I Streuli,L Ramyead,N Silvestrini,P Petignat,J Dubuisson
{"title":"Impact of definitive uterine artery occlusion on ovarian reserve markers in laparoscopic myomectomy: a randomized controlled trial with 2-year follow-up.","authors":"I Streuli,L Ramyead,N Silvestrini,P Petignat,J Dubuisson","doi":"10.1093/humrep/deaf070","DOIUrl":"https://doi.org/10.1093/humrep/deaf070","url":null,"abstract":"STUDY QUESTIONDoes definitive occlusion of uterine arteries have a short- or long-term impact on ovarian reserve markers in reproductive-age women undergoing laparoscopic myomectomy?SUMMARY ANSWERPreventive definitive uterine artery occlusion (UAO) during laparoscopic myomectomy reduces intraoperative blood loss but does not impact serum AMH levels after short- and long-term follow-up in reproductive-age women.WHAT IS KNOWN ALREADYUterine leiomyomas are the most common benign tumours in women of reproductive age. For symptomatic women willing to retain their uterus, especially for a future pregnancy, the current gold standard is surgical myomectomy for subserous/intramural leiomyoma. Temporary or definitive occlusion of uterine arteries can be performed to control bleeding during surgery but its impact on ovarian reserve markers is still unclear. A single randomized trial with a 1-year follow-up demonstrated that temporary bilateral UAO during laparoscopic myomectomy slightly decreased AMH levels at postoperative day 2 but has no significant impact at 3, 6, and 12 months after surgery.STUDY DESIGN, SIZE, DURATIONWe conducted a randomized controlled trial with a 2-year follow-up evaluating the effect of definitive occlusion of uterine arteries on ovarian reserve markers via sequential measures of AMH levels and AFC by ultrasound assessment. The study included 58 women with symptomatic leiomyoma type FIGO 3 to 6 scheduled for laparoscopic myomectomy between July 2015 and October 2021. Patient allocation was disclosed to the surgeon just before starting the procedure; women were blinded to group allocation throughout the study.PARTICIPANTS/MATERIALS, SETTING, METHODSPatients were randomized in two groups: the UAO group (laparoscopic myomectomy with preventive occlusion of uterine arteries) (n = 29 women) and the no-UAO group (laparoscopic myomectomy without occlusion of uterine arteries but with intra-myometrial injection of vasoconstrictive agents) (N = 29 women). Serum AMH levels and AFC were evaluated at baseline (T0) and followed at 1 month (T1), 3 months (T3), 6 months (T6), 12 months (T12), and 24 months (T24) after surgery. Intraoperative blood loss, evolution of uterine bleeding and pain symptoms, and leiomyoma recurrence were also evaluated as secondary outcomes. Pregnancies and live births were monitored.MAIN RESULTS AND THE ROLE OF CHANCEWomen in both groups did not differ in their baseline characteristics in terms of age, body mass index, ethnicity, parity, wish to become pregnant, hormonal treatment, leiomyoma number and size, baseline haemoglobin levels, uterine bleeding symptoms, baseline serum AMH levels, and AFC. The mean operative time was similar between both groups. Mean blood loss during surgery was on average 138 (±104) ml in the UAO group versus 436 (±498) ml in controls (P < 0.001). In the UAO group, 0% had an intraoperative blood loss >500 ml versus 32.1% in the no-UAO group (P < 0.01). Regarding clinical symptoms, most pati","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"43 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144145918","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":"Novel insights into the lipid signalling in human spermatozoa","authors":"Steven Serafini, Cristian O’Flaherty","doi":"10.1093/humrep/deaf085","DOIUrl":"https://doi.org/10.1093/humrep/deaf085","url":null,"abstract":"Infertility, affecting one in six couples worldwide, poses significant health and social challenges. While both male and female factors contribute to infertility, male infertility causes remain underexplored, with about 34% of cases classified as unexplained. A few studies focus on the role of lipids in male fertility, and some lipids are rising as key players in spermatozoa. This review highlights the importance of lipids, particularly phospholipids, neutral lipids, and glycolipids, in spermatozoa during capacitation