Human reproduction最新文献

{"title":"Intracytoplasmic sperm injection versus conventional in vitro fertilization in infertile couples with normal total sperm count and motility: does sperm morphology matter?","authors":"Toan D Pham, Vinh Q Dang, Vu N A Ho, Cam T Tran, Dung T P Nguyen, Lan N Vuong, Tuong M Ho, Ben W Mol, Rui Wang","doi":"10.1093/humrep/deae252","DOIUrl":"10.1093/humrep/deae252","url":null,"abstract":"<p><strong>Study question: </strong>Among couples with infertility and normal total sperm count and motility, can sperm morphology be used as a biomarker to identify couples who benefit more from ICSI over conventional IVF (c-IVF) on fertility outcomes?</p><p><strong>Summary answer: </strong>Based on this secondary analysis of a large randomized clinical trial (RCT), sperm morphology has limited value as a biomarker to identify couples who benefit more from ICSI over c-IVF on live birth, ongoing pregnancy, clinical pregnancy or total fertilization failure.</p><p><strong>What is known already: </strong>Our recent RCT showed that ICSI did not result in higher live birth rates in couples with normal total sperm count and motility. It is unclear whether sperm morphology can be used as a biomarker to identify couples who benefit more from ICSI over c-IVF in this population.</p><p><strong>Study design, size, duration: </strong>This was a secondary analysis of an open-label, multi-centre, RCT comparing ICSI versus c-IVF in 1064 couples with infertility and normal total sperm count and motility. In this secondary study, we evaluated the effectiveness of ICSI over c-IVF in relation to sperm morphology.</p><p><strong>Participants/materials, setting, methods: </strong>Couples were eligible if they had ≤2 previous IVF/ICSI attempts, and the male partner had normal total sperm count and motility according to the fifth edition of the WHO laboratory manual for the examination and processing of human semen. Sperm morphology was measured from samples obtained during the first consultation and data for sperm morphology were available in partners of all participants in this trial. The outcomes of interest were live birth, ongoing pregnancy, clinical pregnancy, and total fertilization failure. We first conducted a logistic regression analysis with an interaction term (sperm morphology as a continuous variable by treatment (ICSI versus c-IVF)) on the four outcomes. We also used restricted cubic spline analysis to evaluate non-linear interaction and plotted the treatment effects of ICSI over c-IVF at different sperm morphology levels and the predicted probability of these outcomes in both ICSI and c-IVF groups.</p><p><strong>Main results and the role of chance: </strong>The median proportion of sperm with normal morphology in both groups was 3% (Interquartile range 1-6%). Live birth rates were (184/532) 34.6% for ICSI versus (166/532) 31.2% for c-IVF. No significant interaction was found between sperm morphology and treatment effect of ICSI versus c-IVF on the rates of live birth, ongoing pregnancy, clinical pregnancy, and total fertilization failure (P = 0.181, 0.153, 0.168, and 0.788 respectively). In the analyses using restricted cubic splines, no evidence of interaction between sperm morphology and the treatment effect was found. Interaction figures showed that the treatment effect of ICSI over c-IVF at different sperm morphology levels was fluctuating around no e","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"23-29"},"PeriodicalIF":6.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11700896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638776","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":"Particulate air pollution at the time of oocyte retrieval is independently associated with reduced odds of live birth in subsequent frozen embryo transfers.","authors":"S J Leathersich, C S Roche, M Walls, E Nathan, R J Hart","doi":"10.1093/humrep/deae259","DOIUrl":"10.1093/humrep/deae259","url":null,"abstract":"<p><strong>Study question: </strong>Does exposure to particulate matter (PM) air pollution prior to oocyte retrieval or subsequent frozen embryo transfer (FET) affect the odds of live birth?</p><p><strong>Summary answer: </strong>Live birth rates are lower when particulate matter (PM2.5 and PM10) levels are higher prior to oocyte retrieval, regardless of the conditions at the time of embryo transfer.</p><p><strong>What is known already: </strong>Exposure to air pollution is associated with adverse reproductive outcomes, including reduced fecundity and ovarian reserve, and an increased risk of infertility and pregnancy loss. It is uncertain whether the effect on ART outcomes is due to the effects of pollution on oogenesis or on early pregnancy.