Journal of Assisted Reproduction and Genetics最新文献

{"title":"Influence of combined oral contraceptive pill before PPOS protocol on egg donors and recipients' outcomes: an international multicenter retrospective study.","authors":"Sara Maggi, Silvia Bontà, Antonio Forgiarini, Greet Lammens, Simona Franzò, Giulia Zamagni, Lodovico Parmegiani, Gabriella Zito, Giuseppe Ricci, Luis Alberto Quintero Espinel","doi":"10.1007/s10815-025-03519-0","DOIUrl":"https://doi.org/10.1007/s10815-025-03519-0","url":null,"abstract":"<p><strong>Purpose: </strong>This study aims to evaluate whether using a combined oral contraceptive pill (COCP) pre-treatment before controlled ovarian hyperstimulation (COH) may negatively influence ovarian response in donors and treatments outcomes in recipients when a progestin-primed ovarian stimulation (PPOS) protocol is used in oocyte donation treatments.</p><p><strong>Methods: </strong>Multicenter retrospective cohort study evaluating outcomes of 397 COH cycles in oocyte donors, with and without COCP pre-treatment. The retrieved oocytes were used for 216 oocyte donation cycles in recipients.</p><p><strong>Results: </strong>In donors, the No-COCP group obtained a higher number of total, MII, and useful oocytes, similar stimulation days, total FSH dose used, and cancellation rate due to low response, while the COCP group showed significantly higher cancellations for low LH levels, indicative of long-lasting pituitary suppression COCP related. In recipients, both groups showed similar fertilization rate and blastocyst formation rate. Miscarriage rate (MR) was significantly higher in the COCP group, while higher implantation rate, ongoing pregnancy rate (OPR), and live birth rate (LBR) were obtained in the No-COCP group.</p><p><strong>Conclusions: </strong>Donor response to COH with PPOS protocol appears to be negatively influenced by COCP pre-treatment, with implications for oocyte donation treatment outcomes in recipients, including higher MR and lower OPR/LBR. Further studies are needed to confirm these findings.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic and functional analysis reveals novel mutations in meiotic genes underlying non-obstructive azoospermia.","authors":"Ying Liu, Jingping Li, Lejun Li, Yuanyuan Zhou, Yankun Wang, Yanhua Han, Jia Fei, Fan Jin","doi":"10.1007/s10815-025-03505-6","DOIUrl":"https://doi.org/10.1007/s10815-025-03505-6","url":null,"abstract":"<p><strong>Purpose: </strong>To identify novel pathogenic mutations in meiotic genes underlying non-obstructive azoospermia (NOA) through whole-exome sequencing analysis.</p><p><strong>Materials and methods: </strong>Whole-exome sequencing was performed on 31 NOA patients. Novel variants were identified through bioinformatic analysis and validated by Sanger sequencing. The pathogenicity of variants was assessed through functional studies including protein structural analysis, conservation analysis, and minigene splicing assays.</p><p><strong>Results: </strong>We identified novel pathogenic mutations in four meiotic genes. Most significantly, we discovered the first human case of a homozygous nonsense mutation in MAEL (c.514C > T, p.Gln172Ter) in a patient from a consanguineous family. Additionally, we found novel compound heterozygous mutations in MSH5 (c.648-2A > G and c.1133T > C) and REC114 (c.659_706dup and c.123C > A), and a heterozygous splice-site mutation in DMRT1 (c.968-2A > G). Functional analyses revealed that these mutations disrupted critical meiotic processes through aberrant splicing, protein truncation, or structural alterations.</p><p><strong>Conclusion: </strong>Our findings expand the mutation spectrum of meiotic genes in male infertility and provide new insights into the genetic basis of spermatogenic failure. The identification of novel mutations, particularly the first reported homozygous MAEL mutation, enhances our understanding of meiotic arrest in human spermatogenesis and provides valuable information for genetic counseling.