Human reproduction最新文献

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P-404 Trends in Oocyte Vitrification: Patient Demographics and Outcomes from 2015 to 2023 P-404卵母细胞玻璃化的趋势:2015年至2023年的患者人口统计和结果
IF 6.1 1区 医学
Human reproduction Pub Date : 2025-06-28 DOI: 10.1093/humrep/deaf097.710
Á Llaneza, A Bullido, C Andrés, S Cortés, L Serrano, J A Horcajadas
{"title":"P-404 Trends in Oocyte Vitrification: Patient Demographics and Outcomes from 2015 to 2023","authors":"Á Llaneza, A Bullido, C Andrés, S Cortés, L Serrano, J A Horcajadas","doi":"10.1093/humrep/deaf097.710","DOIUrl":"https://doi.org/10.1093/humrep/deaf097.710","url":null,"abstract":"Study question How have the demographics and clinical outcomes of patients undergoing oocyte vitrification evolved over the period 2015-2023? Summary answer Oocyte vitrification has increased, with more foreign patients, decreasing mean age, and more vitrified oocytes. Warming rates remain low, and survival correlates with ovarian reserve. What is known already Oocyte vitrification is a widely used fertility preservation strategy. Age and ovarian reserve markers impact success, but long-term trends remain underexplored. Understanding demographic and clinical shifts, including nationality trends, survival rates, and warming rates, is essential for refining fertility preservation strategies and patient counseling. Study design, size, duration A retrospective cohort study including 936 patients who underwent oocyte vitrification between 2015-2023 at a single fertility center. Trends in patient demographics, ovarian reserve, survival rates, and vitrification outcomes were analyzed using linear regression models. Participants/materials, setting, methods Patients undergoing vitrification were included. Data analyzed: nationality, age, AMH, AFC, vitrified/warmed oocytes, and survival rates. Statistical tests identified trends and associations in survival and warming rates. Main results and the role of chance Patient numbers increased from 35 (2015) to 306 (2023). Mean age declined (-0.30 years/year, p = 0.007), with an overall mean of 36.4 years (2015-2023). AMH remained stable (2.33 ng/mL in 2015 vs. 2.01 ng/mL in 2023, p = 0.840). Vitrified oocytes rose (248 in 2015 vs. 910 in 2023, p = 0.002). Oocyte survival rates were negatively correlated with age (-0.81, p < 0.01) and positively with AMH (0.89) and AFC (0.99). In the available data, the mean oocyte survival rate for the 37-40 age group was 63.9%, while insufficient data were available for other age groups. As to warming rates 45.7% of 2015 patients underwent warming, compared to 5.6% from 2023. Limitations, reasons for caution Single-center data limits generalizability. External factors such as policy changes and economic shifts may influence trends. Limited survival rate data for specific age groups restricts definitive conclusions on age-related trends. Wider implications of the findings Decreasing patient age highlights evolving fertility awareness. The increasing international patient demand underscores the importance of accessible reproductive care policies. The association between ovarian reserve markers and survival rates can enhance fertility preservation counseling. Trial registration number No","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"53 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144503582","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}
引用次数: 0
P-524 The influence of age on the timing of milestones in gender identity development and fertility preservation P-524年龄对性别认同发展和生育能力保持的里程碑时间的影响
IF 6.1 1区 医学
Human reproduction Pub Date : 2025-06-28 DOI: 10.1093/humrep/deaf097.830
T Seeland, A L Zippl, D Riedl, B Toth, K Feil
{"title":"P-524 The influence of age on the timing of milestones in gender identity development and fertility preservation","authors":"T Seeland, A L Zippl, D Riedl, B Toth, K Feil","doi":"10.1093/humrep/deaf097.830","DOIUrl":"https://doi.org/10.1093/humrep/deaf097.830","url":null,"abstract":"Study question This study aims to investigate whether the age of milestones in gender identity development (GID) varies between generational cohorts. Summary answer Generational cohort influences the age of reaching milestones in gender identity development (e.g. coming out). What is known already Socio-economic changes and evolving societal perceptions of transgender and gender-diverse (TGD) individuals have had a significant impact on the trajectories of GID among younger generations. Factors such as increased access to genderaffirming healthcare and positive media representation have likely contributed to earlier gender identity awareness among younger TGD individuals. This may subsequently influence key milestones in GID, including coming out and initiating hormone therapy. Study design, size, duration Data for the study was collected between 2017 and 2021 