{"title":"The elusive function of AMH signaling in folliculogenesis.","authors":"Michael W Pankhurst","doi":"10.1007/s10815-025-03657-5","DOIUrl":"https://doi.org/10.1007/s10815-025-03657-5","url":null,"abstract":"","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086300","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}
Qiaomei Zheng, Jie Li, Shaozhan Chen, Jinhua Wang, Lihong Chen
{"title":"Beyond oocyte quantity: the paradoxical role of poor ovarian response in live birth outcomes among endometriosis patients undergoing IVF/ICSI-ET.","authors":"Qiaomei Zheng, Jie Li, Shaozhan Chen, Jinhua Wang, Lihong Chen","doi":"10.1007/s10815-025-03661-9","DOIUrl":"https://doi.org/10.1007/s10815-025-03661-9","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate the impact of poor ovarian response (POR) on live birth outcomes in endometriosis patients undergoing IVF/ICSI-ET, despite the expected association between reduced oocyte yield and poorer prognosis.</p><p><strong>Methods: </strong>Patients were divided into two groups as endometriosis group (n = 55) and tubal factor group (n = 107). The primary outcomes included clinical pregnancy rate, live birth rate per embryo transfer cycle, and cumulative live birth rate. Secondary outcomes were controlled ovarian hyperstimulation (COH) results and embryo parameters.</p><p><strong>Results: </strong>The incidence rate of POR increased significantly in endometriosis group (18.9% vs. 5.60%, P < 0.05). Similarly, the number of oocytes retrieved, the number of D3 high quality embryos, and the number of available embryos were fewer in endometriosis group (P < 0.05). However, total number of available embryos, clinical pregnancy rates per transfer cycle, live birth rates per transfer cycle, and cumulative birth rate were found to be similar in both groups (P > 0.05). The presence of POR was found to have no significant impact on the cumulative live birth rate among patients with endometriosis.</p><p><strong>Conclusions: </strong>While linked to fewer oocytes per cycle, POR does not predict poorer IVF/ICSI-ET outcomes in endometriosis patients. Patient age, not POR or endometriosis itself, is the primary determinant of live birth success. This study challenges the conventional emphasis on oocyte quantity, advocating for a paradigm shift toward individualized, quality-focused ART strategies in endometriosis-related infertility.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080811","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}
Rossella Cannarella, Claudia Leanza, Sandrine Chamayou, Andrea Crafa, Federica Barbagallo, Antonino Guglielmino, Sandro La Vignera, Aldo E Calogero
{"title":"Impact of male factors on morphokinetic parameters: a prospective analysis using time-lapse monitored embryos.","authors":"Rossella Cannarella, Claudia Leanza, Sandrine Chamayou, Andrea Crafa, Federica Barbagallo, Antonino Guglielmino, Sandro La Vignera, Aldo E Calogero","doi":"10.1007/s10815-025-03658-4","DOIUrl":"https://doi.org/10.1007/s10815-025-03658-4","url":null,"abstract":"<p><strong>Introduction: </strong>Time-lapse technology enables recording embryo morphokinetic parameters, which are associated with embryonic competence and assisted reproductive technology (ART) outcomes. While female factors such as age and BMI are known to influence these parameters, the role of male factors remains understudied.</p><p><strong>Aim: </strong>This study aimed to evaluate the influence of male factors on preimplantation embryo morphokinetics.</p><p><strong>Methods: </strong>In this prospective observational study, 1,210 embryos from infertile couples undergoing Intracytoplasmic sperm injection (ICSI) or intracytoplasmic morphologically-selected sperm injection (IMSI) were monitored using time-lapse imaging. Male data, including age, BMI, sperm concentration, and sperm DNA fragmentation (SDF) were collected. Multiple regression analysis assessed the association between paternal factors and morphokinetic parameters, adjusting for female confounders.</p><p><strong>Results: </strong>After adjustment, male age and BMI were found to significantly influence embryo developmental stages (from time to pronuclei appearance to t4 and t6 for age, from time to pronuclei appearance to t2 and t8 for BMI). The impact of sperm concentration was less consistent, and no significant relationship was observed with SDF.