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144181463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toward accurate vaginal microbiome profiling: protocol, bioinformatics, and core microbiota characterisation.","authors":"Isabella M Davidson, Elham Nikbakht, Larisa M Haupt, Paul J Dunn","doi":"10.1007/s10815-025-03509-2","DOIUrl":"https://doi.org/10.1007/s10815-025-03509-2","url":null,"abstract":"<p><strong>Purpose: </strong>Rising demand for assisted reproductive technologies (ART) with limited improvements in success rates has driven interest in the impact of the vaginal microbiome on fertility outcomes. In order to fully examine the relationship between the vaginal microbiome and fertility outcomes, methodologies and technological developments must be standardised and benchmarked to provide the most accurate assessment of microbial population representation.</p><p><strong>Methods: </strong>This study sought to investigate the utility of 16S sequencing and bioinformatic approaches using nanopore sequencing to characterize core vaginal microbiota in a healthy Australian cohort of reproductive-age women.</p><p><strong>Results: </strong>Optimisation and comparison of different PCR strategies for whole 16S amplification was undertaken, along with the generation of bioinformatic analysis strategies. Initial qPCR identified the 27F-YM (MIX) primer as the most sensitive for C. trachomatis. However, nanopore sequencing revealed no detectable C. trachomatis across all six samples. Among the bioinformatic tools, Porechop with NanoCLUST most accurately identified microbial presence. Community state type (CST) I-characterised by Lactobacillus crispatus dominance-was identified as the most common CST (66%), aligning with patterns of a healthy vaginal microbiome.</p><p><strong>Conclusion: </strong>The findings highlight a Lactobacillus-rich microbiome as the most common among healthy females; however, further refinement-potentially through a metagenomics approach-is recommended to address 16S rRNA primer limitations to enable improved accuracy of microbial detection for the vaginal microbiome.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144173947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Germ cells and the aging niche: a systems approach to reproductive longevity.","authors":"Mega Obukohwo Oyovwi, Ejime A Chijiokwu, Arientare Rume Rotu, Ejayeta Jeroh, Kehinde Henrietta Babawale, Ngozichika Obiageli Keke, Aisuodionoe Eromosele Michael","doi":"10.1007/s10815-025-03518-1","DOIUrl":"https://doi.org/10.1007/s10815-025-03518-1","url":null,"abstract":"<p><p>The intersection of aging and reproductive decline presents a significant challenge in human health, with fertility rates decreasing sharply in later life for both sexes. This review delves into the intricate relationship between germ cells, the fundamental units of reproduction, and their surrounding microenvironment, known as the niche. Emphasizing that reproductive longevity is not solely determined by the intrinsic properties of germ cells, but rather by the complex interplay with their niche, a dynamic system that changes with age. We highlight evidence from model organisms like Drosophila and C. elegans demonstrating how age-related changes in niche signaling impact germ cell function. A systems biology approach, integrating multi-omics data (genetics, epigenetics, cellular behavior), is crucial to fully understanding this complex interaction. Specifically, we discuss the role of epigenetic modifications, such as DNA methylation and histone acetylation, in modulating niche-germ cell communication. This approach offers a comprehensive view of the aging reproductive system and opens up avenues for therapeutic interventions aimed at modulating the niche and potentially extending reproductive lifespan. Future research focused on unraveling the specific molecular mechanisms underlying the niche-germ cell interaction will be pivotal in developing strategies to combat age-related reproductive decline.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144182079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oocyte and zygote development potential in minimal stimulation, natural cycle and conventionally stimulated IVF: an international multi-centre retrospective cohort study.","authors":"Isotta Martha Magaton, Ikbale Siercks, Martina Nordin, Roxana Maria Popovici, Eva Maria Boogen, Stefan Eisenhardt, Natalie Reeka, Jan-Simon Lanowski, Marie Roumet, Michael von Wolff","doi":"10.1007/s10815-025-03508-3","DOIUrl":"https://doi.org/10.1007/s10815-025-03508-3","url":null,"abstract":"<p><strong>Purpose: </strong>The aim of this research is to assess the development potential of oocytes and zygotes obtained from Natural cycle IVF (NC-IVF), different minimal stimulation IVF (Min stim-IVF) and conventionally stimulated IVF (cIVF) treatment protocols.