Human reproduction最新文献

{"title":"P-235 Impact of repeated vitrification and biopsy on clinical outcomes: a comparative study of once-frozen and thaw-biopsy-refreeze embryos","authors":"L Lai, B Jones, M Y Thum, J Nicopoullos, R Faris, K Glynn, T Bracewell-Milnes","doi":"10.1093/humrep/deaf097.543","DOIUrl":"https://doi.org/10.1093/humrep/deaf097.543","url":null,"abstract":"Study question Does the transfer of thaw-biopsy-refreeze embryos have different clinical outcomes than the transfer of biopsied once-frozen embryos? Summary answer There were no significant differences in clinical outcomes (implantation, clinical pregnancy, live birth rates) between once-frozen and TBR embryos. What is known already Genetic testing of previously unbiopsied frozen embryos through “thaw, biopsy, refreeze” (TBR) has become common as pre-implantation genetic testing for aneuploidy (PGT-A) has become mainstream. However, it remains uncertain whether embryos undergoing multiple vitrification cycles exhibit diminished pregnancy outcomes due to potential damage from repeated freezing and thawing. This study aimed to compare clinical outcomes between once-frozen and TBR (twice-frozen) embryos. Additionally, we investigated whether once-biopsied and twice-biopsied TBR embryos differed in their clinical outcomes. Study design, size, duration This retrospective, single-centre cohort study included 421 embryos from patients undergoing assisted reproductive technology (ART) treatment: 374 once-frozen embryo transfers were performed in 305 patients. 47 TBR embryo transfers in 44 patients, of which 36 were once-biopsied and 11 were twice-biopsied. The primary endpoints were implantation rate (IR), clinical pregnancy rate (CPR), live birth rate (LBR), and miscarriage rate (MR). Embryo transfers involving embryos biopsied between May 2022 and March 2024 were included. Participants/materials, setting, methods Once-frozen embryos were cultured to Day 5 or 6, biopsied, frozen, and later thawed for transfer. Once-biopsied TBR embryos were frozen (without prior biopsy), then thawed, biopsied, refrozen, and thawed again for transfer. Twice-biopsied TBR embryos were biopsied, frozen, thawed, biopsied again, refrozen, and thawed for transfer. Main results and the role of chance There were no significant differences in clinical outcomes between once-frozen and TBR embryos: IR (64% vs 66%), CPR (56% vs 52%), and LBR (50% vs 52%). Among TBR embryos, once-biopsied and twice-biopsied showed no significant differences in IR (67% vs 64%), CPR (57% vs 36%), LBR (57% vs 36%), or MR (5.7% vs 27%). This suggested that a second vitrification cycle and a repeated biopsy did not negatively impact pregnancy outcomes. Limitations, reasons for caution With 47 TBR embryos, this study represents one of the largest investigations of TBR embryos to date. However, 11 twice-biopsied embryos was likely an insufficient sample to detect statistical differences between once- and twice-biopsied TBR embryos. Given the absolute differences in clinical outcomes, large studies and meta-analyses would be valuable. Wider implications of the findings This study has key implications for cases where the initial biopsy yields inconclusive genetic results, occurring in around 2% of PGT-A cases at this centre. As patients with poorer prognoses often have fewer retrieved eggs, TBR embryos could ","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":"144503727","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-004 Multi-center, external validation of a novel artificial intelligence (AI) model that predicts blastocyst PGT-A results from mature oocytes","authors":"N Mercuri, J Fjeldstad, S Corsac, D Nayot, A Krivoi","doi":"10.1093/humrep/deaf097.004","DOIUrl":"https://doi.org/10.1093/humrep/deaf097.004","url":null,"abstract":"Study question Is a model developed to predict euploid blastocyst development from mature oocytes generalizable across varying geographic locations? Summary answer A non-invasive AI model predicts euploid blastocyst development from mature oocytes with an AUC of 0.68 on a large dataset from 5 clinics (4 countries). What is known already MAGENTA is an AI-based model that assesses mature oocyte images and provides a score (0-10) correlated to its likelihood of developing to a blastocyst-stage embryo. An