</p><p><strong>Conclusions: </strong>These findings highlight the role of male factors, particularly age and BMI, in influencing embryo morphokinetics, even after accounting for female confounders. This underscores the potential for clinical interventions targeting paternal health to optimize ART outcomes. Additionally, the study reinforces the importance of considering both parental contributions in ART success, particularly the increasingly recognized influence of male age.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075040","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":"Endocrine disruptors and male infertility: multi-omics identification of key genes in non-obstructive azoospermia.","authors":"Yanggang Hong, Yirong Wang, Jiajun Li, Wanyi Shu, Haolin Chen, Congde Chen","doi":"10.1007/s10815-025-03664-6","DOIUrl":"https://doi.org/10.1007/s10815-025-03664-6","url":null,"abstract":"<p><strong>Purpose: </strong>Environmental endocrine-disrupting chemicals (EDCs) are increasingly implicated in male infertility, yet the gene-level mechanisms by which EDCs contribute to non-obstructive azoospermia (NOA) remain unclear. This study aimed to identify EDC-related genes that are causally linked to NOA and uncover their potential roles in reproductive dysfunction.</p><p><strong>Methods: </strong>We integrated transcriptomic analysis of GEO datasets, EDC-associated gene data from the Comparative Toxicogenomics Database (CTD), and Mendelian randomization (MR) to prioritize candidate genes with causal relevance to male infertility. Phenome-wide association study (PheWAS) was conducted to assess systemic effects. EDC-gene interactions were visualized, and single-cell RNA sequencing (scRNA-seq) was used to validate cell-type-specific gene expression in the testis.</p><p><strong>Results: </strong>A total of 136 genes were identified at the intersection of differentially expressed genes in NOA and EDC-related genes. MR analysis highlighted PPP6R1 and AP1M2 as causally linked to male infertility. PheWAS revealed a significant association between PPP6R1 and cardiovascular traits (p < 1 × 10<sup>-6</sup>), suggesting pleiotropic effects. Interaction analysis identified 26 EDCs targeting these genes, including thiram, bisphenol A, and sodium arsenite. The scRNA-seq confirmed downregulation of both genes in germ cells of NOA patients.</p><p><strong>Conclusion: </strong>Our multi-omics approach suggests a potential EDC-gene-NOA axis, identifying PPP6R1 and AP1M2 as candidate genes whose expression may be influenced by environmental exposure in the context of male infertility. These findings deepen mechanistic understanding of NOA pathogenesis and support future research into environmental and molecular targets for diagnosis and prevention.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069617","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}
Gonzalo Oubiña, María May, María Silvia Bianchi, Melanie Neira, Eugenia Matzkin, Mónica Frungieri, Natalia Pascuali, Mayra Bordaquievich, Dalhia Abramovich, Fernanda Parborell
{"title":"Melatonin alleviates cyclophosphamide-induced ovarian toxicity in mice.","authors":"Gonzalo Oubiña, María May, María Silvia Bianchi, Melanie Neira, Eugenia Matzkin, Mónica Frungieri, Natalia Pascuali, Mayra Bordaquievich, Dalhia Abramovich, Fernanda Parborell","doi":"10.1007/s10815-025-03638-8","DOIUrl":"https://doi.org/10.1007/s10815-025-03638-8","url":null,"abstract":"<p><strong>Purpose: </strong>Anticancer drugs like cyclophosphamide (CTX) cause severe ovarian damage, often leading to infertility, while current fertility preservation methods are invasive and costly. This study investigates whether melatonin (MEL) can protect ovarian function in a CTX-induced premature ovarian failure (POF) mouse model, offering a potential noninvasive and cost-effective fertoprotective approach.</p><p><strong>Methods: </strong>A CTX-induced POF mouse model was used to assess MEL's protective effects. Ovarian function was evaluated by analyzing follicle counts, ovarian weight, serum hormone levels, apoptosis markers, histopathological changes, vascular integrity, and antioxidant defences.