Human reproduction最新文献

{"title":"Reduced live birth rates following ART in adenomyosis patients: a matched control study","authors":"M Bourdon, A Mimouni, C Maignien, M Casalechi, P Vigano, C Bordonne, A E Millisher, C Patrat, L Marcellin, C Chapron, P Santulli","doi":"10.1093/humrep/deaf052","DOIUrl":"https://doi.org/10.1093/humrep/deaf052","url":null,"abstract":"STUDY QUESTION How does adenomyosis affect live birth rates (LBRs) in women undergoing ART compared to a matched control population? SUMMARY ANSWER Women with adenomyosis, matched with controls for age, blastocyst count, and top-quality blastocyst count, exhibited reduced LBR following IVF/ICSI treatment. WHAT IS KNOWN ALREADY Adenomyosis, a benign uterine disorder, is believed to hinder implantation due to anatomical, hormonal, and immune disruptions. Its precise impact on LBRs following ART, however, remains controversial, with studies presenting inconsistent outcomes. It is uncertain whether adenomyosis directly reduces ART success or if confounding factors such as age or embryo quality play a more significant role. STUDY DESIGN, SIZE, DURATION This observational study included women aged 18–42 years undergoing IVF/ICSI treatments with a freeze-all strategy from 1 January 2018 to 31 December 2022, each having at least one available blastocyst for transfer. The adenomyosis group consisted of patients with a confirmed diagnosis through pelvic MRI, interpreted by gynecologic radiologists. The control group included women without adenomyosis, who had idiopathic, tubal, and/or male factor infertility. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 285 women with adenomyosis were included. These patients were matched 1:1 with controls based on age, the number of cryopreserved blastocysts, and the number of top-quality blastocysts. The primary outcome was the cumulative LBR per patient following a single oocyte retrieval, with secondary outcomes including clinical pregnancy rate (CPR) and early miscarriage rate (EMR). Both univariate and multivariate analyses were conducted. MAIN RESULTS AND THE ROLE OF CHANCE In this study, 285 women with adenomyosis were matched with 285 controls. The mean age was 35.4 ± 3.3 and 35.5 ± 3.4 years, respectively, with an average of 3.5 ± 2.5 and 3.6 ± 2.6 cryopreserved blastocysts and 0.4 ± 0.7 and 0.4 ± 0.5 top-quality blastocysts, respectively. In the adenomyosis group, MRI revealed internal diffuse adenomyosis in 73.7% of patients, adenomyoma in 3.5%, and external adenomyosis lesions in 46.7%. The cumulative LBR was significantly lower in the adenomyosis group compared to controls (41.4% versus 51.9%; odds ratio = 0.65, 95% CI [0.47–0.91]; P = 0.012). Similarly, the CPR was reduced in the adenomyosis group (53.3% versus 63.9%; P = 0.011). No significant difference was found in the EMR. Multivariate analysis, adjusted for confounders such as freeze-all indication, AMH levels, BMI, infertility type, and ART procedure (IVF versus ICSI), identified adenomyosis as an independent risk factor for reduced LBR (OR = 0.7, 95% CI [0.4–0.9]). These findings indicate that adenomyosis is associated with lower ART success rates. LIMITATIONS, REASONS FOR CAUTION Patients included in this study were from a specialized referral center focusing on the management of endometriosis and adenomyosis, potentially introducing selection","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"58 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143745111","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":"Risk factors for recurrent implantation failure as defined by the European Society for Human Reproduction and Embryology.","authors":"Can Wang, Youhui Lu, Miaoxian Ou, Lingxuan Qian, Yingying Zhang, Yuxin Yang, Lu Luo, Qiong Wang","doi":"10.1093/humrep/deaf042","DOIUrl":"https://doi.org/10.1093/humrep/deaf042","url":null,"abstract":"<p><strong>Study question: </strong>What are the unrecognized risk factors for recurrent implantation failure (RIF) as defined in the ESHRE recommendation?</p><p><strong>Summary answer: </strong>Anti-Müllerian hormone (AMH) is the strongest predictor for RIF, followed by chronic endometritis (CE), intrauterine adhesions, and BMI.