Human reproduction最新文献

{"title":"O-125 Ultra-fast vs. traditional warming: a study on human oocyte and blastocyst survival, in vitro development, and reproductive success","authors":"G Tribbioli, L Peinado, F Lolicato, L Acin, S Rovira, F Moffa, M Antich, S Novo","doi":"10.1093/humrep/deaf097.125","DOIUrl":"https://doi.org/10.1093/humrep/deaf097.125","url":null,"abstract":"Study question Does Ultra-Fast Warming achieve similar results to the Traditional Warming protocol for human oocytes and embryos? Summary answer Ultra-Fast Warming achieves comparable outcomes to the Traditional Warming protocol while significantly reducing processing time and improving overall IVF efficiency. What is known already Cryopreservation of oocytes and embryos is one of the most widely used techniques in assisted reproduction, reaching its highest efficiency through vitrification. However, traditional protocols are time-consuming for embryologists to perform. Recently, protocols have emerged that significantly reduce vitrification and warming times. Despite this, there is still no evidence using human oocytes and embryos to confirm the effectiveness of these protocol modifications. In this study, we compare the efficiency of the Traditional Warming protocol (TW) used to date with the emerging Ultra-Fast Warming protocol (UFW) in IVF cycles involving human oocytes and embryos. Study design, size, duration In this retrospective study, 688 single-blastocyst cryotransfer (UFW: 317, TW: 371) and 36 ICSI cycles (UFW: 18, TW: 18; 412 MII) with donor oocytes (DO), performed in 2024, were analyzed. Samples were previously vitrified with standard protocol (12’–15’ in equilibration solution, 90’’ in vitrification solution). TW protocol: specimens were incubated 1’ in thawing solution, 3’ in dilution solution, and 6’ in washing solution; UFW protocol: 1’ in thawing solution, then transferred into culture medium. Participants/materials, setting, methods Groups were comparable. For cryotransfer cycles, oocyte age (UFW: 28.6±6.0; TW: 29.4±6.3; p = 0.078), recipient age (UFW: 40.6±5.0; TW: 40.7±4.8; p = 0.883), gamete origin (DO: UFW: 70.4%, TW: 68.8%, p = 0.649; sperm donor: UFW: 35.2%, TW: 41.8%, p = 0.060), blastocyst quality (≥3BB: UFW: 92.6%, TW: 89.9%, p = 0.218), and culture day (Day 5: UFW: 83.3%, TW: 82.0%, p = 0.645) were evaluated. Oocyte donors ages (UFW: 25.7±3.4; TW: 24.9±3.6; p = 0.535) and proportions of donor sperm (UFW: 11/18; TW: 8/18; p = 0.505) were equipollent. Main results and the role of chance For the 317 single transfers performed using the UFW protocol, 324 blastocysts were devitrified, achieving a survival rate of 97.8%, which was comparable to the TW protocol (371/378 = 98.1%; p = 0.793). Once transferred, pregnancy (UFW: 60.9%, TW: 61.2%; p = 0.935), clinical pregnancy (UFW: 53.0%, TW: 52.3%; p = 0.639), and miscarriage rates (UFW: 7.1%, TW: 11.3%; p = 0.161) were statistically equivalent. All pregnancies remain ongoing at the time of analysis. Regarding oocytes, survival rates were higher in cycles using the UFW protocol (91.8±12.9%) compared to TW cycles (85.2±22.4%), though not statistically significant (p = 0.259). Fertilization (UFW: 65.4±24.6%, TW: 70.7±16.9%; p = 0.383), ICSI-induced degeneration (UFW: 8.4±12.9%, TW: 4.8±8.4%; p = 0.379) and blastocyst formation rates (UFW: 47.4±25.8%, TW: 43.7±26.3%; p = 0.682) we","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"48 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144503534","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":"P-210 LC3B mediates the decay of maternal mRNAs through autophagy to affect ZGA and early embryonic development","authors":"D Liu","doi":"10.1093/humrep/deaf097.519","DOIUrl":"https://doi.org/10.1093/humrep/deaf097.519","url":null,"abstract":"Study question The mechanism of LC3B mediated degradation of maternal mRNAs. Effects of failure of critical maternal mRNAs degradation on ZGA and embryonic development. Summary answer In early embryos, LC3B binds to maternal decay mRNAs and carries them into the lysosome for degradation. What is known already It has been reported that LC3B has RNA binding function and can promote mRNAs degradation in HEK 293T cells. Failure of degradation of maternal mRNAs in early embryos results in failure of ZGA initiation and arrest of embryonic development. Study design, size, duration In this study, the expression of LC3B and the dynamic changes of autophagy activity in early embryos were identified