Human reproduction最新文献

{"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}

{"title":"Identification of plasma protein biomarkers for endometriosis and the development of statistical models for disease diagnosis","authors":"E M Schoeman, S Bringans, K Peters, T Casey, C Andronis, L Chen, M Duong, J E Girling, M Healey, B A Boughton, D Ismail, J Ito, C Laming, H Lim, M Mead, M Raju, P Tan, R Lipscombe, S Holdsworth-Carson, P A W Rogers","doi":"10.1093/humrep/deae278","DOIUrl":"https://doi.org/10.1093/humrep/deae278","url":null,"abstract":"STUDY QUESTION Can a panel of plasma protein biomarkers be identified to accurately and specifically diagnose endometriosis? SUMMARY ANSWER A novel panel of 10 plasma protein biomarkers was identified and validated, demonstrating strong predictive accuracy for the diagnosis of endometriosis. WHAT IS KNOWN ALREADY Endometriosis poses intricate medical challenges for affected individuals and their physicians, yet diagnosis currently takes an average of 7 years and normally requires invasive laparoscopy. Consequently, the need for a simple, accurate non-invasive diagnostic tool is paramount. STUDY DESIGN, SIZE, DURATION This study compared 805 participants across two independent clinical populations, with the status of all endometriosis and symptomatic control samples confirmed by laparoscopy. A proteomics workflow was used to identify and validate plasma protein biomarkers for the diagnosis of endometriosis. PARTICIPANTS/MATERIALS, SETTING, METHODS A proteomics discovery experiment identified candidate biomarkers before a targeted mass spectrometry assay was developed and used to compare plasma samples from 464 endometriosis cases, 153 general population controls, and 132 symptomatic controls. Three multivariate models were developed: Model 1 (logistic regression) for endometriosis cases versus general population controls, Model 2 (logistic regression) for rASRM stage II to IV (mild to severe) endometriosis cases versus symptomatic controls, and Model 3 (random forest) for stage IV (severe) endometriosis cases versus symptomatic controls. MAIN RESULTS AND THE ROLE OF CHANCE A panel of 10 protein biomarkers were identified across the three models which added significant value to clinical factors. Model 3 (severe endometriosis vs symptomatic controls) performed the best with an area under the receiver operating characteristic curve (AUC) of 0.997 (95% CI 0.994–1.000). This model could also accurately distinguish symptomatic controls from early-stage endometriosis when applied to the remaining dataset (AUCs ≥0.85 for stage I to III endometriosis). Model 1 also demonstrated strong predictive performance with an AUC of 0.993 (95% CI 0.988–0.998), while Model 2 achieved an AUC of 0.729 (95% CI 0.676–0.783). LIMITATIONS, REASONS FOR CAUTION The study participants were mostly of European ethnicity and the results may be biased from undiagnosed endometriosis in controls. Further analysis is required to enable the generalizability of the findings to other populations and settings. WIDER IMPLICATIONS OF THE FINDINGS In combination, these plasma protein biomarkers and resulting diagnostic models represent a potential new tool for the non-invasive diagnosis of endometriosis. STUDY FUNDING/COMPETING INTEREST(S) Subject recruitment at The Royal Women’s Hospital, Melbourne, was supported in part by funding from the Australian National Health and Medical Research Council (NHMRC) project grants GNT1105321 and GNT1026033 and Australian Medical Research Future Fund gr","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"113 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142884134","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":"Self-reported diagnoses of dietary allergens and fecundability in a North American cohort","authors":"Sydney K Willis, Krystal E Kuan, Elizabeth E Hatch, Holly M Crowe, Amelia K Wesselink, Kenneth J Rothman, Sunni L Mumford, Lauren A Wise","doi":"10.1093/humrep/deae277","DOIUrl":"https://doi.org/10.1093/humrep/deae277","url":null,"abstract":"STUDY QUESTION To what extent are self-reported diagnoses of food allergies associated with fecundability, the per-cycle probability of conception? SUMMARY ANSWER Fecundability was not appreciably associated with self-reported food allergy diagnoses, number of food allergies, age at first diagnosis, or time since last allergic reaction. WHAT IS KNOWN ALREADY Food allergies are atopic diseases that are characterized by an inappropriate immune response to a normally harmless dietary substance. While some studies have observed associations between atopic disorders and infertility, no study has examined the