</p><p><strong>Study design, size, duration: </strong>This retrospective cohort study included 3659 FETs in 1835 patients between January 2013 and December 2021, accounting for all FETs performed at a single clinic over the study period. The primary outcome was the live birth rate per FET. Outcome data were missing for two embryo transfers which were excluded. Daily levels of PM2.5, PM10, nitric oxide, nitrogen dioxide, sulphur dioxide, ozone and carbon monoxide were collected during the study period and calculated for the day of oocyte retrieval and the day of embryo transfer, and during the preceding 2-week, 4-week, and 3-month periods.</p><p><strong>Participants/materials, setting, methods: </strong>Clinical and embryological outcomes were analysed for their association with pollution over 24 hours, 2 weeks, 4 weeks, and 3 months, with adjustment for repeated cycles per participant, age at the time of oocyte retrieval, a quadratic age term, meteorological season, year, and co-exposure to air pollutants. Multi-pollutant models were constructed to adjust for co-exposures to other pollutants. Median concentrations in pollutant quartiles were modelled as continuous variables to test for overall linear trends; a Bonferroni correction was applied to maintain an overall alpha of 0.05 across the four exposure periods tested.</p><p><strong>Main results and the role of chance: </strong>Increased PM2.5 exposure in the 3 months prior to oocyte retrieval was associated with decreased odds of live birth (linear trend P = 0.011); the odds of live birth when PM2.5 concentrations were in the highest quartile were reduced by 34% (OR 0.66, 95% CI 0.47-0.92) when compared to the lowest quartile. A consistent direction of effect was seen across other exposure periods prior to oocyte retrieval, with an apparent dose-dependent relationship. Increased exposure to PM10 particulate matter in the 2 weeks prior to oocyte retrieval was associated with decreased odds of live birth (linear trend P = 0.009); the odds of live birth were decreased by 38% (OR 0.62, 95% CI 0.43-0.89, P = 0.010) when PM10 concentrations were in the highest quartile compared with the lowest quartile. Consistent trends were not seen across other exposure perio","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":"110-118"},"PeriodicalIF":6.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824274","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":"Hypophosphatemia is a frequent finding in infertile men and is associated with low motile sperm count","authors":"Sam Kafai Yahyavi, Gustav Wall-Gremstrup, Benedicte Probst-Drejer, Frederikke Bay Toft, Mads Joon Jorsal, Rune Holt, Lise Aksglaede, Niels Jørgensen, Anders Juul, Martin Blomberg Jensen","doi":"10.1093/humrep/deae293","DOIUrl":"https://doi.org/10.1093/humrep/deae293","url":null,"abstract":"STUDY QUESTION Is serum phosphate linked with semen quality and reproductive hormones in infertile men? SUMMARY ANSWER Hypophosphatemia is a frequent finding in infertile men and is associated with lower number of motile sperm. WHAT IS KNOWN ALREADY Phosphate is available in fluid from all segments of the male reproductive tract in concentrations manyfold higher than in serum. However, the role of phosphate in male fertility is largely unknown. STUDY DESIGN, SIZE, DURATION This cross-sectional study included 1242 men referred due to infertility between January 2017 and May 2020 at the Department of Growth and Reproduction, Rigshospitalet, Copenhagen. PARTICIPANTS/MATERIALS, SETTING, METHODS Each man underwent a physical examination, had semen parameters assessed, and had blood analyzed prospectively for concentrations of phosphate, ionized calcium, alkaline phosphatase, parathyroid hormone, serum 25-hydroxyvitamin D (25OHD), and reproductive hormones. After 246 men were excluded due to serious comorbidities, 1242 were included in the analyses. MAIN RESULTS AND THE ROLE OF CHANCE Infertile men have a high prevalence of mild (25.5%, 0.66–0.80 mmol/l) and moderate hypophosphatemia (10.9%, 0.32–0.65 mmol/l). The percentages of motile spermatozoa and progressively motile spermatozoa were lower in men with moderate hypophosphatemia than in men with mild hypophosphatemia or normophosphatemia (44%, 49%, 51%, P = 0.040, and 32%, 35%, 41%, P = 0.036, respectively). The total numbers of motile and progressively motile spermatozoa were also lower (13, 12, 18 million, P = 0.009, and 10, 9, 14 million, P = 0.006, respectively). Serum concentrations of total and free estradiol were highest in men with moderate hypophosphatemia (97.5, 96.2, 92.1 pmol/l, P = 0.004, and 2.4, 2.3, 2.2 pmol/l, P = 0.034, respectively). LIMITATIONS, REASONS FOR CAUTION The study question is compromised by the descriptive study design. It remains to be shown whether there exist a causal link between serum phosphate and semen quality in infertile men WIDER IMPLICATIONS OF THE FINDINGS As fertility stands as a critical concern in the world, there is a need to find regulators of fertility during adulthood to identify possible treatments. Therefore, the precise mechanisms through which hypophosphatemia may impact sperm motility remain needs to be further clarified. STUDY FUNDING/COMPETING INTEREST(S) This study was supported by Novo Nordisk Foundation, Beckett Foundation, Medical doctor Sofus Carl Emil Friis and spouse Olga Doris Friis’s Grant, Candys Foundation, and The Innovation Foundation. There was no influence from any sponsor on the study design, and the authors have nothing to declare. TRIAL REGISTRATION NUMBER N/A.","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"26 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142908302","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":"Comparison of fresh testicular sperm aspiration and use of either thawed pre-frozen sperm or oocyte freezing: impact on cumulative live birth rates for couples experiencing ejaculation failure","authors":"Shaoquan Zhan, Geng An, Jiayu Gan, Hongzi Du, Xin Fu, Chunyan Wang, Yuling Mao, Xiangjin Kang, Jianqiao Liu, Hanyan Liu","doi":"10.1093/humrep/deae290","DOIUrl":"https://doi.org/10.1093/humrep/deae290","url":null,"abstract":"STUDY QUESTION Is there a difference in the cumulative live birth rate (CLBR) after fresh testicular sperm aspiration (TESA) compared with the use of either pre-frozen sperm or oocyte freezing for couples experiencing ejaculation failure on the day of oocyte retrieval? SUMMARY ANSWER After adjusting for confounding factors, the use of pre-frozen sperm or the freezing and thawing of oocytes appeared to be as effective as TESA in achieving CLBRs for couples experiencing temporary ejaculation failure. WHAT IS KNOWN ALREADY Male patients may be concerned about experiencing temporary ejaculation failure on the day of their partner’s oocyte retrieval, in which case they may choose surgical sperm retrieval, oocyte freezing on the day, or have their sperm frozen in advance. However, the clinical efficacy of these three options has not yet been evaluated. STUDY DESIGN, SIZE, DURATION A retrospective data analysis was conducted on 65 178 oocyte retrieval cycles at a university-affiliated IVF center from January 2012 to May 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS The overall characteristics, completed cycle characteristics, and clinical outcomes were analyzed among couples with ejaculation failure who underwent three distinct clinical interventions, with those receiving TESA serving as the control group. The primary outcome measure was the CLBR, and the secondary outcome measures were the clinical pregnancy rate (CPR) and live birth rate (LBR) per embryo transfer. A robust (modified) Poisson regression model was used to evaluate the association between the three clinical options for ejaculation failure and CLBRs. MAIN RESULTS AND ROLE OF CHANCE Of the eligible oocyte retrieval cycles, 756 cycles (1.2%) experienced ejaculation failure, with 640 cycles completing treatment. These treatments included 325 cycles using TESA, 227 cycles utilizing pre-frozen sperm, and 88 cycles involving frozen–thawed oocytes. The CLBRs for the TESA, thawed-sperm and thawed-oocyte groups were 36.9%, 48.9%, and 34.1%, respectively, showing a statistically significant difference (P = 0.007). Specifically, the thawed-sperm group demonstrated a significantly higher CLBR compared to the TESA group, while no significant difference was observed between the TESA and thawed-oocyte groups. Similarly, the CPRs and LBRs per embryo transfer for the three groups were 37.4%, 50.0%, and 41.8%, respectively (P = 0.005), and 29.9%, 39.6%, and 33.0%, respectively (P = 0.030). Again, the thawed-sperm group showed a significantly higher CPR and a significantly higher LBR, but no significant differences for the thawed-oocyte group, compared to the TESA group. Notably, the significant differences in both CLBR and LBR emerged after the second embryo transfer. However, after adjusting for multiple