and the acrosome reaction (AR). The dynamic lipid profile of human spermatozoa is crucial for their development, maturation, and fertilization capability. During epididymal maturation, sperm undergo crucial biochemical changes, including increased production of phosphatidylcholine and sphingomyelin, which enhance membrane integrity and mobility. Increased levels of ceramide affect membrane fluidity and signalling necessary for sperm function. As spermatozoa enter the female reproductive tract, they adjust their lipid content for capacitation and fertilization. Lipid signalling is crucial for human spermatozoa, influencing their viability and fertilization potential during transit through the female reproductive tract. Lysophosphatidic acid, abundant in seminal plasma, enhances sperm motility, facilitates the AR by promoting glycolysis and calcium influx, and is important for maintaining sperm viability. The remodelling of lipid rafts, enriched in cholesterol and sphingolipids, is essential for signal transduction and capacitation. Sphingolipids, particularly sphingosine 1-phosphate and ceramide, play significant roles in sperm capacitation and AR by promoting reactive oxygen species production and calcium signalling, respectively. Understanding these lipid dynamics will increase our knowledge of the complexity of sperm metabolism.","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"1 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144130676","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}
Diana M Tordoff, Stephanie A Leonard, Jiaqi Zhang, Ava Snow, Brent Monseur, Mahri A Bahati, Cassie Armea-Warren, Daniel Moretti, Micah E Lubensky, Annesa Flentje, Mitchell R Lunn, Juno Obedin-Maliver
{"title":"Methods of family building used by sexual and gender minority adults in the United States","authors":"Diana M Tordoff, Stephanie A Leonard, Jiaqi Zhang, Ava Snow, Brent Monseur, Mahri A Bahati, Cassie Armea-Warren, Daniel Moretti, Micah E Lubensky, Annesa Flentje, Mitchell R Lunn, Juno Obedin-Maliver","doi":"10.1093/humrep/deaf098","DOIUrl":"https://doi.org/10.1093/humrep/deaf098","url":null,"abstract":"STUDY QUESTION What methods are used by sexual and gender minority (SGM) parents to build their families? SUMMARY ANSWER SGM parents used diverse methods to build their families, which varied both by gender identity and age. WHAT IS KNOWN ALREADY Despite experiencing significant barriers to becoming parents, 63% of SGM adults aged 18–35 years old are considering having children or expanding their family. Data on US same-sex couples demonstrate that although most same-sex parents (68%) are genetically related to their children, they are more likely to adopt, foster, and be step-parents compared with different-sex couples. STUDY DESIGN, SIZE, DURATION Cross-sectional analysis of 2018–2020 data from The PRIDE Study, a community-engaged longitudinal cohort study of SGM adults living in the USA. This analysis included 2122 SGM parents with 4712 children (median of 2 children per parent). PARTICIPANTS/MATERIALS, SETTING, METHODS Primary exposures were SGM subgroups (cisgender sexual minority men, cisgender sexual minority women, gender diverse people assigned female at birth [AFAB], gender diverse people assigned male at birth [AMAB], transgender men, and transgender women) and age cohorts (18–39, 40–54, and 55 and older). The primary outcome was method of family building, grouped into three overarching categories defined as (1) pregnancy from sexual activity, (2) pregnancy without sexual activity (e.g. use of donor gametes, surrogacy), and (3) a method other than pregnancy (e.g. adoption, fostering, step-parenting). We used logistic regression models to evaluate differences in methods of family building used by SGM subgroup and age groups. MAIN RESULTS AND THE ROLE OF CHANCE Overall, 56% of SGM adults became parents through pregnancy from sexual activity, 14% became parents through pregnancy without sexual activity, and 28% became parents from a method other than pregnancy. Transgender women, gender diverse parents, and cisgender men had a higher odds of using pregnancy through sexual activity to become parents and were less likely to become parents using pregnancy without sexual activity compared with cisgender women. Conversely, transgender