Human reproduction最新文献

{"title":"Clinical prediction models for in vitro fertilization outcomes: a systematic review, meta-analysis, and external validation","authors":"C H Tian, L Y Liu, Y F Huang, H J Yang, Y Y Lai, C L Li, D Gan, J Yang","doi":"10.1093/humrep/deaf013","DOIUrl":"https://doi.org/10.1093/humrep/deaf013","url":null,"abstract":"STUDY QUESTION What is the best-performing model currently predicting live birth outcomes for IVF or ICSI? SUMMARY ANSWER Among the identified prognostic models, McLernon’s post-treatment model outperforms other models in both the meta-analysis and external validation of a Chinese cohort. WHAT IS KNOWN ALREADY With numerous similar models available across different time periods and using various predictors in IVF prognostic models, there is a need to summarize and evaluate them, due to a lack of validated evidence distinguishing high-quality from low-quality prediction tools. However, there is a notable dearth of research in the form of meta-analysis or external validation assessing the performance of models in predicting live births in this field. STUDY DESIGN, SIZE, DURATION The researchers conducted a comprehensive literature review in PubMed, EMBASE, and Web of Science, using keywords related to prognostic models and IVF/ICSI live birth outcomes. The search included studies published up to 3 April 2024, and was limited to English language studies. PARTICIPANTS/MATERIALS, SETTING, METHODS The review included studies that developed or validated prognostic models for IVF live birth outcomes while providing clear reports on model characteristics. Researchers extracted and analysed the data in accordance with the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and other model-related guidelines. For model effects in meta-analysis, the choice would be based on the heterogeneity assessed using the I2 statistic and the Cochrane Q test. Model performance was evaluated by assessing their area under the receiver operating characteristic curves (AUCs) and calibration plots in the studies. MAIN RESULTS AND THE ROLE OF CHANCE This review provides a comprehensive summary of data derived from 72 studies with an overall ROB of high or unclear. These studies contained a total of 132 predictors and 86 prognostic models, and then meta-analyses were performed for each of the five selected models. The total random effects of Templeton’s, Nelson’s, McLernon’s pre-treatment and post-treatment model demonstrated AUCs of 0.65 (95% CI: 0.61–0.69), 0.63 (95% CI: 0.63–0.64), 0.67 (95% CI: 0.62–0.71), and 0.73 (95% CI: 0.71–0.75), respectively. The total fixed effects of the intelligent data analysis score (iDAScore) model estimated an AUC of 0.66 (95% CI: 0.63–0.68). The external validation of the initial four models in our cohort produced AUCs ranging from 0.53 to 0.58, and the calibration was confirmed through calibration plots. LIMITATIONS, REASONS FOR CAUTION While the focus on English-language studies and live birth outcomes may constrain the generalizability of the findings to diverse populations, this approach equips clinicians, who view live births as the ultimate objective, with more precise and actionable reference guidelines. WIDER IMPLICATIONS OF THE FINDINGS This study represents the first meta-analysis in the fi","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"17 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143470697","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 presence, clarity, and consistency of definitions in pregnancy outcomes in infertility trials: a systematic review","authors":"Qian Feng, Wentao Li, Wanlin Li, Rui Wang, James Crispin, Salvatore Longobardi, Thomas D’Hooghe, Ben W Mol","doi":"10.1093/humrep/deaf022","DOIUrl":"https://doi.org/10.1093/humrep/deaf022","url":null,"abstract":"STUDY QUESTION How frequently do infertility trials report live birth and pregnancy, and how consistently were their definitions reported? SUMMARY ANSWER One-third of 1425 infertility trials published in the last decade reported live birth, with one in eight reporting clinical pregnancy, ongoing pregnancy, and live birth concurrently; absent, ambiguous, or heterogeneous definitions were common. WHAT IS KNOWN ALREADY Absent or inconsistent outcome definitions in randomized controlled trials (RCTs) limit their interpretation and complicate subsequent evidence synthesis. While reporting live birth in infertility trials has been a long-running recommendation, the extent to which this is adhered to, and the temporal trend of adherence, is unclear. Furthermore, it is unknown if outcome reporting in infertility trials is clear and consistent. STUDY DESIGN, SIZE, DURATION We studied all RCTs in infertility published between 2012 and 2023. We aimed to assess (i) whether biochemical