additional model has been recently developed to further predict the likelihood of euploid blastocyst development from the same oocyte images yet also incorporates oocyte age and MAGENTA’s assessments as key features. This Ploidy-AI model provides additional insight reflective of the oocyte’s potential chromosomal complement–enhancing the clinical utility of assessments. With the development of a new AI model, external validation of its performance is necessary to ensure generalizability across different geographies and patient demographics. Study design, size, duration This is a retrospective study that included 13,307 images of mature oocytes obtained from 5 clinics in 4 countries (1603 patients, 1949 cycles) including Argentina (C1; mean age 32.6±7.0, BMI unavailable), Brazil (C2; mean age 38.1±3.6, BMI 38.3), Spain (C3; mean age 38.7±3.8, BMI 20.4 and C4; mean age 38.9±3.4, BMI 21.8), and USA (C5; mean age 37.2±4.1; BMI 27). Images were obtained immediately post-ICSI from Embryoscope or GERI Time-Lapse incubators between the years 2020-2024. Participants/materials, setting, methods 13,307 oocyte images were assessed by MAGENTA and the Ploidy-AI model to predict each oocyte’s likelihood of developing into a euploid blastocyst (0-100%). Oocytes that did not develop into a blastocyst (n = 7385) or those that developed into an aneuploid blastocyst (n = 3534) were labelled the negative outcome, whereas those that developed into euploid blastocysts (n = 2388) were labeled the positive outcome. Untested or mosaic blastocysts were excluded. Main results and the role of chance On 13,307 mature oocytes, the Ploidy-AI model achieved an AUC of 0.68, sensitivity 0.54, and specificity 0.71. Oocytes that failed blastulation or developed into an aneuploid blastocyst had significantly lower median model-predicted euploid probability (n = 10,919, 0.20) than those that developed into an euploid blastocyst (n = 2388, 0.28) by Mann-Whitney U-test (p < 0.001). Additionally, model-predicted euploid probabilities were divided into quartiles (Q) according to the distribution within this dataset—Q1 (n = 3327), Q2 (n = 3327), Q3 (n = 3326), Q4 (n = 3327). A significant, stepwise positive increase in true euploid development rate for oocytes within each quartile of model-predicted probabilities was observed by pairwise-proportions test with Bonferroni correction (all p < 0.001): Q1(6%), Q2(14%), Q3(22%), and Q4(30%). Subgroup analysis by Clinic revealed consis","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":"144503445","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-173 Pro","authors":"M M Dolmans","doi":"10.1093/humrep/deaf097.173","DOIUrl":"https://doi.org/10.1093/humrep/deaf097.173","url":null,"abstract":"Estrogens play a critical role in the pathogenesis of endometriosis, so it is logical to assume that lowering estradiol levels with oral gonadotropin-releasing hormone (GnRH) antagonists would be effective, especially in women who fail to respond to progestogens. Indeed, due to progesterone resistance, oral contraceptives and progestogens are ineffective in one-third of women affected by endometriosis. Oral GnRH antagonists have therefore been evaluated for management of premenopausal women with endometriosis-associated pelvic pain. Oral GnRH antagonists bind to and block the GnRH receptor, resulting in a dose-dependent drop in luteinizing hormone and follicle-stimulating hormone production, which in turn leads to a dose-dependent decline in estrogen. High doses of GnRH antagonists promote full suppression of estradiol secretion to serum levels below 20 pg/ml, but add-back therapy (ABT) may then be needed to manage hypoestrogenic side effects. Lower doses of oral GnRH antagonists maintain estradiol values within the target range of 20-60 pg/ml, which could be ideal to alleviate symptoms linked to endometriosis. There is a place for GnRH antagonists in the management of symptomatic endometriosis, with different molecules available on the market (elagolix, relugolix, linzagolix) at different doses and with or without ABT. Multicenter, prospective, randomized, placebo-controlled, double-blind studies have shown that oral GnRH antagonists significantly reduce dysmenorrhea and non-menstrual pelvic pain (NMPP) by 6 months of therapy. -One of the first papers on this