</p><p><strong>Methods: </strong>International multi-centre retrospective cohort study including 1483 NC-IVF, 1208 Min stim-IVF, and 1892 cIVF cycles performed in 8 IVF centres between 01.2022 and 03.2023. The five Min stim-IVF protocols analysed included low dose clomiphene citrate, aromatase inhibitors, low dose (≤ 100 IU) gonadotropins, each alone or in combination. For each IVF protocol, we assessed and modelled the transition probabilities of (i) each observed oocyte developing into a zygote, (ii) each observed zygote developing into a gestational sac and (iii) each observed zygote developing into a live birth.</p><p><strong>Results: </strong>All modelled transition probabilities were found to be maximal in NC-IVF, minimal in cIVF with Min stim-IVF in between. The probability of transition from oocyte to zygote was 0.72 for NC-IVF, 0.56 to 0.65 for Min stim-IVF protocols and 0.54 for cIVF. The probability of transition from zygote to gestational sac was 0.21 for NC-IVF, 0.14 to 0.19 for Min stim-IVF and 0.09 for cIVF protocols and from zygote to live birth 0.16 for NC-IVF, 0.09 to 0.16 for Min stim-IVF and 0.06 for cIVF protocols.</p><p><strong>Conclusions: </strong>The transition probabilities of oocytes and zygotes appears to be higher in NC-IVF, followed by Min stim-IVF and then cIVF, suggesting that increasing dosages of gonadotropins might have a negative effect on oocyte/zygote development potential.</p><p><strong>Trial registration: </strong>Clinicaltrial.gov: NCT05125497. Registration date 03.11.2021.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144159313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polygenic scores for dizygotic twinning: insights into the genetic architecture of female fertility.","authors":"Nikki Hubers, Christian M Page, René Pool, Hamdi Mbarek, Nils Lambalk, Velja Mijatovic, Lannie Ligthart, Jenny van Dongen, Siri Håberg, Elizabeth C Corfield, Jeffrey J Beck, Erik A Ehli, Nicholas G Martin, Gonneke Willemsen, Jennifer R Harris, Jouke-Jan Hottenga, Dorret I Boomsma","doi":"10.1007/s10815-025-03515-4","DOIUrl":"10.1007/s10815-025-03515-4","url":null,"abstract":"<p><strong>Purpose: </strong>Natural dizygotic twinning (DZT) results from hyper-ovulation and is an indicator of female fertility. However, some traits linked to DZ twinning are also associated with infertility. We examined the relationship between DZT and female (in)fertility using recent GWAS findings.</p><p><strong>Methods: </strong>We investigated the genetic architecture of DZT and compared polygenic scores (PGS) for DZT between mothers of naturally conceived DZ twin pregnancies and mothers who required fertility treatments (MAR) in the Netherlands Twin Register (NTR) and the Norwegian Mother, Father, and Child Cohort Study (MoBa). We also calculated genetic correlations between DZT and seven fertility related traits.</p><p><strong>Results: </strong>DZT has a low polygenicity, with only 0.20% of SNPs estimated to have a nonzero effect. The DZT PGS explains 1.6% of variance in DZT liability, and we observe an odds ratio of 2.29 between the first and the tenth PGS deciles. The DZT PGS distinguishes between mothers of naturally conceived pregnancies and mothers who received MAR and is associated with a shorter time to pregnancy in mothers of singletons. The lowest PGSs were observed for mothers who received hormonal ovulation induction, indicating maternal fertility issues. DZT showed genetic correlations with anovulatory infertility (r_g =  - 0.698) and PCOS (r_g =  - 0.278), and endometriosis (r_g = 0.279).</p><p><strong>Conclusions: </strong>Female fertility appears to exists on a genetic spectrum, with anovulation/infertility at one end and DZT at the other. Results suggest that the DZT PGS can be of added value to evaluate female fertility and be incorporated in clinical practice in the future.