Sophie Hu, Sophie Lalonde-Bester, Jenna Salem, Sheffinea Koshy, Donna Vine, Tyrone G Harrison, Jennifer M Yamamoto, Jamie L Benham
{"title":"Validity of administrative health data case definitions for identifying polycystic ovary syndrome: a systematic review and meta-analysis","authors":"Sophie Hu, Sophie Lalonde-Bester, Jenna Salem, Sheffinea Koshy, Donna Vine, Tyrone G Harrison, Jennifer M Yamamoto, Jamie L Benham","doi":"10.1093/humrep/deaf094","DOIUrl":"https://doi.org/10.1093/humrep/deaf094","url":null,"abstract":"STUDY QUESTION What is the validity of published administrative health data case definitions of polycystic ovary syndrome (PCOS) compared with reference standards? SUMMARY ANSWER Due to the limited number of eligible studies, drawing definitive conclusions is challenging; however, this review highlights significant gaps and variability in current PCOS case definitions, underscoring the need for standardized case definitions in future research. WHAT IS KNOWN ALREADY Administrative health data offer the opportunity to evaluate health outcomes and disease epidemiology at a population-level. Currently, the validity of existing administrative health data case definitions for PCOS is unknown. STUDY DESIGN, SIZE, DURATION A systematic review of the literature was conducted on full-text English-language articles up to July 2023, using the MEDLINE and EMBASE databases. PARTICIPANTS/MATERIALS, SETTING, METHODS Two reviewers independently screened titles, abstracts and full texts, extracted data, assessed study quality and graded validity. A random effects meta-analysis was conducted to pool reported validity measures and heterogeneity was examined. MAIN RESULTS AND THE ROLE OF CHANCE The review included four eligible articles consisting of three cross-sectional studies and one retrospective cohort study. Two studies defined PCOS using the Rotterdam Criteria, one study used self-report, and one used a clinical gold standard. All case definitions included the International Classification of Diseases (ICD)-9 code 256.4 for ‘polycystic ovaries’ and three studies used E28.2 for ‘polycystic ovarian syndrome’. Three studies reported positive predictive value (PPV), which ranged from 30 to 96%. One study reported both PPV (96%) and sensitivity (50%) for one case definition. The pooled PPV estimate for the ICD code-based case definitions was 88% (95% confidence interval 82-95%; I2 = 100%). One study reported fair agreement (percent agreement= 90.3, κ = 0.27, percent agreement bias adjusted κ = 0.81). Overall, the risk of bias of the included studies was low. LIMITATIONS, REASONS FOR CAUTION There were limited number of validations and precision indices of validations. WIDER IMPLICATIONS OF THE FINDINGS Further validation of these case definitions in other administrative health datasets, and development of novel coding algorithms is required to inform future population-based studies in PCOS. STUDY FUNDING/COMPETING INTEREST(S) No external funding was used and there are no disclosures. REGISTRATION NUMBER PROSPERO CRD42023385617","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"42 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144083176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Linda G Kahn, Alison E Hipwell, Mia Charifson, Rui Ling, Kim N Cajachagua-Torres, Akhgar Ghassabian
{"title":"Maternal polycystic ovarian syndrome and offspring psychopathology and neurodevelopment","authors":"Linda G Kahn, Alison E Hipwell, Mia Charifson, Rui Ling, Kim N Cajachagua-Torres, Akhgar Ghassabian","doi":"10.1093/humrep/deaf079","DOIUrl":"https://doi.org/10.1093/humrep/deaf079","url":null,"abstract":"Polycystic ovarian syndrome (PCOS) is a common female endocrinologic condition that affects both the metabolic and reproductive systems and is the most frequent cause of anovulatory infertility. It is also associated with a range of psychiatric outcomes in individuals, including bulimia nervosa, schizophrenia, bipolar disorder, depression, anxiety, and personality disorders. At the same time, evidence suggests that hyperandrogenism, the characteristic trait of PCOS, may impair fetal neurodevelopment. Epidemiological studies have linked maternal PCOS with a variety of behavioral and psychiatric conditions in offspring including autism spectrum disorder and attention deficit hyperactivity disorder. In this review, we explore evidence for potential underlying biological mechanisms that might explain these observed associations, discuss the complex interplay between genetics and various environmental factors across generations, and highlight avenues for future research.","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"4 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144067161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mark E Gill,Manuel Fischer,Christian De Geyter,Antoine H F M Peters