firstly. Subsequently, the mRNAs targeted by LC3B were detected. After knockdown or overexpression of LC3B and activation or inhibition of autophagy in embryos, the expression of maternal mRNAs and ZGA genes as well as embryonic development were examined. Finally, the co-localization of maternal mRNAs, LC3B and lysosome were detected. The study lasted for nearly two years. Participants/materials, setting, methods Female and male ICR mice aged 6-8 weeks were selected for this study. PN5, early 2 cell and late 2 cell embryos were collceted for RIP seq. Control group and LC3B knockdown group, control group and LC3B overexpression group, control group and autophagy activation group, control group and autophagy inhibition group were set up, and late 2 cell embryos were collected for RNA seq. The blastocyst rate was calculated by culture embryos in vitro. Main results and the role of chance In this study, we found that autophagy activity changes dynamically in different stages of early embryos, and autophagy activity as well as the expression of LC3B are higher in late 2 cell embryos. By performing RIP seq in early embryos, we found that LC3B, a key protein of autophagy, can binding to maternal mRNAs and promotes the decay process. Further experiments indicated that autophagy inhibition or LC3B knockdown leads to maternal decay failure and ZGA failure, while autophagy activation or LC3B overexpression promotes maternal decay and ZGA. We found that LC3B mediates the degradation of maternal mRNAs through the autophagy pathway. Limitations, reasons for caution This study needs to further explore whether LC3B mediated maternal mRNAs degradation has other pathways or whether it is synergistic with classical maternal mRNAs degradation pathways. Wider implications of the findings Autophagy activity is decreased in aged embryos. The reason for the decreased developmental potential of aged embryos may be the failure of maternal mRNAs degradation, which leads to the failure of ZGA and the decrease of embryonic developmental potential. Activating autophagy in aged embryos may improve embryonic development. Trial registration number No","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"7 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144503570","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":"P-628 Bisphenol exposure and its impact on telomere length and ovarian reserve in reproductive-age women","authors":"E E Lara-Molina, V Garrigós, A Vázquez, D Amorós, M Florensa, X Tao, A Ballesteros, A Chisvert, R González-Martín, F Dominguez","doi":"10.1093/humrep/deaf097.934","DOIUrl":"https://doi.org/10.1093/humrep/deaf097.934","url":null,"abstract":"Study question Do concentrations of bisphenols (BPs) in follicular fluid (FF), serum, and urine influence telomere length (TL) in leukocytes and cumulus cells of reproductive-age women? Summary answer Higher concentrations of BPs in FF and urine are associated with leukocyte telomere shortening and reduced antral follicle count. What is known already Exposure to BPs, primarily present in plastics, adversely affects oocyte quality and female fertility. Elevated urinary BP levels are associated with meiotic cell cycle arrest, abnormal meiotic spindle formation, chromosomal misalignment, reduced antral follicle counts, and diminished oocyte yield in IVF patients. However, the specific mechanisms affecting oocyte health remain unclear. In vitro studies show BP exposure inhibits telomerase activity and shortens telomeres in leukocytes; yet its effects on TL in ovarian follicle cells, and consequently on female reproductive aging, remain unstudied. Study design, size, duration This prospective, non-interventional cohort study included 134 egg donors who underwent controlled ovarian stimulation following the clinic’s standard protocol. On the day of vaginal oocyte retrieval, samples of blood (leukocytes and plasma), urine, FF, and cumulus cells were collected. Relative TL was measured in leukocytes (LTL) and cumulus cells (CCTL). Additionally, nine bisphenols (BPA, BPAP, BPAF, BPB, BPC, BPE, BPF, BPS, and BPZ) were quantified in serum, urine, and FF samples. Participants/materials, setting, methods The nine BPs were analyzed using a miniaturized sorptive dispersive microextraction method. Genomic DNA from leukocytes and cumulus cells was isolated for TL measurements. Relative TL was assessed using a SYBR-Green real-time quantitative PCR protocol. Generalized linear models examined