</p><p><strong>What is known already: </strong>Advanced age is a well-known risk factor for implantation failure, and the definition of RIF was stratified by age in the 2023 ESHRE recommendation. However, the literature identifies other risk factors, including CE, endometriosis, BMI, endometrial polyps, intrauterine adhesions, hydrosalpinx, uterine malformation, submucosal myoma, polycystic ovary syndrome, thyroid dysfunction, rheumatic diseases, and hyperprolactinemia, to be associated with implantation failure. In addition, our clinical experience suggests AMH and a history of previous livebirth affect RIF. It remains unclear which of these factors are the best predictors of RIF.</p><p><strong>Study design, size, duration: </strong>A cohort study drawn from ART cycles between June 2019 and June 2022.</p><p><strong>Participants/materials, setting, methods: </strong>Two hundred and ninety-eight RIF patients and 2056 controls (women who achieved successful embryo implantation within 1-2 transfer cycles) were identified from 15 329 ART cycles at the Reproductive Medical Center at the First Affiliated Hospital of Sun Yat-sen University. RIF was defined according to the recommendation of ESHRE 2023. Basic characteristics, reproductive history, laboratory indicators (autoantibodies and endocrine factors), ultrasound, laparoscopy, hysteroscopy, hysterosalpingography, biopsy, and immunohistochemistry results were collected from the electronic medical record system. The Random Forest procedure was applied to build a machine learning model for predicting RIF. Overall predictive accuracy was assessed by using the AUC of receiver-operator characteristic curve and calibration plots. The SHapley Additive exPlanations (SHAP) framework was used to interpret the model.</p><p><strong>Main results and the role of chance: </strong>From 32 variables, elevated AMH level and greater number of live births were associated with lower risk of RIF, while CE, intrauterine adhesions, high FSH level, high testosterone level, advanced female age, polyps, history of recurrent pregnancy loss, history of cesarean section, polycystic ovary syndrome, and rheumatic diseases were associated with higher risk of RIF according to the established random forest model. The predictive model yielded AUCs of 0.83 (95% CI: 0.80-0.86) in training dataset and 0.78 (95% CI: 0.73-0.84) in testing dataset. The calibration curve indicated good predictive performance in both training and testing datasets. SHAP values indicated that AMH had the greatest influence on the RIF risks, whereas CE, intrauterine adhesions, and BMI were the second, third, and fourth most significant r","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718688","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":"Risk of major gynecologic surgery before age 40 among daughters of young mothers.","authors":"Clarice R Weinberg, Olga Basso, Aimee A D'Aloisio, Dale P Sandler","doi":"10.1093/humrep/deaf048","DOIUrl":"https://doi.org/10.1093/humrep/deaf048","url":null,"abstract":"<p><strong>Study question: </strong>Is being born of a young mother associated with worse gynecologic health, as indicated by a bilateral oophorectomy or hysterectomy before age 40?</p><p><strong>Summary answer: </strong>Daughters of mothers younger than 25 did not have reduced parity but did have a higher risk of having bilateral oophorectomy or hysterectomy before age 40, particularly if their mother was younger than 20 years at their birth.</p><p><strong>What is known already: </strong>Three recent studies have reported lower fecundability among daughters of mothers younger than 20 years; adverse socioeconomic conditions may explain part of that association.</p><p><strong>Study design, size, duration: </strong>This study reports cumulative, primarily retrospective, accrual of outcomes up to age 40 among 41 450 women recruited into the US-based Sister Study between 2003 and 2009.</p><p><strong>Participants/materials, setting, methods: </strong>The analysis sample included women ≥41 years at the time of the latest follow-up and <66 years at recruitment. Using log-binomial regression, we estimated adjusted relative risks (RRs) of having major gynecologic surgery (bilateral oophorectomy or hysterectomy) before age 40 by age of the participant's mother (G1) when she gave birth to the participant (G2). All models were adjusted for father's age at G2's birth, daughter's self-identified race/ethnicity, and year of birth. We assessed possible effect modification by stratifying the analyses by self-reported G2's family income level during childhood (poor-low, medium-high) and G2's educational level (categorized as below bachelor's degree and bachelor's degree or higher) and, in the following step, by G2's age at first birth.