Emilia Grzęda, Dominika Gutkowska-Kawka, Julia Matuszewska, Ewa Kilańczyk, Monika M Kaczmarek, Łukasz Dylewski, Joanna H Sliwowska
{"title":"Maternal cafeteria diet adversely affects the reproductive parameters of rat offspring in a sex-specific manner.","authors":"Emilia Grzęda, Dominika Gutkowska-Kawka, Julia Matuszewska, Ewa Kilańczyk, Monika M Kaczmarek, Łukasz Dylewski, Joanna H Sliwowska","doi":"10.1186/s12958-025-01412-0","DOIUrl":"https://doi.org/10.1186/s12958-025-01412-0","url":null,"abstract":"<p><strong>Background: </strong>An unhealthy diet contributes significantly to the development of the global obesity epidemic and serves as a risk factor for fertility disorders. Moreover, maternal obesity leads to alterations in the reproductive capacity of the offspring via prenatal and postnatal programming.</p><p><strong>Methods: </strong>To replicate the impact of a diet rich in sugar and fat, which contributes to human obesity, we utilized a cafeteria (CAF) diet in rat mothers to investigate molecular and morphological consequences in the gonads of male and female progeny. Rat mothers were fed either standard (control) or CAF diet before and during pregnancy and lactation. Female and male offspring were sacrificed after weaning at different stages of reproductive maturation-females on postnatal days (PNDs) 30, 35, and 60, and males on PNDs 40 and 60. Ovaries and testis were examined for the expression of the kisspeptin system, including Kiss1, Kiss1r, estrogen (Esr1, Esr2), androgen (Ar), and luteinizing hormone choriogonadotropin (Lhcgr) receptors. Additionally, morphological parameters of the ovaries and testes were evaluated.</p><p><strong>Results: </strong>Male offspring of CAF mothers showed: i) alterations in Ar and Kiss1 mRNA levels, and ii) decreased seminiferous tubules diameter and epithelium height, a reduced number of Sertoli cells, a lower percentage of seminiferous tubules with presented spermatozoa. Female offspring of CAF mothers exhibited: i) disturbed expression of Esr1, Esr2, Ar, and Lhcgr receptors in the ovaries, and ii) a diminished number of primordial and secondary follicles at PND 30 and primary follicles at PND 35.</p><p><strong>Conclusions: </strong>We concluded that the maternal CAF diet leads to sex-specific alterations in the reproductive parameters of offspring.</p>","PeriodicalId":21011,"journal":{"name":"Reproductive Biology and Endocrinology","volume":"23 1","pages":"79"},"PeriodicalIF":4.2,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Impact of endocrine disrupting chemicals (EDCs) on epigenetic regulation in the uterus: a narrative review.","authors":"Yinjing Liang, Qinsheng Lu, Miaojuan Chen, Xiaomiao Zhao, Chu Chu, Chaofan Zhang, Jianhuan Yuan, Huimin Liu, Gendie E Lash","doi":"10.1186/s12958-025-01413-z","DOIUrl":"https://doi.org/10.1186/s12958-025-01413-z","url":null,"abstract":"<p><p>Endocrine disrupting chemicals (EDCs) are ubiquitous in the environment and have been shown to interfere with the endocrine system, leading to adverse effects on reproductive health. In females, EDC exposure has been linked to menstrual irregularities, infertility, and pregnancy complications. Epigenetic regulation, which involves modifications to DNA and histones that do not alter the underlying genetic code, plays a crucial role in female reproduction. EDCs have been shown to disrupt epigenetic mechanisms, leading to changes in gene expression that can have long-term effects on reproductive outcomes. Several EDCs, including bisphenol A (BPA) and phthalates, dioxins, and polychlorinated biphenyls (PCBs), have been shown to alter DNA methylation patterns and histone modifications in female reproductive tissues. These changes can lead to altered expression of genes involved in ovarian function, implantation, and placental development. Here, we integrate epidemiological and experimental evidence from the last 20 years to profile the types of diseases that EDCs trigger in the female reproductive system in relation to the uterus, and the corresponding molecular mechanisms that have been studied. In addition, this review will outline the state of knowledge of EDC epigenetic regulation in the uterus and how it impacts reproductive health, as well as identify areas for future research.