associations between bisphenols, TLs, antral follicle count (AFC), anti-müllerian hormone (AMH), and mature oocytes, estimating mean differences per dose-2fold increase (95% CI). Crude and age-BMI-smoking-adjusted models were applied. Main results and the role of chance Participants had a median age of 25 years [IQR: 21–28] and a BMI of 22.51 kg/m² [IQR: 20.76–24.43]; 45.5% had never smoked. Among the nine BPs evaluated in three biological matrices, only BPA and BPE in FF, and BPZ and BPF in urine, were detected in at least 50% of participants and included in further analysis. The sum of BPs in each biofluid was calculated as a new exposure variable. Mean and interquartile range BP concentrations (ng/mL) were as follows: FF-BPA 1.67 [0.10–5.37], FF-BPE 0.00 [0.00–0.11], FF-∑BP 1.84 [0.11–5.42], U-BPF 0.02 [0.01–0.09], U-BPZ 0.03 [0.00–0.08], and U-∑BP 0.09 [0.03–0.20]. No correlations were observed among biofluids for any bisphenol. In the adjusted models, CCTL was not significantly affected by any bisphenols. However, higher FF-∑BP concentrations were associated with a significant 1% decrease in LTL [0.99 (0.99–1.00), p = 0.023]. Higher urinary BPZ concentrations were signifi","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"2 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144503576","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":"O-276 Laboratory KPIs: Rethinking Metrics and timings","authors":"J Swain","doi":"10.1093/humrep/deaf097.276","DOIUrl":"https://doi.org/10.1093/humrep/deaf097.276","url":null,"abstract":"Laboratory key performance indicators (KPIs) are essential components in a Quality Management Program and instrumental in helping the laboratory track performance in a variety of areas. These KPIs can be used to help ensure the laboratory is achieving some minimal threshold of clinical outcome quality, like fertilization rate or blastocyst development, but can also be used to monitor other activities and efficiencies to help achieve and then improve upon a strategic goal. Importantly, as the requirements of the reproductive laboratory evolve and as technology changes, so must the KPIs. Accepted IVF laboratory quality outcome KPIs will be presented, with suggestions for possible improvements. Discussion of staffing ratios, procedure number and timings, as well as the potential benefit of other operational efficiency KPIs will be discussed. The importance of proper data collection and analytics, with utilization of dashboards for ease of KPI monitoring will be highlighted.","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"7 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144503583","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":"P-081 Sperm DNA fragmentation has a positive correlation with age but may not directly affect IVF/ICSI outcomes","authors":"T T C Bach, M K Nguyen, N A Phung, V T Phung, T T Pham, T H Vu, H D Bach, T H G Truong, H N Le, H A Bach","doi":"10.1093/humrep/deaf097.390","DOIUrl":"https://doi.org/10.1093/humrep/deaf097.390","url":null,"abstract":"Study question Does sperm DNA fragmentation correlate with men’s age and would sperm DNA fragmentation directly affect IVF/ICSI outcomes? Summary answer Sperm DNA fragmentation index was significantly higher in men with advanced age, however, the IVF/ICSI outcomes were not significantly varied in different DNA fragmentation groups. What is known already Sperm DNA fragmentation (SDF) is a common cause of male infertility, and can affect assisted reproductive technology treatment outcomes. Several factors that decide SDF include age, genetics and environmental factors. IVF/ICSI, in which each single sperm is selected, has been shown to resolve the problem of low sperm count, sperm motility and morphology. However, how SDF impacts on IVF/ICSI outcomes remains controversial. In this study, we aim to identify the correlation between age and SDF, and to examine the effects of SDF on IVF/ICSI outccomes. Study design, size, duration From 01/2023-12/2024, male infertile patients who had sperm count ≥ 2mL were indicated for DSF examination if having one of these conditions: advanced age (≥ 45 years old), had bad habits such as: smoking ≥ three cigarettes/day, drinking more than 100 mL of at least 25% by volume alcohol/day, not excercise, or worked in highly hazardous conditions (N = 899 persons). The treatment outcomes of the couples who underwent IVF/ICSI cycles to clinical pregnancy were anlyzed. Participants/materials, setting, methods