Human reproduction open最新文献

{"title":"Why the hypothesis of embryo selection in IVF/ICSI must finally be reconsidered.","authors":"Norbert Gleicher, Sonia Gayete-Lafuente, David H Barad, Pasquale Patrizio, David F Albertini","doi":"10.1093/hropen/hoaf011","DOIUrl":"10.1093/hropen/hoaf011","url":null,"abstract":"<p><p>Embryo selection (ES) during IVF is expected to select the 'best' embryo(s) from among a cycle's embryo cohort and has been a core concept of IVF for over 40 years. However, among 36 492 articles on ES in a recent PubMed search, we were unable to locate even a single one questioning the concept that, beyond standard oocyte and embryo morphology, ES has remained an unproven hypothesis. In unselected patient populations, attempts at ES have universally, indeed, failed to improve cumulative pregnancy and live birth rates. The only benefit ES appears to offer is a marginal shortening in time to pregnancy, and even this benefit manifests only in best-prognosis patients with large oocyte and embryo numbers. Excluding <i>in vitro</i> maturation efforts, oocytes, once retrieved, and their resulting embryos have predetermined finite cumulative pregnancy and live birth chances that cannot be further improved. The hypothesis of ES has, however, remained a driving force for research and the introduction of a multitude of 'add-ons' to IVF. Enormous investments over decades in ES, therefore, should be better redirected from post- to pre-retrieval efforts.</p>","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 2","pages":"hoaf011"},"PeriodicalIF":8.3,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11928228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143694442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of HBV, HCV, or syphilis infections on embryo and pregnancy outcomes in couples undergoing IVF treatment: a matched cohort study.","authors":"Fang Liu, Zheng Wang, Ying Song, Tian Tian, Rong Li, Jie Qiao, Shuo Huang, Yuanyuan Wang","doi":"10.1093/hropen/hoaf015","DOIUrl":"10.1093/hropen/hoaf015","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Do infectious diseases (hepatitis B virus [HBV], hepatitis C virus [HCV], and syphilis) impact embryo quality, pregnancy, and neonatal outcomes following a complete IVF cycle?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;Infections with HBV, HCV, or syphilis do not have detrimental impacts on live birth rates or neonatal outcomes in couples following a complete IVF cycle.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;Maternal or paternal infections with HBV, HCV, or syphilis may decrease the clinical pregnancy rate, result in poorer embryo outcomes, and lower offspring birth weight. However, there is significant controversy regarding these effects across existing studies, highlighting the need for further research.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;This is a retrospective matched cohort study. Data were obtained from the clinical database of couples who underwent IVF treatment at a single academically affiliated fertility clinic from January 2011 to December 2019, with follow-up extending to December 2020. Out of 180 666 complete cycles recorded, 2443 cycles fulfilled our inclusion criteria.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;In cycles that fulfilled our inclusion criteria, there were 1997 cycles in the HBV study group, 154 cycles in the HCV study group, and 292 cycles in the syphilis study group. Each study cycle was paired with four controls based on participant age and the timing of IVF treatment, resulting in 7988 controls for the HBV group, 616 controls for the HCV group, and 1169 controls for the syphilis group. Infections could be either single-parent or biparental. The primary outcome was live birth per complete cycle (i.e. fresh cycle plus subsequent frozen-thawed cycles). Subgroup analyses were conducted dividing cycles into maternal infection and paternal infection.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;In the HBV group, pregnancy outcomes (clinical pregnancy, miscarriage, and live birth rates) and neonatal birth weight were similar to that of the controls. In the HCV group, no significant differences from the controls were observed except for a lower clinical pregnancy rate in the study group (36.4% vs 42.2%, adjusted β and 95% CI: 0.62 [0.39-0.96]). Similarly, no significant differences were found in pregnancy or neonatal outcomes between the syphilis group and the control group. As for subgroup analyses, the male-only HBV infection subgroup showed a higher miscarriage rate in the study group than in the control group (22.5% vs 17.7%, adjusted β and 95% CI: 1.56 [1.07-2.28]). For the HCV and syphilis subgroups, none of the outcomes showed significant differences between either the female-only infection or male-only infection subgroups and the controls.