factors, including female age at oocyte retrieval, type and duration of infertility, female body mass index, number of previous IVF cycles, ovarian stimulation protocol, endometrial thickness on the last","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"34 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142908279","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":"Sexual, relational, and psychological functioning in male partners of women with reported Mayer–Rokitansky–Küster–Hauser syndrome—a case–control study","authors":"F Bleijenberg, P T M Weijenborg, K B Kluivers, S Both","doi":"10.1093/humrep/deae288","DOIUrl":"https://doi.org/10.1093/humrep/deae288","url":null,"abstract":"STUDY QUESTION Do sexual, relational, and psychological functioning of male partners of women with Mayer–Rokitansky–Küster–Hauser (MRKH) syndrome differ from male partners of women without MRKH syndrome? SUMMARY ANSWER Male partners of women with MRKH syndrome did not significantly differ in sexual functioning but reported higher relational satisfaction and less anxiety than the control group. WHAT IS KNOWN ALREADY To date, only a few studies have reported occasionally about sexual, psychological, and relational functioning of partners of women with MRKH syndrome. The results seem to suggest sexual satisfaction in these men, contrary to the more often reported insecurities in women with MRKH syndrome surrounding sexuality and relationships. STUDY DESIGN, SIZE, DURATION In this case–control study, 42 male partners of women with MRKH syndrome and 40 partners of women without the condition were enrolled. PARTICIPANTS/MATERIALS, SETTING, METHODS All participants were recruited through women with MRKH syndrome and age-matched women without the condition who participated in a previous case–control study on sexual, psychological, and relational functioning. Participants live in a heterosexual relationship for at least in the last 6 months and have a basic understanding of the Dutch language. They were administered a set of online questionnaires to assess sexual, relational, and psychological functioning. MAIN RESULTS AND THE ROLE OF CHANCE Partners of women with MRKH syndrome did not differ significantly in overall sexual functioning and had similar percentages of sexual dysfunction and sexual distress as the control group. Partners of women with MRKH syndrome reported significantly less relational dissatisfaction (P = 0.01; Cohen’s d = 0.6) than partners of women without the condition. There was no significant difference in overall psychological functioning or the presence of clinically relevant anxiety and depression, but the men in the MRKH group had a significantly lower anxiety score (P = 0.01; Cohen’s d = 0.6). LIMITATIONS, REASONS FOR CAUTION We were not able to reach a sample size needed for enough power to detect small to medium effect sizes. Confounding factors and selection bias cannot be excluded. WIDER IMPLICATIONS OF THE FINDINGS The study offers new knowledge on a perspective that remains underexposed so far, which makes comparison to previous literature difficult. More research is needed to apply the results in clinical practice. STUDY FUNDING/COMPETING INTEREST(S) This research was supported by the Dutch Scientific Society of Sexology (Nederlandse Wetenschappelijke Vereniging Voor Seksuologie). There was no involvement in the conduct of the research, and the funding was unrestricted. There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER N/A.","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"202 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142887327","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":"Add-ons in medically assisted reproduction: from evidence to clinical practice.","authors":"Munevver Serdarogullari,Omar F Ammar,Mina Mincheva,Claudia Massarotti,Zoya E Ali,Sofia Makieva,Julia Uraji,Juan J Fraire-Zamora,Kashish Sharma,Ioannis Sfontouris,Nick Macklon,Willem Verpoest,Manuela Perrotta,George Liperis","doi":"10.1093/humrep/deae287","DOIUrl":"https://doi.org/10.1093/humrep/deae287","url":null,"abstract":"","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"30 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142887824","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":"Flexible progestin-primed ovarian stimulation versus a GnRH antagonist protocol in predicted suboptimal responders undergoing freeze-all cycles: a randomized non-inferiority trial","authors":"He Cai, Zan Shi, Danmeng Liu, Haiyan Bai, Hanying Zhou, Xia Xue, Wei Li, Mingzhao Li, Xiaoli