</p><p><strong>Main results and the role of chance: </strong>Compared with daughters born to mothers aged 30-34, daughters of mothers <20 and 20-24 years had an RR of 1.74 (95% CI 1.51, 2.00) and 1.35 (1.22, 1.50), respectively, of major gynecologic surgery before age 40. Although lower childhood income, G2 education, and giving birth before age 25 were strongly associated with outcome risk, the RRs changed little after accounting for those factors.</p><p><strong>Limitations, reasons for caution: </strong>This is a descriptive study of a proxy indicator of poor gynecologic health. Furthermore, all information was self-reported and, for nearly all women, recalled after the event. The measures used for socioeconomic status may have been insufficient.</p><p><strong>Wider implications of the findings: </strong>Daughters of younger mothers did not have reduced parity but appeared to have a higher risk of major gynecologic surgery before age 40. This study adds to prior evidence that daughters of young mothers have worse gynecologic health.</p><p><strong>Study funding/competing interest(s): </strong>This research was supported in part by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01-ES","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709740","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":"Swim-up versus density gradients for sperm preparation in infertile couples undergoing intrauterine insemination: a randomized clinical trial.","authors":"Tuyen N D Duong, Vinh Q Dang, Tien K Le, Anh T L Vu, Duy L Nguyen, Toan D Pham, Mai T Nguyen, Phuong T M Nguyen, Tuan M Vo, Chau T H Nguyen, Phuong T B Le, Anh H Le, Cam T Tran, Ben W Mol, Lan N Vuong, Tuong M Ho","doi":"10.1093/humrep/deaf047","DOIUrl":"https://doi.org/10.1093/humrep/deaf047","url":null,"abstract":"<p><strong>Study question: </strong>What is the effectiveness of swim-up (SU) and density gradients (DG) for sperm preparation in infertile couples undergoing IUI?</p><p><strong>Summary answer: </strong>In infertile couples undergoing IUI, SU and DG did not result in statistically significant different live birth rates.</p><p><strong>What is known already: </strong>SU and DG are the two most commonly used techniques for sperm preparation in infertile couples undergoing IUI. In the latest Cochrane review, given the very low quality of available data, the authors were uncertain whether there was a difference in clinical pregnancy rates between the two techniques. Furthermore, live birth rate was not reported in any trial.</p><p><strong>Study design, size, duration: </strong>This open-label, two-centre, randomized clinical trial was conducted at two IVF centres in Vietnam. A sample size of 912 couples was needed to demonstrate a 5% difference between SU and DG (power 0.80, two-sided alpha 5%, loss to follow-up, and cross-over rate 10%). Randomization was performed using a computer-generated random list, with a variable block size of 2, 4, or 6. Assignment to treatment allocation was done via a web portal.</p><p><strong>Participants/materials, setting, methods: </strong>Eligible couples included those who were ≥18 years of age, where the husbands' sperm concentration, progressive motility (PM) rate, and total PM sperm count before sperm preparation were ≥5 × 106/ml, ≥32%, and >5 × 106 (according to the WHO 2010 criteria), respectively. Couples using frozen semen, or couples where the husband's semen was hyperviscous, were not included. On the day of IUI, participants were randomized (1:1 ratio) to undergo either SU or DG. Sperm preparation was performed within 1 h after ejaculation. IUI was performed once at 36-40 h after hCG trigger. Primary outcome was live birth after the first IUI cycle.</p><p><strong>Main results and the role of chance: </strong>Between 7 August 2020 and 29 October 2022, we randomized 456 couples to SU and 456 couples to DG. Live birth after the first IUI cycle occurred in 55 (12.1%) couples in the SU group and 71 (15.7%) couples in the DG group (relative risk 0.77; 95% CI 0.56 to 1.07). There were no statistically significant differences between the two groups in terms of other pregnancy outcomes as well as obstetrics and perinatal outcomes.