Human reproduction最新文献

{"title":"Upregulation of immune genes in the proliferative phase endometrium enables classification into women with recurrent pregnancy loss versus controls","authors":"Laerke H J Andersen, Raquel Sanz Martinez, Yifan Dai, Jens Ole Eriksen, Maria K Gerlach, Lise Grupe Larsen, Nicholas S Macklon, Kristine Juul Hare, Albin Sandelin, Henriette Svarre Nielsen, Thomas Vauvert F Hviid","doi":"10.1093/humrep/deaf051","DOIUrl":"https://doi.org/10.1093/humrep/deaf051","url":null,"abstract":"STUDY QUESTION Does the transcriptome of preconceptional endometrium in the proliferative phase show a specific profile in women with recurrent pregnancy loss (RPL)? SUMMARY ANSWER A specific differential gene expression signature in endometrial samples for women experiencing RPL compared with IVF control women was identified including an RPL subgroup characterized by upregulation of immune-related genes and pathways. WHAT IS KNOWN ALREADY RPL affects 1–3% of couples trying to become parents with both short- and long-term health implications; furthermore, the underlying pathophysiology is complex and heterogeneous with no explanations found for more than half of the couples. Some studies indicate that immunological dysfunction plays a role even preconceptionally and during implantation; however, the few published studies of endometrial transcriptomes from women with RPL have had small sample sizes and focused on the secretory phase of the menstrual cycle. STUDY DESIGN, SIZE, DURATION The study was based on two cohorts of women: an RPL cohort (n = 108) and a control cohort (n = 27). Endometrial samples were collected at two university hospital clinics from March 2013 until February 2019. Dating of the endometrium was made by histological examination by experienced pathologists. PARTICIPANTS/MATERIALS, SETTING, METHODS All women were between 18 and 42 years at the time of collection of the biopsy. RPL was defined as three or more consecutive pregnancy losses or two second-trimester losses or stillbirths. The control group consisted of women referred to IVF/ICSI treatment with a presumed healthy endometrium. All biopsies, except one, were collected in a natural menstrual cycle. In total, 108 women with RPL were subjected to RNA-seq analysis. Seventy-six biopsies were in the proliferative phase, 29 were in the secretory phase, and three could not be classified. For the control women, in total, 27 were included in the RNA-seq analysis; 22 biopsies were in the proliferative phase, one was in the secretory phase, and four could not be classified. Total RNA was extracted from the endometrial biopsies, which had been stored in RNA stabilization solution at −80°C. RNA-seq reads were mapped and quantified using a reference transcriptome and analysed using principal component analysis (PCA), hierarchical clustering, and differential gene expression methods. MAIN RESULTS AND THE ROLE OF CHANCE PCA showed a clear separation of biopsies collected either in the proliferative or secretory phase. For the main analyses, we focused on the women with biopsies in the proliferative phase. PCA and differentially expressed genes (DEGs) revealed that RPL patients were characterized by upregulation of a limited number of immune-related genes and pathways. Further analyses revealed that subjects could describe a gene expression continuum, separable into four different subgroups by the gene expression data, where one subgroup consisted only of IVF controls, one was mixed, an","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"35 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143875730","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":"Thyroid function testing prior to fertility treatment: will we ever agree?","authors":"Sade Dunbar, Rima Dhillon-Smith, Abha Maheshwari","doi":"10.1093/humrep/deaf077","DOIUrl":"https://doi.org/10.1093/humrep/deaf077","url":null,"abstract":"Thyroid disorders are among the most prevalent of medical conditions, especially in women, with the prevalence of both hypo- and hyper-thyroidism being 10-fold more common in women than in men. Thyroid hormones play a key role in subfertility associated with ovulatory dysfunction and miscarriages. While overt thyroid disorders are more often clinically diagnosed, subclinical hypothyroidism (SCH) poses a particular challenge as these patients are usually asymptomatic while their risk for adverse outcomes is higher than in the general population. SCH is biochemically diagnosed when peripheral thyroid