{"title":"Correction: Triggering final follicular maturation for IVF cycles.","authors":"Raoul Orvieto","doi":"10.1186/s12958-025-01363-6","DOIUrl":"10.1186/s12958-025-01363-6","url":null,"abstract":"","PeriodicalId":21011,"journal":{"name":"Reproductive Biology and Endocrinology","volume":"23 1","pages":"26"},"PeriodicalIF":4.2,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468970","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}
Francesca Rossi, Stefania Luppi, Albina Fejza, Elena Giolo, Giuseppe Ricci, Eva Andreuzzi
{"title":"Extracellular matrix and pregnancy: functions and opportunities caught in the net.","authors":"Francesca Rossi, Stefania Luppi, Albina Fejza, Elena Giolo, Giuseppe Ricci, Eva Andreuzzi","doi":"10.1186/s12958-025-01348-5","DOIUrl":"10.1186/s12958-025-01348-5","url":null,"abstract":"<p><p>The extracellular matrix is a complex network of macromolecules that support the growth and homeostatic development of organisms. By conveying multiple signaling cascades, it impacts on several biological processes and influences the behaviour of numerous cell types. During the endometrial cycle and the key events necessary for a correct embryo implantation and placentation, this bioactive meshwork is substantially modified to favour endometrial receptivity and vascular adaptation, trophoblast cell migration, and immune activation as well. A correct extracellular remodeling is fundamental for the establishment of a physiological pregnancy; indeed, the occurrence of altered matrix modifications associates with gestational disorders such as preeclampsia. In the present review, we will critically evaluate the role of pivotal matrix constituents in regulating the key steps of embryo implantation and placentation, provide up-to-date information concerning their primary mechanisms of action and discuss on their potential as a novel source of biomarkers and therapeutic targets.</p>","PeriodicalId":21011,"journal":{"name":"Reproductive Biology and Endocrinology","volume":"23 1","pages":"24"},"PeriodicalIF":4.2,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11827249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426066","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":"The role of different LNG-IUS therapies in the management of adenomyosis: a systematic review and meta-analysis.","authors":"Biyun Zhang, Jinghua Shi, Zhiyue Gu, Yushi Wu, Xiaoyan Li, Chenyu Zhang, Hailan Yan, Qiutong Li, Shiqing Lyu, Yi Dai, Jinhua Leng","doi":"10.1186/s12958-025-01349-4","DOIUrl":"10.1186/s12958-025-01349-4","url":null,"abstract":"<p><strong>Objective: </strong>To summarize evidence on the efficacy and safety of the levonorgestrel-releasing intrauterine system (LNG-IUS) in managing adenomyosis (AM), both as a monotherapy and in combination with other therapies.</p><p><strong>Methods: </strong>We searched Medical Literature Analysis and Retrieval System On-Line: Medline, The Cochrane Library, Embase, SinoMed, China National Knowledge Infrastructure, and Wanfang from the inception to Aug 12, 2024 for articles using the LNG-IUS both alone and combined with other therapies in patients with AM. The primary outcome included dysmenorrhea, menstrual bleeding, uterine volume, endometrial thickness and quality of life. The secondary outcome was the assessment of adverse events. Data synthesis was conducted using random-effects model with significant heterogeneity (I<sup>2</sup> > 50%), otherwise using fixed-effects model.</p><p><strong>Results: </strong>The final analysis included 28 studies. Compared with etonogestrel, LNG-IUS was more effective in reducing uterine volume and associated with a lower risk of weight gain, but showed no significant difference in reducing dysmenorrhea and endometrial thickness. Comparing LNG-IUS with mifepristone, there was no significant difference in terms of quality of life. The combination of LNG-IUS with Gonadotropin-releasing hormone agonists (GnRH-a) was more effective than LNG-IUS alone, providing benefits in reducing dysmenorrhea (mean deviation, MD: -1.14), menstrual bleeding (MD: -11.94), uterine volume (MD: -30.39), endometrial thickness (MD: -0.89), and adverse events. The combination of LNG-IUS with surgical excision was more effective than surgical excision alone, providing benefits in reducing dysmenorrhea (MD: -1.49), menstrual bleeding (MD: -5.13) at 12 months, reducing uterine volume at 6 (MD: -9.23), 12 (MD: -16.53) and 24 (MD: -27.17) months. The combination of LNG-IUS with focused ultrasound ablation (FUA) was more effective than FUA alone, providing benefits in reducing dysmenorrhea (MD: -0.62), menstrual bleeding (MD: 0.17).