</p>","PeriodicalId":21011,"journal":{"name":"Reproductive Biology and Endocrinology","volume":"23 1","pages":"80"},"PeriodicalIF":4.2,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Mechanisms and therapeutic effects of granulocyte colony-stimulating factor in reproduction.","authors":"Lu Zhou, Liming Zhou","doi":"10.1186/s12958-025-01414-y","DOIUrl":"https://doi.org/10.1186/s12958-025-01414-y","url":null,"abstract":"<p><p>Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic cytokine that is primarily secreted by monocytes or macrophages and has traditionally been recognized for its role in stimulating the proliferation and differentiation of neutrophils. Recent research has revealed the presence of G-CSF in non-hematopoietic cells such as vascular endothelial cells, placental cells, and trophoblast cells. This discovery has led to the belief that G-CSF plays a significant role in ensuring the success of pregnancy. In this review, we investigate and summarize the mechanisms of G-CSF in the reproductive system, specifically addressing its roles in endometrial repair at the maternal-fetal interface, trophoblast development, suppression of autoimmunity, ovulation, and its therapeutic effects in reproductive-related diseases. As an important cytokine in normal pregnancy, our study demonstrate that G-CSF could improve endometrial receptivity through multiple mechanisms: not only by inhibiting apoptosis, regulating cytokine expression, and mobilizing cells, but also by increasing the number of endometrial pinopodes and attenuating degeneration, as supported by recent studies. Our aim is to provide a comprehensive reference for future scientific research and clinical treatment endeavors.</p>","PeriodicalId":21011,"journal":{"name":"Reproductive Biology and Endocrinology","volume":"23 1","pages":"78"},"PeriodicalIF":4.2,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ruihua Yan, Jiao Zhang, Hongyun Ma, Yang Wu, Yang Fan
{"title":"Potential of seven insulin resistance indicators as biomarkers to predict infertility risk in U.S. women of reproductive age: a cross-sectional study.","authors":"Ruihua Yan, Jiao Zhang, Hongyun Ma, Yang Wu, Yang Fan","doi":"10.1186/s12958-025-01416-w","DOIUrl":"10.1186/s12958-025-01416-w","url":null,"abstract":"<p><strong>Background: </strong>Insulin resistance(IR) is a key mechanism underlying both obesity and metabolic syndrome, with significant implications for the onset and progression of female infertility. This study systematically examines the associations between seven insulin resistance indicators and the risk of infertility in U.S. women of reproductive age, while also evaluating the diagnostic value of these indicators in predicting infertility.</p><p><strong>Method: </strong>This cross-sectional study analyzed data from the 2013-2018 National Health and Nutrition Examination Survey (NHANES) to explore the relationship between seven insulin resistance indicators and infertility risk. The indicators included the Metabolic Score for Insulin Resistance (METS-IR), Triglyceride-Glucose Index (TyG), Triglyceride-Glucose-Waist Circumference (TyG-WC), Triglyceride-Glucose-Body Mass Index (TyG-BMI), Triglyceride-Glucose-Waist-to-Height Ratio (TyG-WHtR), Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), and Triglyceride/High-Density Lipoprotein Ratio (TG/HDL). Receiver Operating Characteristic (ROC) curves were used to assess the diagnostic accuracy of each insulin resistance indicator in predicting infertility. Additionally, smooth curve fitting and threshold effect analysis were employed to further explore the relationship between insulin resistance indicators with high diagnostic efficacy and infertility.</p><p><strong>Results: </strong>This study included 1,100 women aged 20-45, of whom 140 (12.61%) were diagnosed with infertility. The results revealed significant positive correlations between METS-IR, TyG-BMI, TyG-WC, TyG-WHtR, and infertility risk. Specifically, as TyG-WC and TyG-WHtR levels increased, the risk of infertility rose linearly, while METS-IR and TyG-BMI exhibited a nonlinear positive association with infertility risk. No significant correlations were observed between TyG, HOMA-IR, TG/HDL, and infertility. Finally, ROC curve analysis indicated that METS-IR outperformed the other six insulin resistance indicators in predicting infertility risk.</p><p><strong>Conclusion: </strong>METS-IR, TyG-BMI, TyG-WC, and TyG-WHtR are significantly associated with the risk of infertility in U.S. women of reproductive age, with METS-IR demonstrating the highest predictive power. These findings suggest that METS-IR may have substantial clinical utility in evaluating infertility risk.