men were less likely to use pregnancy through sexual activity (aOR 0.57, 95% CI 0.44, 0.73) and over twice as likely to use methods other than pregnancy (aOR 2.39, 95% CI 1.86, 3.06) compared to cisgender women. Parents aged 18–39 and 40–54 years old were twice as likely to use pregnancy without sexual activity compared with parents aged 55+ years old (Age 18–39: aOR 2.16, 95% CI: 1.55, 2.99; Age 40–54: aOR 1.92, 95% CI: 1.39, 2.66). LIMITATIONS, REASON FOR CAUTION Our convenience sample was predominantly White. We are unable to infer information about the preferred methods or attempted but unsuccessful methods of family building. WIDER IMPLICATIONS OF THE FINDINGS The number of SGM parents is likely to grow, given that younger generations are more likely to identify as SGM, desire children, and have access to me","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"56 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144130387","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":"Detection of minimal residual disease in cryopreserved testicular tissue from (pre)pubertal boys with acute leukemia following first-line therapy","authors":"Aurélie Feraille, Pascaline Etancelin, Shirley Troche, Fabrice Jardin, Nimrod Buchbinder, Pascale Schneider, Magali Dugay, Nathalie Rives, Christine Rondanino, Ludovic Dumont","doi":"10.1093/humrep/deaf093","DOIUrl":"https://doi.org/10.1093/humrep/deaf093","url":null,"abstract":"STUDY QUESTION Is it feasible to detect minimal residual disease (MRD) in cryopreserved testicular tissue (TT) from (pre)pubertal boys diagnosed with acute leukemia using molecular biology techniques? SUMMARY ANSWER This pilot study demonstrates the feasibility of detecting MRD in cryopreserved TT, which could guide the choice of the safest techniques for fertility restoration. WHAT IS KNOWN ALREADY Fertility preservation through testicular tissue freezing (TTF) is offered to (pre)pubertal boys undergoing highly gonadotoxic treatment. However, the risk of reintroducing leukemic cells during fertility restoration has not been adequately addressed. To date, no study has evaluated the feasibility of detecting residual disease using molecular biology within cryopreserved, thawed and unfixed TT. STUDY DESIGN, SIZE, DURATION This pilot study analyzed cryopreserved TT from 14 (pre)pubertal boys diagnosed with acute lymphoblastic leukemia (ALL) or acute myeloblastic leukemia (AML) who had already received first-line chemotherapy and underwent TTF before hematopoietic stem cell transplantation. PARTICIPANTS/MATERIALS, SETTING, METHODS The study included cryopreserved TT from 14 (pre)pubertal boys. Molecular biology techniques, including RT-qPCR and qPCR, were used to detect oncogenic fusion genes or clonal rearrangements of immunoglobulin genes or T-cell receptor (Ig/TCR) in cryopreserved TT samples. MAIN RESULTS AND THE ROLE OF CHANCE MRD was identified in 36% (5 out of 14) of TT samples using molecular biology techniques. A 21% discordance was observed between conventional histopathology and molecular detection, with molecular methods showing higher sensitivity. No significant association was found between clinical or histological characteristics and MRD status in the TT. LIMITATIONS, REASONS FOR CAUTION This study is a pilot study with a small sample size of TT samples from patients with ALL or AML, which may limit the generalizability of the findings. Further studies with larger cohorts are needed to validate our data. WIDER IMPLICATIONS OF THE FINDINGS The detection of MRD in cryopreserved TT using molecular biology techniques could help guide the selection of the safest fertility restoration strategies for leukemic patients by minimizing the risk of reintroducing malignant cells. This approach underscores the importance of cryopreserving TT after complete remission of acute leukemia (AL). STUDY FUNDING/COMPETING INTEREST(S) The study was funded by Rouen University Hospital, GIRCI NO, French Biomedicine Agency, and Ligue National Contre le Cancer. The authors declare no competing interests. TRIAL REGISTRATION NUMBER Not applicable.","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"3 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144097241","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}