</p><p><strong>Results: </strong>MEL coadministration increased the proportion of primary and antral follicles (p < 0.01 and p < 0.05) while reducing atretic follicles (p < 0.05). MEL preserved ovarian weight, maintained primordial follicle counts, and prevented CTX-induced hormone level reductions. MEL also enhanced AMH-positive follicle percentage, reduced apoptosis, and mitigated vascular injury, fibrosis, and blood vessel hyalinization (p < 0.05). Furthermore, MEL restored uterine tissue architecture, improved vascular health by recruiting pericytes and smooth muscle cells (p < 0.05), and enhanced antioxidant defenses through increased expression of superoxide dismutase 1 (SOD1) (p < 0.05).</p><p><strong>Conclusion: </strong>MEL effectively preserves ovarian function in a CTX-induced POF model by protecting follicular development, hormonal balance, vascular integrity, and antioxidant defenses. These findings highlight MEL as a promising, noninvasive, and cost-effective strategy for fertility preservation in female cancer patients undergoing chemotherapy.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074994","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}
WenHan Ma, ShuHua Li, YuJun Chen, Ling Ma, JunHao Lei
{"title":"Non-mosaic Klinefelter syndrome with normal semen parameters and ability to conceive.","authors":"WenHan Ma, ShuHua Li, YuJun Chen, Ling Ma, JunHao Lei","doi":"10.1007/s10815-025-03662-8","DOIUrl":"https://doi.org/10.1007/s10815-025-03662-8","url":null,"abstract":"<p><strong>Background: </strong>Non-mosaic 47,XXY (Klinefelter syndrome, KS) males rarely retain preserved spermatogenesis. Here, we describe a 43-year-old man with intact fertility (prior natural conception, normal semen parameters), challenging conventional phenotypic paradigms.</p><p><strong>Objectives: </strong>To report an exceptional non-mosaic 47,XXY case with preserved fertility and normozoospermia, redefining classic phenotyping norms.</p><p><strong>Materials and methods: </strong>We conducted an observational study of a couple (male, non-mosaic 47,XXY; female, normal karyotype) undergoing two PGT-A cycles. Data included semen analyses, reproductive system ultrasonography, endocrine profiles, and embryo genetic diagnostics.</p><p><strong>Results: </strong>Two PGT-A cycles using fresh/thawed sperm yielded three blastocysts: two aneuploid blastocysts in the first cycle (3BC; 6BC) and one untested blastocyst in the second cycle (4BC). Due to cost constraints, the patient declined euploidy testing in the second cycle. A thawed embryo transfer (FET) was performed with the untested blastocyst, resulting in no pregnancy.</p><p><strong>Conclusion: </strong>This study presents a paradigm-shifting case of successful assisted reproduction in a couple where the male partner has non-mosaic KS with preserved fertility potential. Our findings challenge conventional assumptions about natural conception in KS patients and underscore the need for: (1) comprehensive evaluation of reproductive endocrine function, (2) molecular characterization of the testicular microenvironment, and (3) longitudinal assessment of fertility potential in atypical KS presentations.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145069785","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}
Ye Zheng, Wenyu Liu, Min Su, Shiheng Zhu, Xiufang Li, Hongqiang Xie, Chunzi Lyu, Wei Zhou, Tianxiang Ni, Qian Zhang, Yuan Gao, Junhao Yan
{"title":"Impact of controlled ovarian hyperstimulation protocols on aneuploidy of preimplantation blastocysts in women aged 21-37 years old.","authors":"Ye Zheng, Wenyu Liu, Min Su, Shiheng Zhu, Xiufang Li, Hongqiang Xie, Chunzi Lyu, Wei Zhou, Tianxiang Ni, Qian Zhang, Yuan Gao, Junhao Yan","doi":"10.1007/s10815-025-03650-y","DOIUrl":"https://doi.org/10.1007/s10815-025-03650-y","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to explore whether different controlled ovarian hyperstimulation (COH) protocols were associated with the incidence of aneuploid blastocysts in cycles undergoing preimplantation genetic testing for aneuploidy (PGT-A).</p><p><strong>Methods: </strong>A retrospective analysis was conducted on 5525 blastocysts from 1722 women (21-37 years old) who underwent PGT-A cycles utilizing next-generation sequencing (NGS). The cohorts included 240 cycles employing the gonadotropin-releasing hormone agonist (GnRH-a) short protocol, 698 cycles using the GnRH-a long protocol, and 784 cycles utilizing the GnRH antagonist (GnRH-ant) protocol.