reported 6-month outcomes of high- and low-dose elagolix monotherapy. High-dose elagolix yielded higher dysmenorrhea and NMPP responder rates than low-dose treatment. The twice-daily 200 mg elagolix dose generated clinically meaningful responses in 75–78% of subjects for dysmenorrhea and 67–69% for NMPP. At 150 mg daily, clinically meaningful responses were seen in 52% of women for dysmenorrhea and 67% for NMPP. Patients given the 200 mg elagolix dose showed greater bone mineral density (BMD) loss, namely −3.6% and −3.9% at weeks 36 and 52 respectively. -In the relugolix extension study, sustained improvements in endometriosis-related pain were noted through 104 weeks among patients taking relugolix combination therapy. Responder rates at week 104 were 84.4% for dysmenorrhea and 75.8% for NMPP. After initial least square mean BMD loss of less than 1% at week 24, BMD plateaued by week 36 and was sustained for the entire 104 weeks of treatment. -In a population of 353 women with moderate-to-severe pain linked to endometriosis, once-daily oral 200 mg linzagolix+ABT or 75 mg linzagolix alone provided sustained and clinically meaningful reductions in dysmenorrhea and NMPP for up to 52 weeks, achieving the 2 co-primary endpoints. By the end of treatment at month 12, proportions of subjects with reduced dysmenorrhea, associated with stable or decreased use of analgesics, were 91% in the 200 mg+ABT","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":"144503479","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-169 Is the overnight insemination for cIVF still a gold standard in 2025? Overnight insemination versus short insemination duration (4-6hours) for 14680 oocytes","authors":"B Gonzalez Marti, A C Cordeiro, C Gonzalez Trigo, C Pessah, F Entezami","doi":"10.1093/humrep/deaf097.478","DOIUrl":"https://doi.org/10.1093/humrep/deaf097.478","url":null,"abstract":"Study question Comparison of fertilization rate, embryo features, morphokinetics and pregnancy rate after a conventional overnight insemination (OI) versus a short insemination duration (SID) in cIVF. Summary answer In our cohort, SID improves the accuracy of fertilization assessment, increases the total and top blastulation rates as whereas the pregnancy rate. What is known already Based on the ESHRE guidelines¹, the insemination time (IT) should be decided according to the checking time after 16-18 hours and before pronuclei fading. That’s why, usually the IT takes place in the afternoon of the pick-up and consists of co-incubation of male and female gametes overnight. This timing should theoretically prevent the missing of the premature fading of the pronuclei before fertilization assessment. However, some embryos can display faster events. Incubation of inseminated oocytes in a time-lapse incubator could avoid missed pronuclei observation if the recording begins rapidly after the IT, but this timing doesn’t fit to an OI. Study design, size, duration Prospective observational study in a single private hospital on 1472 patients who underwent cIVF during 2023-2024. According to oocyte retrieval timing, patients were assigned to two groups: 992 patients underwent OI (group A) and 480 patients underwent SID (group B). Fertilization rate, morphokinetics, total blastulation rate, top blastulation rate, clinical pregnancy and miscarriage rates were studied in both groups. Participants/materials, setting, methods Patient’s allocation to study groups was only based on pick-up timing, regardless of indication, female age, or attempt’s rank. After insemination of 14680 oocytes, cumulus-cells were removed and oocytes were transferred into new dishes in the time-lapse at day-1 for the OI (9872 oocytes) and at day-0 for the SID (4808 oocytes). Gardner’s classification was used for blastocyst grading. The statistical analyses were done by chi-square, fisher test and student test using RStudio2023.09.1. Main results and the role of chance No statistical difference was observed for the patients age in group A compared to group B (37.1±4.3 vs 37.4±3.9, p > 0.05). A significant difference was observed in oocyte maturity rate (81.6% vs 77.9%, p < 0.05) and in the observation of 2PN (71.9% vs 66.4%, p < 0.05), 3PN (6.9% vs 11,0%, p < 0.05) and 1PN rates (7.6% vs 4.2%, p < 0.05). However, there was no difference in