at a single center. The study, which used the Innsbrucker Transgender Quality of Life during Hormone Therapy Questionnaire (iTransQoL), included 212 participants. Participants/materials, setting, methods 212 participants who (a) were at least 18 years old, (b) identified as TGD, and (c) provided informed consent were included in the analysis. Participants were categorised by generational cohort and gender identity. Participants were categorised into four generational cohorts: Generation Z (born 1997-2012, n = 97), Millennials (born 1981-1996, n = 85), Generation X (born 1965-1980, n = 24), and Baby Boomers (born 1946-1964, n = 6). The study sample included 115 trans men, 90 trans women, and 7 non-binary individuals. Main results and the role of chance Compared to older cohorts, younger generations, particularly Generation Z, reported significantly earlier onset of key GID milestones. Generation Z expressed a first desire to transition at 12.4 ± 4.7 years, compared to 40.8 ±22.0 years for Baby Boomers. Furthermore, Generation Z exhibited a shorter interval between the first desire to transition and coming out (4.3 ±3.9 years) than Millennials (8.3 ±7.4 years). A notable intergenerational difference emerged in the distribution of gender identity. Generation Z demonstrated a higher prevalence of trans men, with 66.0% self-identifying as such, compared to 29.2% in Generation X and only 16.7% in Baby Boomers. There was a significant disparity in the use of fertility preservation measures between trans men and women. While 23.6% of trans women used such measures, this figure was significantly lower for transmen at 3.7%. Limitations, reasons for caution Only TGD individuals starting hormone therapy were included in this study, which reduced our study population. Still prevalent discrimination against non-binary individuals in healthcare may have resulted in a small number of non-binary individuals. Wider implications of the findings This study highlights the intergenerational differences in the timing of key GID milestones for TGD individuals. This may reflect progress in the visibility of TGD ind","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":"144503584","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}
引用次数: 0
O-104 Determining the pre- and post-fertilization origins of aneuploidies: a new paradigm in assisted reproduction to substantially enhance embryo selection 确定非整倍体受精前和受精后的起源:辅助生殖的新范式,以大大提高胚胎选择
IF 6.1 1区 医学
Human reproduction Pub Date : 2025-06-28 DOI: 10.1093/humrep/deaf097.104
R Essers, S Biglari, A E J Janssen, H G Brunner, M L Van Zwet, M H E C Pieters, W Verpoest, K Van Zomeren, J Van Echten-Arends, A Derijck, S Mastenbroek, A Van den Wijngaard, E Coonen, A Paulussen, M Zamani Esteki
{"title":"O-104 Determining the pre- and post-fertilization origins of aneuploidies: a new paradigm in assisted reproduction to substantially enhance embryo selection","authors":"R Essers, S Biglari, A E J Janssen, H G Brunner, M L Van Zwet, M H E C Pieters, W Verpoest, K Van Zomeren, J Van Echten-Arends, A Derijck, S Mastenbroek, A Van den Wijngaard, E Coonen, A Paulussen, M Zamani Esteki","doi":"10.1093/humrep/deaf097.104","DOIUrl":"https://doi.org/10.1093/humrep/deaf097.104","url":null,"abstract":"Study question To investigate the clinical utility of preimplantation genetic testing for aneuploidy origin (PGT-AO), which determines the meiotic/mitotic origin of aneuploidies and their level of mosaicism. Summary answer PGT-AO together with sequencing-based PGT-M avoids unnecessary transfer of embryos with meiotic trisomies and most monosomies. Determining meiotic/mitotic origin based on mosaicism level is incorrect. What is known already Rising global parental age increases aneuploidy risk in offspring, driving demand for advanced PGT. Preimplantation genetic testing for aneuploidy (PGT-A) is widely used in in vitro fertilization for embryo selection. However, large clinical trials have questioned its efficacy, as current PGT-A may discard viable embryos. PGT-A overlooks the mosaic nature of embryos, causing concern in the field, since it is now evident that mosaic embryos, i.e. embryos that contain both euploid and aneuploid cells, may lead to healthy live births. We evaluated the clinical utility of PGT-AO, which determines the meiotic/mitotic origin of aneuploidies. Study design, size, duration In a nationwide non-selection study, we retrospectively analyzed the genomes of 5,975 embryos sequenced for PGT for monogenic disorders (PGT-M) using either genotyping-by-sequencing (n = 2,493) or whole-genome sequencing (n = 3,482). Genome haplarithmisis determined the meiotic/mitotic origin of aneuploidies and their mosaicism level. The aberrations were correlated with recorded clinical outcomes, such as birth status, heart rate, HCG status, ovarian stimulation protocol and duration, maternal