</p><p><strong>Conclusions: </strong>This study found no clear evidence to recommend single-drug therapy for improving pain and quality of life in AM management within 12 months. Combining LNG-IUS with GnRH-a is effective in alleviating pain, controlling heavy bleeding, reducing lesion volume, reducing the probability of expulsion and irregular bleeding. Postoperative LNG-IUS helps reduce long-term pain and bleeding. In combined FUA, LNG-IUS is effective for managing short-term pain and bleeding.</p><p><strong>Trial registration: </strong>PROSPERO registration number: CRD42024578824.</p>","PeriodicalId":21011,"journal":{"name":"Reproductive Biology and Endocrinology","volume":"23 1","pages":"23"},"PeriodicalIF":4.2,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11823221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414975","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}
Maria Longo, Francesca Liuzzi, Serena De Carlini, Antonio La Marca
{"title":"The role of LH in follicle development: from physiology to new clinical implications.","authors":"Maria Longo, Francesca Liuzzi, Serena De Carlini, Antonio La Marca","doi":"10.1186/s12958-025-01353-8","DOIUrl":"10.1186/s12958-025-01353-8","url":null,"abstract":"<p><p>The process of follicle development is closely regulated by two pituitary gonadotropins: follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Traditionally, folliculogenesis is considered to be divided into a gonadotropin-independent phase and a gonadotropin-dependent phase. Despite this, recent evidence has demonstrated that functional LH receptors are expressed even in smaller follicles during the phase considered to be gonadotropin independent. Luteinizing hormone promotes androgen synthesis within ovarian follicles and seems to significantly contribute to accelerate and enhance the transition from the primordial to the antral stage of folliculogenesis. Thus, LH could play a fundamental role in determining the number of recruitable antral follicles, with a direct impact on the cyclic recruitment of follicles and reproductive potential. Common clinical conditions of pituitary suppression such as hypogonadotropic hypogonadism, other than pregnancy and combined oral contraceptive use, have been considered to analyze the effect of lower serum LH levels on the functional ovarian reserve. This review outlines recent findings on the mechanisms of human follicle development, based on human and animal models, with a direct focus on possible new clinical applications.</p>","PeriodicalId":21011,"journal":{"name":"Reproductive Biology and Endocrinology","volume":"23 Suppl 1","pages":"22"},"PeriodicalIF":4.2,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11808943/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143391624","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":"Comparison of vaginal versus intramuscular progesterone in programmed cycles for frozen-thawed blastocyst transfer in patients with endometriosis.","authors":"Ziqi Jin, Guoxia Yang, Tianrui Wen, Benyu Miao, Chen Wang, Qingyan Zhang, Fang Gu, Yanwen Xu","doi":"10.1186/s12958-025-01354-7","DOIUrl":"10.1186/s12958-025-01354-7","url":null,"abstract":"<p><strong>Background: </strong>Previous studies have shown that due to the presence of endometrium progesterone resistance in patients with endometriosis, it is considered that higher levels of progesterone may be required to achieve live birth during programmed frozen-thawed embryo transfer (FET) cycles. Currently, the optimal progesterone support in FET cycles remains a contentious issue, and it mainly focused on the general infertile population, without specific attention to infertile patients with endometriosis. This study aimed to compare the pregnancy outcomes between vaginal or intramuscular progesterone administration in patients with endometriosis, and to determine whether the stage of endometriosis moderates the differences.