Zhao, Chun Ma, Hui Wang, Tao Wang, Na Li, Wen Wen, Min Wang, Dian Zhang, Ben W Mol, Juanzi Shi, Li Tian","doi":"10.1093/humrep/deae286","DOIUrl":"https://doi.org/10.1093/humrep/deae286","url":null,"abstract":"STUDY QUESTION Are live birth rates (LBRs) per woman following flexible progestin-primed ovarian stimulation (fPPOS) treatment non-inferior to LBRs per woman following the conventional GnRH-antagonist protocol in expected suboptimal responders undergoing freeze-all cycles in assisted reproduction treatment? SUMMARY ANSWER In women expected to have a suboptimal response, the 12-month likelihood of live birth with the fPPOS treatment did not achieve the non-inferiority criteria when compared to the standard GnRH antagonist protocol for IVF/ICSI treatment with a freeze-all strategy. WHAT IS KNOWN ALREADY The standard PPOS protocol is effective for ovarian stimulation, where medroxyprogesterone acetate (MPA) is conventionally administered in the early follicular phase for ovulatory suppression. Recent retrospective cohort studies on donor cycles have shown the potential to prevent premature ovulation and maintain oocyte yields by delaying the administration of MPA until the midcycle (referred to as fPPOS), similar to GnRH antagonist injections. With milder pituitary suppression, the fPPOS protocol may be a less costly option for women expected to have a low or suboptimal response if a fresh embryo transfer is not intended. STUDY DESIGN, SIZE, DURATION This was a non-inferiority, open-label randomized controlled trial conducted at a tertiary assisted reproduction center. A total of 484 participants were randomized in the study between July 2020 and June 2023 with a 1:1 allocation. PARTICIPANTS/MATERIALS, SETTING, METHODS Infertile women with a predicted suboptimal ovarian response (<40 years old, antral follicle count <10, and basal serum FSH < 12 mIU/ml) were randomly assigned to receive either fPPOS treatment or GnRH antagonist treatment. MPA (10 mg) or GnRH antagonist (0.25 mg) was administered daily once the leading follicle reached 14 mm and continued until the day of trigger. All viable embryos were cryopreserved for subsequent frozen-thawed embryo transfer in both groups. The primary endpoint was the proportion of live births per woman within 12 months post-randomization (with a non-inferiority margin of –12.5%). The analysis was assessed in the per-protocol population. MAIN RESULTS AND THE ROLE OF CHANCE Twenty-two women withdrew at the beginning of the stimulation phase due to COVID-19. Eight women did not proceed with the assigned frozen embryo transfer, and six switched from the fPPOS to the antagonist protocol. Overall, 449 women were included in the per-protocol analysis, with 216 in the fPPOS group and 233 in the GnRH antagonist group. The LBRs per woman were 44.4% (96/216) for participants in the fPPOS group and 48.9% (114/233) for participants in the GnRH antagonist group [risk ratio (RR) 0.91 (95% CI, 0.74, 1.11), risk difference (RD) –4.5% (95% CI, –13.7, 4.7)], which did not meet the non-inferiority criterion (–12.5%). Oocyte and embryonic parameters were not significantly different between the two groups. Nine ","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"48 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142887330","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":"Artificial intelligence-based tissue segmentation and cell identification in multiplex-stained histological endometriosis sections","authors":"Scott E Korman, Guus Vissers, Mark A J Gorris, Kiek Verrijp, Wouter P R Verdurmen, Michiel Simons, Sebastien Taurin, Mai Sater, Annemiek W Nap, Roland Brock","doi":"10.1093/humrep/deae267","DOIUrl":"https://doi.org/10.1093/humrep/deae267","url":null,"abstract":"STUDY QUESTION How can we best achieve tissue segmentation and cell counting of multichannel-stained endometriosis sections to understand tissue composition? SUMMARY ANSWER A combination of a machine learning-based tissue analysis software for tissue segmentation and a deep learning-based algorithm for segmentation-independent cell identification shows strong performance on the automated histological analysis of endometriosis sections. WHAT IS KNOWN ALREADY Endometriosis is characterized by the complex interplay of various cell types and exhibits great variation between patients and endometriosis subtypes. STUDY DESIGN, SIZE, DURATION Endometriosis tissue samples of eight patients of different subtypes were obtained during surgery. PARTICIPANTS/MATERIALS, SETTING, METHODS Endometriosis tissue