and paternal age, endometrial thickness, and pregnancy complications. Participants/materials, setting, methods Couples were counseled by clinical geneticists at University Medical Centers (UMCs) of the Netherlands, in Maastricht, Amsterdam, Utrecht, and Groningen, and enrolled in the diagnostic PGT procedure after signing an informed consent form. Embryos (n = 946) eligible for transfer based on PGT-M (i.e. chromosomal aneuploidies were not accounted for) are analyzed by haplarithmisis-based PGT-AO including parental information. This information allows for the detection of chromosomal abnormalities and their mosaicism, and parental and segregational origin. Main results and the role of chance Among 946 transferred embryos, 253 (26.7%) resulted in a live birth, while 693 (73.3%) failed, including implantation failure (n = 546, 78.8%), early embryonic arrest (n = 104, 15.0%) and pregnancy loss (n = 43, 6.2%). All embryos with a meiotic trisomy failed, whereas 17.0% of embryos with a mosaic mitotic trisomy resulted in a healthy live birth. Furthermore, only 6.8% of monosomic embryos lead to a healthy live birth. Remarkably, different ovarian stimulation protocols affected transfer outcomes and aneuploidy rates. Maternal age at ovum pickup is positively correlated with meiotic trisomy rate in contrast to mitotic trisomy rate. Our results show embryos with meioti","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"33 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144513093","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}
引用次数: 0
P-654 The use of dydrogesterone to prevent premature ovulation in shared egg donation cycles is more cost-effective than the use of a flexible GnRH antagonist 在共享捐卵周期中,使用地屈孕酮预防早排卵比使用灵活的GnRH拮抗剂更具成本效益
IF 6.1 1区 医学
Human reproduction Pub Date : 2025-06-28 DOI: 10.1093/humrep/deaf097.960
C G Petersen, L D Vagnini, F C Massaro, B Petersen, J Ricci, C Zamara, A Nicoletti, B C Matuella, C M F Dias, R A Pouza, E V Espirito Santo, A C A Egydio, J B Meziara, J B A Oliveira, J G Franco
{"title":"P-654 The use of dydrogesterone to prevent premature ovulation in shared egg donation cycles is more cost-effective than the use of a flexible GnRH antagonist","authors":"C G Petersen, L D Vagnini, F C Massaro, B Petersen, J Ricci, C Zamara, A Nicoletti, B C Matuella, C M F Dias, R A Pouza, E V Espirito Santo, A C A Egydio, J B Meziara, J B A Oliveira, J G Franco","doi":"10.1093/humrep/deaf097.960","DOIUrl":"https://doi.org/10.1093/humrep/deaf097.960","url":null,"abstract":"Study question Can a fixed progestogen protocol be as effective as a flexible GnRH antagonist protocol in shared egg donation cycles? Summary answer The results using the fixed dydrogesterone protocol were not significantly different from those obtained with the flexible GnRH antagonist protocol, except for being more economical. What is known already Dydrogesterone is a stereoisomer of progesterone and appears to be a highly selective progestin that, owing to its molecular structure, binds almost exclusively to the progesterone receptor.The mechanism of action of progesterone involves a decrease in the LH pulse frequency without affecting the pulse amplitude.Compared with the use of GnRH analogues, progestin-primed ovarian stimulation seems similarly effective and safe in all types of patients undergoing assisted reproductive technology cycles.Specifically, in a shared donation program, the economic factor is preponderant because patients donate half of their eggs in exchange for free IVF but pay for the medications used in the treatment. Study design, size, duration This was a prospective study of 44 patients from a shared egg donation program who underwent their first shared egg donation cycle. None of the patients had a history of genetic diseases in their family. Karyotypes were normal, and the antral follicle count was ≥15. For various strategic reasons (distance, ideal scheduling for the transfer of thawed embryos, etc.), both recipient and donor patients cryopreserved all their embryos. Participants/materials, setting, methods The patients were divided into two groups. In Group I (n = 22), dydrogesterone was administered at a dosage of 20mg/day starting on the 1st day of the menstrual cycle until the day before egg collection. In Group II (n = 22), a GnRH antagonist was administered at a dosage of 0.25mg/day from the time the leading follicle reached 14mm until the day of the ovulatory trigger. Triptorelin acetate(0.2 mg) was administered when the follicles reached ≥17mm in diameter. Main results and the role of chance The mean age of patients in Group I(31.6±2.4y) was not significantly different from that in Group II(30.7±2.9y). The number of antral follicles(ACs) in Group I(26.6±10.6) did not differ from that in Group II(22.1±7.28). In Group I, the mean dose of urinary FSH(2032±580IU) did