{"title":"Normozoospermic infertile men possess subpopulations of sperm varying in DNA accessibility, relating to differing reproductive outcomes.","authors":"Mark E Gill,Manuel Fischer,Christian De Geyter,Antoine H F M Peters","doi":"10.1093/humrep/deaf081","DOIUrl":"https://doi.org/10.1093/humrep/deaf081","url":null,"abstract":"STUDY QUESTIONCan a reliable assay be developed to quantify DNA accessibility in human sperm to help with the assessment of pre-implantation development affected by dense packaging of mammalian sperm's genetic material?SUMMARY ANSWERWe adapted NicE-view, an assay that directly labels accessible DNA, for use in human sperm and applied it to examine spermatozoa from infertile individuals with distinct reproductive outcomes.WHAT IS KNOWN ALREADYExisting data suggest a connection between sperm chromatin compaction and reproductive outcomes. The assays used to generate this data, however, measure chromatin compaction indirectly and thus understanding their meaning is challenging.STUDY DESIGN, SIZE, DURATIONBetween April 2020 to December 2023, 60 normozoospermic infertile men were invited to participate in an experimental study and asked to provide a semen sample.PARTICIPANTS/MATERIALS, SETTING, METHODSAmong the 60 individuals forty had undergone at least one treatment with ART. Among these ART-treated participants, 20 were included in the study because after fertilization only one or no embryos developed during embryo culture (low blastocyst growth rate, LBGR). The other 20 men were included as at least 50% of cultured embryos developed to the blastocyst stage (high blastocyst growth rate). Additionally, 20 previously infertile individuals obtained a pregnancy naturally (NATP) and were included as well. Washed spermatozoa obtained from seminal plasma or prepared by swim-up procedure were processed for NicE-view to determine DNA accessibility as a marker of chromatin condensation using confocal microscopy. Images of more than 3 million spermatozoa were acquired. Computer-assisted image segmentation was used to identify individual sperm heads and DNA accessibility levels were then quantified in each. We also compared NicE-view to chromomycin A3 (CMA3), a conventional marker of chromatin de-condensation, and ATAC-see, an alternative assay for measuring DNA accessibility.MAIN RESULTS AND THE ROLE OF CHANCEBoth semen and swim-up samples of participants contained two well-delineated subpopulations of spermatozoa with distinct DNA accessibility levels, the frequencies of which varied among individuals. Interestingly, individuals with high frequencies of highly accessible sperm DNA, as measured in semen, possessed decreased sperm concentrations. Moreover, participants with high frequency of highly accessible sperm DNA were more common in the LBGR sub-group. Surprisingly, selection of motile sperm by swim-up enriched for sperm with high DNA accessibility in participants from all three sub-groups. Chromatin accessibility measurements by Nice-view were distinct from DNA staining with the fluorescent CMA3 dye, and NicE-view allowed much clearer separation of sperm subpopulations than ATAC-see.LIMITATIONS, REASONS FOR CAUTIONThis was a single-centre study with a cohort of 60 individuals. Sperm samples containing very high frequencies of sperm with increased DNA ac","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"74 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144065565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Reply: The role of light sheet microscopy for non-invasive imaging of live embryos.","authors":"F Horta,E Vargas-Ordaz,A Neild,V J Cadarso","doi":"10.1093/humrep/deaf092","DOIUrl":"https://doi.org/10.1093/humrep/deaf092","url":null,"abstract":"","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"200 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144065566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The role of light sheet microscopy for non-invasive imaging of live embryos.","authors":"Kylie R Dunning,Kishan Dholakia","doi":"10.1093/humrep/deaf091","DOIUrl":"https://doi.org/10.1093/humrep/deaf091","url":null,"abstract":"","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"15 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144065630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M M van Vliet,S Schoenmakers,S P Willemsen,K D Sinclair,R P M Steegers-Theunissen