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144150511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence of psychological problems among individuals and couples during assisted reproductive technology(ART) treatment: a systematic review and meta-analysis.","authors":"Xuan Gu, Jing-Jing Si, Xiao Shan, Wen-Ying Gao, Xiao-Qin Liu","doi":"10.1007/s10815-025-03526-1","DOIUrl":"https://doi.org/10.1007/s10815-025-03526-1","url":null,"abstract":"<p><strong>Background: </strong>The psychological problems of infertile couples deserve more attention given the impact on pregnancy outcomes.</p><p><strong>Aims: </strong>This systematic review and meta-analysis was designed to assess the prevalence of anxiety, depression, and stress in couples during assisted reproductive treatment.</p><p><strong>Materials and methods: </strong>We conducted searches on PubMed, Embase, and Web of Science from the outset until September 2024. Random-effects models were conducted to estimate the pooled prevalence of anxiety, depression and stress. Subgroup analyses were performed to seek potential sources of heterogeneity. The Egger's test was utilized to assess publication bias.</p><p><strong>Results: </strong>The meta-analysis included 40 studies involving 16,042 participants. The pooled prevalence of anxiety, depression and stress symptoms in infertile women were 48.0% (95%CI 36.6%-59.9%), 35.6% (95%CI 28.0%-43.3%) and 52.2% (95%CI 13.2-91.1%) respectively, while those in infertile men were 28.4% (95%CI 15.4%-43.4%) , 18.6% (95%CI 13.4%-23.8%) and 47.2% (95%CI 16.1%-78.4%) respectively. Subgroup analysis revealed the differences in country economic level, continent, assessment instrument and sample size.</p><p><strong>Conclusions: </strong>Many couples experienced anxiety, depression and stress symptoms during assisted reproductive therapy. It is important for healthcare professionals to develop and implement effective strategies for the prevention and intervention of psychological issues.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Less is more: assessing trigger types in planned oocyte cryopreservation cycles.","authors":"Simone Elder, Laura K Kaizer, Mary D Sammel, Cassandra Roeca","doi":"10.1007/s10815-025-03514-5","DOIUrl":"https://doi.org/10.1007/s10815-025-03514-5","url":null,"abstract":"<p><strong>Purpose: </strong>To compare oocyte yield and maturation with dual vs. agonist-only trigger for individuals with unknown fertility undergoing planned oocyte cryopreservation.</p><p><strong>Methods: </strong>Retrospective cohort study of 1002 planned oocyte cryopreservation cycles among 864 patients from January 2010 to March 2023 who received gonadotropin-releasing hormone agonist-only (GnRHa-only) trigger vs. \"dual trigger\" or GnRH-a with human chorionic gonadotropin (HCG) 1500-10,000 IU. The main outcomes were total number of oocytes retrieved, mature oocytes, and maturity rate.</p><p><strong>Results: </strong>After adjusting for age, anti-Müllerian hormone, body mass index, antral follicle count, and max gonadotropin dose, all dual trigger groups had significantly lower oocytes retrieved compared with the GnRHa-only trigger (p-values < 0.02). Additionally, the maturation rate was 10% lower in dual trigger with HCG 10,000 IU compared to GnRH agonist-only trigger (rate ratio = 0.9, p = 0.003). Dual triggers with lower doses of HCG (1500 and 5000 IU) had higher amounts of oocytes retrieved than dual trigger with HCG 10,000 IU, but there was no difference in maturity rate within dual triggers.</p><p><strong>Conclusion: </strong>In a cohort undergoing planned oocyte cryopreservation, the GnRHa-only trigger had higher oocyte yield compared to dual triggers after adjusting for age, anti-Müllerian hormone, body mass index, antral follicle count, and gonadotropin dosing. GnRHa-only triggers have a higher maturity rate than a dual trigger with high HCG. A prospective study is needed to evaluate this further to remove treatment assignment bias.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of nonfunctional CABS1 causing fertilization failure and male infertility in humans: a case report.","authors":"Yilian Huang, Yize Wang, Lou Li, Fei Gong, Ge Lin, Jing Dai","doi":"10.1007/s10815-025-03516-3","DOIUrl":"https://doi.org/10.1007/s10815-025-03516-3","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to identify new genes associated with total fertilization failure (TFF) by intracytoplasmic sperm injection (ICSI).