Human reproduction最新文献

{"title":"Preterm birth in assisted reproduction: the mediating role of hypertensive disorders in pregnancy","authors":"Sindre Hoff Petersen, Bjørn Olav Åsvold, Deborah A Lawlor, Anja Pinborg, Anne Lærke Spangmose, Liv Bente Romundstad, Christina Bergh, Ulla-Britt Wennerholm, Mika Gissler, Aila Tiitinen, Ahmed Elhakeem, Signe Opdahl","doi":"10.1093/humrep/deae261","DOIUrl":"https://doi.org/10.1093/humrep/deae261","url":null,"abstract":"STUDY QUESTION To what extent can hypertensive disorders in pregnancy (HDP) explain the higher risk of preterm birth following frozen embryo transfer (frozen-ET) and fresh embryo transfer (fresh-ET) in ART compared with naturally conceived pregnancies? SUMMARY ANSWER HDP did not contribute to the higher risk of preterm birth in pregnancies after fresh-ET but mediated 20.7% of the association between frozen-ET and preterm birth. WHAT IS KNOWN ALREADY Risk of preterm birth is higher after ART compared to natural conception. However, there is also a higher risk of HDP in pregnancies after ART compared to natural conception, in particular after frozen-ET. HDP increases the risk of both spontaneous and medically indicated preterm birth. It is not known to what extent the higher risk of preterm birth in ART-conceived pregnancies is mediated through HDP. STUDY DESIGN, SIZE, DURATION This registry-based cohort study included singleton pregnancies from the Committee of Nordic ART and Safety (CoNARTaS) cohort from Denmark (1994–2014), Norway (1988–2015), and Sweden (1988–2015). The analysis included 78 300 singletons born after fresh-ET, 18 037 after frozen-ET, and 4 426 682 after natural conception. The exposure was ART conception with either frozen-ET or fresh-ET versus natural conception. The main mediator of interest was any of the following HDP: gestational hypertension, preeclampsia, eclampsia, or chronic hypertension with superimposed preeclampsia. The main outcome was any preterm birth, defined as delivery <37 weeks of gestation. Secondary outcomes were spontaneous and medically indicated preterm birth, and different severities of preterm birth based on the gestational age threshold. PARTICIPANTS/MATERIALS, SETTING, METHODS We linked data from the national Medical Birth Registries, ART registries/databases, and the National Patient Registries in each country using the unique national identity number of the mother. Criteria for inclusion were singleton pregnancies with birth order 1–4 in women aged ≥20 years at delivery. We used logistic regression to estimate odds ratios (ORs) with 95% CIs of preterm birth and decomposed the total effect into direct and mediated (indirect) effects to estimate the proportion mediated by HDP. Main models included adjustment for the year of delivery, maternal age, parity, and country. MAIN RESULTS AND THE ROLE OF CHANCE Pregnancies following frozen-ET had a higher risk of any preterm birth compared to natural conception (occurrence 6.6% vs 5.0%, total effect OR 1.29, 95% CI 1.21–1.37) and 20.7% of the association was mediated by HDP (mediated effect OR 1.05, 95% CI 1.04–1.05). The mediation occurred primarily in medically indicated preterm births. Pregnancies following fresh-ET also had a higher risk of any preterm birth compared to naturally conceived pregnancies (occurrence 8.1% vs 5.0%, total effect OR 1.49, 95% CI: 1.45–1.53), but none of this could be mediated by HDP (mediated effect OR 1.00, 95%CI 1.00–1.","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"81 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805415","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":"Adolescent menstrual cycle pattern, body mass index, endocrine and ovarian ultrasound characteristics of PCOS and future fertility, cardiovascular-, and metabolic health: a 25-year longitudinal follow-up study","authors":"Machiel H A van Hooff, Mirte R Caanen, Henrike E Peters, Joop S E Laven, Cornelis B Lambalk","doi":"10.1093/humrep/deae262","DOIUrl":"https://doi.org/10.1093/humrep/deae262","url":null,"abstract":"STUDY QUESTION What is the predictive value of oligomenorrhea and other PCOS diagnostic characteristics in adolescence (age 15–18 years) for future fertility and cardiovascular and metabolic health at adult age? SUMMARY ANSWER Adolescents with oligomenorrhea are more often treated to conceive but are as likely to have as much children as those with regular periods, while persisting oligomenorrhea may associate more often with cardiovascular or metabolic problems. WHAT IS KNOWN ALREADY Adolescents with oligomenorrhea have a high risk for adult PCOS associated with subfertility due to ovulatory disorders and long-term health risks. Longitudinal studies to estimate the extent