hormone levels are normal, but thyroid-stimulating hormone (TSH) levels are elevated; the condition may also be associated with thyroid autoimmunity (TAI). SCH and TAI may remain latent, asymptomatic or undiagnosed, but SCH can progress to overt hypothyroidism in women with TAI during ovarian stimulation and pregnancy. The lack of consensus on the upper limit of normal for TSH has led to variations in the diagnosis of SCH and therefore variations in thresholds for potential treatment. Consequently, there are variations in recommendations for routine testing in patients seeking fertility treatment. Guidance from the British Thyroid Association, American Thyroid Association (ATA), European Thyroid Association (ETA), and Royal College of Obstetrics and Gynaecology recommends screening using TSH with or without antibody testing while those from the National Institute for Health and Care Excellence and the latest from the American Society of Reproductive Medicine do not recommend routine testing. This paper outlines the discourse and varied recommendations related to routine thyroid function testing, with specific reference to the subfertile population of women, and highlights the discord in opinions that currently exist in this arena. An update of the ATA guideline, which will include women with subfertility and will be endorsed by multiple international bodies (including ESHRE and ETA), is eagerly anticipated.","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"8 6 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143872688","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":"To be or not to be a sperm donor: global factors affecting sperm donation in the 21st century.","authors":"Mina Mincheva,Juan J Fraire-Zamora,Kashish Sharma,George Liperis,Omar F Ammar,Jackson Kirkman-Brown,Dorte L Egeberg,Mariana Veloso Martins,Lucy Frith,Julia Uraji","doi":"10.1093/humrep/deaf073","DOIUrl":"https://doi.org/10.1093/humrep/deaf073","url":null,"abstract":"","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"5 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143876450","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":"Preconception sleep, pregnancy loss, and adverse pregnancy outcomes among women with a history of pregnancy loss","authors":"Joshua R Freeman, Brian W Whitcomb, Elizabeth R Bertone-Johnson, Louise M O’Brien, Galit L Dunietz, Alexandra C Purdue-Smithe, Keewan Kim, Robert M Silver, Enrique F Schisterman, Sunni L Mumford","doi":"10.1093/humrep/deaf074","DOIUrl":"https://doi.org/10.1093/humrep/deaf074","url":null,"abstract":"STUDY QUESTION Are preconception sleep characteristics associated with pregnancy loss and adverse pregnancy outcomes? SUMMARY ANSWER Preconception sleep characteristics were not associated with pregnancy loss, but earlier sleep midpoints were associated with lower risk of adverse pregnancy outcomes, while social jetlag >1 h was associated with greater risk of a composite of adverse pregnancy outcomes. WHAT IS KNOWN ALREADY Short sleep duration in mid-pregnancy has been associated with risk of second-trimester pregnancy loss, preterm birth (PTB), and hypertensive disorders of pregnancy (HDP). The relationships between preconception sleep and pregnancy loss, and adverse pregnancy outcomes have not been well characterized, despite plausible links. STUDY DESIGN, SIZE, DURATION This was a secondary analysis of a randomized controlled trial conducted between 2006 and 2012 that prospectively followed 1228 women who were attempting to become pregnant after a history of pregnancy loss. Women were followed for ≤6 cycles while attempting pregnancy, and throughout pregnancy if they conceived. Over the follow-up, 140 women withdrew from the study. PARTICIPANTS/MATERIALS, SETTING, METHODS This study evaluated baseline, self-reported preconception sleep duration, sleep latency, sleep midpoint, and social jetlag with risk of pregnancy loss and adverse pregnancy outcomes (e.g. PTB, HDP, and gestational diabetes (GDM)) among 1228 women with a history of pregnancy loss in the EAGeR trial. Pregnancy was documented by hCG tests; 797 women became pregnant over the follow-up. Pregnancy losses were defined as any loss after a positive hCG test; there were 188 pregnancy losses. PTB, HDP, and GDM cases were ascertained via medical record abstraction. PTB (n = 53), HDP (n = 62), and GDM (n = 22) were examined as a composite outcome (n = 118) and PTB and HDP were examined individually in exploratory analyses. GDM was not examined individually