Georges Raad, Youmna Mourad, Gaelle El Asmar, Zalihe Yarkiner, Fadi Fakih, Ghina Ghazeeri, Chadi Fakih
{"title":"Cumulus cell DNA fragmentation in relation to oocyte yield and blastocyst quality.","authors":"Georges Raad, Youmna Mourad, Gaelle El Asmar, Zalihe Yarkiner, Fadi Fakih, Ghina Ghazeeri, Chadi Fakih","doi":"10.1530/RAF-26-0103","DOIUrl":"10.1530/RAF-26-0103","url":null,"abstract":"<p><strong>Abstract: </strong>The objective of this study was to evaluate whether cumulus cell (CC) DNA fragmentation is associated with oocyte yield and the probability of obtaining at least one good-quality day-5 blastocyst in intracytoplasmic sperm injection (ICSI) cycles. A prospective cohort study was conducted in 112 infertile couples undergoing ICSI between March 2024 and November 2025. CC DNA fragmentation was assessed using a chromatin dispersion assay and expressed as the percentage of fragmented cells. The primary outcome was the probability of obtaining at least one good-quality day-5 blastocyst (≥3BB). Higher CC DNA fragmentation was negatively correlated with the numbers of collected cumulus-oocyte complexes (COCs) and metaphase II oocytes (all P < 0.05). In adjusted negative binomial regression models, higher DNA fragmentation remained independently associated with fewer collected COCs (incidence rate ratio (IRR): 0.97, 95% confidence interval (CI): 0.96-0.98; P < 0.001) and fewer metaphase II oocytes (IRR: 0.97, 95% CI: 0.96-0.99; P = 0.001). However, no evidence of an association between CC DNA fragmentation and the probability of obtaining at least one good-quality blastocyst was observed after adjustment for female age, BMI and total motile sperm count. These findings suggest that higher CC DNA fragmentation is associated with reduced oocyte yield, whereas its association with blastocyst quality remains uncertain.</p><p><strong>Lay summary: </strong>Eggs develop inside the ovary surrounded by supporting cells called cumulus cells. These cells help nourish the egg and may provide information about its quality. In this study, we investigated whether damage to the DNA of cumulus cells was associated with the outcomes of fertility treatment. We studied 112 couples undergoing intracytoplasmic sperm injection (ICSI) and measured the amount of DNA damage in cumulus cells collected during treatment. We found that higher levels of DNA damage were associated with fewer eggs being obtained. However, DNA damage in cumulus cells was not associated with the chance of obtaining a high-quality blastocyst. These findings suggest that cumulus cell DNA damage may not reflect embryo quality but could provide insight into egg development.</p>","PeriodicalId":101312,"journal":{"name":"Reproduction & fertility","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13650552/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148922407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Biological and clinical factors predicting sperm retrieval success in men with non-obstructive azoospermia.","authors":"Saffet Ozturk","doi":"10.1530/RAF-26-0020","DOIUrl":"10.1530/RAF-26-0020","url":null,"abstract":"<p><strong>Abstract: </strong>Non-obstructive azoospermia (NOA) represents the most severe form of male infertility, characterized by impaired spermatogenesis and consequent failure to produce sufficient sperm. Accordingly, the identification of reliable predictors of testicular sperm presence has become a central focus of contemporary research. In parallel, considerable effort has been directed toward the development of strategies to generate sperm cells. Accumulating evidence indicates that histopathological findings, physical examination parameters, and patient demographics may contribute to the prediction of sperm retrieval outcomes. In addition, circulating reproductive hormone levels, including testosterone, as well as proteomic and transcriptomic profiles derived from semen and testicular tissues, have demonstrated potential utility in predicting success during testicular sperm retrieval. Emerging approaches aimed at sperm generation - such as the application of spermatogonial stem cells, induced pluripotent stem cells, and pharmacological interventions including aromatase inhibitors, estrogen modulators, and hormonal therapies - have also been increasingly investigated. Collectively, these advances suggest that both the prediction of sperm retrieval and the development of sperm production strategies in NOA are evolving rapidly, with promising implications for future clinical practice.</p><p><strong>Lay summary: </strong>Non-obstructive azoospermia (NOA) is a severe form of male infertility in which the testes produce little to no sperm. Determining whether sperm can be retrieved from the testes and whether sperm production can be restored are, therefore, critical clinical challenges. Recent evidence indicates that testicular histopathology, physical examination findings, patient characteristics, and circulating hormone levels, together with advanced molecular analyses, can aid in predicting the likelihood of successful sperm retrieval. In parallel, emerging approaches, including stem cell-based strategies and hormonal therapies, are being investigated to promote sperm production. Overall, advances in both prediction and therapeutic development suggest that achieving sperm retrieval or generation in men with NOA may be more feasible than previously anticipated.