Nina Freiesleben Mørch, Hanne Udengaard, Marie Louise Borch, Michelle Saltoft Skovrup, Bugge Nøhr, Pernille Fog Svendsen
{"title":"Estradiol and progesterone levels in early pregnancy after modified natural, programmed, and gonadotrophin-stimulated frozen embryo transfer cycles: a randomized controlled trial","authors":"Nina Freiesleben Mørch, Hanne Udengaard, Marie Louise Borch, Michelle Saltoft Skovrup, Bugge Nøhr, Pernille Fog Svendsen","doi":"10.1093/humrep/deaf083","DOIUrl":"https://doi.org/10.1093/humrep/deaf083","url":null,"abstract":"STUDY QUESTION Are serum estradiol and progesterone levels higher in women treated with programmed cycle (PC) FET compared to women treated with a gonadotrophin-stimulated (gSC) FET or a modified natural cycle (mNC) FET during early pregnancy? SUMMARY ANSWER Estradiol and progesterone levels are higher on the day of embryo transfer in women treated with PC compared to those treated with a mNC or gSC. WHAT IS KNOWN ALREADY Various FET treatment regimens may affect the maternal hormone balance very differently in early pregnancy. Recent studies show that a PC is associated with increased risk of hypertensive pregnancy disorders, high birth weight, and postpartum hemorrhages. The underlying mechanism is not known but differences in hormone levels could play a role. STUDY DESIGN, SIZE, DURATION This was a parallel open-label randomized controlled drug trial conducted from April 2021 until December 2024. The target sample size was 100 cycles in each treatment arm for a power of 80%. A total of 305 cycles were included and 257 were included in the per-protocol analysis. Ovulatory women were randomized to either a PC or a mNC. Anovulatory women were randomized to a PC or a gSC. Blood samples were obtained at seven consecutive time points from the start of the cycle until gestational age (GA) 9 + 6 weeks. Obstetric and neonatal follow-up was completed through the patients’ digital medical records. Primary outcomes were differences in serum estradiol and progesterone between patient groups and treatment regimens. Secondary outcomes were to compare the type of cycle with reproductive, obstetric, and neonatal outcomes between groups. PARTICIPANTS/MATERIALS, SETTING, METHODS The trial was conducted in the Fertility Clinic at Herlev University Hospital, Denmark. Participants were women aged 18–40 years with BMI ≤35 kg/m2. Only women using autologous frozen blastocysts were eligible and all women had a normal wet cervical wet smear within the last 3 years. MAIN RESULTS AND THE ROLE OF CHANCE For ovulatory women, estradiol and progesterone levels were higher in PCs on the day of embryo transfer day compared to mNCs (estradiol: 0.86 nmol/l vs 0.54 nmol/l, adjusted P &lt; 0.001, progesterone: 68.5 nmol/l vs 40.3 nmol/l, adjusted P &lt; 0.001), and progesterone levels were also higher in PCs at GA 8 + 0 (87.5 nmol/l vs 61.2 nmol/l, adjusted P = 0.02). For anovulatory women, the same trend was observed when comparing PCs to gSCs. Serum estradiol was significantly higher on the day of embryo transfer day (0.96 nmol/l vs 0.54 nmol/l, adjusted P &lt; 0.01), though no significant differences in progesterone were found. We found no differences in pregnancy rates, live birth rates, pregnancy loss rates, or cancelation rates. Ovulatory women treated with PCs had significantly larger children with an estimated treatment difference of 292 grams (P &lt; 0.01) compared to those treated with mNCs. Furthermore, we observed a higher risk of postpartum hemorrhages","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"66 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144097242","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}
Sophie Hu, Sophie Lalonde-Bester, Jenna Salem, Sheffinea Koshy, Donna Vine, Tyrone G Harrison, Jennifer M Yamamoto, Jamie L Benham