</p><p><strong>Methods: </strong>This retrospective cohort study included patients with endometriosis who underwent their first single frozen-thawed blastocyst transfer in a programmed cycle from January 2018 to April 2024 at a university-affiliated reproductive medical center. According to the routes of luteal support, patients were divided into vaginal progesterone and intramuscular progesterone groups. Analyses were conducted using multivariate regression models and subgroup analysis. Interaction tests were employed to determine whether the revised American Society for Reproductive Medicine (r-ASRM) stages of endometriosis moderated the differences between the routes of progesterone administration and pregnancy outcomes.</p><p><strong>Results: </strong>A total of 825 programmed frozen-thawed blastocyst transfer cycles were included in the analysis, with 362 cases using vaginal progesterone and 463 cases using intramuscular progesterone. In the overall cohort, clinical pregnancy rate of the vaginal progesterone group was 49.17%, comparable to 44.06% of the intramuscular progesterone group (aOR 0.82, 95% CI 0.61-1.11). Similarly, there was no statistically significant difference in miscarriage rates between the two groups (16.85% versus 24.51%; aOR 1.57, 95% CI 0.90-2.75). In the subgroup analysis in patients classified as r-ASRM stages I-II, clinical pregnancy rate of vaginal progesterone group was significantly higher than that of intramuscular group (aOR 0.74, 95% CI 0.58-0.93, P = 0.011). Whereas, in patients with stages III-IV, no significant differences in pregnancy outcomes between the two groups were detected. Interaction tests between the routes of progesterone administration and r-ASRM stages were significant (P = 0.036).</p><p><strong>Conclusions: </strong>In the first single frozen-thawed blastocyst transfer cycles for endometriosis patients with r-ASRM stages I-II, vaginal progesterone favours a higher clinical pregnancy rate compared to the intramuscular progesterone.</p>","PeriodicalId":21011,"journal":{"name":"Reproductive Biology and Endocrinology","volume":"23 1","pages":"20"},"PeriodicalIF":4.2,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11800567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365019","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}
Lu Sun, Jiayu Huang, Xuezi Wang, Peng Huang, Baolin Dong, Zehang Liang, Jiahong Wu, Jiancheng Wang
{"title":"Enucleated bone marrow-derived mesenchymal stromal cells regulate immune microenvironment and promote testosterone production through efferocytosis.","authors":"Lu Sun, Jiayu Huang, Xuezi Wang, Peng Huang, Baolin Dong, Zehang Liang, Jiahong Wu, Jiancheng Wang","doi":"10.1186/s12958-025-01352-9","DOIUrl":"10.1186/s12958-025-01352-9","url":null,"abstract":"<p><strong>Background: </strong>Testosterone deficiency (TD) occurs most frequently in older men and can cause many health problems. Testosterone replacement therapy (TRT) is widely used to treat TD, but this regimen can lead to a series of side effects. Stem cell therapy has been wildly studied in vitro. However, due to the multidirectional differentiation potential and heterogeneity of stem cells, it is difficult to achieve the good efficiency and reproducibility in basic research and clinical applications. This study aims to identify a new strategy for the treatment of TD.</p><p><strong>Methods: </strong>Bone marrow-derived mesenchymal stromal cells (BMSCs) were enucleated by Ficoll density gradient centrifugation. The organelles and cellular functions of enucleated BMSCs were analyzed by immunofluorescence staining and flow cytometry. Extracellular vesicles (EVs) were isolated by ultracentrifugation and characterized. For the animal studies, enucleated BMSCs were labelled with Mitotracker and injected into ethane dimethanesulfone (EDS)-treated rats. Testosterone production and spermatogenesis were detected at different time points through various tests. To determine the mechanism of efferocytosis, we analysed the number of macrophages by immunofluorescence staining and quantitative real-time polymerase chain reaction (qRT-PCR).