pregnancy, clinical pregnancy, ongoing pregnancy, and live birth were reported; the temporal trends in reporting these pregnancy outcomes, and compare the characteristics of trials reporting each type of outcome; (ii) whether and how these pregnancy outcomes were defined. PARTICIPANTS/MATERIALS, SETTING, METHODS We systematically searched Embase, Medline, and CENTRAL for RCTs in infertility from January 2012 to August 2023. RCTs involving infertile women that reported either biochemical pregnancy, clinical pregnancy, ongoing pregnancy, or live birth were eligible. Secondary analyses, interim analyses, or conference abstracts were not eligible. Two authors independently screened articles. We extracted pregnancy definitions and trial characteristics primarily using text mining in R, a programming environment for data analysis, and supplemented by manual checking. The accuracy of extracted data was validated in a random sample of 50 articles, with sensitivity and specificity all at or above 90%. MAIN RESULTS AND THE ROLE OF CHANCE We included 1425 infertility RCTs. Among these, 419 (29.4%) reported biochemical pregnancy. While 1359 (95.4%) RCTs reported clinical pregnancy, 404 (28.4%) reported ongoing pregnancy, and 484 (34.0%) reported live birth, only 174 (12.2%) reported all three outcomes. The proportion of trials reporting live birth increased from 23.1% in 2012 to 33.7% in 2023. Trials reporting up to biochemical pregnancy or clinical pregnancy were more likely to be unregistered, smaller, single-centered, and published in non-first quarter journals. Definitions for biochemical, clinical, ongoing pregnancy, and live birth were provided in 68.5% (287/419), 64.5% (876/1359), 70.5% (285/404), and 41.1% (199/484) of articles reporting on these outcomes. Among 876 clinical pregnancy definitions, 63.4% (n = 555) specified the pregnancy confirmation timing. Of the 220 definitions that reported gestational weeks (ranging from 4 to 16 weeks), the most common cut-off was 6 weeks, used","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"50 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143470698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A large-scale genome-wide association study on female genital tract polyps highlights role of DNA repair, cell proliferation, and cell growth.","authors":"Amruta D S Pathare, Jelisaveta Džigurski, Natàlia Pujol-Gualdo, Valentina Rukins, Maire Peters, Reedik Mägi, Andres Salumets, Merli Saare, Triin Laisk","doi":"10.1093/humrep/deaf025","DOIUrl":"https://doi.org/10.1093/humrep/deaf025","url":null,"abstract":"<p><strong>Study question: </strong>Can a large-scale genome-wide association study (GWAS) meta-analysis identify genomic risk loci and likely involved genes for female genital tract (FGT) polyps, provide insights into the biological mechanism underlying their development, and inform of potential overlap with other traits, including endometrial cancer?</p><p><strong>Summary answer: </strong>GWAS meta-analysis of FGT polyps highlights potentially shared mechanisms between polyp development and cancerous processes.</p><p><strong>What is known already: </strong>Small-scale candidate gene studies have focused on biological processes such as oestrogen stimulation and inflammation to clarify the biology behind FGT polyps. However, the exact mechanism for the development of polyps is still elusive. At the same time, a genome-wide approach, which has become the gold standard in complex disease genetics, has never been used to uncover the genetics of the FGT polyps.</p><p><strong>Study design, size, duration: </strong>We performed a GWAS meta-analysis including a total of 36 984 women with FGT polyps (International Classification of Diseases (ICD-10) diagnosis code N84) and 420 993 female controls (without N84 code) of European ancestry from the FinnGen study (11 092 cases and 94 394 controls), Estonian Biobank (EstBB, 14 008 cases and 112 799 controls), and the Pan-UKBB study (11 884 cases and 213 800 controls).</p><p><strong>Participants/materials, setting, methods: </strong>GWAS meta-analysis and functional annotation of GWAS signals were performed to identify genetic risk loci and prioritize genes in associated loci. To explore associations with other traits, we performed a look-up of associated variants across multiple traits and health conditions, genetic correlation analysis, and phenome-wide association study (PheWAS) with ICD-10 diagnosis codes.