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Limitations reasons for caution: &lt;/strong&gt;Although potential confounders were considered and adjusted for, residual bias may still exist due to the study design. The inclusion","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 2","pages":"hoaf015"},"PeriodicalIF":8.3,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143766027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Visceral and subcutaneous adipose tissue in children born after ART with frozen and fresh embryo transfers.","authors":"Annesofie R Olsen, Louise L Asserhøj, Anja Pinborg, Tine D Clausen, Gorm Greisen, Rikke B Jensen, Katharina M Main, Niels G Vejlstrup, Per L Madsen, Ikram Mizrak","doi":"10.1093/hropen/hoaf014","DOIUrl":"10.1093/hropen/hoaf014","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Is the ratio of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) comparable between children following ART and natural conception (NC)?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;Children conceived by frozen embryo transfer (FET) had slightly lower VAT/SAT ratios than children following NC; no difference in VAT/SAT ratio was observed in children born following fresh embryo transfer (Fresh-ET) as compared to those born from NC.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;The VAT/SAT ratio is closely related to the metabolic profile, with a high ratio increasing the risk of cardiometabolic diseases. To our knowledge, no studies have reported the VAT/SAT ratio in children following ART.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;This prospective exploratory observational cohort study included 150 singletons aged 7-10 years. All children were born in eastern Denmark. The study was conducted between November 2018 and August 2020.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;This is a sub-study of the 'Health in Childhood following Assisted Reproductive Technology' (HiCART) study. The children were conceived after FET (n = 50), Fresh-ET (n = 50), and NC (n = 50), and children conceived by NC were matched to ART children by sex and birth year. The children underwent abdominal MRI for the quantification of abdominal adipose tissues along with measurements of blood pressure, fasting blood samples, anthropometric measurements, and dual-energy X-ray absorptiometry scans. The volumes of VAT and SAT were semi-automatically quantified, blinded for the mode of conception. The level of statistical significance was set to a &lt;i&gt;P&lt;/i&gt;-level below 0.05. Multivariable linear regression analysis of the VAT/SAT ratio was performed to adjust for confounders in a five-step approach: Model 1: Adjusted for child age and sex; Model 2: Model 1 plus maternal age at delivery and maternal BMI at pregnancy; Model 3: Model 2 plus birth weight and child BMI; Model 4a: Model 3 plus maternal educational level; Model 4b: Model 3 plus pubertal status. The confounders were selected based on their association with metabolic risk factors according to previous studies.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;As previously reported in the HiCART studies, there were no differences between the groups in anthropometric measurements including BMI, lean body mass, blood pressure, or triglycerides. The crude VAT/SAT ratio differed significantly between the three groups (mean (SD); FET 0.26 (0.08), Fresh-ET 0.29 (0.07), NC 0.30 (0.08), ANOVA-&lt;i&gt;P&lt;/i&gt; = 0.014). Pairwise comparison revealed that children conceived after FET had lower crude VAT/SAT ratio than children conceived after NC (&lt;i&gt;P&lt;/i&gt; = 0.007) with a mean difference of -0.04, 95% CI (-0.07; -0.01), and a tendency for a lower VAT/SAT ratio as compared to the Fresh-ET group (&lt;i&gt;P&lt;/i&gt; = 0.059) with a mean difference of -0.03, 95% CI (-0.06; 0.","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 2","pages":"hoaf014"},"PeriodicalIF":8.3,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11975283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143805008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biopsy vs comprehensive embryo/blastocyst analysis: a closer look at embryonic chromosome evaluation.","authors":"Jian Xu, Zhiheng Chen, Meiyi Li, Ling Sun","doi":"10.1093/hropen/hoaf013","DOIUrl":"10.1093/hropen/hoaf013","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Compared with embryonic cytogenetic constitution of biopsied samples in human pre-implantation embryos, are there any differences in whole embryos?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;Whole embryos exhibit a significantly higher euploidy rate and reduction in mosaic aneuploidy rate compared to biopsied samples.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;Much of the existing evidence of cytogenetic constitution of human pre-implantation embryos is based on biopsied cells obtained from blastomeres or trophectoderm biopsies. The mosaic rate of biopsies taken from blastocyst trophectoderm ranges widely, from 2% to 25%.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;We investigated the embryonic cytogenetic constitution of 221 whole human embryos/blastocysts from 2019 to 2022, including 41 high-quality blastocysts, 57 low-quality blastocysts, and 123 arrested embryos/blastocysts.