due to insufficient numbers. Log-Poisson models were used to estimate relative risks (RR) and 95% CIs for associations between preconception sleep characteristics, and pregnancy loss or adverse pregnancy outcomes with adjustment for age, BMI, lifestyle, and sociodemographic factors. Stabilized inverse probability weights were applied to address potential selection bias from loss to follow-up and from restricting to pregnancy. MAIN RESULTS AND THE ROLE OF CHANCE Preconception sleep characteristics were not associated with risk of pregnancy loss. Preconception sleep duration and sleep latency were not associated with risk of the composite adverse pregnancy outcome. Early preconception sleep midpoints were associated with a lower risk of the composite adverse pregnancy outcome (first vs second tertile RR; 0.63, 95% CI: 0.40, 0.98) and preconception social jetlag was associated with a higher risk of the composite adverse pregnancy outcome (>1 vs ≤1 h RR; 1.65, 95% CI: 1.11, 2.44). LIMITATIONS, REASONS FOR CAUTION Preconceptio","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"13 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866438","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 phenotypic and genetic association between endometriosis and immunological diseases.","authors":"Nina Shigesi,Holly R Harris,Hai Fang,Anne Ndungu,Matthew R Lincoln,,,Chris Cotsapas,Julian Knight,Stacey A Missmer,Andrew P Morris,Christian M Becker,Nilufer Rahmioglu,Krina T Zondervan","doi":"10.1093/humrep/deaf062","DOIUrl":"https://doi.org/10.1093/humrep/deaf062","url":null,"abstract":"STUDY QUESTIONIs there an increased risk of immunological diseases among endometriosis patients, and does a shared genetic basis contribute to this risk?SUMMARY ANSWEREndometriosis patients show a significantly increased risk of autoimmune, autoinflammatory, and mixed-pattern diseases, including rheumatoid arthritis, multiple sclerosis, coeliac disease, osteoarthritis, and psoriasis, with genetic correlations between endometriosis and osteoarthritis, rheumatoid arthritis, and multiple sclerosis, and a potential causal link to rheumatoid arthritis.WHAT IS KNOWN ALREADYThe epidemiological evidence for an increased risk of immunological diseases among women with endometriosis is limited in scope and has varied in robustness due to the opportunity for biases. The presence of a biological basis for increased comorbidity across immunological conditions has not been investigated. Here we investigate the phenotypic and genetic association between endometriosis and 31 immune conditions in the UK Biobank.STUDY DESIGN, SIZE, DURATIONPhenotypic analyses between endometriosis and immune conditions (17 classical autoimmune, 10 autoinflammatory, and 4 mixed-pattern diseases) were conducted using two approaches (8223 endometriosis, 64 620 immunological disease cases): (i) retrospective cohort study design to incorporate temporality between diagnoses and (ii) cross-sectional analysis for simple association. Genome-wide association studies (GWAS) and meta-analyses for those immune conditions that showed phenotypic association with endometriosis (1493-77 052 cases) were conducted.PARTICIPANTS/MATERIALS, SETTING, METHODSComprehensive phenotypic association analyses were conducted in females in the UK Biobank. GWAS for immunological conditions were conducted in females-only and sex-combined study populations in UK Biobank and meta-analysed with existing largest available GWAS results. Genetic correlation and Mendelian randomization (MR) analyses were conducted to investigate potential causal relationships. Those immune conditions with significant genetic correlation with endometriosis were included in multi-trait analysis of GWAS to boost discovery of novel and shared genetic variants. These shared variants were functionally annotated to identify affected genes utilizing expression quantitative trait loci (eQTL) data from GTEx and eQTLGen databases. Biological pathway enrichment analysis was conducted to identify shared underlying biological pathways.MAIN RESULTS AND THE ROLE OF CHANCEIn both retrospective cohort and cross-sectional analyses, endometriosis patients were at significantly increased (30-80%) risk of classical autoimmune (rheumatoid arthritis, multiple sclerosis, coeliac disease), autoinflammatory (osteoarthritis), and mixed-pattern (psoriasis) diseases. Osteoarthritis (genetic correlation (rg) = 0.28, P = 3.25 × 10-15), rheumatoid arthritis (rg = 0.27, P = 1.5 × 10-5) and multiple sclerosis (rg = 0.09, P = 4.00 × 10-3) were significantly genetically cor","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"108 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866439","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":"An interpretable artificial intelligence approach to differentiate between blastocysts with similar or same morphological grades.","authors":"Hang Liu,Longbin Chen,Guanqiao Shan,Chen Sun,Changfu Lu,Hongqing Liao,Shuoping Zhang,Shaonan Dong,Xinxin Xu,Qiuyun Yan,Fei Gong,Zhuoran Zhang,Changsheng Dai,Wenyuan Chen,Haocong Song,Lei Chen,Shanshan Wang,Haixiang Sun,Ge Lin,Yu Sun,Yifan Gu","doi":"10.1093/humrep/deaf066","DOIUrl":"https://doi.org/10.1093/humrep/deaf066","url":null,"abstract":"STUDY QUESTIONCan a quantitative method be developed to differentiate between blastocysts with similar or same inner cell mass (ICM) and trophectoderm (TE) grades, while also reflecting their potential for live birth?SUMMARY ANSWERWe developed BlastScoringNet, an interpretable deep-learning model that quantifies blastocyst ICM and TE morphology with continuous scores, enabling finer differentiation between blastocysts with similar or same grades, with higher scores significantly correlating with higher live birth rates.WHAT IS KNOWN ALREADYWhile the Gardner grading system is widely used by embryologists worldwide, blastocysts having similar or same ICM and TE grades cause challenges for embryologists in decision-making. Furthermore, human assessment is subjective and inconsistent in predicting which blastocysts have higher potential to result in live birth.STUDY DESIGN, SIZE, DURATIONThe study design consists of three main steps. First, BlastScoringNet was developed using a grading dataset of 2760 blastocysts with majority-voted Gardner grades. Second, the model was applied to a live birth dataset of 15 228 blastocysts with known live birth outcomes to generate blastocyst scores. Finally, the correlation between these scores and live birth outcomes was assessed. The blastocysts were collected from patients who underwent IVF treatments between 2016 and 2018. For external application study, an additional grading dataset of 1455 blastocysts and a live birth dataset of 476 blastocysts were collected from patients who underwent IVF treatments between 2021 and 2023 at an external IVF institution.PARTICIPANTS/MATERIALS, SETTING, METHODSIn this retrospective study, we developed BlastScoringNet, an interpretable deep-learning model which outputs expansion degree grade and continuous scores quantifying a blastocyst's ICM morphology and TE morphology, based on the Gardner grading system. The continuous ICM and TE scores were calculated by weighting each base grade's predicted probability and summing the predicted probabilities. To represent each blastocyst's overall potential for live birth, we combined the ICM and TE scores using their odds ratios (ORs) for live birth. We further assessed the correlation between live birth rates and the ICM score, TE score, and the OR-combined score (adjusted for expansion degree) by applying BlastScoringNet to blastocysts with known live birth outcomes. To test its generalizability, we also applied BlastScoringNet to an external IVF institution, accounting for variations in imaging conditions, live birth rates, and embryologists' experience levels.MAIN RESULTS AND THE ROLE OF CHANCEBlastScoringNet was developed using data from 2760 blastocysts with majority-voted grades for expansion degree, ICM, and TE. The model achieved mean area under the receiver operating characteristic curve values of 0.997 (SD 0.004) for expansion degree, 0.903 (SD 0.031) for ICM, and 0.943 (SD 0.040) for TE, based on predicted probabilities for e","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"24 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143862015","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":"Racial and ethnic disparities in fecundability: a North American preconception cohort study","authors":"Lauren A Wise, Molly N Hoffman, Sharonda M Lovett, Ruth J Geller, Nina L Schrager, Ugochinyere Vivian Ukah, Amelia K Wesselink, Jasmine A Abrams, Renee Boynton-Jarrett, Wendy Kuohung, Andrea S Kuriyama, Matthew O Hunt, David R Williams, Collette N Ncube","doi":"10.1093/humrep/deaf067","DOIUrl":"https://doi.org/10.1093/humrep/deaf067","url":null,"abstract":"STUDY QUESTION To what extent are there racial and ethnic disparities in fecundability in North America? SUMMARY ANSWER In a North American preconception cohort