association between food allergies and fecundability, the per-cycle probability of conception. STUDY DESIGN, SIZE, DURATION A prospective cohort study including 7711 females trying to conceive without fertility treatment at enrollment (2018–2022) and followed for up to 12 months. PARTICIPANTS/MATERIALS, SETTING, METHODS We analyzed data from an internet-based prospective cohort of pregnancy planners in North America. At baseline, female participants completed an online questionnaire on demographic, medical, and lifestyle factors that included questions on food allergy diagnoses, age at diagnosis, and time since last reaction. Participants completed bimonthly follow-up questionnaires for up to 12 months to ascertain pregnancy status. The analysis included 7711 PRESTO participants with ≤6 menstrual cycles of pregnancy attempt time at enrollment (2018–2022). We used proportional probabilities regression models to estimate fecundability ratios (FRs) and 95% CIs, adjusted for demographic, lifestyle, and behavioral characteristics. MAIN RESULTS AND THE ROLE OF CHANCE A total of 1028 (13%) participants reported a history of diagnosed food allergy, with the most commonly reported allergy being dairy or shellfish. A history of diagnosed food allergy (vs none) was not appreciably associated with fecundability (FR = 0.93, 95% CI: 0.86–1.02), though specific allergens were associated with fecundability in opposing directions (e.g. inverse association with egg and positive association with soy). We observed non-monotonic associations between fecundability and number of food allergies, age at first allergy diagnosis, and time since last allergic reaction. Inverse associations between self-reported diagnosed food allergens (all types combined) and reduced fecundability were slightly stronger among those with BMI ≥25 (FR = 0.90, 95% CI: 0.80–1.01) than those with BMI <25 (FR = 0.97, 95% CI: 0.86–1.10) and among those born ≥1990 (FR = 0.91, 95% CI: 0.80–1.03) compared with those born <1990 (FR = 0.96, 95% CI: 0.86–1.08). LIMITATIONS, REASONS FOR CAUTION Non-differential misclassification of food allergies was likely given that we relied on self-reported diagnoses. Confounding by unmeasured dietary factors may have influenced associations between specific food allergens and fecundability, if participants were deficient in specific nutrients because th","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"26 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142884384","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":"Biosimilars versus the originator of follitropin alfa for ovarian stimulation in ART: a systematic review and meta-analysis","authors":"Kokkoni I Kiose, Ashleigh Storr, Efstratios M Kolibianakis, Ben W Mol, Christos A Venetis","doi":"10.1093/humrep/deae274","DOIUrl":"https://doi.org/10.1093/humrep/deae274","url":null,"abstract":"STUDY QUESTION Is the probability of pregnancy different between women using biosimilars versus the originator of follitropin alfa for ovarian stimulation in ART? SUMMARY ANSWER Meta-analysis of eight randomized clinical trials (RCTs) suggests that live birth, clinical, and ongoing pregnancy rates are significantly lower with biosimilars of follitropin alfa compared to the originator. WHAT IS KNOWN ALREADY All biosimilars of follitropin alfa have received regulatory approval by demonstrating non-inferiority in the number of retrieved oocytes compared to the originator. Nevertheless, the most clinically relevant outcome in ART for both clinicians and patients is live birth. A meta-analysis published in 2021 suggested that biosimilars of follitropin alfa are associated with lower live birth rates compared to the originator. Since then, more relevant RCTs have been published, and thus an updated critical synthesis of the available evidence is urgently warranted. STUDY DESIGN, SIZE, DURATION A systematic review and meta-analysis were performed to compare biosimilars versus the originator of follitropin alfa in women undergoing ovarian stimulation for ART. A literature search was conducted until January 2024 in MEDLINE, Embase, Cochrane CENTRAL, Scopus, Web of Science, WHO, Clinicaltrials.gov, and others to identify eligible RCTs. The primary outcome was live birth. Secondary outcomes included clinical and ongoing pregnancy, duration of gonadotrophin administration and total FSH dose, number of oocytes retrieved, and ovarian hyperstimulation syndrome (OHSS). PARTICIPANTS/MATERIALS, SETTING, METHODS Data were extracted independently by two reviewers. Quality was assessed using the RoB-2 Tool by Cochrane, and a sensitivity analysis was performed by excluding studies having high