not differ significantly from that in Group II(2094±630IU). In Group I, the total number of oocytes collected(15.4±8.2) and the number of oocytes in metaphase II(12.8±7.6) were not significantly different from those obtained in Group II(total number of oocytes collected:14.6±5.8; number of oocytes in metaphase II:10.7±5.4). Table 1 shows the data. In these 44 patients, there was no premature follicular rupture. On the other hand, the mean number of vials of the GnRH antagonist was 5.3±1.2, i.e., a total mean cost of US$400 per cycle. The average number of days using the dydrogesterone blockade was 11.4±1.5, with a box of 28 tablets(10mg) costing US$11.","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"27 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144513096","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}
引用次数: 0
O-253 Obstetric outcome after endometriosis surgery with parametrial involvement and uterine artery section or occlusion: a prospective observational study O-253子宫内膜异位症手术伴伴子宫动脉切开或闭塞的产科结局:一项前瞻性观察研究
IF 6.1 1区 医学
Human reproduction Pub Date : 2025-06-28 DOI: 10.1093/humrep/deaf097.253
A K Stepniewska, R Pellegrini, C Zorzi, S Baggio, G Roviglione, F Bruni, F Ferrari, G D'Ancona, M Albanese, P De Mitri, M Miceli, R Gentile, A Inzoli, C Alboni, M Ceccaroni
{"title":"O-253 Obstetric outcome after endometriosis surgery with parametrial involvement and uterine artery section or occlusion: a prospective observational study","authors":"A K Stepniewska, R Pellegrini, C Zorzi, S Baggio, G Roviglione, F Bruni, F Ferrari, G D'Ancona, M Albanese, P De Mitri, M Miceli, R Gentile, A Inzoli, C Alboni, M Ceccaroni","doi":"10.1093/humrep/deaf097.253","DOIUrl":"https://doi.org/10.1093/humrep/deaf097.253","url":null,"abstract":"Study question Does the uterine devascularization related to uterine artery section or coagulation during parametrial endometriosis surgery influence the obstetric outcome in the future? Summary answer Uterine devascularization during surgery for parametrial endometriosis is related to a significantly higher frequency of preterm birth, gestational hypertension, preeclampsia, and placenta previa. What is known already Endometriosis may require surgical treatment because of pain or organ damage. Surgery for deep endometriosis, included parametrectomy, is regulary performed in referral centers and may preceed spontaneous or assisted conception. Removal of parametrial endometriosis, in particular surrounding ureters, may require sacrificing uterine vessels, with a potentially increased risk of pregnancy complications in the future.While endometriosis is itself related to an enhanced risk of several obstetric complications, including premature labor, small for gestational age (SGA) infants, intrauterine growth restriction (IUGR), hypertensive disorders, placenta previa and obstetric bleeding, little is known about the influence of surgery on obstetric outcome. Study design, size, duration A single-center prospective observational study (Etics Committe approval: OB-END-VASC - Prog. 362CET) performed in a Referral Center for Endometriosis. All consecutive patients, who underwent surgery for endometriosis with parametrectomy from January 2010 to December 2023 were invited to participate. Inclusion criteria were: age 23-46 years, pregnancy after surgery, informed consent to study participation. Surgical data analyzed included uterine devascolarization, associated surgical procedures, concomitant adenomyosis. Obstetric data included modality of conception, pregnancy and delivery outcome. Participants/materials, setting, methods During the study period, a total of 3989 women underwent laparoscopic parametrectomy for deep endometriosis in Our Refferal Center for Endometriosis (IRCCS Sacred Heart Hospital, Negrar). A total of 594 women who experienced at least one pregnancy after surgery, completed the follow-up and informed consent, and these participants were ultimately included in the study. Two groups of patients could be identified: PV group (preserved vascularization) and UD group (uterine devascularization related to uterine artery section/occulsion). Main results and the role of chance Out of 594 women, 88.05% (523/594) underwent parametrectomy with preservation of both uterine arteries (PV group), whereas in 11.95 % patients (71/594) parametrectomy was accompanied by uterine devascularization (UD group) which was achieved through coagulation 35.2% (25/71), application of clips 15.5 % (11/71), or a combination of sectioning with coagulation/clipping 49.30% (35/71), either unilaterally 92.96% or bilaterally 7.04% (66/71 vs 5/71). The overall preterm birth rate was 14.2%, with 29.5 % occurring in the UD- group compared to 12.2%in the PV-group. (p &l","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"28 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144513098","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}