</p><p><strong>Main results and the role of chance: </strong>Our GWAS meta-analysis revealed 16 significant (P < 5 × 10-8) genomic risk loci. Based on exonic variants in GWAS signals, we prioritized EEFSEC, ODF3, PRIM1, PLCE1, LRRC34/MYNN, EXO1, and CHEK2 which are involved in DNA repair, cell proliferation, and cell growth. Several of the identified genomic loci have previously been linked to endometrial cancer and/or uterine fibroids, highlighting the potentially shared mechanisms underlying tissue overgrowth and cancerous processes. Genetic correlation analysis revealed a positive correlation with body mass index and reproductive traits, that can be classified as symptoms or risk factors of endometrial polyps (EPs), whereas a negative correlation was observed between FGT polyps and both menopause (genetic correlation estimate (rg) = -0.29, SE = 0.08, P = 8.8×10-4) and sex hormone-binding globulin (SHBG) (rg = -0.22, SE = 0.04, P = 2.4×10-8). On the phenotypic level, the strongest associations were observed with endometriosis, uterine fibroids, and excessive, frequent, and irregular menstruation.</p><p><","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476166","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":"Insights into embryo transfer strategies from a medical imaging perspective.","authors":"Yanxia Jia","doi":"10.1093/humrep/deaf010","DOIUrl":"https://doi.org/10.1093/humrep/deaf010","url":null,"abstract":"","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425317","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":"Reply: Insights into embryo transfer strategies from a medical imaging perspective.","authors":"Zheng Wang, Yuanyuan Wang, Rong Li","doi":"10.1093/humrep/deaf011","DOIUrl":"https://doi.org/10.1093/humrep/deaf011","url":null,"abstract":"","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425318","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":"Effect of maternal previous pregnancy on children’s pubertal development: an 8-year pubertal cohort","authors":"Qin Zhang, Jie Zhang, Xinyi Feng, Di Wu, Zixuan Chen, Yan Li, Qin Liu","doi":"10.1093/humrep/deaf015","DOIUrl":"https://doi.org/10.1093/humrep/deaf015","url":null,"abstract":"STUDY QUESTION Does the maternal pregnancy history affect the course of their offspring’s pubertal development? SUMMARY ANSWER Maternal pregnancy history, particularly adverse outcomes, significantly influences the timing of menarche and the tempo of breast development in girls. WHAT IS KNOWN ALREADY Preliminary evidence indicates that parity may affect the onset of puberty, mainly as reflected by changes in the timing of pubic and axillary hair development. STUDY DESIGN, SIZE, DURATION This 8-year cohort, conducted semi-annually, was recruited from four primary schools. The average follow-up duration was 6.09 years (range: 2–8 years). PARTICIPANTS/MATERIALS, SETTING, METHODS The study cohort comprised 1390 children, including 710 girls and 680 boys, with age ranges of 6.58–19.26 years and 5.81–19.28 years, respectively, over an 8-year follow-up period. The primary exposure was whether the mother has a history of pregnancy prior to the birth of the child, including childbearing, miscarriage, and other adverse pregnancy outcomes. Pubertal milestones as assessed by a professional, including breast and genital development, were modeled using logistic regression, and the age of menarche was documented for girls. Associations between maternal pregnancy history and pubertal progression in both genders were analyzed using generalized linear regression models. MAIN RESULTS AND THE ROLE OF CHANCE Girls from non-first pregnancies experienced a delayed age at menarche by 0.22 years (95% CI: 0.05, 0.38) and a more rapid tempo of breast development (0.06; 95% CI: 0.01, 0.11) compared to those from first pregnancies, particularly among girls with a history of maternal adverse pregnancy outcomes. The effect of maternal pregnancy history on pubertal development was less pronounced in boys than in girls. LIMITATIONS, REASONS FOR CAUTION The sample was relatively small, and the cohort also lacks sufficient data due to missing data points and some study participants still maturing. While model fitting aids in describing incomplete pubertal development, the logistic growth mixed-effects model’s assumptions about growth curves may not fully reflect reality. WIDER IMPLICATIONS OF THE FINDINGS Maternal pregnancy history, particularly adverse outcomes, can markedly influence pubertal progression in girls. Previous studies have shown that the timing and tempo of pubertal development impact adolescent psychological and behavioral health, and have implications for reproductive health and diseases in adulthood. Optimal pregnancy planning by mothers is essential for enhancing the well-being of both mother and offspring. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by Chongqing Natural Science Foundation project (CSTB2023NSCQ-MSX0133), National Natural Science Foundation of China (81973067), National Youth Science Fund Project (81502825), and Program for Youth Innovation in Future Medicine, Chongqing Medical University (W0054). This study was conducted accordin","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"9 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143417442","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":"Reduction in minipubertal gonadotropin levels alters reproductive lifespan and ovarian follicular loss in female mice.","authors":"Mélanie Chester, Marie M Devillers, Raphaël Corre, Frank Giton, Fatoumata Souaré, Claire-Hélène Petrovic, Éloïse Airaud, Daniel Quintas, Sakina Mhaouty-Kodja, Lydie Naulé, Céline J Guigon","doi":"10.1093/humrep/deaf019","DOIUrl":"https://doi.org/10.1093/humrep/deaf019","url":null,"abstract":"<p><strong>Study question: </strong>What is the effect of attenuating the physiological hypergonadotropic activity encountered at minipuberty on female reproductive function in a mouse model?</p><p><strong>Summary answer: </strong>Decreasing the surge of gonadotropins at minipuberty extended reproductive lifespan, coinciding with alterations in neuroendocrine and ovarian aging.</p><p><strong>What is known already: </strong>Minipuberty is characterized by the tremendous activation of the gonadotrope axis, as evidenced by elevated levels of gonadotropins regulating folliculogenesis and the synthesis of ovarian hormones, but its role in fertility remains unclear.</p><p><strong>Study design, size, duration: </strong>To determine the link between gonadotrope axis activity at minipuberty and reproductive parameters, we used a pharmacological approach to suppress gonadotropin levels in Swiss mice by injecting daily a GnRH receptor antagonist (GnRHR) (Ganirelix, 10 µg/mouse) or its vehicle between 10 and 16 postnatal days, to cover the entire duration of minipuberty. We analyzed the onset of puberty and estrous cyclicity as well as fertility in young (3-5 months) and middle-aged (11 months) mice from control (CTR) and antagonist-treated groups (n = 17-20 mice/age and treatment group). Ovaries and brains were collected, fixed, and sectioned (for histology, follicle count, and immunohistochemistry) or frozen (for analysis of follicular markers, aging, and inflammation) from adult females, and blood was collected by cardiac puncture for hormonal assays (n = 3-8 mice/age and treatment group).</p><p><strong>Participants/materials, setting, methods: </strong>To analyze the initiation of puberty, we monitored vaginal opening and performed vaginal smears in CTR and antagonist-treated mice. We studied estrous cyclicity on vaginal smears at the beginning of reproductive life. Mice were mated several times with males to assess fertility rates, delay of conception, and litter size. To evaluate ovarian function, we counted follicles at different stages and corpora lutea, and we determined the relative intra-ovarian abundance of key follicular markers by real-time RT-PCR, as well as the levels of circulating anti-Müllerian hormone (AMH) and progesterone by ELISA and GC-MS, respectively. We also analyzed features of ovarian aging and inflammation by histology and by measuring the relative intra-ovarian abundance of some markers using real-time RT-PCR. To determine the impact on neuroendocrine determinants related to the CTR of reproduction, we analyzed circulating gonadotropin levels using Luminex assays as well as kisspeptin and GnRH immunoreactivity in the hypothalamus by immunohistochemistry.</p><p><strong>Main results and the role of chance: </strong>Our results show that the treatment had no impact on the initiation of puberty, estrous cyclicity, or fertility at the beginning of reproductive life. However, it increased reproductive lifespan, as shown by the higher","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414108","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 ART-ET screening tool: an easy-to-use non-invasive screening method to predict difficult embryo transfers in advance.","authors":"Baris Ata, Barbara Lawrenz, Laura Melado, Raquel Del Gallego, Carol Coughlan, Francisco Ruiz, Laura Marqueta Marques, Ahmed El-Damen, Ibrahim Elkhatib, Human M Fatemi","doi":"10.1093/humrep/deaf002","DOIUrl":"https://doi.org/10.1093/humrep/deaf002","url":null,"abstract":"<p><strong>Study question: </strong>What is the diagnostic performance of the ART-ET screening tool, an easy-to-use non-invasive screening tool for prediction of difficult embryo transfers?</p><p><strong>Summary answer: </strong>A simple scoring of transvaginal ultrasound examination of the cervical canal can predict difficult embryo transfers with high specificity, positive likelihood ratio, and accuracy; the inclusion of cervical position and history of cesarean without a vaginal delivery improved predictive performance.