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;The cytogenetic constitution of whole embryos/blastocysts was assessed using next-generation sequencing. Mosaicism was diagnosed using a cut-off threshold of 30-70%, with embryos displaying 30-70% aneuploid cells classified as mosaic.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;Among high-quality blastocysts, the euploidy rate was 82.9%, with a remarkably low mosaic aneuploidy of only 2.5%. The euploidy rates of viable low-quality blastocysts and arrested embryos/blastocysts were 38.6% and 13.0%, respectively. The mosaic aneuploidy rate decreased progressively with embryonic development, from 93.2% at the cleavage stage to 40% at the blastocyst stage. Chaotic aneuploidy was the primary factor (66.1%, 39/59) contributing to embryonic arrest at the cleavage stage. Additionally, 26.1% of embryos/blastocysts exhibited segmental aneuploidy, with segmental duplications (30.6%, 22/72) and deletions (54.2%, 39/72) being the most common types of segmental aneuploidy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Limitations reasons for caution: &lt;/strong&gt;The sample size in this study is relatively small, especially in the subgroup analysis. Furthermore, whole-embryo analysis is not a foolproof diagnostic method, since it may underestimate the presence of mosaicism.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Wider implications of the findings: &lt;/strong&gt;The cytogenetic constitution of whole embryos provides a more accurate reflection of their physiological state compared to biopsied samples. The low mosaic aneuploidy rate in high-quality blastocysts supports the practice of transferring mosaic embryos in patients without euploid embryos. If blastocysts reach stage III by Day 6 post-fertilization, nearly half are euploid, suggesting that extending embryo culture to Day 7 may be beneficial in cases where high-quality embryos are lacking.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study funding/competing interests: &lt;/strong&gt;This study was supported by the Natural Science Foundation of Guangdong Province (No. 2023A1515010250) and Pilot Program-China Reprodu","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 2","pages":"hoaf013"},"PeriodicalIF":8.3,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11928226/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143694393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Uterine smooth muscle tumours with uncertain malignant potential: reproductive and clinical outcomes in patients undergoing fertility-sparing management.","authors":"Umberto Leone Roberti Maggiore, Francesco Fanfani, Giovanni Scambia, Ilaria Capasso, Emanuele Perrone, Giuseppe Parisi, Gian Franco Zannoni, Francesca Falcone, Alessandra Di Giovanni, Mario Malzoni, Anna Myriam Perrone, Francesco Mezzapesa, Pierandrea De Iaco, Simone Garzon, Pier Carlo Zorzato, Stefano Uccella, Fabio Barra, Stefano Bogliolo, Simone Ferrero, Veronica Iannuzzi, Dorella Franchi, Tommaso Bianchi, Tommaso Grassi, Robert Fruscio, Giulia Vittori Antisari, Giovanni Roviglione, Marcello Ceccaroni, Fulvio Borella, Stefano Cosma, Alberto Revelli, Jvan Casarin, Anna Giudici, Fabio Ghezzi, Matteo Marchetti, Giulia Spagnol, Roberto Tozzi, Francesca Filippi, Michela Molgora, Giovanna Scarfone, Biagio Paolini, Stefano Fucina, Valentina Chiappa, Antonino Ditto, Giorgio Bogani, Francesco Raspagliesi","doi":"10.1093/hropen/hoaf009","DOIUrl":"https://doi.org/10.1093/hropen/hoaf009","url":null,"abstract":"<p><strong>Study question: </strong>Can patients with uterine smooth muscle tumours of uncertain malignant potential (STUMP) be effectively and safely managed with fertility-sparing treatment?</p><p><strong>Summary answer: </strong>This multicentre retrospective study demonstrates that fertility-sparing management for patients diagnosed with STUMP is both feasible and safe.</p><p><strong>What is known already: </strong>Few studies, involving a limited number of patients, have investigated fertility-sparing management for STUMP in women with future pregnancy aspirations.</p><p><strong>Study design size duration: </strong>This multicentre retrospective study was conducted in collaboration with 13 Italian institutions specializing in gynaecologic oncology. The primary objective was to evaluate the reproductive outcomes of the included patients, while the secondary objective was to analyse their clinical outcomes.</p><p><strong>Participants/materials setting methods: </strong>A total of 106 patients with a histological diagnosis of STUMP who underwent fertility-sparing treatment for uterine tumours were included. Patient data were collected from 13 referral centres across Italy, and reproductive and clinical outcomes were documented during follow-up. The median (range) length of follow-up was 48 (7-191) months.