</p><p><strong>Results: </strong>A significantly elevated rate of blastocyst aneuploidy was observed in the GnRH-a short protocol group relative to both the long protocol and antagonist protocol groups (44.05% vs. 36.00% vs. 37.90%). Multivariable regression analyses, with the GnRH-a long protocol serving as the reference category, indicated that the short protocol was independently correlated with higher aneuploidy rates (OR = 1.30, 95% CI 1.06-1.60, P = 0.012). This association was particularly evident among younger patients (< 35 years) possessing preserved ovarian reserve (AMH ≥ 1.2 ng/mL) (OR = 1.38, 95% CI 1.02-1.87, P = 0.036). Although non-significant, the short protocol also trended towards a higher aneuploidy rate compared to the antagonist protocol (OR = 1.12, 95% CI 0.89-1.41, P = 0.32).</p><p><strong>Conclusions: </strong>The findings suggest that, in the population studied (21-37 years), the GnRH-a short protocol is associated with a higher incidence of blastocyst aneuploidy compared to the long protocol, particularly in younger individuals (< 35 years) with normal ovarian reserve (AMH ≥ 1.2 ng/mL). These results highlight the need for tailored COH protocol selection based on patient characteristics in PGT-A cycles.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145064700","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":"The impact of double vitrification and warming procedures on pregnancy and neonatal outcomes following single euploid blastocyst transfer.","authors":"Miaomiao Jia, Juanzi Shi, Wenhao Shi, Xia Xue","doi":"10.1007/s10815-025-03642-y","DOIUrl":"https://doi.org/10.1007/s10815-025-03642-y","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate the impact of multiple vitrification-warming on clinical outcomes of embryos that have undergone preimplantation genetic testing (PGT).</p><p><strong>Methods: </strong>This retrospective, single-center study involved 512 single frozen euploid blastocyst transfer cycles conducted between January 2018 and January 2024. Using propensity score matching, 105 patients who underwent double vitrification-warming with single biopsy (DVSB) were matched in a 1:4 ratio with 407 patients in the control group, who underwent single biopsy with single vitrification-warming (SVSB). Post-warming suitability for biopsy and clinical outcomes of subsequent frozen-thawed embryo transfer (FET) cycles were evaluated. Obstetrical and neonatal outcomes were also assessed.</p><p><strong>Results: </strong>A total of 453 blastocysts were warmed, of which 417 (92.1%) exhibited sufficient quality to undergo trophectoderm biopsy. In FET cycles, a significant reduction in the live birth rate was observed with the additional vitrification-warming step (DVSB: 49.5% vs. SVSB: 61.2%). The pregnancy loss rate in the DVSB group was significantly higher compared to the SVSB group (20.6% vs. 12.2%). Neonatal outcomes, including sex ratio, preterm birth rate, and low birth weight rate, did not differ significantly between the two groups.</p><p><strong>Conclusion: </strong>This study suggests that the inclusion of an additional vitrification-warming step in PGT may adversely affect pregnancy outcomes. Furthermore, only a portion of thawed embryos are able to re-expand and progress to the biopsy stage. PGT patients should be informed that undergoing a second vitrification-warming cycle may reduce the likelihood of a successful pregnancy.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058410","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}
Amelia G Kelly, Morgan S Levy, Padmaja Sundaram, Alyssa D Brown, Alberto J Caban-Martinez, Roohi Jeelani, Vineet M Arora, Arghavan Salles
{"title":"Family-building patterns of proceduralist and non-proceduralist physicians.","authors":"Amelia G Kelly, Morgan S Levy, Padmaja Sundaram, Alyssa D Brown, Alberto J Caban-Martinez, Roohi Jeelani, Vineet M Arora, Arghavan Salles","doi":"10.1007/s10815-025-03611-5","DOIUrl":"10.1007/s10815-025-03611-5","url":null,"abstract":"<p><strong>Purpose: </strong>Little is known about differences in the risk of infertility, family-building patterns, and childcare habits of proceduralists compared to non-proceduralists. This cross-sectional study examines variations in family-building patterns and childcare habits between proceduralists and non-proceduralists.