</p><p><strong>Results: </strong>The injection of enucleated BMSCs (Cargocytes) into the testes of EDS-treated rats restored the levels of serum testosterone, increased the number of Leydig cells (LCs), and improved spermatogenesis. We found that enucleated BMSCs underwent apoptosis earlier than BMSCs did. Subsequently, testicular interstitial macrophages phagocytosed apoptotic enucleated BMSCs through efferocytosis. Efferocytosis promoted macrophage polarization from the M1 to the M2 phenotype, reduced the expression of proinflammatory cytokines, and decreased the levels of inflammation and oxidative stress.</p><p><strong>Conclusions: </strong>In summary, this study pioneered the application of stromal cell enucleation technology to repair tissue damage in the reproductive system, explored the potential of cell burial in the treatment of reproductive system diseases and provided a new approach for the clinical treatment of male infertility.</p>","PeriodicalId":21011,"journal":{"name":"Reproductive Biology and Endocrinology","volume":"23 1","pages":"21"},"PeriodicalIF":4.2,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11800438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143365138","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":"Cardiovascular disease risk prediction by Framingham risk score in women with polycystic ovary syndrome.","authors":"Mina Amiri, Maryam Mousavi, Mahsa Noroozzadeh, Fereidoun Azizi, Fahimeh Ramezani Tehrani","doi":"10.1186/s12958-025-01346-7","DOIUrl":"10.1186/s12958-025-01346-7","url":null,"abstract":"<p><strong>Background: </strong>Despite the documented increased cardiovascular disease (CVD) risk in women with polycystic ovary syndrome (PCOS), no specific risk prediction tools are recommended for these patients. We aimed to assess the validity of the Framingham Risk Score (FRS) as a predictor of CVD risk in PCOS patients.</p><p><strong>Methods: </strong>In a community-based prospective study, 4,435 women from the Tehran Lipid and Glucose Study (TLGS) cohort were analyzed. Among them, 215 women aged 30 years or older were diagnosed with PCOS. A Cox proportional hazards model applied to assess the relationship between the FRS and CVD event. Model accuracy was evaluated using the C-statistic, while discrimination and calibration were assessed via the ROC curve, area under the ROC curve (AUC) statistics, and the Hosmer- Lemeshow test.</p><p><strong>Results: </strong>The Cox proportional hazards (HRs) model revealed that the CVD risk increased by 38% for each one-unit increase in the FRS [HR: 1.38 (95% CI: 1.14, 1.66)] in PCOS patients. The FRS had a C-statistic of 0.765, which indicated a satisfactory fit for CVD prediction in this population. The AUC of the ROC curve was 0.82, which demonstrated a good discrimination of the FRS. The Hosmer-Lemeshow test showed that the predicted probabilities of CVD were consistent with the observed CVD rates (p = 0.217), indicating a good calibration.</p><p><strong>Conclusions: </strong>This study revealed a significant increase in CVD risk among PCOS patients. The FRS effectively predicts a 38% increment in CVD risk for every one-unit increase in the FRS. Our study further validated the FRS as a predictor of CVD risk in these patients.</p>","PeriodicalId":21011,"journal":{"name":"Reproductive Biology and Endocrinology","volume":"23 1","pages":"19"},"PeriodicalIF":4.2,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143190344","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":"Association between sleep during pregnancy and birth outcomes: a prospective cohort study.","authors":"Libing Huang, Huanjun Chen, Fuhui Yao, Zhonghan Sun, Shijiao Yan, Yuwei Lai, Chuanzhu Lv, Xiong-Fei Pan, Rixing Wang, Xingyue Song","doi":"10.1186/s12958-025-01350-x","DOIUrl":"10.1186/s12958-025-01350-x","url":null,"abstract":"<p><strong>Objective: </strong>A prospective cohort study was conducted to investigate sleep status during the early and second trimester of pregnancy in pregnant women on adverse birth outcome, such as preterm birth, low birth weight and small for gestational age.