</p><p><strong>Limitations, reasons for caution: </strong>The main limitation of the study was its open-label design, due to the nature of the interventions.</p><p><strong>Wider implications of the findings: </strong>In infertile couples undergoing IUI, SU and DG can both be used for sperm preparation. The decision on which to use might depend more on practical factors such as processing time and how easy it is to standardize the method.</p><p><strong>Study funding/competing interest(s): </strong>The study was funded by My Duc Hospital, Ho Chi Minh City, Vietnam. B.W.M. is supported by a NHM","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709746","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":"Patients with endometriosis in the vagina, bowel, or bladder experience a prolonged diagnostic delay: an observational study.","authors":"M E Madsen, D Hartwell, L K A Kähler, L Dyrved, B H Ejsing, L E Vexø, S E Thomassen, M C Havemann, A E Sakse, K Røssaak, M Nyegaard, H S Nielsen","doi":"10.1093/humrep/deaf046","DOIUrl":"https://doi.org/10.1093/humrep/deaf046","url":null,"abstract":"<p><strong>Study question: </strong>Do the diagnostic delay and symptoms differ between endometriosis patients with advanced disease, defined as endometriosis involving the vagina, intestine, rectovaginal septum, or bladder (eVIRB), compared to patients without endometriosis in these locations (non-eVIRB)?</p><p><strong>Summary answer: </strong>Patients with advanced endometriosis had a significantly longer diagnostic delay, an earlier onset of symptoms, and more intense pain during menstruation.</p><p><strong>What is known already: </strong>Endometriosis patients often experience years of symptoms before diagnosis. Whether there is an association between the length of this diagnostic delay and advanced disease remains unclear. Confirming such an association would underscore the importance of early diagnosis to ensure appropriate treatment, which may reduce the risk of irreversible organ damage and high-risk surgery for patients.</p><p><strong>Study design, size, duration: </strong>This is an observational cohort study of 129 patients undergoing endometriosis surgery conducted over a 3-year period. The first patient was operated on in November 2019. All patients reported retrospective questionnaire data, and surgeons described surgical findings.</p><p><strong>Participants/materials, setting, methods: </strong>The patients were operated on for predominantly moderate to severe endometriosis at a Tertiary Endometriosis Centre in Denmark. The diagnostic delay was calculated from questionnaire data and related to intraoperative findings. Selected symptoms were compared.</p><p><strong>Main results and the role of chance: </strong>The median diagnostic delay was 5 years. However, the patients with eVIRB (n = 75) experienced a significantly longer median diagnostic delay of 9 years compared to non-eVIRB patients (n = 54), who had a median delay of only 2 years (P = 0.005). The odds ratio of having eVIRB was 5-fold (95% CI 2.18-11.61, P < 0.001) increased if the diagnostic delay exceeded 5 years, and they reported a significantly earlier onset of endometriosis symptoms. Both groups reported numerous pain symptoms, with a significant difference observed only in responses regarding severe period cramps requiring bed rest and use of painkillers. The eVIRB group had used hormones significantly longer and had taken painkillers more regularly due to pelvic pain.</p><p><strong>Limitations, reasons for caution: </strong>The retrospective data may be affected by recall bias. This study describes associations between a prolonged diagnostic delay and advanced disease, not causality.