The DSF test used the Halosperm kit (Halotech) based on the Sperm Chromatin Dispersion (SCD) technique. The patients were divided into three groups: Low DSF if the sperm DNA fragmentation index (DFI) ≤15%, Moderate (DFI from 15-30%), High (DFI≥30%). The correlation between the men’s age and the DSF were examined. The results of IVF/ICSI cycles (fertilization, blastulation, beta-hCC positive, clinical pregnancy rate) were compared among these DSF groups. T-Test and Chi-Square test were applied. Main results and the role of chance Totally, 899 men were tested for DSF: 556 men had low DSF, 232 had moderate, and 111 men had high DSF. The average ages of Low, Moderate and High DSF groups were 36.5 ± 5.3, 37.76 ± 5.7, and 40.32 ± 7.6 years old, respectively. P values of the ages (Moderate vs Low DSF group) was 0.003 and the ages (High vs Low DSF group) was P < 0.001. We analyzed based on the ages: Men with age ≤30 years old (yo) had average DFI=14.3% (N = 105); >30, ≤35 yo had average DFI=13.0% (N = 245); >35, ≤40 yo group had average DFI=15.1% (N = 314), P = 0.05 while compared to lower aged group; >40, ≤45 yo had average DFI=20.6% (N = 170), P < 0.01; and >45 yo had average DFI=22.7% (N = 65), P < 0.01. DFI may increase by age and the older men have higher DSF. N = 427 couples underwent IVF/ICSI (271 in Low, 109 in Moderate, and 47 in High DSF group). No significant difference in the wives’s ages (∼31 yo), the number of oocytes collected (∼14), fertilization rate (87%) and blas","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"87 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144503728","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":"O-299 Ooplasm-mediated sperm nuclear decondensation for genome editing of the mammalian male gamete","authors":"A B De Jesus, E Lari, G Beroukhim, B Zhang, P Xie, Z Rosenwaks, G Palermo","doi":"10.1093/humrep/deaf097.299","DOIUrl":"https://doi.org/10.1093/humrep/deaf097.299","url":null,"abstract":"Study question Can CRISPR-Cas9 efficiently edit a specific gene in a single spermatozoon using an ooplasm-mediated mechanism? Summary answer The ooplasm-mediated approach induced the decondensation of the male gamete nucleus enabling CRISPR-Cas9 access to the sperm genome successfully editing the coat pigment gene. What is known already CRISPR-Cas9 has been applied to edit somatic and germline cells through microinjection, electroporation, or transfection. Early heritable genome editing (HGE) efforts focused on S-phase or zygote stage but encountered mosaicism and loss of heterozygosity. To overcome these limitations, editing at the gamete level emerged as a promising strategy. While genome editing in oocytes is considered feasible, sperm DNA editing presents greater difficulty due to highly compacted chromatin structure surrounding the protamine cores. Attempts in sperm membrane permeabilization facilitated CRISPR-Cas9 entry, but genomic editing was unsuccessful. We aim to overcome chromatin condensation by using intrinsic ooplasmic machinery to decondense sperm genome. Study design, size, duration Over the past year, oocytes were divided into two groups: one for embryo genome editing and the other for sperm genome editing via Oocyte-Mediated Sperm Decondensation (OMSD). In the OMSD approach, a single spermatozoon was injected into an enucleated oocyte to generate haploid embryo with only paternal DNA. CRISPR-Cas9 targeting the Tyr gene with Tyr-specific sgRNA was utilized in both cohorts to induce a knockout, resulting in an albino phenotype. Participants/materials, setting, methods B6D2F1 mice were used to retrieve metaphase II oocytes and spermatozoa. A subset of oocytes was enucleated for the OMSD approach, while other oocytes remained intact. All oocytes were injected with a spermatozoon, together with Tyr-specific sgRNA and Cas9 protein. Embryos were cultured to 8-cell stage, and genomic DNA was analyzed by T7E1 cleavage assay to assess genome editing efficiency. Control embryos were generated from intact oocytes using the standard HGE approach. Main results and the role of chance In this study, a total of 173 oocytes were used, with 46 intact oocytes undergoing standard embryo genome editing and 127 enucleated oocytes for OMSD experiments. After Piezo-ICSI with a CRISPR-Cas9 solution, fertilization of intact oocytes occurred at a rate of 82.6% (38/46). Following 48 hours of culture, 86.8% (33/38) of diploid embryos reached the 8-cell stage. Amplification