</p><p><strong>Methods: </strong>Multivariable logistic regression models were used to analyze the association of sleep status during the early and second trimester of pregnancy with adverse birth outcomes and generated the odds ratio and 95% confidence interval.</p><p><strong>Results: </strong>5,418 pregnant women were included in the analysis. In the multivariable model, compared with 7.1-8 h/night, sleep ≤ 7 h/night during second trimester increases the risk of preterm birth (OR: 1.43, 95% CI: 1.12,1.85), and the risk of preterm birth was decreased in pregnant women who slept > 9 h/night (OR: 0.79, 95% CI: 0.53,0.93). Sleep quality, and sleep changes in the early and second trimesters, and sleep duration in the early pregnancy were not statistically associated with preterm birth, low birth weight and small for gestational age.</p><p><strong>Conclusions: </strong>Short sleep duration during pregnancy is associated with a higher risk of preterm birth and longer sleep duration at night is associated with a lower risk of preterm birth, but the latter needs further verification. Sleep status during pregnancy was not associated with low birth weight and small for gestational age. In order to reduce risk of adverse birth outcomes, sleep problems in pregnant women should be strengthened during pregnancy care.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":21011,"journal":{"name":"Reproductive Biology and Endocrinology","volume":"23 1","pages":"18"},"PeriodicalIF":4.2,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143190342","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}
T G Knowles, J A García-Velasco, M Toribio, N Garrido, A I Barrio Pedraza, C Colomé Rakosnik, A Salazar Vera, R Milnes
{"title":"Continuous overnight monitoring of body temperature during embryo transfer cycles as a proxy for establishing progesterone fluctuations by comparison with P4 blood progesterone results: a prospective, observational study.","authors":"T G Knowles, J A García-Velasco, M Toribio, N Garrido, A I Barrio Pedraza, C Colomé Rakosnik, A Salazar Vera, R Milnes","doi":"10.1186/s12958-024-01329-0","DOIUrl":"10.1186/s12958-024-01329-0","url":null,"abstract":"<p><strong>Background: </strong>A prospective, observational study to identify relationships between body temperature and levels of peripheral P4 blood progesterone, and examine if these differ according to body temperature cycle pattern.</p><p><strong>Methods: </strong>62 data points from 18 patients undergoing hormone assisted embryo transfer cycles at IVIRMA IVF clinics in Madrid, Mallorca and Malaga, Spain volunteered to use OvuSense, an intra-vaginal body temperature monitor. Primary outcome measures were OvuSense Raw and Smooth Temperature (ST) (°C), P4 (ng/ml).</p><p><strong>Secondary outcome measures: </strong>Ongoing Pregnancy, Miscarriage or biochemical pregnancy. Graphical time based comparison analyses and multilevel regression analyses using MLwiN 3.10 [Charlton C, Rasbash J, Browne WJ, Healy M, Cameron B. MlwiN Version 3.10. Centre for Multilevel Modelling. University of Bristol; 2024.] software were conducted.</p><p><strong>Results: </strong>A graphical analysis showed an apparent relationship between P4 levels and Temperature taken on P4 blood draw day. A multilevel regression analysis using MLwiN 3.10 Centre for Multilevel Modelling. University of Bristol software investigated this relationship, allowing between-patient variation to be accounted for and estimated. This established a strong linear relationship between LnP4 and ST, and cross correlation was carried out which identified the optimum predictor of levels of LnP4 was ST measured on the day prior to blood sampling. Further graphical analyses showed an apparent lower luteal level of P4 for cycles flagged as atypical by OvuSense, and for negative outcomes, except on embryo transfer day.</p><p><strong>Conclusions: </strong>The results provide extremely strong evidence of a linear relationship between LnP4 and Smooth Temperature (ST) measured the day before blood sampling (Z = 15.6, p < 0.0001, 2 sided). This suggests that ST could provide a less invasive, continuous, and more practical method of assessing P4 response. Secondary outcomes may be related to ST pattern established during an embryo transfer cycle. Further investigation is required to establish the value of the ST pattern for improving outcomes.</p>","PeriodicalId":21011,"journal":{"name":"Reproductive Biology and Endocrinology","volume":"23 1","pages":"17"},"PeriodicalIF":4.2,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792532/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143123487","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}