</p><p><strong>Wider implications of the findings: </strong>This study is the first to describe an association between advanced endometriosis and a prolonged diagnostic delay after adjusting for total years of hormonal use and age at surgery. Future research should concentrate on strategies to achieve earlier diagnosis for patients presenting with this advanced form of the disease, given ","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700362","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":"Optimizing Y-chromosome microdeletion screening in Chinese male infertility patients: a large-scale multi-centre study on incidence","authors":"Wei-Kang Chen, Zu-Bo Liu, Tong-Tong Lin, Yuan-Yuan Zhou, Le-Jun Li, Zhong-Yan Liang, Jing-Gen Wu, Fu Luo, Ke-Da Yu, Feng-Bin Zhang, Jing-Ping Li","doi":"10.1093/humrep/deaf043","DOIUrl":"https://doi.org/10.1093/humrep/deaf043","url":null,"abstract":"STUDY QUESTION What is the optimal sperm concentration threshold for screening Y-chromosome microdeletions (YCMs) in male infertility patients? SUMMARY ANSWER This study identified three clinically relevant screening thresholds: an receiver operating characteristic (ROC)-optimal cutoff at 0.45 million sperm/ml, a high-sensitivity cutoff at 8 million sperm/ml, and a cost-effective threshold at 1 million sperm/ml. WHAT IS KNOWN ALREADY YCMs are the second most common genetic cause of male infertility, however, current screening thresholds remain controversial due to limited supporting evidence. STUDY DESIGN, SIZE, DURATION This retrospective multi-centre cohort study included 6806 male patients who underwent fertility assessments and azoospermia factor (AZF) gene testing between September 2013 and January 2024. PARTICIPANTS/MATERIALS, SETTING, METHODS ROC analysis was used to determine the AUC to show the effectiveness of sperm concentration for predicting AZF deletions. The sensitivity and specificity of different sperm concentration screening thresholds were measured. MAIN RESULTS AND THE ROLE OF CHANCE The incidence of YCMs was found to be 12.71% in non-obstructive azoospermia patients, 13.35% in patients with sperm concentrations between 0 and 1 million/ml, and 3.56% in those between 1 and 5 million/ml. ROC analysis demonstrated that sperm concentration was a good predictor of AZF deletions (AUC: 0.75, 95% CI: 0.74–0.77). The optimal threshold of 0.45 million/ml yielded a sensitivity of 86.84%, specificity of 59.97%, positive predictive value (PPV) of 13.48%, and negative predictive value (NPV) of 98.45%. A threshold of 8 million/ml achieved maximum sensitivity of 100.00% and NPV of 100.00%, but with specificity of 30.32% and PPV of 9.34%. The model showed good calibration with a Brier score of 0.06 and a goodness-of-fit test P-value of 0.726. Cost-effectiveness analysis revealed that a threshold of 1 million/ml provided the lowest incremental cost-effectiveness ratio. LIMITATIONS, REASONS FOR CAUTION Firstly, despite being the largest cohort study to date, our data primarily originated from eastern China, particularly the Zhejiang region. A nationwide multi-centre study could further validate our findings across different Chinese populations. Secondly, our cost-effectiveness analysis uses general gross domestics product-based willingness-to-pay thresholds, while disease-specific thresholds might be more appropriate and could be explored through nationwide surveys. Moreover, it is important to note that our cost-effectiveness findings are specifically based on the Chinese healthcare system and may not be directly applicable to other countries due to variations in healthcare systems, insurance coverage, and patient payment responsibilities across different regions globally. Another limitation of our cost-effectiveness analysis is that it may not fully capture the complex downstream implications of YCM detection in non-azoospermic men, where the ","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"61 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677712","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":"Bias due to non-consent in assisted reproductive treatment cohort studies: consent for disclosure to non-contact research in the Human Fertilisation and Embryology Authority register","authors":"Fiskani J M Kondowe, Matthew Gittins, Peter Clayton, Daniel R Brison, Stephen A Roberts","doi":"10.1093/humrep/deaf045","DOIUrl":"https://doi.org/10.1093/humrep/deaf045","url":null,"abstract":"STUDY QUESTION Is patient consent to research associated with the distribution of population characteristics and study outcomes in ART cohort studies? SUMMARY ANSWER The distribution of population characteristics in the patient consent subset differs from that in the non-consent subset and is not fully representative of the general ART population; thus, study results of population subsets requiring patient consent may be subject to bias. WHAT IS KNOWN ALREADY Non-consent in epidemiological studies may bias study results if the consent subset differs systematically from the