of the 584-bp region of the target site from extracted DNA confirmed gene modification in 90.9% (30/33) of the edited diploid embryos. In the OMSD cohort, enucleated oocytes fertilized as 1PN derived pseudo-zygote at a rate of 54.2% (58/107), and cleavage was lower, with only 34.5% (20/58) progressing to the 8-cell stage. Sperm genome modification was confirmed in 71.0% (22/31) of the embryos. While enucleation reduces cleavage, the overall gene modification efficiency remains high. Trans","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"25 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144513092","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":"P-430 The impact of age on reproductive outcomes of euploid embryos: gamete provider age is irrelevant, but woman’s age at transfer significantly reduces success rates","authors":"L Martiñá Rivas, A Rodríguez Isern, D Company Regàs, P Andrade, S Rovira Fontanals, F Moffa, M Antich Díaz, S Novo Bruña","doi":"10.1093/humrep/deaf097.736","DOIUrl":"https://doi.org/10.1093/humrep/deaf097.736","url":null,"abstract":"Study question Do the ages of the providers of the gametes or the woman’s age at transfer influence reproductive outcomes in single euploid blastocyst transfers? Summary answer Woman’s age at transfer significantly reduces pregnancy, clinical pregnancy and live birth rates (p < 0.05), while the age of gamete providers has no significant impact What is known already Reproductive success in assisted reproductive technologies (ART) depends on gamete and embryo quality, and uterine receptivity. While advanced maternal age is associated with reduced outcomes, the extent to which this is driven by gamete age or uterine factors remains unclear. Euploid embryos offer a unique opportunity to isolate these effects, as they remove the confounding influence of chromosomal aneuploidy, a known contributor to failed implantation and live birth. However, evidence regarding the relative impact of gamete and recipient age on the success of euploid embryo transfers is still limited, necessitating further investigation. Study design, size, duration This retrospective cohort study analyzed 757 single euploid blastocyst transfers from February-2019 to February-2024. Given that the focus of the study is on the age of the gamete provider and woman’s age at transfer, IVF cycles using both autologous and donor gametes were included. After blastocyst biopsy, PGT-A was performed using next-generation sequencing (NGS). PGT-A was indicated for advanced maternal age or to reduce time-to-pregnancy. Participants/materials, setting, methods Data were stratified by oocyte provider age (<35, 35–37, 38–40, >40 years), sperm provider age (≤40, >40), and woman’s age at transfer (<38, 38–42, 43–45, >45 years). Pregnancy, clinical pregnancy, miscarriage, and live birth rates were compared. For gamete age groups, the impact on post-vitrification survival of biopsied blastocysts was analyzed. Significant results included embryo quality comparisons using the proportion of blastocysts ≥3BB transferred. Chi-square tests with p-value <0.05 were considered significant. Main results and the role of chance The age of the gamete providers did not impact the survival of vitrified biopsied blastocysts, with survival rates consistently around 98% across all age groups (oocyte: p = 0.499; sperm: p = 0.419). Oocyte provider age (<35, 35–37, 38–40, >40 years) showed no significant effect on pregnancy (69.2%, 76.1%, 67.4%, 69.4%; p = 0.634), clinical pregnancy (61.1%, 69.0%, 62.0%, 59.2%; p = 0.615), or live birth rates (53.4%, 59.2%, 49.6%, 57.1%; p = 0.581). Similarly, sperm provider age (≤40, >40 years) did not influence pregnancy (68.9%, 70.6%; p = 0.249), clinical pregnancy (60.6%, 63.7%; p = 0.726), or live birth rates (53.3%, 53.9%; p = 0.871). In contrast, woman’s age at transfer (<38, 38–42, 43–45, >45 years) significantly impacted the success of euploid embryo transfers. Pregnancy rates decreased with age stati","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"149 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144513099","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":"P-330 The differential expression of transcription factors OTX2 and SOX15 in follicular fluid and Cumulus cells of patients with endometriosis","authors":"M Mohammad Esmaeili, A Dalman, S Allahverdi Meygooni, F Bashirian Alvars, R Favaedi, F Hassani, M