{"title":"First-trimester maternal folate and vitamin B12 concentrations and their associations with first-trimester placental growth: the Rotterdam Periconception Cohort.","authors":"M M van Vliet,S Schoenmakers,S P Willemsen,K D Sinclair,R P M Steegers-Theunissen","doi":"10.1093/humrep/deaf095","DOIUrl":"https://doi.org/10.1093/humrep/deaf095","url":null,"abstract":"STUDY QUESTIONAre maternal folate and vitamin B12 concentrations associated with first-trimester placental growth?SUMMARY ANSWERMaternal folate concentrations and commencement of folic acid supplements prior to conception, as compared to following conception, are positively associated with first-trimester placental volume (PV), whereas no associations were found for maternal vitamin B12 concentrations.WHAT IS KNOWN ALREADYBesides the protective effect of folic acid supplement use against neural tube defects and other adverse birth outcomes, the preconceptional commencement of folic acid supplements is positively associated with postpartum placental size, although conflicting outcomes have been reported. Studies in mice show an association with vitamin B12 deficiency and decreased placental weight postpartum.STUDY DESIGN, SIZE, DURATIONBetween January 2010 and December 2020, 480 pregnancies (727 longitudinal ultrasound measurements) with known maternal folate and/or vitamin B12 blood concentrations in the first trimester and 875 pregnancies (1430 longitudinal ultrasound measurements) with known timing of folic acid supplement initiation were included in the Rotterdam Periconception Cohort, a prospective, hospital-based observational cohort.PARTICIPANTS/MATERIALS, SETTING, METHODSRed blood cell (RBC) folate and serum vitamin B12 concentrations were determined in first-trimester maternal blood, and the timing of folic acid supplement use was collected using validated questionnaires. PV was measured from serial 3-dimensional ultrasounds performed at 7, 9, and 11 weeks of gestation. Linear mixed models were used to assess the associations between maternal folate and vitamin B12 concentrations with first-trimester PVs. Analyses were adjusted for gestational age at ultrasound, maternal age, BMI, geographical background, education level, parity, smoking, mode of conception, and the other B vitamins. For validation, the association between the timing of folic acid supplement initiation (pre- or postconception) and PV was assessed.MAIN RESULTS AND THE ROLE OF CHANCEThe median RBC folate concentration was 1395 nmol/l (IQR 1169-1588) and the median serum vitamin B12 concentration was 314 pmol/l (IQR 241-391). For RBC folate, the smallest PVs were found in women in the lowest quartile, with the largest difference as compared to women in the fourth quartile: 3√PV (β = -0.141, 95% CI = -0.249 to -0.033, P = 0.010), corresponding to a 1.79 cm3 (-18.7%) and a 6.99 cm3 (-9.9%) smaller PV at 7 and 11 weeks of gestation, respectively. Additionally, PV was significantly smaller in women who initiated folic acid supplements following rather than prior to conception: 3√PV (β=-0.129, 95% CI = -0.207 to -0.051, P = 0.001) corresponding to a 1.69 cm3 (-16.9%) and a 6.62 cm3 (-8.9%) smaller PV at 7 and 11 weeks of gestation, respectively. We found no significant association between maternal serum vitamin B12 concentrations and PV.LIMITATIONS, REASONS FOR CAUTIONThe observa","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"30 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144065628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"SHR7280, an oral gonadotropin-releasing hormone antagonist, for the prevention of premature luteinizing hormone surge in controlled ovarian hyperstimulation: a dose-finding, phase 2 trial.","authors":"Hongbin Chi,Ying Song,Lei Jin,Xueru Song,Xiaohong Wang,Qianhong Ma,Yunxia Cao,Xiaoyan Liang,Jichun Tan,Yichun Guan,Feiyang Diao,Yanping Li,Zeli Li,Yuqi Sun,Chang Shu,Hong Chen,Kai Shen,Jie Qiao","doi":"10.1093/humrep/deaf082","DOIUrl":"https://doi.org/10.1093/humrep/deaf082","url":null,"abstract":"STUDY QUESTIONWhat is the minimum effective dose of SHR7280, a novel oral GnRH antagonist, to prevent a premature LH surge in women undergoing controlled ovarian hyperstimulation