of these risks with input starting at adolescence and covering the complete reproductive lifespan are lacking. STUDY DESIGN, SIZE, DURATION A 25-year prospective follow-up study based on a unique population-based adolescent study on menstrual irregularities performed between 1990 and 1997, the Pubertal Onset of Menstrual Cycle abnormalities, a Prospective study (POMP study). Of the 271 invited adults, 160 (59%) participated. PARTICIPANTS/MATERIALS, SETTING, METHODS We contacted stratified samples of the POMP study cohort two decades after the initial study for a questionnaire assessing PCOS features, fertility history, pregnancy outcome, metabolic, and cardiovascular health. One hundred and sixty subjects completed the questionnaire. The mean adolescent age was 15.3 years, and the women were 39.6 years at the time of follow-up. One hundred and eight subjects had a regular menstrual cycle as adolescents and 52 were oligomenorrheic. MAIN RESULTS AND THE ROLE OF CHANCE Of those with adolescent regular menstrual cycles 12 never tried to conceive, 4 tried but never conceived and 92 of 96 (96%) conceived, 89 of 96 (93%) delivering at least one living child. The median number of children was two. The mean time to pregnancy (TTP) was 8.4 months in the women with regular periods as adolescents and 13.2 months in case of oligomenorrhea (P = 0.08) and subfertility was present in respectively 18% and 26%. 47 of 52 adolescents with oligomenorrhea tried to conceive and 45 succeeded to have at least one live birth. Twenty-eight per cent of the subjects reported a change over time of their menstruation pattern. Fifty per cent of the girls with adolescent oligomenorrhea developed a regular cycle and 16% of those with regular periods changed to oligomenorrhea with significantly more reported subfertility (40%, P = 0.04). In case of persistent oligomenorrhea, a significant proportion (40%) underwent fertility treatment (P = 0.04). Adult BMI did not differ between groups. The risk for pregnancy-induced hypertension or pre-eclampsia was comparable between the groups. Gestational diabetes developed in three subjects each with persistent oligo amenorrhea. Adult diabetes, hypertension, and hypercholesterolemia were also mostly reported in case of persistent oligomenorrhea. In this group, the prevalenc","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"1 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805482","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 web-based Pleasure&Pregnancy programme in the treatment of unexplained infertility: a randomized controlled trial.","authors":"F Dreischor, E A F Dancet, C B Lambalk, H W van Lunsen, D Besselink, J van Disseldorp, J Boxmeer, E A Brinkhuis, B J Cohlen, A Hoek, M de Hundt, C A H Janssen, M Lambers, J Maas, A Nap, D Perquin, M Verberg, H R Verhoeve, J Visser, L van der Voet, M H Mochtar, M Goddijn, E Laan, M van Wely, I M Custers","doi":"10.1093/humrep/deae220","DOIUrl":"10.1093/humrep/deae220","url":null,"abstract":"<p><strong>Study question: </strong>Does offering the Pleasure&Pregnancy (P&P) programme rather than expectant management improve naturally conceived ongoing pregnancy rates in couples diagnosed with unexplained infertility?</p><p><strong>Summary answer: </strong>The P&P programme had no effect on the ongoing pregnancy rates of couples with unexplained infertility.</p><p><strong>What is known already: </strong>Underpowered studies suggested that face-to-face interventions targeting sexual health may increase pregnancy rates. The impact of an eHealth sexual health programme had yet to be evaluated by a large randomized controlled trial.</p><p><strong>Study design, size, duration: </strong>This is a nationwide multi-centre, unblinded, randomized controlled superiority trial (web-based randomization programme, 1:1 allocation ratio). This RCT intended to recruit 1164 couples within 3 years but was put on hold after having included 700 couples over 5 years (2016-2021). The web-based P&P programme contains psychosexual information and couple communication, mindfulness and sensate focus exercises aiming to help maintain or improve sexual health, mainly pleasure, and hence increase pregnancy rates. The P&P programme additionally offers information on the biology of conception and enables couples to interact online with peers and via email with coaches.