</p><p><strong>Main results and the role of chance: </strong>Of the 106 patients, 47 (44.3%) patients actively tried to conceive after fertility-sparing surgery, and 27 of them (57.4%) achieved a pregnancy. Among the patients trying to conceive, 12 (25.5%) women had more than one pregnancy after surgery for STUMP. At follow-up, 23 (21.7%) out of the 106 women had a recurrence of uterine disease. Furthermore, a higher rate of recurrence was observed among patients who became pregnant (17 out of 27 women (63.0%)) compared with those who did not (6 out of 79 women (7.6%); <i>P</i> < 0.001). Only two cases (1.9%) of malignant relapse were recorded, and one patient with a leiomyosarcoma recurrence died.</p><p><strong>Limitations reasons for caution: </strong>The primary limitation of this study is the inherent biases associated with its retrospective design.</p><p><strong>Wider implications of the findings: </strong>This multicentre retrospective study represents the largest case series to date examining the reproductive and clinical outcomes of patients undergoing conservative treatment for STUMP. The findings suggest that patients can be counselled on the feasibility and safety of fertility-sparing management, which should be considered by clinicians as both safe and effective.</p><p><strong>Study funding/competing interests: </strong>No funding was received, and there are no competing interests.</p><p><strong>Trial registration number: </strong>N/A.</p>","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 2","pages":"hoaf009"},"PeriodicalIF":8.3,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11906398/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143652452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fertility preservation in women with endometriosis.","authors":"Antonio La Marca, Michela Semprini, Elisa Mastellari, Valeria Donno, Martina Capuzzo, Carlo Alboni, Simone Giulini","doi":"10.1093/hropen/hoaf012","DOIUrl":"10.1093/hropen/hoaf012","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Endometriosis is a chronic disease that can compromise fertility in up to 30-50% of affected patients, and it is estimated that patients affected by endometriosis represent about 10% of patients undergoing ART treatments. The hypothesized underlying mechanisms explaining infertility are various, but great attention has been given to the relationship between ovarian endometriomas and reduced ovarian reserve.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective and rationale: &lt;/strong&gt;Infertility in patients with endometriosis does not have univocal management, since surgical therapy can increase the chances of natural conception, but at the same time increases the risk of damage to the ovarian reserve. In some cases, IVF procedures should be considered instead of surgery, within a personalized strategy. It has therefore been proposed that patients with endometriosis are eligible for fertility preservation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Search methods: &lt;/strong&gt;This article is based on a critical review of literature on peer-reviewed article indexing databases including PubMed, Scopus and Medline, using as keywords: 'fertility preservation', 'oocyte vitrification', 'endometriosis', 'endometrioma', 'ovarian reserve' and '&lt;i&gt;in vitro&lt;/i&gt; fertilization'.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Outcomes: &lt;/strong&gt;Data regarding the feasibility of oocyte cryopreservation in patients with endometriosis have increased over recent years, indicating that these patients seem to have the same number of oocytes retrieved and IVF outcomes similar to those who perform fertility preservation for other indications. However, probably due to a reduced ovarian reserve, several cycles of ovarian stimulation may be needed to gather a suitable number of retrieved oocytes per patient. Age, ovarian reserve, and previous ovarian surgery are the main factors affecting the success of fertility preservation. Bilateral endometriomas, a history of unilateral endometrioma surgery with a contralateral recurrence, and preoperative reduced ovarian reserve are the most common indications for fertility preservation. The choice between primary surgery and ART is often complex, requiring a therapeutic strategy tailored to the patient's clinical characteristics and needs, such as age, type and severity of endometriosis lesions, presence of symptoms, surgical history, and desire for pregnancy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Limitations reasons for caution: &lt;/strong&gt;The development of endometriosis-related infertility and the severity of ovarian damage due to endometriosis lesions &lt;i&gt;per se&lt;/i&gt; or their surgical treatment are difficult to predict, and data are lacking concerning which subgroups of patients with endometriosis might benefit most from fertility preservation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Wider implications: &lt;/strong&gt;Women with endometriosis, and in particular women with bilateral ovarian endometriomas or recurrent surgery on the ovaries, should be advised about risk of ovarian reserve damage. Oocyte cryopreservation is an established technique t","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 2","pages":"hoaf012"},"PeriodicalIF":8.3,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11930344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143694533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Paternal age and neonatal outcomes: a population-based cohort study.","authors":"Wenxue Xiong, Xijia Tang, Lu Han, Li Ling","doi":"10.1093/hropen/hoaf006","DOIUrl":"10.1093/hropen/hoaf006","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Is paternal age associated with neonatal outcomes?