Shahoseini","doi":"10.1093/humrep/deaf097.638","DOIUrl":"https://doi.org/10.1093/humrep/deaf097.638","url":null,"abstract":"Study question What effect does endometriosis have on the expression level of transcription factors OTX2 and SOX15 as oocyte maturation markers in follicular fluid and Cumulus cells? Summary answer Endometriosis reduces the expression level of OTX2 and SOX15 into follicular fluid and Cumulus cells which can negatively affect oocyte maturation and quality. What is known already The relationship between endometriosis and infertility is further complicated by the fact that it’s a chronic disease marked by the development of endometrial-like tissue outside the uterus. It also results in anatomical abnormalities, hormonal imbalances, and inflammatory responses that negatively affect oocyte viability, maturation, and quality as well as reproductive outcomes. Since it is challenging to directly assess oocyte quality, analysis of follicular fluid and Cumulus cells is often used as an alternative approach. The increase in these two genes' expression during oocyte maturation illustrates the importance of choosing these two particular transcription factors, OTX2 and SOX15, for this investigation. Study design, size, duration This study, conducted from October 2023 to February 2025, involved 30 women with stages III or IV endometriosis and 30 control participants. Follicular fluid and Cumulus cell samples were collected after obtaining informed consent. Inclusion criteria included women aged 18-45 years with regular menstrual cycles and undergoing GnRH agonist or antagonist protocols. Exclusion criteria encompassed HPV, HSV-2, PCOS, diminished ovarian reserve, endometrial abnormalities, and history of inflammatory diseases. Participants/materials, setting, methods In this study, RNA was extracted from follicular fluid and Cumulus cell samples from women with and without endometriosis. cDNA synthesis followed, and real-time PCR was performed to assess gene expression. Data were analyzed using GraphPad Prism software, employing the independent t-test for normally distributed data and the Mann-Whitney U test for non-parametric distributed data. Statistical significance was set at a p-value of ≤ 0.05. Main results and the role of chance The main results of this study demonstrate that women diagnosed with stages III or IV endometriosis exhibited significantly decreased (p-value<0.0001) expression levels of transcription factors OTX2 and SOX15 in their follicular fluid and Cumulus cell samples when compared to the control group. This decrease in expression was correlated with clinical observations revealing a significant in both the total number of oocytes (p-value=0.0553) and the number of mature metaphase II (MII) oocytes (p-value=0.0205), as well as a lower history of pregnancy (p-value=0.026) in endometriosis patients. Although other demographics such as age, Body Mass Index (BMI), Luteinizing Hormone (LH), Follicle-Stimulating Hormone (FSH), and Anti-Müllerian Hormone (AMH) levels, duration of ovarian stimulation, and history of abortion did not show a","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"3 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144513117","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":"P-600 Loss of nucleoporin NUP210L and chromatin protein BAF-L together, but not separately cause male infertility in the mouse revealing their redundant roles in nuclear integrity","authors":"M Mitchell, M Al Dala Ali, G Longepied, C Metzler-Guillemain","doi":"10.1093/humrep/deaf097.906","DOIUrl":"https://doi.org/10.1093/humrep/deaf097.906","url":null,"abstract":"Study question Could colocalised spermatid-specific genes Banf2 and Nup210l, whose individual loss has no effect on male fertility, have redundant functions at the caudal nuclear envelope? Summary answer Banf2 and Nup210l are required together for nuclear integrity and male fertility by organising microtubules into the manchette and preventing nuclear invagination. What is known already Nup210l encodes a transmembrane nucleoporin and Banf2 encodes BAF-L a paralogue and binding partner of the chromatin protein BAF. NUP210L and BAF-L localise to the caudal nuclear pole in human elongating spermatids. Nuclear pores are also reorganised into a dense array at the caudal pole during spermatid elongation. The inactivation of either of these genes in the mouse has no effect on male fertility. In human, the biallelic loss of NUP210L has been described in a single case of an infertile man