non-consent subset and is thus not representative of the full study population. ART cohort datasets may be biased if they require patients to consent to use their data. As an example, from September 2009 onwards, ART patients in the UK have been asked for specific ‘consent to disclosure of identifying information’ (CD) for research studies. STUDY DESIGN, SIZE, DURATION This cohort study utilized an anonymized version of the Human Fertilisation and Embryology Authority (HFEA) dataset containing all CD and non-CD autologous ART treatment cycles (n = 819 512) conducted from 2004 to 2018 in the UK. A live birth (LB) subset of 155 986 singletons born during the same period was used to analyse child outcomes. Additionally, an aggregated version of the HFEA dataset was used to explore CD trends by clinic type (National Health Service [NHS], private, or both NHS and privately funded). PARTICIPANTS/MATERIALS, SETTING, METHODS The dataset containing all gamete cycles was used to explore factors associated with giving CD and to compare LB outcome trends (number of LBs per yearly treatment cycles started) between CD and non-CD cycles. The LB subset was used to compare the birthweight outcomes (low birthweight (LBW = birthweight < 2500 g or otherwise) and macrosomia (birthweight ≥4000 g or otherwise)) between CD and non-CD cycles. Logistic regression models explored the association between CD and population characteristics and the impact of CD on birthweight outcomes over the calendar years. Each regression model was adjusted for potential confounders: for all models (maternal age, ethnicity, previous IVF cycles, previous pregnancies, previous LBs, causes of infertility (tubal, endometriosis, male factor, ovulatory, unknown), and embryo transfer type and stage); for LB and birthweight models (ICSI, elective single embryo transfer, and ovarian stimulation); and additionally for birthweight models (child sex and gestation). MAIN RESULTS AND THE ROLE OF CHANCE During the study period, CD rates increased from 16% at its inception in 2009 to 64% in 2018. Fewer cycles from older patients (40–44 years old) and ethnic minorities (Black and Asian) gave CD. Cycles with previous ART treatments and LBs had lower rates of giving CD. CD was also associated with LB rates (higher in the CD group) and LBW (slightly more prevalent in the non-CD group). CD rates were consistently higher in NHS-only fun","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"71 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677716","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":"Pregnancy outcomes with increasing maternal age, greater than 40 years, in donor oocyte cycles.","authors":"Sabbagh Riwa, Meyers Alison, Korkidakis Ann, Heyward Quetrell, Penzias Alan, Sakkas Denny, Vaughan Denis, Toth Thomas","doi":"10.1093/humrep/deaf044","DOIUrl":"https://doi.org/10.1093/humrep/deaf044","url":null,"abstract":"<p><strong>Study question: </strong>Do IVF outcomes differ in patients over the age of 40 using donor oocytes?</p><p><strong>Summary answer: </strong>Even with the use of donor oocytes, maternal age appears to have an impact on live birth (LB) rate and perinatal outcomes.</p><p><strong>What is known already: </strong>Maternal age has a significant impact on the outcome of IVF, mainly attributed to age-related oocyte chromosomal factors.</p><p><strong>Study design, size, duration: </strong>This was a retrospective cohort study between 1 January 2015 and 31 December 2021.</p><p><strong>Participants/materials, setting, methods: </strong>This study included all patients who had a single embryo transfer cycle using donor oocytes during the study period. The study was conducted at a single university-affiliated fertility center. Data on BMI, paternal age, and type of cycle (natural vs programmed) were evaluated in relation to miscarriages and LBs when comparing age groups of 40-44, 45-49, and ≥50. Generalized estimating equation (GEE) models with logit functions were used to control for confounding variables.