引用次数: 0
P-205 A video-based system for extracting osmotic behavior and morphological dynamics: a foundation for predictive models in oocyte cryopreservation survival 基于视频的渗透行为和形态动力学提取系统:卵母细胞低温保存存活预测模型的基础
IF 6.1 1区 医学
Human reproduction Pub Date : 2025-06-28 DOI: 10.1093/humrep/deaf097.514
A Antich, S Novo Bruña, S Rovira, F Moffa, M Antich
{"title":"P-205 A video-based system for extracting osmotic behavior and morphological dynamics: a foundation for predictive models in oocyte cryopreservation survival","authors":"A Antich, S Novo Bruña, S Rovira, F Moffa, M Antich","doi":"10.1093/humrep/deaf097.514","DOIUrl":"https://doi.org/10.1093/humrep/deaf097.514","url":null,"abstract":"Study question Can video-derived osmotic and morphological data during vitrification protocols serve as a foundation for future predictive models in oocyte cryopreservation survival? Summary answer Dynamic parameters such as dehydration velocity, circularity, and area changes provide a foundation for future predictive models in oocyte cryopreservation survival. What is known already Artificial intelligence (AI) is increasingly used in assisted reproduction laboratories, primarily through time-lapse microscopy of embryo culture or static image analysis. These AI models achieve high predictive accuracy by training on large datasets but function as “black boxes,” providing results without biological explanations. Unlike other medical AI applications, those in reproductive medicine lack mechanistic validation and rely on correlations rather than causal insights. Furthermore, European law (Article 22, GDPR) prohibits decisions affecting human lives from being based solely on AI predictions. This highlights the urgent need for biologically interpretable, validated models that integrate dynamic physiological data into AI-driven reproductive assessments. Study design, size, duration A prospective study (October 2023–January 2024) analyzed 37 oocytes from 10 donors. Immature oocytes discarded 4 hours post-retrieval were cultured for 24 hours to promote maturation. Oocytes were exposed to equilibration solution of the vitrification protocol (1/2 concentration for 3 min, then 2/3 for 3 min). Video recordings captured osmotic responses using an inverted microscope and micromanipulator. A holding pipette stabilized each oocyte, while a covering pipette facilitated media transitions for precise exposure. Participants/materials, setting, methods A custom software pipeline analyzed videos to extract area change, circularity, and roundness. Oocyte dehydration and deplasmolysis velocities were quantified, along with circularity and roundness differentials. Descriptive statistics assessed data distribution, Pearson correlations identified variable relationships, and stepwise regression determined key osmotic response predictors. The dataset was structured for machine learning applications, allowing AI-driven models to refine oocyte selection criteria and optimize cryopreservation strategies in assisted reproduction. Main results and the role of chance The analysis of osmotic and morphological parameters extracted from video recordings revealed significant variability in oocyte responses during vitrification. Descriptive statistics showed that the minimum area averaged 0.797±0.041%, while the difference in area was 20.26±4.12%, indicating substantial volume reduction during dehydration. The minimum circularity was 0.847±0.033, suggesting shape alterations under osmotic stress. Correlational analyses identified key relationships between parameters. Dehydration velocity during phase 1 showed strong positive correlations with phase 2 dehydration velocity (r = 0.79, p &","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"644 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144513105","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}
引用次数: 0
P-284 DLGAP5 mutations cause female infertility and oocyte maturation defects with abnormal meiotic process via regulating PI3K-AKT pathway P-284 DLGAP5突变通过调控PI3K-AKT通路导致女性不育和卵母细胞成熟缺陷,减数分裂过程异常
IF 6.1 1区 医学
Human reproduction Pub Date : 2025-06-28 DOI: 10.1093/humrep/deaf097.592
M Wang, L Zhu, L Jin