</p><p><strong>Participants/materials, setting, methods: </strong>Heterosexual couples with unexplained infertility and a Hunault-prognosis of at least 30% chance of naturally conceiving a live-born child within 12 months were included, after their diagnostic work-up in 41 Dutch secondary and tertiary fertility centres. The primary outcome was an ongoing pregnancy, defined as a viable intrauterine pregnancy of at least 12 weeks duration confirmed by an ultrasound scan, conceived naturally within 6 months after randomization. Secondary outcomes were time to pregnancy, live birth, sexual health, and personal and relational well-being at baseline and after 3 and 6 months. The primary analyses were according to intention-to-treat principles. We calculated relative risks (RRs, pregnancy rates) and a risk difference (RD, pregnancy rates), Kaplan-Meier survival curves (live birth over time), and time, group, and interactive effects with mixed models analyses (sexual health and well-being).</p><p><strong>Main results and the role of chance: </strong>Totals of 352 (one withdrawal) and 348 (three withdrawals) couples were allocated to, respectively the P&P group and the expectant management group. Web-based tracking of the intervention group showed a high attrition rate (57% of couples) and limited engagement (i.e. median of 16 visits and 33 min total visitation time per couple). Intention-to-treat analyses showed that 19.4% (n = 68/351) of the P&P group and 22.6% (n = 78/345) of the expectant management group achieved a naturally conceived ongoing pregnancy (RR = 0.86; 95% CI = 0.64-1.15, RD = -3.24%; 95% CI -9.28 t","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"2711-2721"},"PeriodicalIF":6.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11630088/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365083","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":"Female-age-dependent changes in the lipid fingerprint of the mammalian oocytes.","authors":"Simona Bisogno, Joanna Depciuch, Hafsa Gulzar, Maria Florencia Heber, Michał Kobiałka, Łukasz Gąsior, Adrianna Bereta, Anna Pieczara, Kinga Fic, Richard Musson, Gabriel Garcia Gamero, Maria Pardo Martinez, Alba Fornés Pérez, Martina Tatíčková, Zuzana Holubcova, Małgorzata Barańska, Grażyna Ewa Ptak","doi":"10.1093/humrep/deae225","DOIUrl":"10.1093/humrep/deae225","url":null,"abstract":"<p><strong>Study question: </strong>Can oocyte functionality be assessed by observing changes in their intracytoplasmic lipid droplets (LDs) profiles?</p><p><strong>Summary answer: </strong>Lipid profile changes can reliably be detected in human oocytes; lipid changes are linked with maternal age and impaired developmental competence in a mouse model.</p><p><strong>What is known already: </strong>In all cellular components, lipid damage is the earliest manifestation of oxidative stress (OS), which leads to a cascade of negative consequences for organelles and DNA. Lipid damage is marked by the accumulation of LDs. We hypothesized that impaired oocyte functionality resulting from aging and associated OS could be assessed by changes in LDs profile, hereafter called lipid fingerprint (LF).</p><p><strong>Study design, size, duration: </strong>To investigate if it is possible to detect differences in oocyte LF, we subjected human GV-stage oocytes to spectroscopic examinations. For this, a total of 48 oocytes derived from 26 young healthy women (under 33 years of age) with no history of infertility, enrolled in an oocyte donation program, were analyzed. Furthermore, 30 GV human oocytes from 12 women were analyzed by transmission electron microscopy (TEM). To evaluate the effect of oocytes' lipid profile changes on embryo development, a total of 52 C57BL/6 wild-type mice and 125 Gnpat+/- mice were also used.</p><p><strong>Participants/materials, setting, methods: </strong>Human oocytes were assessed by label-free cell imaging via coherent anti-Stokes Raman spectroscopy (CARS). Further confirmation of LF changes was conducted using spontaneous Raman followed by Fourier transform infrared (FTIR) spectroscopies and TEM. Additionally, to evaluate whether LF changes are associated with developmental competence, mouse oocytes and blastocysts were evaluated using TEM and the lipid dyes BODIPY and Nile Red. Mouse embryonic exosomes were evaluated using flow cytometry, FTIR and FT-Raman spectroscopies.</p><p><strong>Main results and the role of chance: </strong>Here we demonstrated progressive changes in the LF of oocytes associated with the woman's age consisting of increased LDs size, area, and number. LF variations in oocytes were detectable also within individual donors. This finding makes LF assessment a promising tool to grade oocytes of the same patient, based on their quality. We next demonstrated age-associated changes in oocytes reflected by lipid peroxidation and composition changes; the accumulation of carotenoids; and alterations of structural properties of lipid bilayers. Finally, using a mouse model, we showed that LF changes in oocytes are negatively associated with the secretion of embryonic exosomes prior to implantation. Deficient exosome secretion disrupts communication between the embryo and the uterus and thus may explain recurrent implantation failures in advanced-age patients.