the global fertilization (2PN+3PN) rate (79.0% vs 77.0%, p > 0.05). There were also significant differences in both fertilization and extended culture failures (6.0% vs 9.0%, p < 0.05 and 15.0% vs 11.0%, p < 0.05). Total blastulation rate was statistically different (66.3% vs 73.2%, p < 0.05) and likewise the top blastulation rate (46.3% vs 50.9%, p < 0.05). The pregnancy rate per transfer and per cycle in the two groups were statistically different (36.0% vs 47.0% and 22.0%; 28.8%, p ","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":"144503532","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-274 Development of peri-implantation embryo culture method using endometrial cells","authors":"M Fujiwara, T Nii, C Meno","doi":"10.1093/humrep/deaf097.582","DOIUrl":"https://doi.org/10.1093/humrep/deaf097.582","url":null,"abstract":"Study question There is no culture method that can analyze embryo-endometrium interactions during peri-implantation embryo development. Summary answer We developed a culture method that can analyze the roles of endometrial cells (ECs) during peri-implantation embryo development in mice. What is known already To better understand the mechanisms of peri-implantation embryo development, several methods of culturing embryo have been developed. Embryo culture methods utilizing hydrogels or extracellular matrix components can analyze embryonic development from blastocyst to egg cylinder stage. However, these methods cannot investigate embryo-endometrium interactions. While embryo culture methods with ECs allow the study of embryo-endometrium interactions, such as attachment and invasion, no embryo culture method with ECs supports embryo development from blastocyst to egg cylinder stage. To evaluate peri-implantation embryo-endometrium interactions, a culture method capable of analyzing peri-implantation embryo development needs to be developed. Study design, size, duration First, the ECs used for co-culturing with embryo were selected. A mouse embryo collected from the uterus was cultured with spheroid derived from mouse ECs (EC spheroid) for 24–72 hours. The embryo’s developmental stage and the expression of the implantation marker Cox2 in ECs were analyzed by immunofluorescence staining. Furthermore, to analyze the effects of ECs on peri-implantation embryo development, we developed an embryo culture method combined with a gene expression regulation system. Participants/materials, setting, methods ECs were isolated from 3.5 dpc uteri or from uteri at each stage of estrous cycle. ECs were cultured and their decidualization potential was assessed by immunofluorescence staining. A 4.5 dpc embryo was co-cultured on an EC spheroid or in the hole of an EC spheroid. For the gene expression regulation system, fluorescent-labelled siRNA and several transfection reagents were used. The transfection efficiency was evaluated by flow cytometry. Main results and the role of chance To select endometrial cells for co-culture, the characteristics of ECs at each stage were compared. 3.5 dpc ECs showed superior spheroid forming capacity and decidualization characterized by nuclear enlargement and prolactin expression. An embryo cultured on 3.5 dpc EC spheroid attached to surface of the spheroid after 24 hours. The attached embryo did not grow after 48 hours. Next, prior to co-culturing, a hole was made in the 3.5 dpc EC spheroid, and an embryo was cultured in the hole. After 72 hours, the embryo was developed into egg cylinder stage in the EC spheroid. The developed embryo had Reichert’s membrane. Furthermore, expression of Cox2 (implantation marker) was observed around the implantation site. In addition, we established a method for transient gene expression regulation in ECs using siRNA and transfection reagent. The transfection efficiency was more than 90% without th","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"66 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144503533","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-034 Gaining insight into the chemical exposome of deep endometriosis using metabolomics","authors":"G Cano-Sancho, A L Royer, T Lefebvre, M Campas, Y Guitton, T Freour, B Le Bizec, P De Tullio, S Ploteau, J P Antignac","doi":"10.1093/humrep/deaf097.034","DOIUrl":"https://doi.org/10.1093/humrep/deaf097.034","url":null,"abstract":"Study