for ART?SUMMARY ANSWERSHR7280 at 200 mg once every 12 h (Q12h) was the minimal effective dose to suppress an LH surge and was associated with high-quality embryos, and a high clinical pregnancy rate. SHR7280 was well-tolerated and safe.WHAT IS KNOWN ALREADYCurrently, all approved GnRH antagonists for preventing a premature LH surge are injectable, peptide-based formulations, which can cause inconvenience and injection site reactions. There is a significant unmet need for an orally available GnRH antagonist to address this issue. SHR7280 has previously demonstrated effective suppression of LH levels in healthy volunteers in phase 1 trials.STUDY DESIGN, SIZE, DURATIONThis multi-center, open-label, dosing-finding phase 2 trial was conducted between 26 January 2022 and 3 August 2023 in 85 infertile women.PARTICIPANTS/MATERIALS, SETTING, METHODSThe starting dose of SHR7280 was 300 mg Q12h, followed by dose exploration in two lower dose groups (200 mg Q12h and 200 mg Q24h) sequentially. Dose exploration was terminated if an LH surge occurred. SHR7280 was administrated orally starting on Day 5 of recombinant human FSH stimulation until hCG administration. The primary endpoint was the rate of premature LH surge inhibition during SHR7280 treatment.MAIN RESULTS AND THE ROLE OF CHANCEEighty-five patients received SHR7280: 300 mg Q12h, n = 40; 200 mg Q12h, n = 42; 200 mg Q24h, n = 3. The mean ( ± SD) duration of SHR7280 treatment was 5.7 ± 1.2, 5.7 ± 1.3, and 3.7 ± 0.6 days, respectively. The rate of LH surge inhibition was 99% (95% CI 94-100) in all patients, 100% (95% CI 91-100) in the 300 mg Q12h group, 100% (95% CI 92-100) in the 200 mg Q12h group, and 67% (95% CI 9-99) in the 200 mg Q24h group. Two hundred milligrams Q12h was established as the minimal effective dose. Embryological and pregnancy outcomes were comparable in the 300 and 200 mg Q12h groups. In the 200 mg Q12h group, the mean ( ± SD) number of oocytes retrieved per patient, two-pronucleate zygotes, and high-quality embryos was 10.7 ± 4.6, 6.9 ± 3.2, and 3.9 ± 2.6, respectively; among patients receiving fresh embryo transfer, 62% (95% CI 44-78) were tested positive for serum β-hCG and 53% (95% CI 35-70) were confirmed to be clinically pregnant per transfer. No spontaneous ovulation occurred on the day of oocyte retrieval. In all 85 patients, treatment-related adverse events were reported in 1 (1%; mild in severity) patient.LIMITATIONS, REASONS FOR CAUTIONThe sample size was moderate and there was no standard peptide-based GnRH antagonist as a control group. Additionally, the performance of SHR7280 in specific populations, such as patients with diminished ovarian reserve and at high risk of OHSS, remains to be established. Further research is also needed to determine the recommended dose in patients with high BMI, in","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"42 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144065568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
L Chaput,S Dollet,E Eymard-Pierre,B Pereira,C Lucas,A-S Grémeau,A Tchirkov,G Marteil,F Brugnon
{"title":"Analysis of maturation dynamics and oocyte nuclear quality after rescue-IVM and semi-automated vitrification.","authors":"L Chaput,S Dollet,E Eymard-Pierre,B Pereira,C Lucas,A-S Grémeau,A Tchirkov,G Marteil,F Brugnon","doi":"10.1093/humrep/deaf078","DOIUrl":"https://doi.org/10.1093/humrep/deaf078","url":null,"abstract":"STUDY QUESTIONWhat is the optimal stage (immature vs mature) and most efficient vitrification technique (semi-automated vs manual) to ensure the safety of the rescue-IVM (r-IVM) procedure for oocyte cryopreservation?SUMMARY ANSWERHuman oocytes should be cryopreserved after r-IVM at the mature stage (r-MII oocytes) by semi-automated or manual vitrification.WHAT IS KNOWN ALREADYr-IVM of immature oocytes may increase the number of oocytes cryopreserved for fertility preservation. However, the best stage and vitrification system (semi-automated or manual) for cryopreserving oocytes with the least possible impact on nuclear quality is unclear.STUDY DESIGN, SIZE, DURATIONFrom January 2020 to June 2024, a prospective study was conducted on patients undergoing ICSI, including cases with at least one immature germinal vesicle (GV) stage oocyte on the day of oocyte collection, resulting in a total of 414 oocytes.PARTICIPANTS/MATERIALS, SETTING, METHODSThe study included 175 patients under 37 years old with no ovulatory disorder and undergoing ICSI. A total of 414 immature