{"title":"P-284 DLGAP5 mutations cause female infertility and oocyte maturation defects with abnormal meiotic process via regulating PI3K-AKT pathway","authors":"M Wang, L Zhu, L Jin","doi":"10.1093/humrep/deaf097.592","DOIUrl":"https://doi.org/10.1093/humrep/deaf097.592","url":null,"abstract":"Study question Are discs large-associated protein 5 (DLGAP5) variants associated with human oocyte maturation abnormality and female infertility? Summary answer Mutations in DLGAP5 cause human female infertility by inducing oocyte maturation defects via regulating PI3K-AKT pathway. What is known already Various forms of oocyte maturation defects have been reported, and an increasing number of pathogenic genes have been identified. At present, the known genetic causes of abnormal oocyte development can only account for a minority of female infertility, and the candidate genes responsible for oocyte maturation defects remain largely under investigation. This study aimed to identify novel genetic causes responsible for human oocyte maturation abnormality and female infertility. Study design, size, duration Whole-exome sequencing (WES) analyses were performed on infertile patients with abnormal oocyte development to identify novel genetic causes. Participants/materials, setting, methods We performed WES on infertile female patients and analyzed the possible impact of the variants of candidate genes on protein expression. And knockout mouse was established to investigate the role of candidate genes in mouse oocyte development. Main results and the role of chance Three infertile female patients from two families with oocyte maturation lag were identified to carry a homozygous nonsense mutation c.1101C>G, p.Tyr367* in DLGAP5, which is first reported as candidate pathological gene for human infertility. This mutation caused severe impairment in the DLGAP5 expression in the affected oocytes, leading to abnormal embryo development. Further cell experiments elucidated that DLGAP5 participates in cell division, and its depletion or mutation can induce G2/M arrest. The depletion of DLGAP5 in human oocytes by microinjection of siRNAs resulted in abnormal spindles and reduced germinal vesicle breakdown and polar body 1 extrusion rate. In addition, a similar phenotype of abnormal oocyte development was observed in Dlgap5-deficient mouse oocytes, which could be rescued by DLGAP5 cRNA microinjection. Furthermore, Dlgap5 knockout altered expression of genes involving in meiosis process and deactivated PI3K-AKT signaling pathway in oocytes. And PI3K-AKT activators facilitated the oocyte maturation resumption in Dlgap5-deficient mice. Limitations, reasons for caution The mutation in DLGAP5 was identified in only three patients from two families. The sample size was too limited, and more comprehensive gene screening is needed to confirm our results. Further screening and exploration are required to comprehend the penetrance of the candidate pathogenicity-related genes comprehensively. Wider implications of the findings Our study expands the current spectrum of pathogenic genes responsible for abnormal oocyte maturation and provides crucial insights into clinical consultation, genetic diagnosis, and treatment strategies among infertile patients. Trial registrati","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":"144513109","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}
引用次数: 0
P-411 Ceratonia siliqua extract protects the ovarian reserve in a breast cancer mouse model treated with high-dose Cyclophosphamide 高剂量环磷酰胺治疗的乳腺癌小鼠模型中,P-411白藜芦醇提取物可保护卵巢储备
IF 6.1 1区 医学
Human reproduction Pub Date : 2025-06-28 DOI: 10.1093/humrep/deaf097.717
F Z Kiani, N Panahi, P Eftekhari-Yazdi, P Afsharian
{"title":"P-411 Ceratonia siliqua extract protects the ovarian reserve in a breast cancer mouse model treated with high-dose Cyclophosphamide","authors":"F Z Kiani, N Panahi, P Eftekhari-Yazdi, P Afsharian","doi":"10.1093/humrep/deaf097.717","DOIUrl":"https://doi.org/10.1093/humrep/deaf097.717","url":null,"abstract":"Study question Can Ceratonia siliqua extract (CSE) mitigate cyclophosphamide (CPA)-induced ovarian damage in a breast cancer mouse model undergoing chemotherapy, without compromising the efficacy of tumor treatment? Summary answer Yes, Ceratonia siliqua extract, a potent antioxidant, protected the ovarian reserve by modulating Bax/Bcl-2-mediated apoptosis, while enhancing the anti-tumor effects of cyclophosphamide without adverse effects. What is known already Breast cancer is the most common cancer in women worldwide. Cytotoxic chemotherapy can lead to premature ovarian insufficiency and reduced ovarian reserve in survivors. While ART-based approaches effectively restore fertility, they fall short in long-term ovarian function maintenance. Infertility-related side effects can significantly impact survivors' quality of life. Antioxidant systems and redox homeostasis may rescue impaired AMH production in damaged ovarian follicles, maintaining reserves and preventing exhaustion. Ceratonia siliqua extract, a potent antioxidant, selectively protects normal cells from alkylating agent-induced damage, while exerting pro-apoptotic effects on cancer cells. Its success in preserving male fertility suggests potential for female fertility preservation. Study design, size, duration A controlled experimental study was conducted over five weeks using 6-week-old female BALB/c mice (n = 20). Mice were divided into 4 groups: Control, CSE-only, CPA-only, and CSE+CPA (n = 5 per group). An orthotopic 4T1 murine breast cancer model was established (tumor diameter = <5 mm). CSE (800 mg/kg) was administered orally for seven days before CPA chemotherapy and continued for 14 days after the final CPA dose. CPA (150 mg/kg) was given in two doses, eight hours apart. Participants/materials, setting, methods Mice were sacrificed at two time points: day 14 and day 21 post-CPA administration. On day 14, two mice were sacrificed for sample collection: blood serum for AMH measurement (ELISA), ovaries for histology and Bax/Bcl-2 qRT-PCR. Remaining mice underwent ovarian stimulation for IVF and sample collection on day 21. Blood serum and ovarian tissues were collected. Right ovarian tissue was used for histological follicle count, and left ovaries for qRT-PCR quantification of Bax/Bcl-2 expression levels. Main results and the role of chance CPA treatment significantly reduced ovarian reserve, as evidenced by a lower primordial follicle count (P < 0.05) and an increased number of growing follicles (P < 0.05), indicating enhanced follicular activation. Serum AMH levels were significantly higher in the CSE+CPA group compared to CPA-only (P < 0.05), suggesting a protective effect on granulosa cells. The number of MII oocytes in CSE+CPA mice was 2.6 times higher than in the CPA-only group (P < 0.01), with improved fertilization and blastocyst development rates (P < 0.05).Gene expression analysis showed increased Bax and decreased Bcl-2 expressi","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"46 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144513126","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}
引用次数: 0
P-202 Comparative analysis of one-step ultrafast versus multi-step conventional warming protocols: a retrospective study of 2,548 single frozen embryo transfers 一步超快与多步常规升温方案的比较分析:2548例单冷冻胚胎移植的回顾性研究
IF 6.1 1区 医学
Human reproduction Pub Date : 2025-06-28 DOI: 10.1093/humrep/deaf097.511
M Regincos, M J Zamora, N Correa, A Quintana-Vehí, A Pujol, D Mataro, A Rodríguez-Aranda, I Miguel-Escalada, M Popovic
{"title":"P-202 Comparative analysis of one-step ultrafast versus multi-step conventional warming protocols: a retrospective study of 2,548 single frozen embryo transfers","authors":"M Regincos, M J Zamora, N Correa, A Quintana-Vehí, A Pujol, D Mataro, A Rodríguez-Aranda, I Miguel-Escalada, M Popovic","doi":"10.1093/humrep/deaf097.511","DOIUrl":"https://doi.org/10.1093/humrep/deaf097.511","url":null,"abstract":"Study question Does the one-step ultrafast warming protocol impact blastocyst survival, quality, and clinical pregnancy outcomes compared to conventional warming in single frozen embryo transfer (FET) cycles? Summary answer One-step ultrafast warming demonstrated comparable blastocyst quality, blastocyst survival rates, and clinical pregnancy outcomes to multi-step conventional warming. What is known already Conventional blastocyst warming protocols are effective but require multiple steps. This prolonged process increases the risk of procedural variability and may potentially impact clinical outcomes. Recently proposed one-step ultrafast warming protocols simplify the process, reducing handling time and minimizing stress on embryos during warming. Recent studies have demonstrated comparable blastocyst survival and developmental outcomes with ultrafast warming, however comprehensive data on clinical outcomes remains limited. Study design, size, duration This retrospective cohort study evaluated 2,677 single FET cycles performed in a single IVF center between January 2023 and November 2024. Blastocysts were warmed using Kitazato® media, applying either ultrafast (n = 796) or conventional multi-step (n = 1,881) protocols. Both groups followed identical laboratory and clinical procedures, with the choice of warming method determined by the time period. We analyzed biochemical and clinical pregnancy rates following 2,548 single blastocyst transfers (ultrafast: n = 719; conventional: n = 1,829). Participants/materials, setting, methods Blastocysts were warmed using either the conventional (1-min thawing solution, TS; 3-mins dilution solution, DS; 5-mins washing solution, WS; transfer to culture media) or ultrafast warming protocol (1-min TS, hold in WS; transfer to culture media). Blastocyst survival rates and clinical outcomes were compared using univariate analyses (Mann-Whitney U test and Pearson’s Chi-squared test) and logistic regression models, adjusting for key clinical variables. P-values <0.05 were considered significant. Main results and the role of chance Mean maternal age (±SD) was similar between groups (ultrafast: 40.5 (±5.1) years; conventional: 40.7 (±5.2) years). Post-warming survival rates were comparable in both univariate (98.6% ultrafast, n = 785/796 vs. 97.7% conventional, n = 1838/1881, p = 0.171) and adjusted analyses (OR = 