</p><p><strong>Methods: </strong>Whole-exome sequencing (WES) was performed on a patient presenting with TFF by ICSI. To assess the spermatozoa's morphology and ultrastructure, hematoxylin and eosin (H&E) staining and transmission electron microscopy (TEM) were employed. Furthermore, immunofluorescence staining (IF) and western blot (WB) techniques were utilized to investigate the alterations in expression and localization of CABS1 following the transfection of two mutant plasmids. Co-immunoprecipitation (Co-IP) was conducted to investigate in interaction of wild-type/mutant CABS1 with another perinuclear theca protein ACTL9. IF was conducted on spermatozoa from the patient to detect the expression levels of CABS1 and PLCζ.</p><p><strong>Results: </strong>Homozygous mutations in CABS1 were identified in a patient with TFF after ICSI. A high proportion of spermatozoa collected from this man exhibited abnormal morphology and low motility. TEM revealed an absence of the acrosome in the spermatozoa. In vitro experiments have demonstrated that the nonsense mutation in CABS1 leads to truncation of the protein and a reduction in its interaction with ACTL9. IF analysis of spermatozoa from the patient showed a weakened and a diffuse signal for CABS1, along with abnormal localization of the sperm-borne oocyte activation factor PLCζ, ultimately leading to TFF.</p><p><strong>Conclusion: </strong>Our results suggest that CABS1 may be crucial for acrosome formation and the localization of PLCζ. Mutations in CABS1 may lead to teratozoospermia, TFF, and male infertility.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144127463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First follicular fluid cf-mtDNA sequencing unveils ovarian stimulation-induced mutations impacting oocyte quality and IVF success.","authors":"Marc Ventayol-Guirado, Jessica Hernandez-Rodriguez, Joana Florit, Maria Victoria Llull-Alberti, Raquel Barragan, Joana Francesca Ferragut, Jaume Martorell, Damian Heine-Suñer, Iciar Martinez, Antonia Picornell, Laura Torres-Juan, Laura Peralta","doi":"10.1007/s10815-025-03511-8","DOIUrl":"https://doi.org/10.1007/s10815-025-03511-8","url":null,"abstract":"<p><strong>Purpose: </strong>Cell-free mitochondrial DNA (cf-mtDNA) has emerged as a promising non-invasive method to predict embryo implantation potential. This study presents the first sequencing of cf-mtDNA in follicular fluid, aiming to explore the impact of ovarian stimulation treatment on the accumulation of mtDNA mutations and assess their implications for IVF outcomes.</p><p><strong>Methods: </strong>We selected 24 women aged 27 to 35 from the Assisted Reproduction Unit based on inclusion criteria requiring them to be undergoing their first IVF cycle without known infertility issues. For each participant, blood samples were collected prior to ovarian stimulation, and follicular fluid samples were obtained at the time of oocyte retrieval. Long-PCR amplification and next-generation sequencing were used to identify mtDNA mutations.</p><p><strong>Results: </strong>Ovarian stimulation-induced mtDNA mutations in follicular fluid were identified primarily in the D-loop region of the mitochondrial genome. These mutations were correlated with low oocyte counts and poor embryo quality, ultimately reducing IVF success rates. The accumulation of these mutations followed a time-dependent pattern, with longer stimulation durations resulting in higher mutation rates and lower pregnancy outcomes. Prolonged stimulations may exacerbate oxidative stress, negatively impacting oocyte quality.</p><p><strong>Conclusions: </strong>By introducing the first sequencing of follicular fluid cf-mtDNA, this study establishes a direct link between ovarian stimulation-induced mtDNA mutations and reduced IVF efficacy, highlighting them as non-invasive biomarkers for predicting IVF outcomes. Future research may focus on optimizing stimulation protocols or incorporating antioxidants to minimize mtDNA mutations, improving oocyte quality and overall IVF success rates for patients.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144127460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}