</p>","PeriodicalId":21011,"journal":{"name":"Reproductive Biology and Endocrinology","volume":"23 1","pages":"77"},"PeriodicalIF":4.2,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12102792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144143404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Early menopause in mothers and the risks of pre-diabetes and type 2 diabetes mellitus in female and male offspring: a population-based cohort study.","authors":"Mahsa Noroozzadeh, Maryam Mousavi, Marzieh Saei Ghare Naz, Maryam Farahmand, Fereidoun Azizi, Fahimeh Ramezani Tehrani","doi":"10.1186/s12958-025-01405-z","DOIUrl":"10.1186/s12958-025-01405-z","url":null,"abstract":"<p><strong>Background: </strong>Genetic factors and an unfavorable intrauterine environment may contribute to the development of metabolic disorders in offspring later in life. The present study aims to investigate and compare the risks of pre-diabetes mellitus (pre-DM), type 2 diabetes mellitus (T2DM) and abnormal glucose tolerance in female and male offspring with early maternal menopausal age versus those with normal maternal menopausal age, later in life.</p><p><strong>Methods: </strong>In this prospective population-based study, there were 1,516 females and 1,563 males with normal maternal menopausal age, as well as 213 females and 237 males with early maternal menopausal age. Unadjusted and adjusted cox regression models were used to assess the hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between early maternal menopausal age with pre-DM, T2DM and abnormal glucose tolerance in offspring. Statistical analysis was performed using the STATA software package; the significance level was set at P < 0.05.</p><p><strong>Results: </strong>The present study revealed a higher risk of pre-DM in female offspring with early maternal menopausal age compared to females with normal maternal menopausal age (unadjusted HR (95% CI): 1.42 (0.98, 2.05); P = 0.06 (marginal significant) and adjusted HR (95% CI): 1.47 (1.00, 2.16); P = 0.04). Additionally, a higher risk of abnormal glucose tolerance among female offspring with early maternal menopausal age in adjusted model was observed (HR (95% CI): 1.13 (0.99-1.29); P = 0.06, marginal significant). However, no significant differences were observed in the risks of developing pre-DM and abnormal glucose tolerance in male offspring with early maternal menopausal age compared to males with normal maternal menopausal age in both unadjusted and adjusted models. No significant difference was observed in the risk of T2DM in the offspring with early maternal menopausal age compared to offspring with normal maternal menopausal age.</p><p><strong>Conclusions: </strong>This pioneering study, characterized by a long-term follow-up, demonstrated that early maternal menopausal age is associated with an increased risk of developing pre-DM in female offspring later in life. It may be advisable to implement screening for pre-DM and glucose metabolism disorders in these female offspring.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":21011,"journal":{"name":"Reproductive Biology and Endocrinology","volume":"23 1","pages":"76"},"PeriodicalIF":4.2,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12096570/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abazar Esmaeili, Vahid Esmaeili, Abdolhossein Shahverdi, Mohamadreza Baghaban Eslaminejad
{"title":"Engineered extracellular vesicles: a breakthrough approach to overcoming sperm cryopreservation challenges.","authors":"Abazar Esmaeili, Vahid Esmaeili, Abdolhossein Shahverdi, Mohamadreza Baghaban Eslaminejad","doi":"10.1186/s12958-025-01407-x","DOIUrl":"10.1186/s12958-025-01407-x","url":null,"abstract":"<p><p>Freezing sperm for artificial insemination (AI) has been common for decades, but this method causes damage to sperm, which affects its viability and fertility. Various strategies have been used to treat sperm cryopreservation complications, but their results are still not satisfactory. The latest approach in this field is using extracellular vesicles (EVs). The role of EVs in reproduction, such as spermatogenesis, sperm capacitation, and fertility has been proven. EVs can deliver proteins, lipids, nucleic acids, and other molecules to the sperm for repair. The EVs carry proteins, lipids, nucleic acids, and other molecules, which could be involved in sperm quality, functionality or fertility. The application of EV derived from animal and human cell sources for cryoinjury treatment indicates the improvement of sperm quality after freeze-thawing. In addition, different EV engineering methods regarding various EV cargos could be more influential for cryopreserved sperm treatment because they could provide EV customized content for delivering to cryoinjured sperm, according to their unique needs to enhance viability and fertility. In this review, first, we reminded the sperm cryopreservation complications, and next explained the conventional and modern strategies for overcoming them. Then, we have pointed out the role of EV in sperm development and the following mentioned the study results of using EV from different cell sources in sperm cryoinjuries repair. Also, we suggested several predisposing molecules (including microRNAs and proteins) for EV engineering to treat sperm cryopreservation complications by indirect engineering procedure, including genetic manipulation and incubation with therapeutic molecules, and direct engineering procedure, including electroporation, sonication, incubation, saponin permeabilization, extrusion, CaCl2-heat shock, and freeze/thawing. Finally, we discussed the limitations of EV application and ethical considerations in this context. In the meantime, despite these limitations, we pointed out the promising potential of the EV engineering strategies to reduce infertility rates by helping to overcome sperm cryopreservation challenges.