question Do environmental chemicals play a role on deep endometriosis through metabolic disruption? Summary answer The present study support that women with deep endometriosis exhibit a specific metabolic profile associated to the internal exposure of persistent organic pollutants. What is known already A growing list of pollutants seems to be able to interact with and metabolic signaling pathways involved in the onset and progression of endometriosis. Up to date, most of research on environmental pollutants have focused on endocrine disrupting mechanisms, whereas their involvement on the metabolic shift observed on endometriosis lesions have not been studied yet. Persistent organic pollutants (POPs) such as organochlorine pesticides (OCPs) or per-/polyfluorinated substances (PFAS), have shown the capacity to alter the normal metabolic function through different mechanisms, including mitochondrial dysfunction or energy homeostatic imbalance. Previous metabolomic studies have failed to identify robust predictive biomarkers of endometriosis. Study design, size, duration We conducted an observational metabolomic-wide case-control study with French women undergoing surgery for endometriosis or In vitro fertilization, with and without surgically confirmed endometriosis (n = 137). A “meet-in-the-middle” systematic review of observational and experimental studies was conducted to identify metabolic pathways overlapping POPs and endometriosis in order to support the biological plausibility. Participants/materials, setting, methods Women’s serum was analyzed using gas and liquid chromatography coupled to high-resolution mass spectrometry (HRMS) to measure the levels of 14 polychlorinated biphenyls (PCB), six OCPs and six PFAS. A comprehensive targeted metabolomic profiling was conducted using HRMS and 1H nuclear magnetic resonance (1H NMR). An ultra-targeted study including inflammatory mediators oxylipins and twenty-six free fatty acids was conducted by liquid and gas chromatography coupled to tandem mass spectrometry, respectively. Main results and the role of chance The PCB180, PCB167 and the pesticide trans-nonachlor were associated with a higher risk of deep endometriosis. Women with endometriosis exhibited a distinctive metabolic profile, with elevated serum levels of lactate, ketone bodies and multiple amino acids and lower levels of bile acids, phosphatidylcholines (PCs), cortisol and hippuric acid. The pesticide c was positively associated with deep endometriosis risk and the alteration of 2-hydroxybutyrate pathway. In turn, negative associations were found between the fluorinated industrial pollutant, perfluoroundecanoic acid (PFUnA) and levels of prostaglandin E2, 15-hydroxyeicosatetraenoic acid (15HETE) and 5-HETE. Levels of 5-HETE and 8,9-epoxyeicosatrienoic acid were found to be at lower levels in women with endometriosis-related infertility. Limitations, reasons for caution This study has a limited sample size, and the cross-sectional","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"70 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144503717","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-364 Ovarian follicular density in women with BRCA1 and BRCA2 mutations: new insights into the negative impact on ovarian reserve","authors":"M Maletta, C Forastiere, R Vicenti, M Doglioli, D Raimondo, R Seracchioli","doi":"10.1093/humrep/deaf097.670","DOIUrl":"https://doi.org/10.1093/humrep/deaf097.670","url":null,"abstract":"Study question Assessing follicular density in ovarian biopsies from women with breast cancer carrying BRCA1 and BRCA2 mutations who underwent ovarian tissue cryopreservation (OTC). Summary answer Follicular density appeared to be lower in women with BRCA1/BRCA2 mutations compared to those without the mutation; however, this difference did not reach statistical significance. What is known already BRCA1 mutation carriers have been reported to experience a 25% reduction in AMH levels, whereas evidence regarding the association between BRCA2 mutations and AMH levels remains inconsistent. Only one study has examined follicular density in ovarian biopsy tissue from women with breast cancer carrying BRCA1 or BRCA2 mutations. In this study, no significant differences were reported in follicular