risk of bias. Meta-analysis was performed using the random or fixed effects model depending on the presence or not of significant (>50%) statistical heterogeneity (I2). Results were combined using the intention-to-treat principle and are reported as risk ratio (RR) or weighted-mean-difference (WMD) with 95% CIs. MAIN RESULTS AND THE ROLE OF CHANCE Eight RCTs (n = 2987) (published between 2015 and 2023) were identified, assessing seven biosimilar products of follitropin alfa. The number of patients included in the eligible studies ranged from 100 to 1100. Three of the RCTs were deemed to be at high risk of bias. The duration of gonadotrophin administration was shorter in the biosimilars group (WMD: –0.19 days, 95% CI: –0.34 to –0.05; I2 = 0%, 5 studies, n = 2081), while no difference was observed in the total dose of FSH (WMD: –34.69 IUs, 95% CI: –74.54 to 5.16; I2 = 15.53%, 5 studies, n = 2081). No difference was observed in the number of oocytes retrieved (WMD: 0.27, 95% CI: –0.43 to 0.96; I2 = 10.7%, 6 studies, n = 1527) and OHSS rates (RR: 1.17, 95% CI: 0.90–1.52; I2 = 0%, 8 studies, n = 2986) between the two groups. A significantly lower live birth rate was observed us","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"140 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142884386","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":"One-step warming of vitrified human cleavage and blastocyst stage embryos does not adversely impact embryo survivability and subsequent developmental potential","authors":"Masashi Shioya, Ryoko Hashizume, Miki Okabe-Kinoshita, Katsushi Kojima, Sumie Nishi, Shun Nakano, Kaori Koga, Maki Fujita, Keiichi Takahashi","doi":"10.1093/humrep/deae283","DOIUrl":"https://doi.org/10.1093/humrep/deae283","url":null,"abstract":"STUDY QUESTION Does one-step warming (OW), a simplified embryo warming protocol, adversely affect survival and developmental potential in vitrified cleavage or blastocyst stage embryos compared to standard multi-step warming (SW)? SUMMARY ANSWER OW showed no detrimental effects on survival and developmental potential compared to SW in cleavage and blastocyst stage embryos. WHAT IS KNOWN ALREADY While standard embryo warming protocols involve a multi-step procedure using a stepwise osmotic solution to avoid a rapid influx of water into the embryo, recent studies suggest that eliminating the stepwise warming process does not reduce embryo survival and embryo transfer outcomes. However, previous reports have focused primarily on pregnancy rates, and a more detailed analysis of the effects of rapid osmotic pressure changes on embryos is necessary to standardize the protocol. STUDY DESIGN, SIZE, DURATION This preliminary study includes donated 377 vitrified human embryos (177 cleavage and 200 blastocyst stage) from 210 patients approved for discard at the patient’s consent. The embryos were randomly allocated and warmed using either SW or OW protocols. In the SW protocol, embryos were rinsed with a stepwise osmotic solution (thawing, dilution, and washing solutions), and the process was completed with a 13-min warming period. In the OW protocol, embryos were only rinsed in a single solution (thawing solution) for 1 min. PARTICIPANTS/MATERIALS, SETTING, METHODS Post-warming embryos were cultured using a time-lapse incubator. Survival rate and developmental potential, including the occurrence of abnormal morphokinetics and the time required for blastocyst formation after warming of cleavage stage embryos, were compared between SW and OW. Embryos that developed into the blastocyst stage were morphologically evaluated. In the warming of blastocyst stage embryos, the survival rate was determined by the presence of blastocoel expansion, and the proportion of full re-expanded blastocysts was observed at 3- and 24-h post-warming. An in vitro adhesion assay was also performed on blastocysts after culture, and adhesion rate and outgrowth area were measured 24, 48, and 72 h after culture with fibronectin-precoated dishes. MAIN RESULTS AND THE ROLE OF CHANCE OW did not negatively impact survival rates in either cleavage (100% in both OW and SW groups) or blastocyst stage embryos (99% in both groups). Cleavage stage embryos warmed by OW had superior or comparable rates of morulation (96 vs 85%, P = 0.0387), blastulation (78 vs 73%, P = 0.4044), full-blastocyst formation (60 vs 53%, P = 0.3196), and expanded-blastocyst formation (56 vs 49%, P = 0.4056) compared to those warmed by SW. Time-lapse monitoring analysis revealed that the frequency of collapses was reduced in OW (30 vs 50%, P = 0.0410). Additionally, all other abnormal morphokinetics were equivalent