D Gilboa, Akhil Garg, M Shapiro, M Meseguer, Y Amar, N Lustgarten, N Desai, T Shavit, V Silva, A Papatheodorou, A Chatziparasidou, S Angras, J H Lee, L Thiel, C L Curchoe, Y Tauber, D S Seidman
{"title":"Application of a methodological framework for the development and multicenter validation of reliable artificial intelligence in embryo evaluation.","authors":"D Gilboa, Akhil Garg, M Shapiro, M Meseguer, Y Amar, N Lustgarten, N Desai, T Shavit, V Silva, A Papatheodorou, A Chatziparasidou, S Angras, J H Lee, L Thiel, C L Curchoe, Y Tauber, D S Seidman","doi":"10.1186/s12958-025-01351-w","DOIUrl":"10.1186/s12958-025-01351-w","url":null,"abstract":"<p><strong>Background: </strong>Artificial intelligence (AI) models analyzing embryo time-lapse images have been developed to predict the likelihood of pregnancy following in vitro fertilization (IVF). However, limited research exists on methods ensuring AI consistency and reliability in clinical settings during its development and validation process. We present a methodology for developing and validating an AI model across multiple datasets to demonstrate reliable performance in evaluating blastocyst-stage embryos.</p><p><strong>Methods: </strong>This multicenter analysis utilizes time-lapse images, pregnancy outcomes, and morphologic annotations from embryos collected at 10 IVF clinics across 9 countries between 2018 and 2022. The four-step methodology for developing and evaluating the AI model include: (I) curating annotated datasets that represent the intended clinical use case; (II) developing and optimizing the AI model; (III) evaluating the AI's performance by assessing its discriminative power and associations with pregnancy probability across variable data; and (IV) ensuring interpretability and explainability by correlating AI scores with relevant morphologic features of embryo quality. Three datasets were used: the training and validation dataset (n = 16,935 embryos), the blind test dataset (n = 1,708 embryos; 3 clinics), and the independent dataset (n = 7,445 embryos; 7 clinics) derived from previously unseen clinic cohorts.</p><p><strong>Results: </strong>The AI was designed as a deep learning classifier ranking embryos by score according to their likelihood of clinical pregnancy. Higher AI score brackets were associated with increased fetal heartbeat (FH) likelihood across all evaluated datasets, showing a trend of increasing odds ratios (OR). The highest OR was observed in the top G4 bracket (test dataset G4 score ≥ 7.5: OR 3.84; independent dataset G4 score ≥ 7.5: OR 4.01), while the lowest was in the G1 bracket (test dataset G1 score < 4.0: OR 0.40; independent dataset G1 score < 4.0: OR 0.45). AI score brackets G2, G3, and G4 displayed OR values above 1.0 (P < 0.05), indicating linear associations with FH likelihood. Average AI scores were consistently higher for FH-positive than for FH-negative embryos within each age subgroup. Positive correlations were also observed between AI scores and key morphologic parameters used to predict embryo quality.</p><p><strong>Conclusions: </strong>Strong AI performance across multiple datasets demonstrates the value of our four-step methodology in developing and validating the AI as a reliable adjunct to embryo evaluation.</p>","PeriodicalId":21011,"journal":{"name":"Reproductive Biology and Endocrinology","volume":"23 1","pages":"16"},"PeriodicalIF":4.2,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11783712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075334","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}