</p><p><strong>Limitations, reasons for caution: </strong>Due t","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"2754-2767"},"PeriodicalIF":6.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11630086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375326","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":"One fresh cleavage-stage single embryo transfer (SET) plus one frozen-thawed blastocyst-stage SET or one fresh cleavage-stage double embryo transfer? A retrospective matched cohort study.","authors":"Zheng Wang, Fang Liu, Kailun Hu, Tian Tian, Rui Yang, Yuanyuan Wang, Rong Li, Ben W Mol, Jie Qiao","doi":"10.1093/humrep/deae245","DOIUrl":"10.1093/humrep/deae245","url":null,"abstract":"<p><strong>Study question: </strong>Are there significant differences in fertility outcomes between transferring two cleavage-stage embryos in a single fresh cycle and transferring one cleavage-stage embryo in a fresh cycle and one blastocyst-stage embryo in the subsequent frozen-thawed cycle?</p><p><strong>Summary answer: </strong>In women aged <38 years with two embryos available, transferring one cleavage-stage embryo in a fresh cycle and one blastocyst-stage embryo in the subsequent frozen-thawed cycle increased live birth rates and decreased multiple live birth rates compared to transferring two cleavage-stage embryos in a single fresh cycle.</p><p><strong>What is known already: </strong>The strategy of repeated single embryo transfer (SET) has emerged as a solution to address the reduced live birth rates associated with SET per cycle. There is substantial evidence indicating that the cumulative live birth rate after repeated SET is comparable to that of double embryo transfer (DET), while significantly reducing the incidence of multiple pregnancies. Evidence regarding the outcomes of transferring two cleavage-stage embryos in a single fresh cycle versus transferring one cleavage-stage embryo in one fresh cycle and one blastocyst-stage embryo in the subsequent frozen-thawed cycle is scarce.</p><p><strong>Study design, size, duration: </strong>This study is a retrospective matched cohort study, where data were gathered from the clinical database of women who underwent IVF treatment at the Reproductive Center of Peking University Third Hospital between January 2011 and December 2019, with follow-up extending until December 2021.</p><p><strong>Participants/materials, setting, methods: </strong>The study group included cycles with a fresh cleavage-stage SET and a subsequent frozen-thawed blastocyst-stage SET (2xSET, N = 976). Fresh cleavage-stage DET was the control group (DET, N = 976). Included cycles were divided into subgroups based on age (≥38 years vs <38 years) and total number of utilizable (transferred or cryopreserved) embryos (=2 vs >2).</p><p><strong>Main results and the role of chance: </strong>The duration of infertility, prevalence of unexplained infertility, and controlled ovarian stimulation regimes differed significantly between the two groups and were adjusted for in the further analysis. We observed a significant increase in clinical pregnancies (55.5% vs 42%, adjusted odds ratio (OR) 1.87 [1.55-2.26]) and live births (44.8% vs 34.5%, adjusted OR 1.63 [1.35-1.97]) in favor of the 2xSET group. The preterm birth rate was lower in the study group (adjusted OR 0.64 [0.42-0.96]). Neonatal birth weight of singletons was similar between the two groups (adjusted B 4.94 g [-84.5 to 94.4]). The beneficial effect on the live birth rate disappeared in cases where aged 38 years and older or when only two embryos were utilizable.</p><p><strong>Limitations, reasons for caution: </strong>This study is limited by differences in baseline chara","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"2702-2710"},"PeriodicalIF":6.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564372","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":"Outcomes of female fertility preservation with cryopreservation of oocytes or embryos in the Netherlands: a population-based study.","authors":"M Elena Ter Welle-Butalid, Josien G Derhaag, Bo E van Bree, Ingeborg J H Vriens, Mariëtte Goddijn, Eva M E Balkenende, Catharina C M Beerendonk, Anna M E Bos, Irene Homminga, Sofie H Benneheij, H C van Os, Jesper M J Smeenk, Marieke O Verhoeven, Casandra C A W van Bavel, Vivianne C G Tjan-Heijnen, Ron J T van Golde","doi":"10.1093/humrep/deae243","DOIUrl":"10.1093/humrep/deae243","url":null,"abstract":"<p><strong>Study question: </strong>What are the reproductive outcomes of patients who cryopreserved oocytes or embryos in the context of fertility preservation in the Netherlands?