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;Paternal age is independently associated with preterm birth (PTB) and caesarean section.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;Advanced maternal age has long been recognized as a major risk factor for adverse neonatal outcomes. However, the association between paternal age and neonatal outcomes are not well established, yet it is biologically plausible that an increasing number of genetic and epigenetic sperm abnormalities in older males may contribute to adverse neonatal outcomes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;This population-based cohort study was based on the National Free Preconception Checkups Project between 1 January 2014 and 31 December 2019 in Guangdong Province, China. Paternal age at the maternal last menstrual period was measured. The main outcomes included caesarean section, PTB, small for gestational age (SGA) and perinatal infant death (PID).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;A total of 783 988 mother-neonate-father trios were included in this study. A modified Poisson regression model was employed to estimate relative risk (RR) and 95% CI and logistic regression models were used to analyse the relative importance of predictors. We used restricted cubic splines to flexibly model the non-linear dose-response association between paternal age and neonatal outcomes. We also assessed additive interactions between paternal and maternal age on neonatal outcomes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;Neonates born to fathers aged 35-44 years had higher risks of caesarean section (RR: 1.07; 95% CI: 1.06-1.09) and PTB (RR: 1.15; 95% CI: 1.10-1.19) compared with neonates of fathers aged 25-34 years, after adjustment for confounders. The increased risks of PTB associated with paternal age appeared to be 'dose' dependent, with a J-shaped association curve (&lt;i&gt;P&lt;/i&gt; for non-linearity&lt;0.001). The relative importance of paternal age in predicting PTB and caesarean section was similar to, or even higher than, that of maternal age. The combined effects of advanced maternal and paternal age appeared to be less than additive joint effects (relative excess risk due to interaction&lt;0). The association of paternal age with SGA or PID was not statistically significant (&lt;i&gt;P &lt;/i&gt;&gt;&lt;i&gt; &lt;/i&gt;0.05).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Limitations reasons for caution: &lt;/strong&gt;As with all observational studies, residual confounding could not be ruled out. Only couples who planned to conceive were included.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Wider implications of the findings: &lt;/strong&gt;In this population-based cohort study, paternal age was independently associated with caesarean section and PTB. These findings may be clinically useful in preconception counselling on parental age-related pregnancy risks. Our findings emphasize the need to further investigate the public health implications of increasing p","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 1","pages":"hoaf006"},"PeriodicalIF":8.3,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11878789/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143560188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-omics analysis of uterine fluid extracellular vesicles reveals a resemblance with endometrial tissue across the menstrual cycle: biological and translational insights.","authors":"Apostol Apostolov, Danilo Mladenović, Kadi Tilk, Andres Lõhmus, Vesselin Baev, Galina Yahubyan, Alberto Sola-Leyva, Mathilde Bergamelli, André Görgens, Cheng Zhao, Samir E L Andaloussi, Aive Kalinina, Ganesh Acharya, Fredrik Lanner, Merli Saare, Maire Peters, Paola Piomboni, Alice Luddi, Andres Salumets, Elina Aleksejeva","doi":"10.1093/hropen/hoaf010","DOIUrl":"10.1093/hropen/hoaf010","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Does the molecular composition of uterine fluid extracellular vesicles (UF-EVs) reflect endometrial tissue changes across the menstrual cycle?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;Concordance between endometrial tissue and UF-EVs exists on miRNA and mRNA levels along the menstrual cycle phases and UF-EV surface proteomic signatures suggest EVs originate from several major endometrial cell populations.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;The clinical value of endometrial receptivity testing is restricted by invasiveness and the use of only one omics level of input. There is promising evidence that UF-EVs can reflect changes in mid-secretory endometrium, highlighting the potential to establish endometrial receptivity testing right before embryo transfer. However, the dynamic changes of UF-EVs molecular cargo have not been directly compared to endometrial tissue on multiple omics levels.