study, we observed large differences in fecundability across racial and ethnic groups. WHAT IS KNOWN ALREADY Several studies in the United States (USA) have shown that Black women tend to wait longer for fertility treatment and are less likely to seek medical care for infertility than White women. Among those who seek infertility treatment, there are large racial disparities in access to treatment and treatment success rates. However, research has been limited and conflicting on the extent to which fertility measures such as fecundability (per-cycle probability of conception) vary by race and ethnicity. STUDY DESIGN, SIZE, DURATION We examined the associations of race and ethnicity with fecundability in Pregnancy Study Online (PRESTO), a prospective preconception cohort study of US and Canadian residents aged 21–45 years who were actively trying to conceive without the use of fertility treatment at enrollment (2013–2024). We restricted the analysis to 18 573 participants with fewer than 12 cycles of pregnancy attempt time at enrollment. PARTICIPANTS/MATERIALS, SETTING, METHODS Participants self-reported data on race and ethnicity on a baseline questionnaire and completed bimonthly follow-up questionnaires for up to 12 months to update data on pregnancy status. We estimated fecundability ratios (FRs) and 95% confidence intervals (CI) using proportional probabilities regression models. We stratified by pregnancy attempt time at enrollment, reproductive history, country of residence, age, and educational attainment. In sensitivity analyses, we applied inverse probability of continuation weights to account for differential loss-to-follow-up. We also calculated the cumulative incidence of infertility during 12 cycles of attempt time by race and ethnicity using life-table methods to account for censoring. MAIN RESULTS AND THE ROLE OF CHANCE Compared with non-Hispanic White participants, fecundability was appreciably lower among participants who identified as non-Hispanic Black (FR = 0.60, 95% CI: 0.52–0.70), non-Hispanic American Indian/Alaskan Native/Indigenous (FR = 0.70, 95% CI: 0.44–1.11), non-Hispanic multiracial (FR = 0.89, 95% CI: 0.81–0.99), or Hispanic other/unknown race (FR = 0.77, 95% CI: 0.65–0.90). Results were similar when we performed various sensitivity analyses including: application of inverse probability of continuation weights to account for differential loss-to-follow-up; stratification by age and educational attainment; and restriction of analyses to (i) participants with <3 cycles of pregnancy attempt time at enrollment, (ii) nulligravid participants without an infertility history, and (iii) US residents. The 12-cycle cumulative incidence of infertility (i.e. clinical definition) among participants with <2 cycles of attempt time at entry also differed meanin","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"29 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143847083","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":"Prevalence of endometriosis in Mayer-Rokitansky-Küster-Hauser syndrome variants: a systematic review and meta-analysis.","authors":"Paolo Vercellini,Francesca Caprara,Martina Piccini,Agnese Donati,Paola Viganò,Edgardo Somigliana,Sonia Cipriani","doi":"10.1093/humrep/deaf057","DOIUrl":"https://doi.org/10.1093/humrep/deaf057","url":null,"abstract":"STUDY QUESTIONIn patients with Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS; population), is the presence of functional endometrium (FE) in uterine remnants (URs) (exposure), compared with the absence of FE in UR/absence of UR (comparison), associated with a higher prevalence of endometriosis (outcome)?SUMMARY ANSWERThe aggregate prevalence of endometriosis was considerably higher in MRKHS patients with FE (MRKHSFE+) than in those without FE (MRKHSFE-).WHAT IS KNOWN ALREADYThe pathogenesis of endometriosis is not fully understood. The finding of pelvic endometriosis in patients with MRKHS is one of the main objections to the retrograde menstruation (RM) hypothesis. The recent advent of high-resolution ultrasonography and magnetic resonance imaging (MRI) allowed the reliable preoperative identification of FE concealed within UR, and histopathological examination after UR removal is no longer the only means of verifying the presence of a mucosal component. A similar prevalence of endometriosis in MRKHSFE+ and MRKHSFE- patients, as assessed by preoperative ultrasound (US) and/or MRI, would essentially rule out the RM/implantation theory, whereas a substantially