</p><p><strong>Main results and the role of chance: </strong>A total of 1660 single embryo transfer cycles using donor oocytes in patients ≥40 years were performed during the study period. Of these, 969 were in patients aged 40-44, 607 in patients 45-49, and 84 in patients ≥50 years of age. The presence of an LB was significantly lower in patients 45-49 compared to those 40-44 (P = 0.023). The LB rate remained lower in patients >50 but was not statistically significant. This relationship persisted after adjusting for BMI, paternal age, cycle type, and type of oocyte donor (fresh vs frozen oocyte donor) (P = 0.016). Moreover, the birthweight was lower in the older age groups (45-49 and ≥50) compared to the reference group of patients aged 40-44 (P = 0.004).</p><p><strong>Limitations, reasons for caution: </strong>The presence of an LB was lower in patients aged 45-49 and ≥50 compared to 40-44; however, this finding was not statistically significant for the ≥50 age group, likely due to the smaller sample size compared to the other two age groups. The use of preimplantation genetic testing for aneuploidy (PGT-A) was not included since only a minority of patients using donor oocytes underwent PGT-A. The inclusion of both fresh and frozen donor oocytes may also be deemed a limitation, as some studies have indicated better outcomes from fresh compared to frozen donor oocytes.</p><p><strong>Wider implications of the findings: </strong>Maternal age, beyond its relation to oocyte quality, was shown to affect the achievement of an LB. This is an important finding to include in patient counseling, particularly for those proceeding with donor oocytes.</p><p><strong>Study funding/competing interest(s): </strong>No authors report conflicts of interest or disclosures. There was no study funding.</p><p><strong>Trial registration number: </strong>N/A.</p>","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669135","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":"Plasma metabolites associated with endometriosis in adolescents and young adults","authors":"Nan Lin, Oana A Zeleznik, Allison F Vitonis, Ashley Laliberte, Amy L Shafrir, Julian Avila-Pacheco, Clary Clish, Kathryn L Terry, Stacey A Missmer, Naoko Sasamoto","doi":"10.1093/humrep/deaf040","DOIUrl":"https://doi.org/10.1093/humrep/deaf040","url":null,"abstract":"STUDY QUESTION What are the plasma metabolomics profiles associated with endometriosis in adolescents and young adults? SUMMARY ANSWER Our findings show dysregulation of plasma metabolomic profiles in adolescents and young adults with endometriosis, revealing systemic elevation of fatty acyls and ceramides in endometriosis cases compared to controls. WHAT IS KNOWN ALREADY Endometriosis is a gynecologic disease often presenting with severe pelvic pain impacting around 200 million reproductive-aged women worldwide. However, little is known about the pathophysiology and molecular features of endometriosis diagnosed during adolescence and young adulthood. STUDY DESIGN, SIZE, DURATION We conducted a cross-sectional analysis including 190 laparoscopically confirmed endometriosis cases and 120 controls who participated in The Women’s Health Study: From Adolescence to Adulthood, which enrolled participants from 2012 to 2018. Control participants were females without a diagnosis of endometriosis enrolled from the same clinics as the cases or recruited from the general population. Among the cases, 81 had blood samples collected before and after surgery. PARTICIPANTS/MATERIALS, SETTING, METHODS Plasma metabolites were measured in blood collected at enrollment using liquid chromatography–tandem mass spectrometry, and a total of 430 known metabolites were evaluated in our analysis. We used linear regression adjusting for age at blood draw, BMI, hormone use, and fasting status at blood draw. Metabolite set enrichment analysis (MSEA) was used to identify metabolite classes. Number of effective tests (NEF) and false discovery rate (FDR) were used for multiple testing correction. MAIN RESULTS AND THE ROLE OF CHANCE The median age was 17 years for endometriosis cases and 22 years for controls. The majority of endometriosis cases had rASRM stage I or II (&amp;gt;95%). We identified 63 plasma metabolites associated with endometriosis (NEF &amp;lt; 0.05). Endometriosis cases had higher levels of plasma metabolites associated with proinflammatory response [e.g. eicosatrienoic acid (β = 0.61, 95% CI = 0.37, 0.86)], increased oxidative stress response [e.g. xanthine (β = 0.64, 95% CI = 0.39, 0.88)], and downregulation of metabolites related to apoptosis [glycocholic acid (β = −0.80, 95% CI = −1.04, −0.56)]. MSEA revealed increased fatty acyls (FDR = 2.3e−4) and ceramides (FDR = 6.0e−3) and