between OW and SW (P > 0.05); moreover, the time required for blastocyst formation (P > 0.05)","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"31 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142879690","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":"Association between antinuclear antibodies and pregnancy prognosis in recurrent pregnancy loss patients","authors":"H Yoshihara, S Goto, Tamao Kitaori, M Sugiura-Ogasawara","doi":"10.1093/humrep/deae280","DOIUrl":"https://doi.org/10.1093/humrep/deae280","url":null,"abstract":"STUDY QUESTION Can antinuclear antibodies (ANA) affect the subsequent live birth rate (LBR) in patients with unexplained recurrent pregnancy loss (RPL) in the absence of antiphospholipid antibodies (aPL)? SUMMARY ANSWER Women with unexplained RPL have a high probability of live birth following a positive pregnancy test (>70%), being similar between those with positive and negative ANA testing, regardless of the cut-off value. WHAT IS KNOWN ALREADY The RPL guidelines of the ESHRE state that ‘ANA testing can be considered for explanatory purposes’. However, there have been a limited number of studies on this issue and sample sizes have been small, and the impact of ANA on the pregnancy prognosis is unclear. STUDY DESIGN, SIZE, DURATION A retrospective cohort study was conducted at Nagoya City University Hospital between 2006 and 2019. The study included 1021 women with RPL without known cause. PARTICIPANTS/MATERIALS, SETTING, METHODS Hysterosalpingography or 3D-ultrasound, chromosome analysis for both partners, blood tests for aPL, ANA, hypothyroidism, and diabetes mellitus were performed before a subsequent pregnancy. ANAs were measured by indirect immunofluorescence on Hep-2 cell slides. The cutoff dilution used was 1:40. In addition, patients were classified according to the ANA pattern on immunofluorescence staining: homogeneous, speckled, nucleolar, centromeric, peripheral, cytoplasmic, and others. LBRs were compared between ANA-positive and ANA-negative patients after excluding patients with antiphospholipid antibody syndrome, an abnormal chromosome in either partner and a uterine anomaly. MAIN RESULTS AND THE ROLE OF CHANCE Considering the cut-off value = 1:40 dilution, the subsequent LBRs were 72.5% (256/353) for the ANA-positive group and 73.2% (489/668) for the ANA-negative group; odds ratio (OR) = 0.97, 95% CI = 0.72–1.29. After excluding the miscarriages occurring from embryonic aneuploidy, the biochemical pregnancy losses, and the ectopic pregnancies, LBRs were 92.8% (256/276) for the ANA-positive group and 93.0% (489/526) for the ANA-negative group: OR = 0.97 (95% CI = 0.55–1.70). Considering the cut-off value = 1:80 dilution, the subsequent LBRs were 75.0% (87/116) for the ANA-positive group and 72.7% (658/905) for the ANA-negative group; OR = 1.13 (95% CI = 0.72–1.76). After excluding the miscarriages occurring from embryonic aneuploidy, the biochemical pregnancy losses, and the ectopic pregnancies, LBRs were 89.7% (87/97) for the ANA-positive group and 93.3% (658/705) for the ANA-negative group: OR = 0.62 (95% CI = 0.30–1.27). Considering the cut-off value = 1:160 dilution, the subsequent LBRs were 82.4% (28/34) for the ANA-positive group and 72.6% (717/987) for the ANA-negative group; OR = 1.76 (95% CI = 0.72–4.29). After excluding the miscarriages occurring from embryonic aneuploidy, the biochemical pregnancy losses, and the ectopic pregnancies, LBR were 93.3% (28/30) for the ANA-positive group and 92.9% (717/772) for the ","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"20 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142866992","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":"Damage mechanisms of bisphenols on the quality of mammalian oocytes","authors":"Ashutosh N Pandey, Pramod K Yadav, Karuppanan V Premkumar, Meenakshi Tiwari, Mano Mohan Antony, Ajai K Pandey, Shail K Chaube","doi":"10.1093/humrep/deae284","DOIUrl":"https://doi.org/10.1093/humrep/deae284","url":null,"abstract":"The extensive use of bisphenols in the plastics industry globally is a major growing concern for human health. Bisphenol compounds are easily leached out from plastic containers to food, beverages, and drinking water and contaminate the natural environment. Daily exposure of bisphenol compounds increases their load and impairs various organs, including the reproductive system. Bisphenol compounds directly or indirectly affect ovarian functions, such as folliculogenesis, steroidogenesis, oogenesis, and thereby oocyte quality. Bisphenol A (BPA) and its structural analogues act as endocrine disruptors and induce generation of reactive oxygen species (ROS) within the ovary. Excess levels of ROS induce death pathways in follicular steroidogenic cells and affect ovarian steroidogenesis. The reduced level of estradiol-17β impairs follicular growth and development that reduces the number and quality of oocytes. In addition, excess levels of ROS in follicular fluid trigger meiotic instability, which further deteriorates oocyte quality. The high level of ROS generates oxidative stress that triggers various death pathways in germ cells as well as in oocytes, induces follicular atresia, and depletes ovarian reserve. Although growing evidence indicates the destructive effects of bisphenol compounds at the level of ovary, potential effects and underlying mechanisms that deteriorate oocyte quality remain poorly understood. Therefore, this review summarizes the mechanisms by which bisphenols cause damage to the ovary, impair oocyte quality, and affect women's fertility.","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"119 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142867037","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":"A pilot study of transcriptomic preimplantation genetic testing (PGT-T): towards a new step in embryo selection?","authors":"David Ortega-Jaén, Carlos Mora-Martinez, Antonio Capalbo, Amparo Mifsud, Mireia Boluda-Navarro, Amparo Mercader, Ángel Martín, María Luisa Pardiñas, Julia Gil, María José de los Santos","doi":"10.1093/humrep/deae265","DOIUrl":"https://doi.org/10.1093/humrep/deae265","url":null,"abstract":"STUDY QUESTION Is it possible to predict an euploid chromosomal constitution and identify a transcriptomic profile compatible with extended embryonic development from RNA sequencing (RNA-Seq) data? SUMMARY ANSWER It has been possible to obtain a karyotype comparable to preimplantation genetic testing for aneuploidy (PGT-A), in addition to a transcriptomic signature of embryos which might be suggestive of improved implantation capacity. WHAT IS KNOWN ALREADY Conventional assessment of embryo competence, based on morphology and morphokinetic, lacks knowledge of molecular aspects and faces controversy in predicting ploidy status. Understanding the embryonic transcriptome is crucial, as gene expression influences development and implantation. PGT has improved pregnancy rates, but problems persist when high-quality euploid embryos do not reach term. In fact, only around 50–60% implant, of which 10% result in miscarriage. Comprehensive approaches, including RNA-Seq, offer the potential to discover molecular markers of reproductive competence, and could theoretically be combined with extended-embryo culture platforms up to Day 14 that can be utilized as a proxy to study embryo development at post-implantation stages. STUDY DESIGN, SIZE, DURATION This prospective pilot cohort study was conducted from March 2023 to August 2023. A total of 30 vitrified human blastocysts with previous PGT-A diagnosis on Day 5 (D5) or Day 6 (D6) of development were analysed: n = 15 euploid and n = 15 aneuploid. Finally, 21 embryo samples were included in the study; the rest (n = 9) were excluded due to poor quality pre-sequencing data (n = 7) or highly discordant data (n = 2). PARTICIPANTS/MATERIALS, SETTING, METHODS Following warming and re-expansion, embryos underwent a second trophectoderm (TE) biopsy. The embryos were then cultured until day 11 to assess their development. Biopsy analysis by RNA-Seq, studied the differential expressed genes (DEG) to compare embryos which did not or did attach to the plate: unattached embryos (n = 12) versus attached embryos (n = 9). Thus, we also obtained a specific transcriptomic signature of embryos with a “theoretical” capacity for sustained implantation, based on plate attachment on day 11. MAIN RESULTS AND THE ROLE OF CHANCE The digital karyotype obtained by RNA-Seq showed good concordance with the earlier PGT-A data, with a sensitivity of 0.81, a specificity of 0.83, a Cohen’s Kappa of 0.66, and an area under the ROC of 0.9. At the gene level, 76 statistically significant DEGs were found in the comparison unattached versus attached embryos (Padj < 0.05; FC > 1). To address the functional implications of these differences, significantly deregulated pathways according to GO and KEGG categories were identified. The mural trophectoderm (TE) of the unattached blastocysts showed 63 significantly deregulated terms, displaying upregulation in autophagy, apoptosis, protein kinase and ubiquitin-like protein ligase activity, and","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"25 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142884092","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}