oocytes were collected and divided into five groups. The control group included fresh in vitro-matured oocytes (IVM, n = 81). After r-IVM, oocytes were vitrified by a semi-automated technique (IVM+VITg group, n = 63) or a closed manual procedure (IVM+VITm group, n = 66). Before r-IVM, oocytes were vitrified using both techniques (VITg+IVM group, n = 113 and VITm+IVM group, n = 91). The fresh IVM group combined IVM, IVM+VITg, and IVM+VITm groups.Survival rates of oocytes were evaluated 2-h post-warming. r-IVM was performed in a time-lapse incubator , allowing the assessment of r-IVM rates and maturation kinetics, including GV breakdown (GVBD) and first polar body extrusion timings. We assessed the quality of oocyte nuclear maturation through the evaluation of meiotic spindle polarity and chromosomes alignment by 3D analysis of confocal microscopy images and aneuploidy rate by array-CGH (a-CGH).MAIN RESULTS AND THE ROLE OF CHANCEThe oocyte post-warming survival rate was lower when semi-automated vitrification was performed before r-IVM (50% for VITg+IVM group) compared with the three other groups (88% for IVM+VITg, 93% for IVM+VITm, and 80% for VITm+IVM, adjusted P-value < 0.001). IVM rates were not different between the three groups (fresh IVM: 80%, VITg+IVM: 80% and VITm+IVM: 69%, Pa = 0.131). Longer GVBD timings were observed when semi-automated vitrification was performed before r-IVM (VITg+IVM: 10.4 h) compared with Fresh IVM (7.9 h, Pa = 0.003). The percentages of oocytes with bipolar spindles or/and aligned chromosomes were not different between the five groups. Similarly, there was no difference in aneuploidy rates (monosomy or trisomy) between the five study groups (Pa = 0.847). Shorter GVBD timings were observed for oocytes with a bipolar spindle or aligned chromosomes (7.8 h) than for oocytes with a non-bipolar spindle or misaligned chromosomes (10.1 h, Pa = 0.011).LIMITATIONS, R","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"15 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144065567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Single-cell proteomics analysis of human oocytes during GV-to-MI transition.","authors":"Zeling Zhang,Lei Luo,Shiwei Fan,Shun Bai,Bo Xu","doi":"10.1093/humrep/deaf086","DOIUrl":"https://doi.org/10.1093/humrep/deaf086","url":null,"abstract":"STUDY QUESTIONWhich proteins are involved in the transition of human oocytes from the germinal vesicle (GV) to metaphase I (MI) phase?SUMMARY ANSWERA total of 2369 proteins were identified, including 149 with significantly differential expression, 79 with upregulated expression in MI oocytes and 70 with downregulated expression.WHAT IS KNOWN ALREADYDuring oocyte maturation, maternal proteins and RNA are stored to support early embryo development. However, GV oocytes matured in vitro have a lower chance of developing into blastocysts than MI oocytes. Therefore, identifying key differentially expressed proteins between the GV and MI stages can provide a better understanding of human oocyte development and maturation mechanisms and improve the utilization of oocytes.STUDY DESIGN, SIZE, DURATIONIn total, 16 oocytes at the GV and MI stages were collected from female patients who underwent ovulation induction due to male factor infertility requiring embryo retrieval for ICSI. Differential proteins were identified in 16 oocytes using liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis, and the expression of several differential proteins was verified by immunofluorescence (IF). RNA interference was employed to identify the functions of specific proteins during oocyte maturation.PARTICIPANTS/MATERIALS, SETTING, METHODS16 immature human oocytes discarded during ICSI cycles (eight GV oocytes and eight MI oocytes) were collected from 10 female patients. Two cohorts of oocytes underwent zona pellucida removal, lysis, and enzymatic digestion prior to peptide detection using LC-MS/MS methodology. Peptide detection outcomes were subjected to differential protein screening and functional annotation employing distinct analytical algorithms and datasets. To corroborate the sequencing findings, proteins exhibiting notable differential expression were authenticated via IF. Concerning protein functionality, siRNA was introduced during the GV phase, and oocyte maturation was evaluated through observation of polar body extrusion, alongside assessment of siRNA interference efficacy via IF analysis.MAIN RESULTS AND THE ROLE OF CHANCEA total of 2369 proteins