</p>","PeriodicalId":21011,"journal":{"name":"Reproductive Biology and Endocrinology","volume":"23 1","pages":"75"},"PeriodicalIF":4.2,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12093887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rossella Cannarella, Michele Rubulotta, Alessia Leonardi, Andrea Crafa, Antonio Calvo, Federica Barbagallo, Sandro La Vignera, Aldo E Calogero
{"title":"Effects of ketogenic diets on polycystic ovary syndrome: a systematic review and meta-analysis.","authors":"Rossella Cannarella, Michele Rubulotta, Alessia Leonardi, Andrea Crafa, Antonio Calvo, Federica Barbagallo, Sandro La Vignera, Aldo E Calogero","doi":"10.1186/s12958-025-01411-1","DOIUrl":"10.1186/s12958-025-01411-1","url":null,"abstract":"<p><strong>Background: </strong>This systematic review and meta-analysis aimed to evaluate the effects of ketogenic diet (KD) and very-low-energy ketogenic therapy (VLEKT) protocols on various health outcomes in patients with polycystic ovary syndrome (PCOS) and increased body weight.</p><p><strong>Methods: </strong>A systematic search was conducted across Scopus, PubMed, Cochrane, and Embase databases from their inception through January 2025, using a predefined search strategy. Studies were selected based on the PICOS criteria. Data extraction focused on anthropometric measures, glycometabolic and lipid profiles, and hormone levels. Controlled studies were analyzed to evaluate the effects of high-fat KDs and VLEKT compared to low calorie diets (LCDs). Additionally, uncontrolled studies were included, and the outcomes following high-fat KDs or VLEKT were compared to baseline values (before-after study design). A sub-analysis was also performed to compare VLEKT with high-fat KDs. We assessed the quality of the evidence, as well as heterogenity, sensitivity, and publication bias.</p><p><strong>Results: </strong>A total of 10 studies were included in the analyses, comprising three randomized controlle studies (RCTs), one non-randomized intervention study, four cohort studies, and two case series. Two RCTs comparing VLEKT and high-fat KDs with LCDs found no significant effect on body weight. However, both high-fat KDs and VLEKT were associated with reductions in body mass index (BMI) and fat mass percentage in patients with PCOS. Significant improvements in weight, BMI, fat mass, and lean mass were observed following high-fat KDs or VLEKT interventions compared to baseline values, with no substantial differences between the two diet types. Regarding glycometabolic outcomes, both high-fat KDs and VLEKT reduced serum glucose levels and the homeostatic model assessment index compared to LCDs, with VLEKT showing slightly more favorable effects. In terms of the lipid profile, both high-fat KDs and VLEKT lowered total cholesterol and triglyceride levels, and VLEKT showing greater efficacy in triglyceride reduction. Hormonal analyses from two RCTs showed that both high-fat KDs and VLEKT were associated with lower serum luteinizig hormone (LH) levels compared to LCDs. Additionally, both high-fat KDs and VLEKT led to reductions in LH and total testosterone levels relative to baseline, with VLEKT showing a slight advantage in lowering LH and follicle-stimulating hormone levels.</p><p><strong>Conclusions: </strong>High-fat KDs and VLEKT show beneficial effects on weight, body composition, glycometabolic parameters, and hormone profile in women with PCOS. VLEKT may provide additional advantages, particularly in reducing fat mass and lowering triglyceride levels. Further studies with larger sample sizes and more robust study designs are needed to confirm these findings.</p>","PeriodicalId":21011,"journal":{"name":"Reproductive Biology and Endocrinology","volume":"23 1","pages":"74"},"PeriodicalIF":4.2,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12090672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hu Tan, Li Huang, Wenjuan Liu, Jin Yan, Li Li, Yujiang Wang, Yuqiang Huang, Zonghui Xiao, Fenghua Liu, Xiqian Zhang