</p><p><strong>Summary answer: </strong>This study shows that after a 10-year follow-up period, the utilization rate to attempt pregnancy using cryopreserved oocytes or embryos was 25.5% and the cumulative live birth rate after embryo transfer was 34.6% per patient.</p><p><strong>What is known already: </strong>Fertility preservation by freezing oocytes or embryos is an established treatment for women with a risk of premature ovarian failure (caused by a benign or oncological disease) or physiological age-related fertility decline. Little is known about the success of cryopreservation, the utilization rate of oocytes or embryos, or the live birth rates.</p><p><strong>Study design, size, duration: </strong>A retrospective observational study was performed in the Netherlands. Data were collected between 2017 and 2019 from 1112 women who cryopreserved oocytes or embryos more than 2 years ago in the context of fertility preservation in 10 IVF centers in the Netherlands.</p><p><strong>Participants/materials, setting, methods: </strong>A total of 1112 women were included in this study. Medical files and patient databases were used to extract data. Women were categorized based on indication of fertility preservation: oncological, benign, or non-medical. To indicate statistical differences the t-test or Mann-Whitney U test was used. Kaplan-Meier analyses were used for time endpoints, and log-rank analyses were used to assess statistical differences. The study protocol was approved by the medical ethics committee.</p><p><strong>Main results and the role of chance: </strong>Fertility preservation cycles have been performed increasingly over the years in the Netherlands. In the first years, less than 10 cycles per year were performed, increasing to more than 300 cycles per year 10 years later. Initially, embryos were frozen in the context of fertility preservation. In later years, cryopreservation of oocytes became the standard approach. Cryopreservation of oocytes versus embryos resulted in comparable numbers of used embryos (median of 2) for transfer and comparable live birth rates (33.9% and 34.6%, respectively). The 5-year utilization rate was 12.3% and the 10-year utilization rate was 25.5%. The cumulative clinical pregnancy rate was 35.6% and the cumulative live birth rate was 34.6% per patient. Those who had fertility preservation due to benign diseases returned earlier to use their cryopreserved embryos or oocytes.</p><p><strong>Limitations, reasons for caution: </strong>The follow-up period after the fertility preservation procedure varied between patients in this study and not all frozen oocytes or embryos had been used at the end of this study. This might have led to underestimated outcomes reported in this study. Furthermore, intention to treat cannot be fully determin","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"2693-2701"},"PeriodicalIF":6.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11630040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545091","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":"Paternal age, de novo mutations, and offspring health? New directions for an ageing problem.","authors":"Robert John Aitken","doi":"10.1093/humrep/deae230","DOIUrl":"10.1093/humrep/deae230","url":null,"abstract":"<p><p>This Directions article examines the mechanisms by which a father's age impacts the health and wellbeing of his children. Such impacts are significant and include adverse birth outcomes, dominant genetic conditions, neuropsychiatric disorders, and a variety of congenital developmental defects. As well as age, a wide variety of environmental and lifestyle factors are also known to impact offspring health via changes mediated by the male germ line. This picture of a dynamic germ line responsive to a wide range of intrinsic and extrinsic factors contrasts with the results of trio studies indicating that the incidence of mutations in the male germ line is low and exhibits a linear, monotonic increase with paternal age (∼two new mutations per year). While the traditional explanation for this pattern of mutation has been the metronomic plod of replication errors, an alternative model pivots around the 'faulty male' hypothesis. According to this concept, the genetic integrity of the male germ line can be dynamically impacted by age and a variety of other factors, and it is the aberrant repair of such damage that drives mutagenesis. Fortunately, DNA proofreading during spermatogenesis is extremely effective and these mutant cells are either repaired or deleted by apoptosis/ferroptosis. There appear to be only two mechanisms by which mutant germ cells can escape this apoptotic fate: (i) if the germ cells acquire a mutation that by enhancing proliferation or suppressing apoptosis, permits their clonal expansion (selfish selection hypothesis) or (ii) if a genetically damaged spermatozoon manages to fertilize an oocyte, which then fixes the damage as a mutation (or epimutation) as a result of defective DNA repair (oocyte collusion hypothesis). Exploration of these proposed mechanisms should not only help us better understand the aetiology of paternal age effects but also inform potential avenues of remediation.