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;This cross-sectional study included fertile women from four menstrual cycle phases: proliferative and early-, mid-, and late-secretory phases. In total, 26 paired samples of UF and endometrial tissue were collected. mRNA and miRNA were sequenced, and differential analysis was performed on consecutive phases. UF-EVs were profiled for various protein surface markers associated with different cell types. EVs from epithelial endometrial organoid-conditioned culture media were used as a reference of pure epithelial endometrial EVs.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;Paired UF and endometrial tissue samples were collected from 26 fertile, reproductive-age women. EV isolation from UF was validated using electron microscopy and western blotting, and particle numbers were measured by nanoparticle tracking analysis. The transcriptome and miRNome of UF-EVs and endometrial tissue were sequenced, and differential expression analysis was conducted on consecutive phases of the menstrual cycle. Bead-based EV flow cytometry targeting 37 surface protein markers was used to characterize EVs from UF and endometrial organoids.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;Surface proteome analysis revealed that UF-EVs from the mid-secretory phase had significantly increased expression of natural killer cell marker CD56 (&lt;i&gt;P&lt;/i&gt; &lt; 0.005), pan-leukocyte marker CD45 (&lt;i&gt;P&lt;/i&gt; &lt; 0.005), pan-T-cell marker CD3 (&lt;i&gt;P&lt;/i&gt; &lt; 0.005), and coagulation-related protein CD142 (&lt;i&gt;P&lt;/i&gt; &lt; 0.005) compared to those from the proliferative phase, whereas markers associated with endometrial epithelial cells (CD29, CD133, and CD326) did not significantly change across the menstrual cycle. Transcriptomic analysis highlighted differential expression of histone and metallothionein genes that correlated between paired UF-EVs and endometrial tissues in each tested menstrual cycle phase. Principal component analysis of miRNomes of paired UF-EVs and endometrial tissue samples","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 2","pages":"hoaf010"},"PeriodicalIF":8.3,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11904304/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143627034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Significantly increased load of hereditary cancer-linked germline variants in infertile men.","authors":"Anu Valkna, Anna-Grete Juchnewitsch, Lisanna Põlluaas, Kristiina Lillepea, Stanislav Tjagur, Avirup Dutta, Kristjan Pomm, Margus Punab, Maris Laan","doi":"10.1093/hropen/hoaf008","DOIUrl":"10.1093/hropen/hoaf008","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;What is the load and profile of hereditary cancer-linked germline variants in infertile compared to fertile men?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;This study showed almost 5-fold enrichment of disease-causing findings in hereditary cancer genes in infertile compared to fertile men (6.9% vs 1.5%, &lt;i&gt;P &lt;/i&gt;=&lt;i&gt; &lt;/i&gt;2.3 × 10&lt;sup&gt;-4&lt;/sup&gt;).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;Epidemiological studies have revealed that men with low sperm count have a 2-fold higher risk of developing cancer during their lifetime. Our recent study observed a 4-fold increased prevalence of cancer in men with monogenic infertility compared to the general male population (8% vs 2%). Shared molecular etiologies of male infertility and cancer have been proposed.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;This retrospective study analyzed germline likely pathogenic and pathogenic (LP/P) variants in 157 hereditary cancer genes in 522 infertile and 323 fertile men recruited to the ESTonian ANDrology (ESTAND) cohort.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;All study participants (n = 845) had been recruited and phenotyped at an Andrology Clinic. Identification of LP/P variants in the cancer gene panel was performed from an exome sequencing dataset generated for the study cohort. All variants passed an automated filtering process, final manual assessment of pathogenicity, and experimental confirmation using Sanger sequencing. Retrospective general health records were available for 36 out of 41 (88%) men with LP/P findings.