Human reproduction最新文献

{"title":"Hematologic cancers in women: from fertility preservation to post-cancer fertility outcomes.","authors":"E Goldenberg,C Sonigo,S Rakrouki,C Vinolas,F Eustache,V Puy,C Willekens,J Lazarovici,C Sifer,C Becquart,A Mayeur,A Benoit,M Grynberg,M Peigné","doi":"10.1093/humrep/deaf071","DOIUrl":"https://doi.org/10.1093/humrep/deaf071","url":null,"abstract":"STUDY QUESTIONHow do hematological characteristics affect ovarian reserve, ovarian response to ovarian stimulation, and fertility outcomes?SUMMARY ANSWERAlthough lymphoma characteristics impact serum AMH levels, they do not affect, per se, the response to ovarian stimulation and the number of mature oocytes recovered at the time of fertility preservation; in addition, fertility in survivors of hematologic malignancies is relatively conserved.WHAT IS KNOWN ALREADYHematologic cancers can affect young women of reproductive age. While survival rates have improved over the years due to advances in treatment protocols, the treatments used can impact fertility. Fertility preservation methods, such as oocyte or ovarian tissue cryopreservation, are increasingly offered, but concerns remain about reduced ovarian reserve and response to ovarian stimulation in women with these cancers, which may influence the effectiveness of fertility preservation strategies. Moreover, fertility potential after hematologic cancers has been poorly studied.STUDY DESIGN, SIZE, DURATIONThis is a retrospective, observational bi-centric cohort study. All patients with hematologic cancer (lymphoma, leukemia, myeloma, and myelodysplastic syndrome) who underwent fertility preservation before gonadotoxic treatment (n = 286) from January 2013 to March 2023 were included. For fertility after cancer, and use of frozen oocytes/embryos, the endpoint date was 7 July 2023.PARTICIPANTS/MATERIALS, SETTING, METHODSOnly patients with lymphoma were included for analysis of ovarian reserve (n = 238) and ovarian response to ovarian stimulation (n = 230). Low ovarian reserve and impaired ovarian response to ovarian stimulation were defined as AMH <1.2 ng/ml and ≤9 mature oocytes retrieved after ovarian stimulation, respectively, according to POSEIDON criteria. A Cox regression model was used to determine predictive factors of impaired response to ovarian stimulation, low ovarian reserve, and pregnancy after cancer. Cumulative incidence of pregnancy and cumulative use of frozen oocytes/embryos was calculated in all patients suffering from hematological malignancies.MAIN RESULTS AND THE ROLE OF CHANCEThere was an impact of lymphoma characteristics on AMH levels independent of age. After adjustment based on POSEIDON Groups 3 and 4, no specific impact of lymphoma characteristics (e.g. stage, clinical, or biologic B signs) on ovarian response to ovarian stimulation was observed. Regarding post-cancer fertility in the whole population, among the women who tried to conceive, 62% achieved at least one pregnancy, and 85% of these occurred naturally. After adjustment, positive predictive factors for pregnancy were age <35 years, being in a relationship at the first oncofertility consultation, and absence of hematopoietic stem cell transplantation.LIMITATIONS, REASONS FOR CAUTIONLimitations include potential biases due to the heterogeneity of hematological conditions and the retrospective design, which may le","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"35 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893409","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 endometriosis and type and age of menopause: a pooled analysis of 279 948 women from five cohort studies.","authors":"Hsin-Fang Chung,Kunihiko Hayashi,Annette J Dobson,Sven Sandin,Yuki Ideno,Rebecca Hardy,Elisabete Weiderpass,Gita D Mishra","doi":"10.1093/humrep/deaf068","DOIUrl":"https://doi.org/10.1093/humrep/deaf068","url":null,"abstract":"STUDY QUESTIONWhat is the association between endometriosis and the type and age of menopause?SUMMARY ANSWERWomen with endometriosis had a 7-fold increased risk of undergoing surgical menopause rather than natural menopause and were more likely to experience premature or early menopause, both surgically and naturally.WHAT IS KNOWN ALREADYEndometriosis is associated with reduced ovarian reserve, but evidence on its relationship with the type of menopause (surgical vs natural) and timing (especially premature and early menopause) is limited. Women with endometriosis are more likely to undergo hysterectomy and/or oophorectomy (either unilateral or bilateral), but the average age of these surgeries remains unclear.STUDY DESIGN, SIZE, DURATIONThe study analysed individual-level data from 279 948 women in five cohort studies conducted in the UK, Australia, Sweden, and Japan between 1996 and 2022.PARTICIPANTS/MATERIALS, SETTING, METHODSWomen whose menopause type and age could not be determined due to premenopausal hysterectomy with ovarian preservation or use of menopausal hormone therapy were excluded. Endometriosis was identified through self-reports and administrative data. Surgical menopause was defined as premenopausal bilateral oophorectomy. Fine-Gray subdistribution hazard models estimated hazard ratios (HRs) for surgical and natural menopause. Age at menopause was determined by the ages at the final menstrual period or bilateral oophorectomy. Linear regression assessed mean differences in menopause age, while multinomial logistic regression estimated odds ratios (ORs) for categorical menopause age: <40 (premature), 40-44 (early), 45-49, 50-51 (reference), 52-54, and ≥55 years. Spontaneous premature ovarian insufficiency (POI) was defined as natural menopause