producing mainly spermatozoa with a descondensed nucleus and histone retention. Study design, size, duration We created double knockout mice lacking NUP210L and BAF-L based on their colocalisation to the caudal nuclear pole of elongating spermatids in human. We compared the fertility and spermatogenesis of these double knockout mice (n = 10) to control littermates (n = 10) Participants/materials, setting, methods Double mutants were compared to controls by defining sperm parameters and testicular histology. We also used immunofluoresence to study the nuclear lamina, the manchette and the nuclear pore complex array throughout spermiogenesis. Nuclear structure was also studied by transmission electron microscopy. Main results and the role of chance In the mouse, loss of both NUP210L and BAF-L causes a catastrophic failure of spermiogenesis as the spermatids begin elongation (step 10-11), with most elongating spermatids entering apoptosis (determined by TUNEL). Deformation of the nucleus is seen in 90% of round spermatids while a destabilisation of the manchette and the nuclear pore complex array is observed in elongating spermatids. Electron microscopy shows that microtubules invaginate the spermatid nucleus. Our results show that BAF-L and NUP210L are involved in redundant processes that are important for nuclear integrity during spermatid elongation. We conclude that there may be a critical nexus of nuclear pore complex and the chromatin at the caudal nuclear pole during spermatid elongation. Limitations, reasons for caution We present solid data for a functional roles of NUP210L and BAF-L and their redundancy in the mouse, but we do not provide mechanistic information. We cannot be sure that the same redundancy exists in the human. Wider implications of the findings Our study is relevant to infertility and all genetic diseases, presenting an illustration of functional redundancy and non-homologous digenic inheritance. We reveal a critical function for BAF-L and NUP210L in the positioning of manchette microtubules. We show that function can be hidden from genetic approach","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"16 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144513123","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":"O-176 Genetics of teratozoospermia","authors":"P Ray","doi":"10.1093/humrep/deaf097.176","DOIUrl":"https://doi.org/10.1093/humrep/deaf097.176","url":null,"abstract":"Male infertility, affecting over 20 million men worldwide, is a significant health concern with a strong yet underexplored genetic basis. Recent advances in genetic sequencing, particularly the use of whole-exome sequencing (WES), have enabled the identification of many genetic causes of teratozoospermia, including AURKC mutations in macrozoospermia, DPY19L2 defects in globozoospermia, and DNAH1 mutations in patients with flagellar abnormalities, collectively termed multiple morphological abnormalities of the flagella (MMAF). A comprehensive literature review on human genetics, experimental models, and teratozoospermia physiopathology confirmed that DPY19L2 deletions account for over 90% of globozoospermia cases, while two recurrent AURKC mutations explain 70% of macrozoospermia cases. Notably, an AURKC diagnosis indicates that intracytoplasmic sperm injection (ICSI) cannot be successful, while DPY19L2 mutations are associated with very low fertilization rates, which can be improved through artificial oocyte activation (AOA) using calcium ionophore. Over 50 genes have now been linked with the MMAF phenotype, allowing a diagnosis efficiency of approximately 50%. Data from human and animal models shows that MMAF primarily arises from defects in the axoneme, a microtubule-based structure that serves as the backbone and enables the movement of sperm flagella and motile cilia. As a result, in addition to their primary infertility, a proportion of MMAF patients develop a primary ciliary dyskinesia (PCD) suggesting that a pulmonary functional test should be proposed to all. These insights, driven by advances in genetic sequencing, enhance our understanding of teratozoospermia, improve diagnostic strategies, guide genetic counseling and pave the way for preventive medicine and potential personalized treatments targeting defective gene products.","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"4 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144513128","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}