were identified, including 149 with significantly differential expression, 79 with upregulated expression in MI oocytes and 70 with downregulated expression. Gene ontology functional annotation and functional analysis revealed that these differentially expressed proteins are involved mainly in organic matter and cell metabolism, biological regulation, primary metabolism, nitrogen compound metabolism, and other biological processes. Kyoto Encyclopedia of Genes and Genomes analysis revealed that the differentially expressed genes were involved mainly in the following pathways: transport and catabolism, signal transduction, protein folding, and energy and amino acid metabolism. The differentially expressed proteins included actin-related protein 2 (ACTR2), NADH: Ubiquinone Oxidoreductase Core Subunit S1 (ND","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"77 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mauro Cozzolino,Livia Pellegrini,Christian Simon Ottolini,Antonio Capalbo,Daniela Galliano,Antonio Pellicer
{"title":"The clinical impact of oligozoospermia in oocyte donation ICSI cycles using preimplantation genetic test for aneuploidy.","authors":"Mauro Cozzolino,Livia Pellegrini,Christian Simon Ottolini,Antonio Capalbo,Daniela Galliano,Antonio Pellicer","doi":"10.1093/humrep/deaf080","DOIUrl":"https://doi.org/10.1093/humrep/deaf080","url":null,"abstract":"STUDY QUESTIONDo severely impaired sperm concentrations (oligozoospemia) in male factor infertility affect embryo aneuploidy rates and clinical results after IVF oocyte donation cycles?SUMMARY ANSWERSevere oligozoospermia (SO) in IVF cycles utilizing donor oocytes does not significantly affect embryo euploidy rates or IVF outcomes or cumulative live birth rates (CLBRs).WHAT IS KNOWN ALREADYSO has previously been linked to elevated rates of chromosomal abnormalities in spermatozoa and altered rates of embryo development with poorer reproductive outcomes. Nonetheless, the precise impacts of severe male factor infertility on embryonic aneuploidy rates and the success of IVF, in the context of controlled female ages in oocyte donation cycles with preimplantation genetic testing for aneuploidy (PGT-A), are still not fully understood.STUDY DESIGN, SIZE, DURATIONThis retrospective observational cohort study involved 690 IVF oocyte donation cycles undergoing PGT-A from multiple clinics across Europe between January 2017 and December 2023. The study population was divided into three groups based on sperm concentration: SO (<5 million sperm/ml), moderate oligozoospermia (MO, 5-16 million sperm/ml), and a normozoospermia control group (≥16 million sperm/ml) for outcome analysis.PARTICIPANTS/MATERIALS, SETTING, METHODSThe IVF outcomes and variables for couples undergoing oocyte donor cycles were investigated. ICSI was performed in all cycles using fresh sperm samples that were assessed for standard semen parameters with fresh or frozen donated oocytes. All of the resulting embryos were biopsied at the blastocyst stage for PGT-A, and all transfers were of single embryos performed in subsequent cycles after vitrification and warming. Statistical analysis was performed using multivariate regression models to identify correlations between rates of oligozoospermia and clinical, embryological and genetic outcomes.MAIN RESULTS AND THE ROLE OF CHANCEThe study included 690 couples, in the SO (N = 202), MO (N = 102), and the control normozoospermia (N = 386) groups. The SO group had significantly lower sperm motility (P < 0.0001) and significantly reduced fertilization rates compared to the MO and control groups (P < 0.01). However, no statistical difference was observed for the blastocyst formation rate (per fertilized oocyte). Mostly due to the reduced fertilization rates, the number of euploid blastocysts obtained was significantly lower in the SO group (P = 0.007), however, this did not affect the pregnancy, biochemical or clinical miscarriage (P = 0.37, P = 0.22, and P = 0.86), or CLBRs (P = 0.26) after single blastocyst transfers. The multivariate analysis showed no effect of SO or MO on aneuploidy, miscarriage, or live birth rates. Interestingly, the PGT laboratory strategy (<0.001) was associated with the rate of euploid blastocysts but had no significant effect on pregnancy outcomes.LIMITATIONS, REASONS FOR CAUTIONThis is a retrospective observational study f","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"35 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}