</p><p><strong>Methods: </strong>From April to May 2021, a convenience sample of medical students and physicians was recruited through social media and organizational listservs to complete a questionnaire as part of the Study of Physicians and Children: Expectations and Experiences (SPACE). Respondents reported their demographics and family-building path, if applicable. All physicians who indicated their specialty were included. Medical students were excluded. The primary outcomes of interest were the rates of infertility and utilization of assisted reproductive technology (ART). Secondary outcomes included family-building patterns and childcare habits. Procedural vs. non-procedural specialties were categorized based on previously published literature.</p><p><strong>Results: </strong>Including trainee physicians, there were 2519 physician respondents (80.8% of all respondents). The majority identified as women (n = 2246, 89.2%) and as heterosexual (n = 2204, 87.5%). There were 1103 (43.9%) proceduralists and 1416 (56.1%) non-proceduralists. The prevalence of infertility was similar across specialty type (26.8% proceduralists vs. 26.5% non-proceduralists, p = 0.66). The use of ART was higher among proceduralists (27.2% vs. 22.6%, p < 0.01). Proceduralists were more likely to have biological children during residency (38.6% vs. 27.3%, p < 0.001) and to be childless despite desiring biological children (38.2% vs. 35.2%, p < 0.001). For childcare, proceduralists were more likely to rely on nannies (50.2% vs. 41.6%, p < 0.002), while non-proceduralists were more likely to use daycare (60.8% vs. 49.4%, p < 0.001).</p><p><strong>Conclusion: </strong>This study demonstrates key differences in family-building patterns and the use of ART between procedural and non-procedural physicians. Such discrepancies suggest a need to better support physicians, especially those in procedural specialties, who want to have children by implementing more family-friendly policies.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145053619","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}
Markéta Nezvedová, Volodymyr Porokh, Tami Bočková, Václav Pustka, Drahomíra Kyjovská, Barbora Maierová, Soňa Kloudová, Pavel Otevřel, Zuzana Holubcová
{"title":"Non-standardized protein background in IVF media linked to serum-derived albumin supplementation.","authors":"Markéta Nezvedová, Volodymyr Porokh, Tami Bočková, Václav Pustka, Drahomíra Kyjovská, Barbora Maierová, Soňa Kloudová, Pavel Otevřel, Zuzana Holubcová","doi":"10.1007/s10815-025-03616-0","DOIUrl":"https://doi.org/10.1007/s10815-025-03616-0","url":null,"abstract":"<p><strong>Purpose: </strong>To explore the protein compositional variability of IVF media and identify sources of undeclared contaminants that interfere with the detection of embryo-derived signals.</p><p><strong>Methods: </strong>Untargeted and targeted mass spectrometry techniques were used to analyze protein composition in 85 samples of used and unused monophasic IVF media across 13 production lots from two manufacturers. Samples included spent culture media (SCM) from individual embryo cultures, matched controls, and unused (blank) media. Protein-free base media was supplemented with either serum-derived or recombinant human serum albumin (HSA) to evaluate their impact on protein contamination.</p><p><strong>Results: </strong>Proteomic analysis revealed that not only SCM but also unconditioned media contained over 700 undeclared human proteins, many of which are known to be implicated in key cellular pathways. No significant differences were observed between the protein profiles of embryos that reached the blastocyst stage (n = 29) and those arrested at cleavage (n = 24). Instead, protein level variation strongly correlated with media production lot, as shown by targeted analysis of 14 candidate proteins and principal component clustering of 53 SCM samples. Analysis of blank media confirmed substantial lot-to-lot heterogeneity. Supplementation experiments demonstrated that serum-derived HSA introduces undeclared, batch-variable proteins into IVF media, contributing to a non-standardized culture environment and confounding the detection of embryo-derived signals.</p><p><strong>Conclusion: </strong>Serum-derived HSA was identified as the primary source of protein contamination in IVF media. This overlooked protein background contributes to variability in clinical culture conditions, undermines the reproducibility of secretome analyses, and complicates the discovery of reliable biomarkers in SCM.</p>","PeriodicalId":15246,"journal":{"name":"Journal of Assisted Reproduction and Genetics","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145053677","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}