higher prevalence of endometriosis in MRKHSFE+ than in MRKHSFE- patients would challenge the embryonic remnants/coelomic metaplasia hypothesis.STUDY DESIGN, SIZE, DURATIONThis systematic review was restricted to full-length, English-language articles published in peer-reviewed journals between 1 January 1980 and 1 June 2024. The electronic PubMed and Embase databases were searched in June 2024. The keyword 'endometriosis' was used in combination with 'Mayer-Rokitansky-Küster-Hauser syndrome', 'Müllerian agenesis', 'uterine agenesis', 'vaginal agenesis', 'Müllerian anomalies', and 'female genital malformations'. References from relevant publications were screened, and PubMed's 'similar articles' and 'cited by' functions were used.PARTICIPANTS/MATERIALS, SETTING, METHODSStudies were selected if they reported the presence or absence of FE within UR investigated by preoperative US or MRI or histology after surgical removal, and the presence or absence of surgically confirmed endometriosis. Case series and case reports were deemed eligible for inclusion. Studies not specifically stating the intent to search for the presence of endometrium within UR, or not reporting the results of ultrasonography or MRI, or histological examinations were excluded. Two reviewers independently abstracted data. The risk of bias was assessed using a tool specifically devised to ascertain the methodological quality of case series and case reports.MAIN RESULTS AND THE ROLE OF CHANCEA total of 102 studies (29 case series and 73 case reports), comprising 666 MRKHS patients in whom the presence or absence of FE was verified were included. Endometriosis was detected in 71 participants (10.7%; 95% CI, 8.5-13.2%), and its prevalence was 8.6% (51/593; 95% CI, 6.6-11.2%) in case series and 27.4% (20/73; 95% CI, 18.4-38.6%) in","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"30 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143849553","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":"Reclassifying NOBOX variants in primary ovarian insufficiency cases with a corrected gene model and a novel quantitative framework","authors":"Reiner A Veitia, Jamie D Cowles, Sandrine Caburet","doi":"10.1093/humrep/deaf058","DOIUrl":"https://doi.org/10.1093/humrep/deaf058","url":null,"abstract":"STUDY QUESTION How updated expression and genomic data combined with a disease/disorder-specific classification system can be used to correct a gene model for a better evaluation of the pathogenicity of variants found in patients? SUMMARY ANSWER By combining available genomic and transcriptomic data from several species and a quantitative classification framework with primary ovarian insufficiency (POI)-adjusted parameters, we correct the human NOBOX (newborn ovary homeobox) gene model and provide a reclassification of variants previously reported in POI cases. WHAT IS KNOWN ALREADY The NOBOX gene, encoding a gonad-specific transcription factor with a crucial role in early folliculogenesis and considered a major gene involved in POI, is currently described as being expressed as four transcripts, the longest one considered canonical. All the variants identified in POI cases have been evaluated according to this canonical transcript, and the various functional tests have been performed using the corresponding predicted protein. STUDY DESIGN, SIZE, DURATION We refined and corrected the NOBOX gene model using available genomic and RNAseq data in human and 16 other mammalian species. Expression data were selected for tissue specificity, strand specificity, and coverage. The analysis of RNAseq data from different ovarian fetal stages allows for a time-course description of NOBOX isoforms. Literature was scanned to retrieve NOBOX variants reported in POI cases, and NOBOX variants present in ClinVar and GnomAD 4 databases were also retrieved. PARTICIPANTS/MATERIALS, SETTING, METHODS Strand-specific RNAseq data from human fetal ovaries and human adult testes were analysed to infer the correct human NOBOX gene isoforms. The conservation of the gene structure was verified by combining the aligned genomic sequences from 17 mammalian species covering a wide phylogenetic range and the relevant RNAseq data. As changing a gene model implies a reclassification of variants, we set up a quantitative framework with updated variant frequencies from GnomAD4 and POI-adjusted parameters following the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines. Using this framework, we reclassified 44 NOBOX variants reported