density between BRCA-positive women and BRCA-negative patients undergoing ovarian tissue cryopreservation (OTC) for fertility preservation. Study design, size, duration A single center, observational, cross-sectional study carried out in a tertiary level referral center for fertility preservation treatment. All patients who underwent OTC for breast cancer and met inclusion criteria, from January 1st, 2002 (date of establishment of the biobank) to September 30th, 2024, were included in the study. Out of 216 patients, 21 women reported germline mutation: 9 (4.2%) were carriers of the BRCA1 mutation and 13 (6%) of the BRCA2 mutation. Participants/materials, setting, methods The study was carried out in a tertiary level referral center for fertility preservation treatment. The whole study was reported according to the STrengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement and checklist. Medical reports were searched for extraction of the following patient data: age at OTC, BMI, breast cancer treatments before OTC, antral follicular count on preoperative transvaginal ultrasound, anti-müllerian hormone concentration (ng/ml) prior to surgery, follicular density of ovarian tissue sample. Main results and the role of chance No significant difference in follicular density was observed among women without BRCA mutations, those with BRCA1 mutations, and those with BRCA2 mutations. The median follicular density was 4.0/mm² (range 0-74.5) in BRCA-negative women, 3.5/mm² (range 0-20) in women with BRCA1 mutations, and 4.0/mm² (range 0-32) in women with BRCA2 mutations (p = 0.272 and p = 0.703, respectively). After adjusting for age, no statistically significant differences in follicular density were observed according to BRCA1 and BRCA2 mutation status: the median follicular density was 4.6/mm² in BRCA-negative women, 3.1/mm² in women with BRCA1 mutations, and 3.6/mm² in women with BRCA2 mutations (p = 0.428 and p = 0.385, respectively). Limitations, reasons for caution The first limit was the relatively small sample size due to the low prevalence of women with BRCA1 and BRCA2 mutations. Another limitation of the study was the absence of preoper","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"643 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144503725","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-081 Serum metabolic profiling in endometriosis reveals a strong metabolic signature for peritoneal endometriosis","authors":"R Kollarics, D M Selegato, A Marshall, J Jauckus, T Strowitzki, M Zimmermann, A Germeyer","doi":"10.1093/humrep/deaf097.081","DOIUrl":"https://doi.org/10.1093/humrep/deaf097.081","url":null,"abstract":"Study question What are the metabolome differences between the serum of patients with endometriosis and control subjects? What metabolic traits are characteristic of peritoneal and/or ovarian endometriosis? Summary answer Endometriosis patients have high abundance of riboflavin, tryptophan and purine metabolites in serum. Peritoneal endometriosis has stronger metabolic signature than ovarian endometriosis compared to controls. What is known already Endometriosis patients exhibit different metabolic traits compared to healthy subjects. Several metabolomics studies were conducted on different types of samples (serum, plasma, peritoneal fluid, follicular fluid, eutopic/ectopic endometrial tissue, urine, cervical swabs). However, the sample sizes are limited, and inclusion/exclusion criteria vary. Alterations in amino acid levels, (phospho)lipid metabolites, and purine metabolites are described, though results are controversial depending on sample type and study design. Currently, there is no biomarker for endometriosis and its pathomechanism is still unclear. Study design, size, duration Serum samples were obtained before surgery from 338 dysmenorrheic and/or infertile patients undergoing laparoscopic surgery at a university-affiliated fertility center from February 2019 to October 2024. Patients with hormonal treatment, psychiatric medication, immunosuppressive treatment, hyperthyroidism, autoimmune diseases, hyperprolactinaemia, malignancy, systemic diseases, liver-, kidney diseases, and infection were excluded. Patients were divided into groups based on their laparoscopic diagnosis: peritoneal endometriosis (PE, n = 