{"title":"Euploidy rate and pregnancy outcomes in preimplantation genetic testing for aneuploidy cycles using progestin-primed ovarian stimulation versus GnRH antagonist protocol.","authors":"Hu Tan, Li Huang, Wenjuan Liu, Jin Yan, Li Li, Yujiang Wang, Yuqiang Huang, Zonghui Xiao, Fenghua Liu, Xiqian Zhang","doi":"10.1186/s12958-025-01398-9","DOIUrl":"10.1186/s12958-025-01398-9","url":null,"abstract":"<p><strong>Background: </strong>Previous studies has yielded contradictory findings regarding the relationship between controlled ovarian hyperstimulation (COH) protocol and euploid blastocyst rate. This study aimed to investigate whether progestin-primed ovarian stimulation (PPOS) influences the euploidy rate and pregnancy outcomes in preimplantation genetic testing for aneuploidy (PGT-A) cycles compared to GnRH antagonist protocol.</p><p><strong>Methods: </strong>The retrospective study analyzed data from 598 PGT-A cycles conducted between January 2017 and October 2022 utilizing either PPOS (medroxyprogesterone acetate) or the GnRH antagonist protocol. The biopsied trophectoderm from 2218 blastocysts was collected for euploidy analysis via next-generation sequencing.</p><p><strong>Results: </strong>Biopsied blastocyst number was comparable between PPOS group and GnRH antagonist group (3.51 ± 2.93 vs. 3.91 ± 3.19, P = 0.116), although PPOS yielded fewer MII oocytes (10.27 ± 6.59 vs. 11.60 ± 6.71, P = 0.015). The euploidy rate (43.3% vs. 45.0%, P = 0.423), aneuploidy rate (36.9% vs. 36.0%, P = 0.127), and mosaic rate (19.4% vs. 17.6%, P = 0.127) were similar between the PPOS and GnRH antagonist protocols. Additionally, PPOS demonstrated comparable pregnancy outcomes to GnRH antagonist protocol, including clinical pregnancy rates (58.1% vs. 59.8%, P = 0.713) and live birth rates (51.1% vs. 46.9%, P = 0.364). But lower miscarriage rate was shown in the PPOS protocol (7.9% vs. 16.8%, P = 0.019).</p><p><strong>Conclusions: </strong>The PPOS protocol did not negatively impact euploid blastocyst formation or pregnancy outcomes compared to the GnRH antagonist protocol, indicating that medroxyprogesterone acetate was an alternate option to antagonists for women undergoing PGT-A.</p>","PeriodicalId":21011,"journal":{"name":"Reproductive Biology and Endocrinology","volume":"23 1","pages":"73"},"PeriodicalIF":4.2,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12085052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Luyang Zha, Jingzhi Yang, Fei Li, Bo Huang, Yaxin Guo, Lei Jin
{"title":"GnRH-a use before programmed frozen embryo transfer cycles for women with PCOS: a retrospective cohort study.","authors":"Luyang Zha, Jingzhi Yang, Fei Li, Bo Huang, Yaxin Guo, Lei Jin","doi":"10.1186/s12958-025-01403-1","DOIUrl":"10.1186/s12958-025-01403-1","url":null,"abstract":"<p><strong>Background: </strong>Programmed protocols are most commonly chosen as endometrial preparation for women with polycystic ovarian syndrome (PCOS) undergoing frozen-thawed embryo transfer (FET) cycles. However, the efficacy of gonadotropin-releasing hormone agonist (GnRH-a) pretreatment before programmed cycles is still up for debate. This study was to compare the pregnancy and perinatal outcomes of PCOS patients receiving programmed cycles with and without GnRH-a pretreatment as endometrial preparation in FET cycles.</p><p><strong>Methods: </strong>This is a retrospective cohort study conducted in the Reproductive Medicine Centre of Tongji Hospital. The primary analysis included 2733 FET cycles (223 were programmed cycles combined with GnRH-a pretreatment; 2510 were programmed cycles) during Jan. 2016 and Sept. 2022 from 1934 women with PCOS. Patients who had undergone both endometrial preparation protocols were further analyzed as a subgroup. The primary outcomes were pregnancy outcomes including live birth rate, clinical pregnancy rate, biochemical pregnancy loss rate, ectopic pregnancy rate, and multiple pregnancy rate. The secondary outcomes were perinatal outcomes. Propensity score matching (PSM) and generalized estimating equation were employed to eliminate essential confounders and account for patients with multiple cycles. The subgroup analysis included patients who underwent both endometrial preparation regimens and utilized the Wilcoxon's matched pairs test to compare the adjusted pregnancy outcomes rate, calculated by dividing the number of pregnancy outcomes by the number of cycles.