in POI patients and families, 117 NOBOX variants reported in ClinVar, and 2613 NOBOX variants present in GnomAD4. MAIN RESULTS AND THE ROLE OF CHANCE The corrected NOBOX gene model proposes the invalidation of two transcripts, including the canonical one. The two correct isoforms were present in fetal ovarian samples, and only one was detected in adult testes. Only 14 variants remained as possibly causative for POI. Furthermore, this re-evaluation strongly suggests that NOBOX biallelic variants are the most likely cause of POI. LARGE SCALE DATA Large tables are provided as supplementary data sets on the Zenodo repository. LIMITATIONS, REASONS FOR CAUTION The proposed gene model is robust but relies on a","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"17 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143847131","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":"International Committee for Monitoring Assisted Reproductive Technologies (ICMART): world report for cycles conducted in 2017–2018","authors":"Valerie L Baker, Silke Dyer, Georgina M Chambers, Elena Keller, Manish Banker, Jacques de Mouzon, Eman Elgindy, Fu M Bai, Osamu Ishihara, Seung Chik Jwa, Markus S Kupka, Fernando Zegers-Hochschild, G David Adamson","doi":"10.1093/humrep/deaf049","DOIUrl":"https://doi.org/10.1093/humrep/deaf049","url":null,"abstract":"STUDY QUESTION What were the rates of utilization, effectiveness, and safety for assisted reproductive technology (ART) throughout the world in 2017 and 2018, and what trends were observed? SUMMARY ANSWER The total reported number of ART fresh and frozen cycles conducted in 83 participating countries was 2 913 498 in 2017 and 3 303 505 in 2018, with 5-year trends including an increasing proportion of cycles utilizing frozen embryo transfer (FET) and an increasing number of cycles utilizing pre-implantation genetic testing (PGT). WHAT IS KNOWN ALREADY Prior reports from the International Committee Monitoring ART (ICMART) have reported on the utilization, effectiveness, and safety of ART from participating countries, with an increase in the number of cycles and number of participating countries over time. These reports have described regional differences in the utilization of ART overall, as well as differences in the utilization of specific practices such as ICSI, PGT and single embryo transfer. Past reports demonstrated that rates of delivery per cycle have increased and rates of multiple gestations have decreased over time. STUDY DESIGN, SIZE, DURATION This retrospective, cross-sectional survey describes ART procedures performed globally in 2017 and 2018. Data were submitted to ICMART by participating countries from national or regional registries. PARTICIPANTS/MATERIALS, SETTING, METHODS There were 83 countries which provided data for cycles performed in 2017 or 2018, with the majority of countries providing data for both years. Aggregate data are reported for each participating country and analysed using methods developed by ICMART to calculate measures of utilization, effectiveness, and safety. MAIN RESULTS AND THE ROLE OF CHANCE A total of 2 913 498 cycles and 671 012 babies born were reported for treatment performed in 2017, increasing to 3 303 505 cycles and 728 383 babies born for treatment performed in 2018. After imputing data for non-reporting centres in reporting countries, the estimated number of cycles performed in 2017 was 3 107 188 resulting in an estimated 814 588 babies. For 2018, the estimated number of cycles was 3 568 635 resulting in an estimated 870 814 babies. Utilization of ICSI for autologous fresh non-PGT cycles declined slightly compared with 2014 (54.6% in 2017 and 57.3% in 2018 compared with 64.8% in 2014). The percentage of transfers which were of frozen embryos was 55.7 % in 2017 and 57.9% in 2018, up from 38.9% in 2014. Among all countries, including those which reported no ‘freeze all’ cycles, the percentage of ‘freeze all’ cycles was 30.5% in 2017 and 32.7% in 2018, up from 13.1% in 2014. In countries reporting at least one retrieval cycle in which all embryos were frozen, the percentage of retrievals with no fresh embryo transfer increased (36.2% in 2017 and 36.8% in 2018, up from 20.1% in 2014). The number of PGT cycles in 2018 (172 247) was nearly 5-fold higher than the number reported in 2014 (36 512) with w","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"59 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143841447","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}