61), ovarian endometriosis (OE, n = 33), or control group (n = 87). Participants/materials, setting, methods Peritoneal group included ASRM I-II (#Enzian P1-2, O0, T0-2), ovarian group included ASRMI-IV (#Enzian P0-3, O1-2, T0-1) endometriosis stages. Controls had a negative laparoscopic diagnosis for endometriosis. Metabolite profiles were investigated by liquid chromatography (UHPLC-MS) coupled with high-resolution mass spectrometry. Semitargeted and untargeted metabolomics analyses were performed. Semitargeted analysis monitored around 50 metabolites, including vitamins, amino acids, sugar, tryptophan-derivates, and nucleotides. Statistical analyses were conducted to identify metabolic differences between endometriosis patients and controls. Main results and the role of chance Endometriosis groups (PE, OE) have different metabolic profiles compared to symptomatic controls. Interestingly, PE group is well-separated metabolically from both the control and OE groups. OE group shows an intermediate metabolic profile between PE and control groups. Peritoneal endometriosis has a stronger metabolic signature than ovarian endometriosis. Semitargeted analysis revealed significant metabolic alterations in the tryptophan and riboflavin pathways, including kynurenines, indols, and riboflavin intermediates. Limitations, reasons for caution A di","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"1 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144503726","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-083 Endometriosis induces DNA double-strand breaks and triggers apoptosis in oocytes of primordial follicles and its inhibition by melatonin administration","authors":"V Silvana, K Koga, E Maki, A Takeuchi, M Nakajima, M Elsherbini, G Izumi, M Harada, T Hirata, Y Hirota, O W Hiraike, Y Osuga","doi":"10.1093/humrep/deaf097.083","DOIUrl":"https://doi.org/10.1093/humrep/deaf097.083","url":null,"abstract":"Study question What is the involvement of DNA double-strand breaks (DDSBs) signaling pathway in primordial follicle depletion in endometriosis and the role of melatonin in this pathway? Summary answer Endometriosis increases percentages of γH2AX-positive oocytes and triggers apoptosis in primordial follicles, while melatonin prevents ovarian reserve reduction by rescuing oocytes from DDSBs and apoptosis. What is known already Endometriosis causes ovarian reserve reduction; however, its mechanism remains unclear. The percentage of γH2AX-positive primordial follicles is significantly elevated, and the apoptosis of primordial follicles is evident in cyclophosphamide-treated mice. In addition, the percentage of phosphorylated-Ataxia Telangiectasia Mutated (pATM)-positive oocytes and RAD51-positive oocytes is significantly higher in primordial follicles of gamma irradiated mice. Melatonin may prevent ovarian reserve reduction by protecting oocytes from DDSBs during prophase arrest and enhancing DNA repair. There is still insufficient studies on the DDSBs signaling pathway in endometriosis-induced ovarian reserve depletion and the role of melatonin in this pathway. Study design, size, duration Ovarian cortex tissues were obtained from 16 endometriosis patients (E), aged 29-43, who had undergone oophorectomy and 12 age-matched control women (C) without ovarian pathology. Endometriosis model mice (mE; n = 16) and control mice (mC; n = 4) were established from 5 weeks old BALB/c mice on Day 0. Melatonin (30 mg/kg) was administered to mice (n = 13) daily from Day 3 to Day 14. Mice were sacrificed on Day 14 and the ovarian tissues were extracted. Participants/materials, setting, methods Endometriosis model mice were established by intraperitoneal injection of the minced uterus from homologous mice, while control mice were given phosphate buffered saline. Immunohistochemical study using human and mouse ovarian cortex tissue were performed for H2A histone X (γH2AX), pATM, and RAD51 to detect DDSBs pathway and DDSBs repair response. TUNEL assay was performed to detect apoptosis. The positive-stained oocytes of primordial and growing follicles were counted and analyzed using an unpaired student’s T-test. Main results and the role of chance DDSBs consistently occurs in the oocytes of primordial follicles of endometriosis model mice and human ovaries with endometriosis. The