1.66, [95%CI: 0.85-3.24], p = 0.138). The proportion of top-quality (Gardner grades AA, AB, BA, or BB) blastocysts were also similar (p = 0.701) between the ultrafast (57.0%, n = 454/796) and conventional group (56.1%, n = 1056/1881). Biochemical pregnancy rates were higher in the ultrafast group in both univariate (ultrafast: 50.0% vs. conventional: 45.4%, p = 0.032) and adjusted analyses (OR = 1.22, [95%CI: 1.02-1.45], p = 0.026). Nevertheless, this did not translate to improved clinical pregnancy rates, which remained similar between the ultrafast (39.9%) and conventional (37.7%) groups in both uni","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"46 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144513133","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}
引用次数: 0
P-557 Origin of segmental aneuploidy in preimplantation development: Studying >100 IVF embryos reveal novel mechanisms akin to cancer cells with a possible intrachromosomal effect P-557着床前发育中节段性非整倍体的起源:研究bbbb100试管婴儿胚胎揭示了类似于癌细胞的可能的染色体内效应的新机制
IF 6.1 1区 医学
Human reproduction Pub Date : 2025-06-28 DOI: 10.1093/humrep/deaf097.863
B Al Hashimi, N Macklon, S SenGupta, T Gordon, E Linara-Demakakou, B Raikundalia, K Ahuja, D Griffin
{"title":"P-557 Origin of segmental aneuploidy in preimplantation development: Studying >100 IVF embryos reveal novel mechanisms akin to cancer cells with a possible intrachromosomal effect","authors":"B Al Hashimi, N Macklon, S SenGupta, T Gordon, E Linara-Demakakou, B Raikundalia, K Ahuja, D Griffin","doi":"10.1093/humrep/deaf097.863","DOIUrl":"https://doi.org/10.1093/humrep/deaf097.863","url":null,"abstract":"Study question What are the mechanisms underlying segmental aneuploidy (SA) in preimplantation human embryos, and to what extent is there concordance between germ cell layers? Summary answer Segmental aneuploidy (SA) in IVF embryos predominantly arises from paternal meiotic errors, exhibiting deletion-duplications, inversions, and chromothripsis-like mechanisms, with rare SA concordance observed What is known already Segmental aneuploidy (SA) involves the gain or loss of chromosomal segments rather than entire chromosomes, leading to significant embryonic consequences such as implantation failure, spontaneous abortion, and congenital abnormalities. Identified in about 7% of aneuploid biopsies during preimplantation genetic testing for aneuploidy (PGT-A) and preimplantation genetic testing for structural rearrangements (PGT-SR), SA arises from chromosomal breakage and recombination during meiosis or early cleavage. These structural abnormalities disrupt gene dosage, potentially resulting in non-disjunction events or abnormal recombination, which affect normal embryonic development. Understanding SA mechanisms is crucial for improving outcomes in both natural conception and assisted reproductive technologies (ART). Study design, size, duration This single-centre retrospective study examined 101 blastocysts identified as aneuploid with segmental aneuploidy (SA) via a validated NGS-based PGT-A protocol. The protocol enables precise identification of the parental origin of SA (paternal or maternal) by integrating genotyping data with chromosomal copy number variation analysis. This method enhances understanding of SA mechanisms and their implications, contributing valuable insights into embryonic development and improving assisted reproductive technology (ART) outcomes. Participants/materials, setting, methods The participants in this study were couples undergoing IVF cycles with PGT-A from 2020–2024. Ethical approval was secured from IRAS (#294909) and HFEA licence (#R0208). Segmental aneuploidy (SA) was identified in embryos post-PGT-A. Participants provided cheek swabs for parental DNA analysis, and embryo biopsies included samples from the inner cell mass (ICM) and two trophectoderm (TE) biopsies. This approach enabled comprehensive analysis of SA origin and patterns in the context of preimplantation development. Main results and the role of chance In our analysis of a cohort exceeding 100 cases of segmental aneuploidy (SA), we examined both two trophectoderm (TE) biopsies and the inner cell mass (ICM) from each embryo. We frequently observed complex SA aneuploidies characterized by combinations of deletions, duplications, inversions, isochromosomes, and ring chromosomes, often localized to a single chromosome, with a notable prevalence of paternal errors. Interestingly, while mosaicism typically suggests post-zygotic origins, evidence from our data indicates meiotic origins for some cases, supporting the concept of “SA rescue,” where specific chr","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"45 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144503447","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}
引用次数: 0
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