{"title":"Validity of administrative health data case definitions for identifying polycystic ovary syndrome: a systematic review and meta-analysis","authors":"Sophie Hu, Sophie Lalonde-Bester, Jenna Salem, Sheffinea Koshy, Donna Vine, Tyrone G Harrison, Jennifer M Yamamoto, Jamie L Benham","doi":"10.1093/humrep/deaf094","DOIUrl":"https://doi.org/10.1093/humrep/deaf094","url":null,"abstract":"STUDY QUESTION What is the validity of published administrative health data case definitions of polycystic ovary syndrome (PCOS) compared with reference standards? SUMMARY ANSWER Due to the limited number of eligible studies, drawing definitive conclusions is challenging; however, this review highlights significant gaps and variability in current PCOS case definitions, underscoring the need for standardized case definitions in future research. WHAT IS KNOWN ALREADY Administrative health data offer the opportunity to evaluate health outcomes and disease epidemiology at a population-level. Currently, the validity of existing administrative health data case definitions for PCOS is unknown. STUDY DESIGN, SIZE, DURATION A systematic review of the literature was conducted on full-text English-language articles up to July 2023, using the MEDLINE and EMBASE databases. PARTICIPANTS/MATERIALS, SETTING, METHODS Two reviewers independently screened titles, abstracts and full texts, extracted data, assessed study quality and graded validity. A random effects meta-analysis was conducted to pool reported validity measures and heterogeneity was examined. MAIN RESULTS AND THE ROLE OF CHANCE The review included four eligible articles consisting of three cross-sectional studies and one retrospective cohort study. Two studies defined PCOS using the Rotterdam Criteria, one study used self-report, and one used a clinical gold standard. All case definitions included the International Classification of Diseases (ICD)-9 code 256.4 for ‘polycystic ovaries’ and three studies used E28.2 for ‘polycystic ovarian syndrome’. Three studies reported positive predictive value (PPV), which ranged from 30 to 96%. One study reported both PPV (96%) and sensitivity (50%) for one case definition. The pooled PPV estimate for the ICD code-based case definitions was 88% (95% confidence interval 82-95%; I2 = 100%). One study reported fair agreement (percent agreement= 90.3, κ = 0.27, percent agreement bias adjusted κ = 0.81). Overall, the risk of bias of the included studies was low. LIMITATIONS, REASONS FOR CAUTION There were limited number of validations and precision indices of validations. WIDER IMPLICATIONS OF THE FINDINGS Further validation of these case definitions in other administrative health datasets, and development of novel coding algorithms is required to inform future population-based studies in PCOS. STUDY FUNDING/COMPETING INTEREST(S) No external funding was used and there are no disclosures. REGISTRATION NUMBER PROSPERO CRD42023385617","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"42 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144083176","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}
Linda G Kahn, Alison E Hipwell, Mia Charifson, Rui Ling, Kim N Cajachagua-Torres, Akhgar Ghassabian
{"title":"Maternal polycystic ovarian syndrome and offspring psychopathology and neurodevelopment","authors":"Linda G Kahn, Alison E Hipwell, Mia Charifson, Rui Ling, Kim N Cajachagua-Torres, Akhgar Ghassabian","doi":"10.1093/humrep/deaf079","DOIUrl":"https://doi.org/10.1093/humrep/deaf079","url":null,"abstract":"Polycystic ovarian syndrome (PCOS) is a common female endocrinologic condition that affects both the metabolic and reproductive systems and is the most frequent cause of anovulatory infertility. It is also associated with a range of psychiatric outcomes in individuals, including bulimia nervosa, schizophrenia, bipolar disorder, depression, anxiety, and personality disorders. At the same time, evidence suggests that hyperandrogenism, the characteristic trait of PCOS, may impair fetal neurodevelopment. Epidemiological studies have linked maternal PCOS with a variety of behavioral and psychiatric conditions in offspring including autism spectrum disorder and attention deficit hyperactivity disorder. In this review, we explore evidence for potential underlying biological mechanisms that might explain these observed associations, discuss the complex interplay between genetics and various environmental factors across generations, and highlight avenues for future research.","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"4 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144067161","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}
Mark E Gill,Manuel Fischer,Christian De Geyter,Antoine H F M Peters