decreased steroids and steroid derivatives (FDR = 1.3e−4) in endometriosis cases compared to controls. When we examined the changes in plasma metabolite profiles before and after surgery among endometriosis cases, 55 endometriosis-associated metabolites significantly changed from before to after surgery. MSEA revealed steroids and steroid derivatives (FDR = 8.1e−4) significantly increased after surgery, while fatty acyls (FDR = 1.2e−4) significantly decreased after surgery. Ceramides did not change from pre- to post-surgery and were elevated in post-surgical blood compared to controls","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"56 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143661360","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":"Clinical presentation of congenital hypogonadotropic hypogonadism in males with delayed puberty according to genetic etiology: a systematic review and meta-analysis after reclassification of gene variants","authors":"Sebastián Castro, Franco G Brunello, Gabriela Sansó, Agustín Izquierdo, Jonathan Zaiat, Mariela Urrutia, Marcelo Martí, Rodolfo A Rey, Mariana L Tellechea, Romina P Grinspon","doi":"10.1093/humrep/deaf041","DOIUrl":"https://doi.org/10.1093/humrep/deaf041","url":null,"abstract":"STUDY QUESTION Which phenotypes can be confidently linked to a genetic etiology in males with congenital hypogonadotropic hypogonadism (CHH) resulting in absent or arrested puberty? SUMMARY ANSWER In this systematic review and reclassification of the disease-causing potential of gene variants using the recommendations of the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP), we found that absent or arrested puberty in males with CHH was linked to 93 genes, of which 29 were unequivocally disease-causing. WHAT IS KNOWN ALREADY The number of genes and phenotype characterizations associated with CHH in males has rapidly increased since the advent of next-generation sequencing technologies; however, the quality of the evidence for the interpretation of the causal relationship of gene variants is limited due to the lack of systematic criteria applied to the assessment of the pathogenic potential of the variants. STUDY DESIGN, SIZE, DURATION We performed a systematic review of original articles indexed in PubMed until 5 October 2022 and using the search terms ‘((‘hypogonadotropic hypogonadism’ OR Kallmann) AND (sequencing OR mutation OR variant))’ limited to ‘Humans’ and ‘English’. PARTICIPANTS/MATERIALS, SETTING, METHODS After two investigators undertook the literature search independently, titles and abstracts of all records were reviewed by four of the authors to identify those articles to be included in the full-text review. Clinical data and the association with gene variants were extracted from males with delayed or arrested puberty due to CHH according to the article authors’ criteria. Raw sequence variant information was used to reevaluate their pathogenic potential applying the ACMG/AMP guidelines for variant classification with InterVar. Subsequently, we considered the phenotype specificity criteria for sequence variant pathogenicity classification, based on curated genes associated with CHH, and classified patients into three categories: with monogenic disease-causing variants in genes associated with CHH, with variants in genes whose causality is unclear, and with variants that are not disease-causing. MAIN RESULTS AND THE ROLE OF CHANCE From a total of 1083 records, we included 245 publications with 775 male patients with CHH resulting in absent or arrested puberty, carrying 1001 variants in 93 genes. Gene variants were detected by Sanger sequencing in 61.8% of the cases and by next-generation sequencing (NGS) technologies in the rest. After variant reclassification of causality, 278 individuals were not considered to have a bona fide disease-causing gene variant, and 497 patients were reclassified as carrying at least one disease-causing variant associated with CHH. They carried 503 different disease-causing variants in 29 genes. Spontaneous puberty was absent in 85.5% and arrested in 14.5% of the 497 individuals with CHH carrying bona fide disease-causing variants. In males with abs","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"90 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143653330","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}