was formalin-fixed and paraffin-embedded before sectioning and staining by (multiplex) immunohistochemistry. A 6-plex immunofluorescence panel in combination with a nuclear stain was established following a standardized protocol. This panel enabled the distinction of different tissue structures and dividing cells. Artificial intelligence-based tissue and cell phenotyping were employed to automatically segment the various tissue structures and extract quantitative features. MAIN RESULTS AND THE ROLE OF CHANCE An endometriosis-specific multiplex panel comprised of PanCK, CD10, α-SMA, calretinin, CD45, Ki67, and DAPI enabled the distinction of tissue structures in endometriosis. Whereas a machine learning approach enabled a reliable segmentation of tissue substructure, for cell identification, the segmentation-free deep learning-based algorithm was superior. LIMITATIONS, REASONS FOR CAUTION The present analysis was conducted on a limited number of samples for method establishment. For further refinement, quantification of collagen-rich cell-free areas should be included which could further enhance the assessment of the extent of fibrotic changes. Moreover, the method should be applied to a larger number of samples to delineate subtype-specific differences. WIDER IMPLICATIONS OF THE FINDINGS We demonstrate the great potential of combining multiplex staining and cell phenotyping for endometriosis research. The optimization procedure of the multiplex panel was transferred from a cancer-related project, demonstrating the robustness of the procedure beyond the cancer context. This panel can be employed for larger batch analyses. Furthermore, we demonstrate that the deep learning-based approach is capable of performing cell phenotyping on tissue types that were not part of the training set underlining the potential of the method for heterogenous endometriosis samples. STUDY FUNDING/COMPETING INTEREST(S) All funding was provided through departmental funds. The authors declare no competing interests. TRIAL REGISTRATION NUMBER N/A.","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"41 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142887332","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":"More twins expected in low-income countries with later maternal ages at birth and population growth","authors":"D Susie Lee, Kieron J Barclay","doi":"10.1093/humrep/deae276","DOIUrl":"https://doi.org/10.1093/humrep/deae276","url":null,"abstract":"STUDY QUESTION How are the changing maternal age structure and population growth expected to shape future twinning rates in low-income countries? SUMMARY ANSWER With maternal age at birth projected to shift toward older ages, twinning rates are also estimated to increase in most low-income countries by 2050 and even more by 2100. WHAT IS KNOWN ALREADY Many of the sub-Saharan African and South Asian countries are undergoing, and projected to further experience, the shift of maternal age at birth to older ages. Advanced maternal age is a well-established predictor of multiple births at the individual level, but currently, it is unknown how the changes in maternal age distribution are associated with the changes in twinning rates at the population level in low-income countries. STUDY DESIGN, SIZE, DURATION We first estimated age-specific twinning probability based on Demographic Health Surveys and World Fertility Surveys data. We then scaled up the age-specific twinning probability at the population level to estimate changes in the number of twin births in 2050 and 2100 attributable to the estimated shifts in maternal age toward older ages as projected by the UN World Population Prospects (WPP). PARTICIPANTS/MATERIALS, SETTING, METHODS We analyzed ∼3.19 million births that occurred within 10 years before the interview. Majority of the births in our data took place between 1980 and 2015 across 39 countries, where the uptake of medically assisted reproduction (MAR) is known to have been low during the observation period. We estimated country fixed-effects models to obtain country-specific twinning rates and age-specific twinning probability. We applied these estimates to the future number of births projected by the UN WPP, to estimate the number of twin births in 2050 and 2100. MAIN RESULTS AND THE ROLE OF CHANCE With maternal age at birth projected to shift toward older ages, twinning rates are also estimated to increase in most countries by 2050 compared to 2010 (increases from 0.3% to 63% depending on countries), and even more in all studied countries by 2100 (increases from 3.5% to 79%). Due to its large population size, India will continue to have among the largest share of twin births despite its estimated decline of twin births by 10.5% by 2100. Nigeria, due to its not only large and growing population size but also high twinning rate, is expected to contribute the second largest number of twin births. LIMITATIONS, REASONS FOR CAUTION Although the accuracy in maternal recall of multiple births tends to be high, our use of data based on recalled births from the past nonetheless imply a potential bias in our estimation of twinning rates. WIDER IMPLICATIONS OF THE FINDINGS The present study suggests that, even if the spread of MAR remains slow in many low-income countries, twinning rates and number of twin births are expected to grow as an increase in maternal age at birth and population growth continue. Our findings call for more public health at","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"41 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142887817","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":"Sex differences in childhood cancer risk following ART conception: a registry-based study","authors":"L L Oakley, D Kristjansson, M C Munthe-Kaas, H T Nguyen, Y Lee, H I Hanevik, L B Romundstad, R Lyle, S E Håberg","doi":"10.1093/humrep/deae285","DOIUrl":"https://doi.org/10.1093/humrep/deae285","url":null,"abstract":"STUDY QUESTION Does the risk of childhood cancer following ARTs vary by sex? SUMMARY ANSWER In this registry-based study, some childhood cancers showed positive sex- and age-specific associations in children conceived using certain ART modalities, which were not evident in overall combined analyses. WHAT IS KNOWN ALREADY The relationship between ART and risk of childhood cancer has shown diverse outcomes in prior research. Studies examining whether there are sex differences in childhood cancer risk after ART conception are lacking. STUDY DESIGN, SIZE, DURATION This registry-based cohort study included all children born in Norway between 1984 and 2022 (n = 2 255 025), followed until 31 December 2023. PARTICIPANTS/MATERIALS, SETTING, METHODS Children were identified via the Medical Birth Registry of Norway, and information was extracted on whether they were conceived via ART (defined as IVF/ICSI). Of the 2 255 025 children included in the study, 53 694 were ART-conceived. Birth records were linked to the Cancer Registry of Norway. Childhood cancer was defined as a cancer diagnosis according to the International Classification of Childhood Cancer Third Edition (ICCC-3) before the age of 18 years. Cox regression models were used to estimate the age- and sex-specific risk of cancer for ART-conceived children compared to children not conceived via ART. MAIN RESULTS AND THE ROLE OF CHANCE Among all children, 0.25% had a cancer diagnosis before the age of 18 years. The cumulative incidence of cancer was higher in children conceived by ART (IVF/ICSI) than in those not conceived via ART (21.5 vs 17.5 per 100 000 person-years, P = 0.04), and especially higher in boys conceived with ICSI or after cryopreserved embryo transfer. When combining all age groups, both sexes and all cancer types, there was little evidence of increased cancer risk with ART (adjusted hazard ratio (aHR) 1.13, 95% CI 0.94–1.36). However, differences were found when stratifying by age and sex. From age 5–9 years, ART-conceived children had a higher overall risk of cancer (aHR 1.53, 95% CI 1.06–2.20), with a slightly higher estimate in boys (aHR 1.73, 95% CI 1.09–2.74), than in girls (aHR 1.28, 95% CI 0.70–2.33). The risk was not higher up to age 5 years, or after age 10 years. In combined analyses, there was no overall increased risk after ICSI. When stratifying by sex, a higher risk was seen after ICSI for boys (aHR 1.69, 95% CI 1.18–2.42), but not for girls (aHR 0.65, 95% CI 0.37–1.16). The combined risk after cryopreservation (aHR 1.42, 95% CI 0.95–2.13) was driven by a higher risk in boys (aHR 1.79, 95% CI 1.09–2.94), while no evidence of an association was found in girls (aHR 1.01, 95% CI 0.50–2.03). No increased risk was seen with IVF or after fresh transfer for either boys or girls. LIMITATIONS, REASONS FOR CAUTION Childhood cancer is a rare outcome, and some analyses of cancer subtypes were likely underpowered. WIDER IMPLICATIONS OF THE FINDINGS Results from this large registry-","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"87 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142887329","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}