Human reproduction最新文献

{"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}

{"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}

{"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}

{"title":"Correction to: Pregnancy outcomes with increasing maternal age, greater than 40 years, in donor oocyte cycles.","authors":"","doi":"10.1093/humrep/deaf087","DOIUrl":"https://doi.org/10.1093/humrep/deaf087","url":null,"abstract":"","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"125 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143932827","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":"Risk of endometriosis progression in infertile women trying to conceive naturally or using IVF.","authors":"Edgardo Somigliana,Paola Vigano',Dalila Invernici,Gianfranco Fornelli,Camilla Erminia Maria Merli,Paolo Vercellini","doi":"10.1093/humrep/deaf090","DOIUrl":"https://doi.org/10.1093/humrep/deaf090","url":null,"abstract":"The use of hormonal treatments for endometriosis has increased in recent years. Their effectiveness lies in creating a stable hormonal environment, reducing peripheral estrogen levels, and suppressing ovulation and menstruation. Although these agents do not cure endometriosis and symptoms often return after discontinuation, they effectively relieve pain in most cases and help prevent disease progression or recurrence. Women are therefore typically managed with long-term hormonal treatments, with or without surgery. However, this approach is unsuitable for those seeking natural pregnancy or undergoing IVF, as all hormonal treatments hinder conception. For women pursuing natural pregnancy, these treatments should be discontinued for about 1 year, the time needed to diagnose infertility. However, this suspension exposes women to the risk of recurrence or progression and is therefore clinically acceptable only if the woman has a reasonable likelihood of achieving pregnancy naturally. In women with endometriosis who are infertile and therefore require IVF, ovarian stimulation significantly raises estrogen levels-up to 10 times those of a natural cycle-potentially boosting the risk of endometriosis relapse. Evidence is reassuring on this issue even if some limited data suggest that ovarian stimulation may promote deep invasive endometriosis progression. Overall, physicians and patients must balance the chances of natural or ART-assisted pregnancy against the risk of disease recurrence or progression during treatment discontinuation or IVF. This choice is also complicated by the increased risk of severe pregnancy complications in women with endometriosis, possibly depending on the conception method. This review discusses the available evidence that can be helpful in guiding the decision-making process.","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"140 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143932440","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":"Preclinical validation of fast oocyte vitrification and warming protocols with comparable efficiencies to a standard method","authors":"Nuno Costa-Borges, Queralt Matia-Algué, Aila Coello, Enric Mestres, Mònica Acacio, Adolfo Flores-Saiffe Farias, Carolina Castello, Miguel Gallardo, Alejandro Chavez-Badiola, Francisco Marco-Jiménez, Ana Cobo, Jacques Cohen","doi":"10.1093/humrep/deaf069","DOIUrl":"https://doi.org/10.1093/humrep/deaf069","url":null,"abstract":"STUDY QUESTION Can fast vitrification (FV) and fast warming (FW) protocols effectively reduce oocyte exposure times to cryoprotectants while maintaining survival, developmental potential, and laboratory efficiency compared to a standard protocol? SUMMARY ANSWER FV and FW protocols significantly reduce exposure times compared to a standard protocol without compromising oocyte integrity or developmental potential in the animal models tested, offering a more efficient workflow for IVF laboratories. WHAT IS KNOWN ALREADY Vitrification is a widely used oocyte cryopreservation technique in IVF centers, but current protocols are time-consuming and labor-intensive. Additionally, prolonged exposure to cryoprotectants under non-physiological conditions, such as high osmolality and room temperature, raises concerns about oocyte viability and developmental potential. STUDY DESIGN, SIZE, DURATION This preclinical study involved oocytes from two animal models (mouse and rabbit) and a subset of discarded human oocytes. Experimental stages included: (a) evaluation of meiotic