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;Infertile men presented a nearly 5-fold higher load of LP/P findings (36 of 522 cases, 6.9%) compared to fertile subjects (5 of 323, 1.5%; odds ratio (OR) = 4.7, 95% CI 1.81-15.5; &lt;i&gt;P&lt;/i&gt; = 2.3 × 10&lt;sup&gt;-4&lt;/sup&gt;) spanning over 24 hereditary cancer genes. The prevalence of findings was not significantly different between azoospermic and oligozoospermic cases. There was also no enrichment of findings in men with a history of cryptorchidism. By the time of the study, six men carrying hereditary cancer variants had been diagnosed with a tumor. Family members affected with cancer had been documented for 10 of 14 cases with available pedigree health data.Nearly half of the infertile men with LP/P findings (17 out of 36) carried variants in genes belonging to the Fanconi anemia (FA) pathway involved in the maintenance of genomic integrity in mitosis and meiosis, repair of DNA double-stranded breaks, and interstrand crosslinks. Overall, FA-pathway genes &lt;i&gt;BRCA2&lt;/i&gt; (monoallelic) and &lt;i&gt;FANCM&lt;/i&gt; (biallelic) were the most frequently affected loci (five subjects per gene).LP/P findings in pleiotropic genes linked to human development and hereditary cancer (&lt;i&gt;TSC1&lt;/i&gt;, &lt;i&gt;PHOX2B&lt;/i&gt;, &lt;i&gt;WT1&lt;/i&gt;, &lt;i&gt;SPRED1&lt;/i&gt;, &lt;i&gt;NF1&lt;/i&gt;, &lt;i&gt;LZTR1&lt;/i&gt;, &lt;i&gt;HOXB13&lt;/i&gt;) were identified in several patients with syndromic phenotypes. Four cryptorchid ","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 2","pages":"hoaf008"},"PeriodicalIF":8.3,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11889456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Follicle-stimulating hormone stimulates free radical generation without inducing substantial oxidative stress in human granulosa cells.","authors":"Nuan Lin, Koen C van Zomeren, Torsten Plosch, Naomi Hofsink, Teelkien van Veen, Hui Ting Li, Jiazhe Lin, Xiaoling Zhou, Henk Groen, Uwe J F Tietge, Astrid Cantineau, Romana Schirhagl, Annemieke Hoek","doi":"10.1093/hropen/hoaf007","DOIUrl":"10.1093/hropen/hoaf007","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Does FSH induce free radical generation with substantial oxidative damage in human cumulus granulosa cells (cGCs) and mural granulosa cells (mGCs)?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;FSH of both physiological and supraphysiological concentrations induced free radical generation on subcellular levels, most notably in the mitochondria, while the elevated free radical load caused neglectable oxidative damage in both cGCs and mGCs.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;FSH is fundamental for regulation of granulosa cell (GC) function and oocyte maturation, during which a physiological level of reactive oxygen species (ROS) is essential, while excessive amounts lead to oxidative damage. Potential adverse effects of high FSH doses on GCs may be mediated by ROS.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;This prospective experimental study included patients who attended a reproductive medicine center in 2023. cGC and mGC were separately isolated and brought into culture on the day of oocyte retrieval, 36 h after ovulation induction with recombinant hCG (250 mg). Recombinant FSH, at different concentrations, mimicking physiological (6 mIU/ml) and supraphysiological (60 and 600 mIU/ml) conditions, was applied (n = 4 in each group).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;Women aged 20-35 years, undergoing ICSI with at least three follicles, were included. Quantum sensing of cGC and mGC free radicals, detected by either cytoplasm-located fluorescent nanodiamonds (FNDs) or mitochondria-targeted FNDs, was tracked for 2 h following FSH treatment in a magnetometry setup. Mitochondrial function analysis, as well as oxidative damage to DNA/RNA, lipids, and proteins, upon FSH exposure, was examined.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;FSH-induced cytoplasmic and mitochondrial ROS increases in cGC and mGC (&lt;i&gt;P&lt;/i&gt; &lt; 0.01 in all concentrations after 2 h) while showing different patterns along time: cGC showed significantly larger cytoplasmic ROS change compared with mGC to physiological (&lt;i&gt;P&lt;/i&gt; &lt; 0.01) and supraphysiological (&lt;i&gt;P&lt;/i&gt; &lt; 0.05) concentrations of FSH. Significantly larger free radical changes were observed in the mitochondria compared to the cytoplasm in response to FSH (all concentrations in cGCs with &lt;i&gt;P&lt;/i&gt; &lt; 0.05; supraphysiological concentrations in mGCs with &lt;i&gt;P&lt;/i&gt; &lt; 0.05, &lt;i&gt;P&lt;/i&gt; &lt; 0.001, respectively) after 2 h. Mitochondrial basal respiration and ATP production were significantly increased upon FSH exposure to supraphysiological concentrations in both cGCs (&lt;i&gt;P&lt;/i&gt; &lt; 0.01) and mGCs (&lt;i&gt;P&lt;/i&gt; &lt; 0.05). However, no oxidative damage to GC DNA/RNA, proteins, or lipids was found upon FSH exposure at any concentration except elevated lipid peroxidation in the FSH group of 600 mIU/ml (&lt;i&gt;P&lt;/i&gt; &lt; 0.05).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Large scale data: &lt;/strong&gt;N/A.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Limitations reasons for caution: &lt;/strong&gt;The GCs came from females of different ","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 2","pages":"hoaf007"},"PeriodicalIF":8.3,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11893154/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143598415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}