</p><p><strong>What is known already: </strong>Difficult embryo transfer procedures are associated with significantly lower clinical pregnancy and live birth rates, and some interventions may facilitate an anticipated difficult embryo transfer.</p><p><strong>Study design, size, duration: </strong>A diagnostic test study prospectively conducted on 239 single euploid blastocyst transfer procedures between March and December 2023. The sample size was calculated to include about 20 difficult transfer procedures. Physicians conducting the transfers were blinded to screening results.</p><p><strong>Participants/materials, setting, methods: </strong>The study was conducted in two tertiary-level private assisted reproduction centers. The ART-ET Screening tool collected information on patients' body mass index, obstetric history, cervical position, external cervical ostium appearance, and ultrasound examination of the cervical canal. A difficult embryo transfer was defined if one or more of the following occurred during the procedure; use of a malleable obturator to insert the guiding catheter until the internal ostium, use of a forceps to pull the cervix, if there were blood in the transfer catheter following the procedure, if the transfer catheter needed to be reloaded, and if the physician found the procedure difficult.</p><p><strong>Main results and the role of chance: </strong>Ongoing pregnancy rates were 47.6% vs 59.6% after a difficult and easy embryo transfer. With a difficult embryo transfer prevalence of 8.8%, screening score including cervical position, visibility and the length of cervical canal, and obstetric history had the best diagnostic performance with sensitivity of 33.3% (14.59-56.97%), specificity of 99.5% (97.47-99.99%), positive likelihood ratio of 72.67 (9.38-562.73), negative likelihood ratio of 0.67 (0.49-0.91), and an accuracy of 93.7% (89.86-96.45%) for predicting difficult embryo transfers. The simpler cervical ultrasound score also had a good diagnostic performance with a sensitivity of 28.6% (11.28-52.18%), specificity of 98.2% (95.37-99.50%), positive likelihood ratio of 15.57 (4.77-50.84), negative likelihood ratio of 0.73 (0.55-0.95), positive predictive value of 60.0% (31.46-83.03%), negative predictive value of 93.5% (91.59-94.93%), and an accuracy of 93.5% (91.59-94.93%).</p><p><strong>Limitations, reasons for caution: </strong>The diagnostic performance of the proposed ART-ET Screening tool would depe","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143407208","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":"Short and long duration testosterone treatments induce reversable subfertility in female mice using a gestational model of gender-affirming hormone therapy.","authors":"Daniel R Pfau, Evelyn Cho, Jamison G Clark, Robin E Kruger, Ruth K Chan-Sui, Hadrian Kinnear, Cynthia Dela Cruz, Amanda R Schwartz, Vasantha Padmanabhan, Ariella Shikanov, Molly B Moravek","doi":"10.1093/humrep/deaf016","DOIUrl":"https://doi.org/10.1093/humrep/deaf016","url":null,"abstract":"<p><strong>Study question: </strong>How does testosterone gender-affirming hormone therapy (T-GAHT) impact breeding success in female mice?</p><p><strong>Summary answer: </strong>T-GAHT causes reversible subfertility in female mice and persistent changes to reproductive tract anatomy, gene expression, and hormone receptors.</p><p><strong>What is known already: </strong>Adult female mice implanted with capsules containing 10 mg of testosterone mimic many aspects of reproductive phenotypes of T-GAHT patients, who may desire future gestation while pausing T-GAHT. In mice, oocytes retrieved from T-GAHT mice had decreased IVF rates, and T cessation prior to stimulation improved these outcomes. However, the effects of T-GAHT on breeding have not been examined.</p><p><strong>Study design, size, duration: </strong>Adult female CD1 mice were subcutaneously implanted with capsules containing 10 mg of testosterone or blank controls. In separate studies, capsules were removed after 6 ('short') or 12 weeks ('long' n = 15/group), then mice were paired with proven-breeder CD1 males. Breeding pair success and pup development (15-20/group) were measured for first and second litters, then terminal measurements were taken from dams and their adult offspring (10/group).</p><p><strong>Participants/materials, setting, methods: </strong>The reproductive success of explanted T-GAHT and control mice was investigated by pairing them with proven-breeder CD1 males. Regular observations of dams and litters enabled analysis of fertility and the development of male and female pups for two litters. Terminal measures for dams and/or adult offspring focused on endpoints tied to reproductive tract function and gestation, including reproductive hormones, vaginal cytology, sperm analysis and ovarian and uterine anatomy, histology, and gene expression.