</p><p><strong>Results: </strong>The essential baseline variables of the patients were balanced after conducting PSM. Pregnancy outcomes of the total PCOS population exhibited no variances (P > 0.05) between protocols after adjustments. When focusing on patients who had received both protocols, GnRH-a administration was associated with increased adjusted live birth rates (P < 0.001), singleton live birth rates (P < 0.001), multiple live birth rates (P = 0.049), clinical pregnancy rates (P < 0.001), and lower miscarriage rates (P = 0.028). Further analysis of these patients indicated that the pregnancy outcomes of therapy with GnRH-a were superior to those without only in the second transfer cycle. No significant difference was exhibited in singleton perinatal outcomes in terms of gestational age, birth weight, delivery mode, gender, obstetric complications, and adverse birth outcomes between the two groups (P > 0.05).</p><p><strong>Conclusions: </strong>GnRH-a pretreatment before programmed cycles may not affect pregnancy or perinatal outcomes of general women with PCOS in FET cycles but may be beneficial for PCOS patients who did not achieve a live birth during the first cycle receiving a programmed protocol. The conclusion should be considered with caution. Further well-designed studies are required to validate our findings.</p>","PeriodicalId":21011,"journal":{"name":"Reproductive Biology and Endocrinology","volume":"23 1","pages":"72"},"PeriodicalIF":4.2,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12079977/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Huijing Shao, Chang Xu, Haoran Wang, Nan Lu, Hang Gu, Caihong Zhang, Lirong Li, Qianqian Sun, Rui Guan, Beibei Xuan
{"title":"Dissecting the genetic determinants and biological associations between body mass index and female reproductive disorders based on genome-wide association study.","authors":"Huijing Shao, Chang Xu, Haoran Wang, Nan Lu, Hang Gu, Caihong Zhang, Lirong Li, Qianqian Sun, Rui Guan, Beibei Xuan","doi":"10.1186/s12958-025-01406-y","DOIUrl":"https://doi.org/10.1186/s12958-025-01406-y","url":null,"abstract":"<p><strong>Background: </strong>While the phenotypic link between body mass index (BMI) and some female reproductive disorders is well established, the genetic architecture and causal relationships have not been systematically studied. We aimed to create an atlas of the shared genetic associations of BMI and 16 female reproductive disorders and to identify their common risk loci, biological pathways, and potential mechanisms.</p><p><strong>Methods: </strong>We assessed the genetic correlations between BMI and 16 reproductive disorders using summary data from large-scale genome-wide association studies. Cross-trait pleiotropic analysis identified shared loci and genes, while functional annotation and tissue-specific analysis revealed relevant biological pathways and tissues. Multi-trait colocalization analysis examined the role of hormones and metabolites in these traits. Additionally, bidirectional Mendelian randomization (MR) analysis was employed to assess causal relationships between BMI and reproductive outcomes. We also conducted summary data-based MR (SMR) analysis to identify potential drug targets.</p><p><strong>Results: </strong>Our results revealed a significant genetic correlation between BMI and eight female reproductive diseases. Furthermore, we identified 50 shared pleiotropic loci between BMI and these traits, with 21 of them showing significant colocalization, suggesting a complex shared genetic architecture across the genome. In addition, the top biological pathways and tissues enriched with these pleiotropic loci were associated with RNA metabolism, macromolecule biosynthesis, type B pancreatic cell apoptosis, various brain regions, and the pituitary. Moreover, multi-trait colocalization indicated that insulin, lipid metabolites, glucose, glycine, and glutamine mediate shared mechanisms between BMI, gestational diabetes mellitus (GDM), and endometrial cancer. MR analysis suggested BMI may cause several reproductive diseases, with only GDM affecting BMI reversely. Finally, SMR analysis revealed EIF2S2P3 and MCM6, which may have a causative effect on both BMI & GDM and BMI & gestational hypertension.</p><p><strong>Conclusion: </strong>Our results suggest a significant genetic link between BMI and eight female reproductive diseases, highlighting a shared and causal genetic basis. Reducing BMI in women may serve as an effective strategy to lower the risk of female reproductive disorders. The identified pleiotropic loci, genes, and shared pathways could provide new therapeutic targets for both obesity and reproductive diseases, along with their comorbidities.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":21011,"journal":{"name":"Reproductive Biology and Endocrinology","volume":"23 1","pages":"71"},"PeriodicalIF":4.2,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12076840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144079517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}