molecular mechanisms underlying the impact of OEM on follicular development. Initially, miRNA expression profiles in follicular fluid (FF) samples were sequenced from patients with infertility related to OEM (N = 3) and male factor (MF) infertility (N = 3), with the latter serving as the control group. Differentially expressed miRNAs were validated in additional samples from each group (N = 55 in OEM group and N = 45 in MF group) to confirm candidate miRNAs. The study also investigated indicators associated with GCs dysfunction in vitro on rat GCs. Subsequently, rat models of OEM were established through endometrial allogeneic transplantation, and fertility experiments were conducted to assess the let-7/IGF1R axis response to OEM in vivo. Patient samples were collected between May 2018 and April 2019, and the mechanistic study was conducted over the subsequent three years. PARTICIPANTS/MATERIALS, SETTING, METHODS FF and GC samples were obtained from infertile patients undergoing IVF treatment for OEM and MF related infertility. miRNA expression profiles in FF samples were analyzed using second-generation high-throughput sequencing technology, and candidate miRNAs were validated through quantitative PCR (qPCR). In the in vitro experiments conducted with rat GCs, cell proliferation was assessed using the CCK-8 assay, while steroid hormone concentrations were measured using chemiluminescence. ATP content was determined with an ATP assay kit, and levels of ROS were quantified using flow cytometry. A dual luciferase reporter gene assay was employed to identify the target gene of let-7 based on the construction of a IGF1R reporter gene plasmid using 293T cells. Western blotting was utilized to evaluate the expression of IGF1R in GCs, as well as its downstream proteins, and changes in signaling pathways following let-7 agomir/antagomir transfection and/or Igf1r silencing. In the in vivo OEM rat models, alterations in ovarian structure and cyst morphology were observed using hematoxylin and eosin staining. The expressions of let-7 and Igf1r in GCs were e","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"13 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142596798","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":"Reproductive factors and biological aging: the association with all-cause and cause-specific premature mortality","authors":"Gaojie Fan, Qing Liu, Jianing Bi, Qing Fang, Fei Luo, Xiaofeng Huang, Heng Li, Wenwen Guo, Binghai Liu, Lianyan Yan, Youjie Wang, Lulu Song","doi":"10.1093/humrep/deae250","DOIUrl":"https://doi.org/10.1093/humrep/deae250","url":null,"abstract":"STUDY QUESTION Are reproductive factors associated with biological aging, and does biological aging mediate the associations of reproductive factors with premature mortality? SUMMARY ANSWER Multiple reproductive factors are related to phenotypic age acceleration (PhenoAge-Accel), while adherence to a healthy lifestyle mitigates these harmful effects; PhenoAge-Accel mediated the associations between reproductive factors and premature mortality. WHAT IS KNOWN ALREADY Accelerated aging is a key contributor to mortality, but knowledge about the effect of reproductive factors on aging is limited. STUDY DESIGN, SIZE, DURATION This prospective cohort study included 223 729 women aged 40–69 years from the UK biobank in 2006–2010 and followed up until 12 November 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS Reproductive factors were collected through a touchscreen questionnaire. Biological aging was assessed through PhenoAge-Accel. Multiple linear regression models were used to examine the relationships of reproductive factors with PhenoAge-Accel and estimate the modified effect of a healthy lifestyle. Furthermore, we applied mediation analysis to explore the mediating role of PhenoAge-Accel in the associations between reproductive factors and premature mortality. MAIN RESULTS AND THE ROLE OF CHANCE Early menarche (<12 years vs 13 years, β: 0.37, 95% CI: 0.30, 0.44), late menarche (≥15 years vs 13 years, β: 0.18, 95% CI: 0.11, 0.25), early menopause (<45 years vs 50–51 years, β: 0.62, 95% CI: 0.51, 0.72), short reproductive lifespan (<30 years vs 35–39 years, β: 0.81, 95% CI: 0.70, 0.92), nulliparity (vs two live births, β: 0.36, 95% CI: 0.30, 0.43), high parity (≥4 vs 2 live births, β: 0.49, 95% CI: 0.40, 0.59), early age at first live birth (<20 years vs 25–29 years, β: 0.66, 95% CI: 0.56, 0.75), and stillbirth (β: 0.51, 95% CI: 0.36, 0.65) were associated with increased PhenoAge-Accel. Furthermore, PhenoAge-Accel mediated 6.0%–29.7% of the associations between reproductive factors and premature mortality. Women with an unfavorable lifestyle and reproductive risk factors had the highest PhenoAge-Accel compared to those with a favorable lifestyle and without reproductive risk factors. LIMITATIONS, REASONS FOR CAUTION The participants in the UK Biobank were predominantly of White ethnicity; thus, caution is warranted when generalizing these findings to other ethnic groups. WIDER IMPLICATIONS OF THE FINDINGS Our findings reveal the harmful effects of multiple reproductive factors on biological aging and the mediating role of biological aging in the associations between reproductive factors and premature mortality. They highlight the significance of adhering to a healthy lifestyle to slow biological aging as a potential way to reduce premature mortality among women with reproductive risk factors. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by the National Natural Science Foundation of China (82003479, 82073660, 72","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"244 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142596799","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 role of state-of-the-art IVF care as a marker of societal development","authors":"Alexander M Quaas, Eli Y Adashi, Richard J Paulson","doi":"10.1093/humrep/deae238","DOIUrl":"https://doi.org/10.1093/humrep/deae238","url":null,"abstract":"Access to state-of-the-art ART can be viewed as a marker of societal development. The recent Alabama Supreme Court ruling represents a major local setback in the access to state-of-the-art ART. If this isolated local incident becomes a national trend, the USA will lose ground in this emerging area of healthcare, and its citizens will be left with substandard treatment options for the redress of infertility.","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"148 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142596802","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":"Anti-Müllerian hormone signaling in the ovary involves stromal fibroblasts: a study in humans and mice provides novel insights into the role of ovarian stroma.","authors":"Itay Spector, Sanaz Derech-Haim, Ilana Boustanai, Myriam Safrai, Dror Meirow","doi":"10.1093/humrep/deae221","DOIUrl":"10.1093/humrep/deae221","url":null,"abstract":"<p><strong>Study question: </strong>What is the involvement of ovarian stroma in the anti-Müllerian hormone (AMH) signaling pathway and which stromal cells are involved?</p><p><strong>Summary answer: </strong>Mouse and human ovaries show high expression of AMH receptor II (AMHR2) in the stromal fibroblasts surrounding the follicles and activation of the post-AMHR2 pathway by recombinant AMH was evidenced by increased phosphorylation of SMAD1,5 and 9, increased expression AMHR2 and upregulation of αSMA, suggesting fibroblast activation to initiate myofibroblast differentiation.</p><p><strong>What is known already: </strong>AMH secreted by small growing follicles, regulates ovarian activity. It suppresses initial primordial follicle (PMF) recruitment and FSH-dependent growth. AMH signal transduction is mediated by AMHR2, activating intracellular SMAD proteins and other signaling cascades to induce target-gene expression. Although AMHR2 expression has been reported within the follicle unit, there is evidence suggesting it may be identified in the stroma as well.</p><p><strong>Study design, size, duration: </strong>Fresh murine ovaries were extracted from BALB/c mice (6 weeks old; n = 12 and 21 days old; n = 56). Frozen-thawed ovarian fragments were obtained from 10 women, aged 18-35, who had undergone ovarian tissue cryopreservation and donated frozen ovarian tissue for research.</p><p><strong>Participants/materials, setting, methods: </strong>Murine (6 weeks old) and human donor ovaries were immunostained for AMHR2 and Collagen 1α/αSMA/VCAM1, with additional vimentin staining in mice. Murine (21 days old) and human donor ovaries were used for fibroblast isolation and subsequent 7-day cultures. Prior to assessing AMH effects on isolated fibroblast culture, purity validation tests were implemented to ensure the absence of epithelial, immune, endothel, granulosa, and theca ovarian cell populations. The fibroblast culture's homogeneity was validated by RT-qPCR and western-blot assays, confirming negativity for E-cadherin, CD31, aromatase, CYP17A1, and positivity for αSMA and vimentin. Fibroblasts were then subjected to rAMH treatment in vitro (200 ng/ml) for 0-72 h, with an additional time point of 96 h for human samples, followed by RT-qPCR, western blot, and immunocytochemistry (ICC) for AMHR2 expression. AMHR2 post-receptor signaling was examined by pSMAD1,5,9 levels via western blot. Activated fibroblast marker, αSMA, was assessed via western blot and ICC.</p><p><strong>Main results and the role of chance: </strong>Immunostaining of mouse and human ovarian tissue showed that stromal cells around follicles at all developmental stages exhibit high AMHR2 expression, while granulosa cells of growing follicles show considerably lower levels. The majority of these AMHR2-positive stromal cells were identified as fibroblasts (Collagen1α in mice and human; vimentin in mice). RT-qPCR, western blot, and immunostaining were performed on cultured mouse and huma","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"2551-2564"},"PeriodicalIF":6.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371734","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}