percentages of γH2AX-positive oocytes were significantly higher in E (62.9%) than in C (4.7%, p < 0.05) and mE (87.5%) than in mC (25.0%, p < 0.05). pATM as a global regulator in DDSBs repair response and RAD51 as a marker for homologues recombination pathway were analyzed. The percentage of pATM-positive oocytes was significantly lower in E (11.4%) than in C (25.2%, p < 0.05) and mE (18.25%) than in mC (24.75%, p < 0.05). The percentage of RAD51-positive oocytes was significantly higher in mE (87.0%) than in mC (14.5%, p < 0.05). Apoptosis of primordial foll","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"18 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144513091","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-208 Effect of direction of sperm injection (head-first or tail-first) in Piezo-ICSI on single embryo transfer and perinatal outcomes: data from 3,021 transfers and 931 infants","authors":"K Hiraoka, H Nakajo, M Sato, M Osugi, T Sujino, A Komiya, Y Takayanagi, Y Nako, M Tajima, T Ogawa, K Kawai","doi":"10.1093/humrep/deaf097.517","DOIUrl":"https://doi.org/10.1093/humrep/deaf097.517","url":null,"abstract":"Study question Does tail-first injection in human Piezo-ICSI affect single embryo transfer and perinatal outcomes compared with head-first injection? Summary answer Tail-first injection in human Piezo-ICSI does not have an adverse effect on single embryo transfer and perinatal outcomes compared with head-first injection. What is known already ICSI is a crucial technique in human ART. Recently, some researchers have indicated that Piezo-ICSI is clinically more effective than Standard-ICSI. In most studies, Piezo-ICSI has demonstrated significantly higher fertilization rates than Standard-ICSI. Piezo-ICSI removes the need to aspirate cytoplasm into the ICSI needle at membrane breakage. Following membrane breakage, sperm is injected into the cytoplasm. A few studies have assessed the effect of sperm injection direction (head-first or tail-first) on ICSI outcomes for human oocytes. However, there is limited information about the impact of sperm injection direction (head-first or tail-first) in Piezo-ICSI on single embryo transfer and perinatal outcomes. Study design, size, duration This retrospective study included 3,021 single embryo transfer cycles from 1,230 patients treated at two centers between June 2016 and December 2023. Among these, 1,344 single embryo transfer cycles involving 540 patients with head-first injection embryos and 1,677 cycles involving 690 patients with tail-first injection embryos. Nine hundred thirty-one infants were born from 918 deliveries, including 418 infants from 411 deliveries of head-first injection embryos and 513 infants from 507 deliveries of tail-first injection embryos. Participants/materials, setting, methods Single embryo transfer included cleaved embryos and blastocysts. The embryos from head-first and tail-first injections were compared, along with the women’s ages at oocyte pick-up and embryo transfer, pregnancy rates, delivery rates, monozygotic twin rates, sex ratio, infant birth weight, gestational weeks, and birth defect rates following the single embryo transfer. Statistical analysis was performed using either a t-test, Welch’s t-test, or Fisher’s exact test as appropriate. Main results and the role of chance The ratio of single-cleaved embryo transfer cycles of head-first and tail-first injections was 10.9% (146/1344) and 16.5% (276/1677), and the ratio of blastocyst transfer cycles was 89.1% (1198/1344) and 83.5% (1401/1677), respectively. A significant difference was observed between the ratio of single-cleaved embryo transfer and blastocyst transfer cycles between the head-first and tail-first injections. Among the head-first and tail-first injections embryos transfer cycles, there were no significant differences when comparing the average number of the previous oocyte pick up (1.7±0.1 vs. 1.7±0.0), the average number of previous embryo transfer cycles (2.1±0.1 vs. 2.1±0.1), the average age of women at oocyte pick up (36.2±0.1 vs. 36.4±0.1), the average age of women at embryo transfer (36.8±0.1 vs.","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"61 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144513100","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}