</p>","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"2645-2654"},"PeriodicalIF":6.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11630042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371735","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":"24-hour movement behaviours and cardiometabolic markers in women with polycystic ovary syndrome (PCOS): a compositional data analysis.","authors":"E Pesonen, V Farrahi, C J Brakenridge, M M Ollila, L C Morin-Papunen, M Nurkkala, T Jämsä, R Korpelainen, L J Moran, T T Piltonen, M Niemelä","doi":"10.1093/humrep/deae232","DOIUrl":"10.1093/humrep/deae232","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Are 24-h movement composition and time reallocations between the movement behaviours (moderate-to-vigorous physical activity (MVPA), light physical activity (LPA), sedentary behaviour (SB), and sleep) differentially associated with cardiometabolic markers in women with polycystic ovary syndrome (PCOS) relative to women without PCOS?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;There was no difference in 24-h movement composition between the groups, although among women without PCOS, reducing SB time while increasing either MVPA or LPA time was associated with beneficial differences in cardiometabolic markers, whereas in women with PCOS beneficial differences were observed only when SB time was replaced with MVPA.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;Women with PCOS display lower levels of physical activity, higher sedentary time, and less total sleep than women without the syndrome. Exercise interventions among women with PCOS have shown improvements in body composition and insulin sensitivity, while the findings regarding blood pressure, insulin resistance, and lipid profiles are contradictory.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design, size, duration: &lt;/strong&gt;This study was part of a prospective, general population-based Northern Finland Birth Cohort 1966 (NFBC1966) (n = 5889 women). At the 31-year and 46-year follow-up, data collection was performed through postal and clinical examinations, including fasting blood samples and anthropometric measurements. Accelerometer data collection of 14 days (n = 2602 women) and a 2-h oral glucose tolerance test (n = 2780 women) were performed at the 46-year follow-up. Participants were identified as women with or without PCOS at age 31 (n = 1883), and the final study population included those who provided valid accelerometer data at age 46 (n = 857).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials, setting, methods: &lt;/strong&gt;Women with PCOS (n = 192) were identified based on the 2023 International Evidence-based Guideline, while those who exhibited no PCOS features were considered women without PCOS (controls; n = 665). Accelerometer-measured MVPA, LPA, and SB were combined with self-reported sleep to obtain 24-h compositions. Multivariable regression analysis based on compositional data analysis and isotemporal reallocations were performed to investigate the associations between 24-h movement composition and cardiometabolic markers. Isotemporal reallocations were expressed as differences (%Δ) from the sample's mean.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;There was no difference in overall 24-h movement composition between women with PCOS and controls in midlife. The 24-h movement composition was associated with waist circumference, triglycerides, fasting serum insulin, and Homeostatic Model Assessment-insulin resistance (HOMA-IR) in both controls and women with PCOS. Reallocating 15 min from SB to MVPA was associated with favourable differences in cardiometabolic markers","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"2830-2847"},"PeriodicalIF":6.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11629989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375324","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":"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":"10.1093/humrep/deae246","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;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?