spindle integrity; (b) assessment of survival and developmental rates post-warming and ICSI; (c) embryo transfers in mice to evaluate full-term developmental potential; and (d) development and validation of an in silico model for human oocytes. PARTICIPANTS/MATERIALS, SETTING, METHODS Mouse and rabbit oocytes were randomly allocated to either a fast or standard vitrification (SV)/standard warming (SW) protocol. Survival and developmental rates were assessed post-warming. Meiotic spindle integrity and chromosomal alignment were analyzed using immunofluorescence. Full-term development was evaluated through embryo transfers in mice. Theoretical osmotic modeling was performed on human oocytes to predict their behavior under FV conditions, with empirical validation using discarded human oocytes. MAIN RESULTS AND THE ROLE OF CHANCE The FV/FW protocol significantly reduced the time required for vitrification compared to a SV/SW protocol, while maintaining comparable oocyte survival, meiotic spindle integrity, and developmental rates in animal models. In mouse oocytes, the FV/FW protocol achieved the highest survival rate (n = 249 oocytes; 97.2%) not statistically significantly different from the SV/SW protocol (n = 224 oocytes, 94.2%), but significantly higher (P = 0.008) than the SV/FW group (n = 229 oocytes, 91.7%). After ICSI, the SV/SW group reached 83.4% blastocyst rates, followed by the FV/FW group at 80.9%, and the SV/FW group at 75.9%, all comparable to the fresh oocyte control group (n = 123) with 86.4%. Embryo development after ICSI resulted in blastocyst formation rates of 80.9% for the FV/FW protocol compared to 83.4% in the SV/SW and 86.4% in the SV/FW group. Embryo transfer outcomes in mice demonstrated no statistically significant adverse effects on implantation or full-term development, with live birth rates of 38.7% (FV/FW) compared to 47.8% (SV/SW) and 43.2% (SV/FW). Survival rate","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"6 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143920260","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":"Dietary patterns and age at menarche in a prospective study of girls in the USA.","authors":"C P Davis,S Fest,K Cushing-Haugen,T W Kensler,J E Chavarro,H R Harris","doi":"10.1093/humrep/deaf072","DOIUrl":"https://doi.org/10.1093/humrep/deaf072","url":null,"abstract":"STUDY QUESTIONAre dietary patterns associated with age at menarche after accounting for BMI-for-age (BMIz) and height?SUMMARY ANSWERWe observed associations between both the Alternative Healthy Eating Index (AHEI) and the Empirical Dietary Inflammatory Pattern (EDIP) and age at menarche.WHAT IS KNOWN ALREADYDietary patterns have been sparsely examined in relation to age at menarche and no studies have examined the association between the AHEI, a healthier diet, and EDIP, a pro-inflammatory diet, and menarche.STUDY DESIGN, SIZE, DURATIONThe Growing Up Today Study (GUTS) is a prospective cohort of children ages 9-14 years at study enrollment. GUTS enrolled in two waves with enrollment beginning in 1996 (GUTS1) and 2004 (GUTS2). For this analysis, GUTS1 and GUTS2 participants were followed through 2001 and 2008, respectively.PARTICIPANTS/MATERIALS, SETTING, METHODSWe included 7530 participants who completed food frequency questionnaire(s) (FFQ) prior to menarche who then self-reported age at menarche during study follow-up. Cox proportional hazard models were used to calculate multivariable hazard ratios (HRs) and 95% CIs for the associations between two dietary patterns, the AHEI and EDIP, and age at menarche, with and without adjustment for time-varying BMIz and height.MAIN RESULTS AND THE ROLE OF CHANCESix thousand nine hundred ninety-two participants (93%) reported menarche during the study period. On average, participants completed the baseline FFQ 1.75 years prior to menarche. Participants in the highest quintile of AHEI diet score (indicating a healthier diet) were 8% less likely to attain menarche within the next month compared to those in the lowest quintile (95% CI = 0.85-0.99; Ptrend = 0.03). This association remained after adjustment for BMIz and height (corresponding HR = 0.93; 95% CI = 0.86-1.00; Ptrend = 0.04). Participants in the highest quintile of the EDIP score (i.e. most inflammatory diet), were 15% more likely to attain menarche in the next month relative to those in the lowest quintile (95% CI = 1.06-1.25; Ptrend = 0.0004), and the association remained following adjustment