</p><p><strong>Main results and the role of chance: </strong>All but one T-GAHT dams gave birth, but the time between pairing and their first birth was longer than controls after long (22.3 ± 1.3 days vs 24.5 ± 3.1) and short (23.2 ± 1.4 days vs 25.5 ± 4) treatments. Dams given long T-GAHT treatment had fewer pups in their first litters (11.9 ± 2.7 pups vs 7.8 ± 3.1) but pup number was unaltered after short treatment (11.5 ± 2.4 pups vs 11.4 ± 3.7). Further, offspring from first litters displayed accelerated puberty. Fertility differences and offspring developmental effects were absent for second gestations and litters. Despite fertility rescue, several anatomical, genetic, and histological changes persisted in T-GAHT dams after two litters. Offspring reproductive system outcomes were not significantly altered once dam fertility was restored. This study powerfully demonstrates a subfertile phenotype in T-GAHT-treated animals that is rescued over time and identifies gonadotropin and steroid hormone signaling as potential mechanisms for further investigation.</p><p><strong>Large scale data: </strong>No large-scale data were generated in t","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398878","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":"Impact of female age on concentrations of reproductive hormones and oocyte-specific growth factors in follicular fluid from human small antral follicles","authors":"N Friis Wang, L S Mamsen, J Cadenas, G Saritas, K T Macklon, J Fedder, E Ernst, M L Johannsen, S G Kristensen, T Kelsey, A Kumar, B Kalra, K Løssl, C Yding Andersen","doi":"10.1093/humrep/deaf017","DOIUrl":"https://doi.org/10.1093/humrep/deaf017","url":null,"abstract":"STUDY QUESTION Does maternal age impact hormonal secretions from granulosa cells, theca cells, and the oocyte in human small antral follicles? SUMMARY ANSWER Major hormones secreted by granulosa and theca cells, as well as the oocyte-specific TGF-β members—GDF9, BMP15, and the GDF9/BMP15 heterodimer cumulin—maintain a consistent concentration within the follicular fluid of human small antral follicles, regardless of maternal age. WHAT IS KNOWN ALREADY It is well established that female fertility declines with increasing age. However, it is not known whether this decline is exclusively due to a reduction in oocyte quality and quantity or also involves a decline in the hormone-secreting capabilities of granulosa cells, theca cells, and the oocyte itself. STUDY DESIGN, SIZE, DURATION This is a retrospective study of follicular fluid obtained from human small antral follicles collected in connection with cryopreservation of ovarian tissue at the Laboratory of Reproductive Biology, University Hospital Copenhagen, Rigshospitalet, Denmark, between 2010 and 2020 as part of the hospital’s fertility preservation program. PARTICIPANTS/MATERIALS, SETTING, METHODS Follicular fluid samples from human small antral follicles measuring 3–13 mm in diameter from macroscopically normal ovaries of 381 patients aged 5–43 years were included in the study, provided that at least one of the following parameters was measured: AMH, Inhibin A, Inhibin B, oestradiol (E2), progesterone (P4), androstenedione, testosterone, and/or the oocyte-specific TGF-β members GDF9, BMP15, or cumulin. MAIN RESULTS AND THE ROLE OF CHANCE In a linear regression analysis adjusted for follicular volume, female age did not predict the follicular fluid concentrations of AMH, Inhibin B, Inhibin A, E2, androstenedione, testosterone, GDF9, BMP15, or cumulin. Although a significant association was observed between female age and follicular fluid P4 levels, the predictive value of age was poor, accounting for at most 5% of the variation in P4. LIMITATIONS, REASONS FOR CAUTION Hormonal levels may vary with the degree of atresia in each follicle; however, the health status of the small antral follicles in this study was not characterized. Additionally, we cannot exclude possible age-related differences in human follicles larger than 10 mm, as very few of these were included. Furthermore, we did not include women above the age of 43, despite the potential for more pronounced age-related effects in these patients. WIDER IMPLICATIONS OF THE FINDINGS Our results support the idea that the age-related decline in female fertility is primarily due to a reduction in oocyte quality and quantity, but further research is needed to confirm this. STUDY FUNDING/COMPETING INTEREST(S) No specific funding was obtained, and the authors have no conflicts of interest to declare in relation to this work. TRIAL REGISTRATION NUMBER N/A.","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"12 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143371534","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}