{"title":"Normozoospermic infertile men possess subpopulations of sperm varying in DNA accessibility, relating to differing reproductive outcomes.","authors":"Mark E Gill,Manuel Fischer,Christian De Geyter,Antoine H F M Peters","doi":"10.1093/humrep/deaf081","DOIUrl":"https://doi.org/10.1093/humrep/deaf081","url":null,"abstract":"STUDY QUESTIONCan a reliable assay be developed to quantify DNA accessibility in human sperm to help with the assessment of pre-implantation development affected by dense packaging of mammalian sperm's genetic material?SUMMARY ANSWERWe adapted NicE-view, an assay that directly labels accessible DNA, for use in human sperm and applied it to examine spermatozoa from infertile individuals with distinct reproductive outcomes.WHAT IS KNOWN ALREADYExisting data suggest a connection between sperm chromatin compaction and reproductive outcomes. The assays used to generate this data, however, measure chromatin compaction indirectly and thus understanding their meaning is challenging.STUDY DESIGN, SIZE, DURATIONBetween April 2020 to December 2023, 60 normozoospermic infertile men were invited to participate in an experimental study and asked to provide a semen sample.PARTICIPANTS/MATERIALS, SETTING, METHODSAmong the 60 individuals forty had undergone at least one treatment with ART. Among these ART-treated participants, 20 were included in the study because after fertilization only one or no embryos developed during embryo culture (low blastocyst growth rate, LBGR). The other 20 men were included as at least 50% of cultured embryos developed to the blastocyst stage (high blastocyst growth rate). Additionally, 20 previously infertile individuals obtained a pregnancy naturally (NATP) and were included as well. Washed spermatozoa obtained from seminal plasma or prepared by swim-up procedure were processed for NicE-view to determine DNA accessibility as a marker of chromatin condensation using confocal microscopy. Images of more than 3 million spermatozoa were acquired. Computer-assisted image segmentation was used to identify individual sperm heads and DNA accessibility levels were then quantified in each. We also compared NicE-view to chromomycin A3 (CMA3), a conventional marker of chromatin de-condensation, and ATAC-see, an alternative assay for measuring DNA accessibility.MAIN RESULTS AND THE ROLE OF CHANCEBoth semen and swim-up samples of participants contained two well-delineated subpopulations of spermatozoa with distinct DNA accessibility levels, the frequencies of which varied among individuals. Interestingly, individuals with high frequencies of highly accessible sperm DNA, as measured in semen, possessed decreased sperm concentrations. Moreover, participants with high frequency of highly accessible sperm DNA were more common in the LBGR sub-group. Surprisingly, selection of motile sperm by swim-up enriched for sperm with high DNA accessibility in participants from all three sub-groups. Chromatin accessibility measurements by Nice-view were distinct from DNA staining with the fluorescent CMA3 dye, and NicE-view allowed much clearer separation of sperm subpopulations than ATAC-see.LIMITATIONS, REASONS FOR CAUTIONThis was a single-centre study with a cohort of 60 individuals. Sperm samples containing very high frequencies of sperm with increased DNA ac","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"74 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144065565","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":"Reply: The role of light sheet microscopy for non-invasive imaging of live embryos.","authors":"F Horta,E Vargas-Ordaz,A Neild,V J Cadarso","doi":"10.1093/humrep/deaf092","DOIUrl":"https://doi.org/10.1093/humrep/deaf092","url":null,"abstract":"","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"200 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144065566","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 light sheet microscopy for non-invasive imaging of live embryos.","authors":"Kylie R Dunning,Kishan Dholakia","doi":"10.1093/humrep/deaf091","DOIUrl":"https://doi.org/10.1093/humrep/deaf091","url":null,"abstract":"","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"15 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144065630","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}