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;CDC42 deficiency causes endometrial stromal senescence and decidualization defects, impairing uterine receptivity of RIF patients, via activation of Wnt signaling pathway.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;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.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design, size, duration: &lt;/strong&gt;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.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials, setting, methods: &lt;/strong&gt;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.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;Here, we observed remarkably increased levels of stromal senescence and fibrosis, along with stromal CDC42 deficiency, in the endometrium of patients with RIF (P &lt; 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":" ","pages":"2768-2784"},"PeriodicalIF":6.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11630066/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nonlinear correlation between serum vitamin D levels and the incidence of endometrial polyps in infertile women.","authors":"Ruiqiong Zhou, Zhenghong Zhu, Mei Dong, Zhaoyi Wang, Li Huang, Songlu Wang, Xiqian Zhang, Fenghua Liu","doi":"10.1093/humrep/deae241","DOIUrl":"10.1093/humrep/deae241","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Are serum vitamin D levels associated with the incidence of endometrial polyps (EPs) in infertile patients?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;Serum 25(OH)D levels were nonlinearly correlated with the incidence of EPs in infertile women.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;EPs are a common condition that may affect the receptivity of the endometrium in women of reproductive age. Vitamin D regulates cell proliferation and differentiation, apoptosis, angiogenesis, anti-inflammation, and immunomodulation, in addition to its well-known functions in balancing calcium and phosphorus. Previous studies have shown that vitamin D concentrations are associated with reproductive outcomes, and that low vitamin D levels are associated with the incidence of colorectal polyps and nasal polyps. There is little evidence regarding the relationship between EPs and serum vitamin D levels.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design, size, duration: &lt;/strong&gt;We conducted a cross-sectional study using data from Guangdong Women and Children Hospital from January 2019 to October 2023, enrolling 3107 patients.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials, setting, methods: &lt;/strong&gt;A total of 3107 infertile patients who underwent hysteroscopy were included in this study; 642 patients had endometrial polyps and 2465 had a normal uterine cavity. Hysteroscopy findings included risk of EPs, polyp size, percentage of multiple polyps, and incidence of chronic endometritis (CE). Serum vitamin D were assessed by measuring total 25(OH)D using chemiluminescence. According to international guideline recommendations for vitamin D deficiency, patients were divided into two groups: the &lt;50 nmol/l group and the ≥50 nmol/l group. Univariable and multivariable logistic regression models, stratified analyses, and smooth curve fitting were used to examine the relationship between serum 25(OH)D levels and risk of EPs.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;Of all patients, 23.8% (740/3107) were vitamin D deficient (&lt;50 nmol/l). The incidence of EPs was significantly higher in the 25(OH)D &lt; 50 nmol/l group than in the ≥50 nmol/l group (24.9% vs 19.3%; P = 0.001). However, there were no differences in polyp size, proportion of multiple polyps, and presence of CE between the two groups. After controlling for confounders, 25(OH)D ≥ 50 nmol/l (compared with &lt;50 nmol/l) was negatively associated with risk of EPs (adjusted OR, 0.733; 95% CI, 0.598-0.898). Other variables that had an impact on polyp incidence included BMI, type of infertility, CA125, and CD138-positive plasma cells. In addition, a linear regression model between age and serum 25(OH)D levels showed a positive linear association. Subgroup analyses were performed for different age groups, and the risk of EPs was significantly higher in the 25(OH)D &lt; 50 nmol/l group than in the ≥50 nmol/l group, both in the younger subgroup (23.8% vs 19.1%) and in the older subgroup (28.0% vs 19.9%). The smo","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"2685-2692"},"PeriodicalIF":6.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521767","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}