before age 40 years.MAIN RESULTS AND THE ROLE OF CHANCEEndometriosis was identified in 3.7% of women. By the end of follow-up, 7.9% had surgical menopause and 58.2% experienced natural menopause. Using a competing risk model, women with endometriosis had a 7-fold increased risk of surgical menopause (HR: 7.54, 95% CI 6.84, 8.32) and were less likely to experience natural menopause (HR: 0.40, 95% CI 0.33, 0.49). On average, surgical menopause occurred 1.6 years (19 months) earlier (β: -1.59, 95% CI -1.77, -1.42) in women with endometriosis. Among women who experienced natural menopause, it was 0.4 years (5 months) earlier (β: -0.37, 95% CI -0.46, -0.28) for those with endometriosis. Women with endometriosis were twice as likely to experience premature surgical menopause (<40 years) (OR: 2.11, 95% CI 2.02, 2.20) or 1.4 times more likely to develop spontaneous POI (OR: 1.36, 95% CI 1.17, 1.59). They were also at increased odds of early surgical and natural menopause (40-44 years).LIMITATIONS, REASONS FOR CAUTIONThis study could not differentiate between subtypes and stages of endometriosis or assess treatments for ovarian endometrioma, which may impact ovarian reserve. Self-reported menopause t","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"1 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143893408","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":"Genomics in diagnosing primary ovarian insufficiency (POI): the door is open, but the path is still to be paved.","authors":"Omar F Ammar,George Liperis,Kashish Sharma,Zoya E Ali,Patricia Diaz-Gimeno,Filippo Zambelli,Martine A Gould,Vikram Talaulikar,Juan J Fraire-Zamora","doi":"10.1093/humrep/deaf084","DOIUrl":"https://doi.org/10.1093/humrep/deaf084","url":null,"abstract":"","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"7 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143889247","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 Istanbul consensus update: a revised ESHRE/ALPHA consensus on oocyte and embryo static and dynamic morphological assessment†,‡.","authors":",Giovanni Coticchio,Aisling Ahlström,Gemma Arroyo,Basak Balaban,Alison Campbell,Maria José De Los Santos,Thomas Ebner,David K Gardner,Borut Kovačič,Kersti Lundin,M Cristina Magli,Saria Mcheik,Dean E Morbeck,Laura Rienzi,Ioannis Sfontouris,Nathalie Vermeulen,Mina Alikani","doi":"10.1093/humrep/deaf021","DOIUrl":"https://doi.org/10.1093/humrep/deaf021","url":null,"abstract":"STUDY QUESTIONWhat are the current recommended criteria for morphological assessment of oocytes, zygotes, and embryos?SUMMARY ANSWERThe present ESHRE/Alpha Scientists in Reproductive Medicine consensus document provides several novel recommendations to assess oocyte and embryo morphology and rank embryos for transfer.WHAT IS KNOWN ALREADYA previous Alpha Scientists in Reproductive Medicine/ESHRE consensus on oocyte and embryo morphological assessment was published in 2011. After more than a decade, and the integration of time-lapse technology into embryo culture and assessment, a thorough review and update was needed.STUDY DESIGN, SIZE, DURATIONA working group consisting of Alpha Scientists in Reproductive Medicine executive committee members and ESHRE Special interest group of Embryology members formulated recommendations on oocyte and embryo assessment.PARTICIPANTS/MATERIALS, SETTING, METHODSThe working group included 17 internationally recognized experts with extensive experience in clinical embryology. Seven members represented Alpha Scientists in Reproductive Medicine and eight members represented ESHRE, along with to two methodological experts from the ESHRE central office. Based on a systematic literature search and discussion of existing evidence, the recommendations of the Istanbul Consensus (2011) were reassessed and, where appropriate, updated based on consensus within the working group. A stakeholder review was organized after the updated draft was finalized. The final version was approved by the working group, the Alpha executive committee and the ESHRE Executive Committee.MAIN RESULTS AND THE ROLE OF CHANCEThis updated consensus paper provides 20 recommendations focused on the timeline of preimplantation developmental events and morphological criteria for oocyte, zygote, and embryo assessment. Based on duration of embryo culture, recommendations are given on the frequency and timing of assessments to ensure consistency and effectiveness.LIMITATIONS, REASONS FOR CAUTIONSeveral criteria relevant to oocyte and embryo morphology have not been well studied, leading to either a recommendation against their use for grading or for their use in ranking rather than grading. Future updates may require further revision of these recommendations.WIDER IMPLICATIONS OF THE FINDINGSThis document provides embryologists with advice on best practices when assessing oocyte and embryo quality based on the most recent evidence.STUDY FUNDING/COMPETING INTEREST(S)The consensus meeting and writing of the paper were supported by funds from ESHRE and Alpha Scientists in Reproductive Medicine. The working group members did not receive any payment. G.C. declared payments or honoraria for lectures from Gedeon Richter and Cooper Surgical. A.C. declared text book royalties (Mastering Clinical Embryology, published 2024), consulting fees from Cooper Surgical, Gedeon Richter and TMRW Life Sciences, honoraria for lectures from Merck, Ferring, and Gedeon Richter, and p","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"36 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143885472","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":"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}