for BMIz and height (corresponding HR = 1.15; 95% CI = 1.06-1.25; Ptrend = 0.0004).LIMITATIONS, REASONS FOR CAUTIONSelf-reported questionnaires are subject to some error; however, given our prospective study design it is likely this error is non-differential with respect to the outcome.WIDER IMPLICATIONS OF THE FINDINGSOur findings of an association between both the AHEI and EDIP and age at menarche indicate that diet quality may play a role in age at menarche independent of BMI or height.STUDY FUNDING/COMPETING INTEREST(S)This work was supported by the Breast Cancer Research Foundation. The GUTS is supported by the National Institutes of Health U01 HL145386. C.P.D. was supported by National Institutes of Health T32 CA094880. The authors have no conflicts of interest to disclose.TRIAL REGISTRATION NUMBERN/A.","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"101 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143915092","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":"Oncostatin-M: a novel leukocyte-derived factor facilitating the ovulatory process in the human ovary.","authors":"Yohan Choi,Mats Brännström,James W Akin,Ashley Teate,Lane K Christenson,Thomas E Curry,Misung Jo","doi":"10.1093/humrep/deaf076","DOIUrl":"https://doi.org/10.1093/humrep/deaf076","url":null,"abstract":"STUDY QUESTIONDoes leukocyte-derived Oncostatin-M (OSM) regulate the ovulatory process in human dominant follicles?SUMMARY ANSWERLeukocyte-derived OSM activates key signaling pathways in human preovulatory granulosa cells and modulates steroidogenesis, prostaglandin synthesis, and tissue remodeling in human ovulatory follicles.WHAT IS KNOWN ALREADYLeukocytes are essential regulators of ovulation. Our recent single-cell RNA sequencing (scRNA-seq) has identified diverse leukocyte subpopulations in follicular aspirates obtained from IVF patients and revealed the expression of OSM in leukocytes and its receptors (OSMR, LIFR, IL6ST) in follicular cells. However, the function of leukocyte-derived OSM in human ovulatory follicle remains unclear.STUDY DESIGN, SIZE, DURATIONThis study analyzed dominant follicles from naturally cycling women (n = 19) across the periovulatory period and follicular aspirates from IVF patients (n = 12). Primary human granulosa/lutein cells (hGLCs) treated with hCG and/or recombinant human OSM (rhOSM) were used to assess its functional effects.PARTICIPANTS/MATERIALS, SETTING, METHODSOur recent scRNA-seq dataset was used to identify cell types expressing OSM and its receptors in human follicular aspirates. The expression of OSM and its receptors was assessed in dominant follicles by quantitative PCR (qPCR) and immunohistochemistry. hGLCs were treated with hCG and/or rhOSM, and functional analyses included qPCR, western blotting, RNA sequencing, and hormone assays for progesterone (P4), estradiol (E2), and prostaglandin E2 (PGE2) production.MAIN RESULTS AND THE ROLE OF CHANCEBioinformatics analysis of scRNA-seq revealed that OSM is exclusively expressed in leukocytes, whereas its receptors are predominantly expressed in granulosa cells. Immunohistochemistry and qPCR analyses exhibited increased OSM expression in leukocytes and receptor expression in granulosa cells, respectively, after ovulatory hCG administration (P < 0.05). Western blotting demonstrated that rhOSM treatment activated STAT3, ERK1/2, AKT, and p38MAPK pathways in hGLCs. RNA sequencing and following qPCR revealed rhOSM-induced significant transcriptional changes in genes involved in steroidogenesis, prostaglandin synthesis/transport, inflammation, and tissue remodeling (FDR < 0.05). Functionally, rhOSM increased P4 and PGE2 secretion (P < 0.05) while decreasing E2 production (P < 0.05), suggesting a role in ovulation and luteinization.LARGE SCALE DATARNA sequencing datasets are available in the Gene Expression Omnibus under accession number GSE277343.LIMITATIONS, REASONS FOR CAUTIONThis study was conducted using in vitro hGLC cultures, which may not fully recapitulate in vivo ovulatory dynamics. Additionally, the findings are specific to human samples and require validation in other mammalian species.WIDER IMPLICATIONS OF THE FINDINGSThese results suggest that leukocyte-derived OSM is a key cytokine regulating ovulatory events, providing novel insights into the im","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"39 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143915093","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}