</p>","PeriodicalId":101312,"journal":{"name":"Reproduction & fertility","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13641138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148979046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Rapamycin co-exposure fails to reduce cisplatin-induced damage in GC6-spg spermatogonial cell line.","authors":"Wafiya Jibrin, Rod T Mitchell, Federica Lopes","doi":"10.1530/RAF-26-0044","DOIUrl":"10.1530/RAF-26-0044","url":null,"abstract":"<p><strong>Lay summary: </strong>In the UK, every day about five children receive a diagnosis of cancer. Although the majority (over 80%) will survive, some will become infertile depending on the severity of the treatment received during childhood. Currently, there are no medical treatments available to protect male fertility. This study assessed if rapamycin, a drug currently used to treat other medical conditions, which has been shown in experimental studies to help protect female fertility from cancer treatment, could be used to protect male fertility. Results showed that rapamycin did not prevent overall loss and damage of the cells that will develop into sperm. Further studies are needed to find medical strategies to preserve young boys' fertility.</p>","PeriodicalId":101312,"journal":{"name":"Reproduction & fertility","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13427972/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148458183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
N Kuscu, H Long, K Delray, S Lane, J Davies, C Becker, S A Williams
{"title":"Patient-specific in vitro follicle development in response to ovarian freezing and culture.","authors":"N Kuscu, H Long, K Delray, S Lane, J Davies, C Becker, S A Williams","doi":"10.1530/RAF-25-0196","DOIUrl":"10.1530/RAF-25-0196","url":null,"abstract":"<p><strong>Abstract: </strong>Ovarian tissue cryopreservation is currently the only fertility preservation option for young girls, yet little is known about follicle health and development after freezing in previously treated young cancer patients. This study investigated the effect of cryopreservation on follicle health and developmental potential in ovarian tissue from paediatric and adolescent cancer patients by comparing fresh and cryopreserved tissue from six girls aged 10-16 years, five of whom had received prior cancer treatment. Tissues were cultured in vitro for 2 or 8 days, and follicle morphology, health, developmental stage, and density were assessed by histological analysis. Data were analysed using advanced statistical models, including generalized linear mixed models, to account for patient variability. Fresh ovarian tissue contained approximately 15% healthy follicles by Day 8 of culture, whereas cryopreserved tissue showed complete follicular depletion, with 0% healthy follicles remaining. These findings demonstrate the detrimental effects of both the freeze-thaw process and extended in vitro culture on follicle health and development in paediatric and adolescent ovarian tissue. Statistical analyses confirmed the significant impact of cryopreservation, as cryopreserved tissue failed to maintain any healthy follicles beyond 1 week in culture, and substantial inter-patient variability was observed (P < 0.05), highlighting the influence of individual patient factors. Overall, these findings help resolve discrepancies in the literature regarding follicle survival after ovarian tissue cryopreservation in young cancer patients and underscore the importance of personalized fertility preservation strategies, given the significant inter-patient variability observed. The insights gained offer potential avenues for refining cryopreservation and culture protocols.</p><p><strong>Lay summary: </strong>Young girls undergoing cancer treatment often rely on ovarian tissue freezing as their only fertility preservation option, yet it remains unclear how well this approach maintains follicle health. Follicles are functional units of the ovary that contain immature eggs and are fundamental to future fertility. In this study, we compared fresh and frozen ovarian tissue from girls aged 10-16 years, most of whom had received chemotherapy, and examined follicle health and developmental potential during in vitro culture. Fresh tissue retained a small proportion of healthy follicles after eight days, whereas frozen tissue showed a complete loss of healthy follicles, with considerable differences observed between patients. These findings show that the freeze-thaw process and subsequent culture have a severe impact on follicle health in paediatric and adolescent ovarian tissue. Our work highlights the importance of improving and tailoring fertility preservation methods for young cancer patients and provides important evidence that current approaches to ovari","PeriodicalId":101312,"journal":{"name":"Reproduction & fertility","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13393308/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148451293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Vincent Jaehyun Shim, Kwang Sung Ahn, Soon Young Heo, Man Ryul Lee, Na Ahn, Sangho Roh
{"title":"Explainable AI consensus for grading human blastocysts and blastoids.","authors":"Vincent Jaehyun Shim, Kwang Sung Ahn, Soon Young Heo, Man Ryul Lee, Na Ahn, Sangho Roh","doi":"10.1530/RAF-26-0050","DOIUrl":"10.1530/RAF-26-0050","url":null,"abstract":"<p><strong>Graphical abstract: </strong></p><p><strong>Abstract: </strong>The morphological evaluation of human blastocysts is a critical yet subjective step in clinical assisted reproductive technology (ART), often limited by inter-observer variability. To establish a standardized and objective grading system for both clinical blastocysts and stem cell-derived blastoids, we developed an explainable artificial intelligence-driven multi-model consensus framework. Our methodology utilized a large-scale dataset of 14,846 bright-field images (14,640 blastocysts and 206 blastoids), with the Gardner grading system (Grades 1-5) established as the ground truth by experienced embryologists. High-quality embryos were defined as those reaching expansion Grades 4 or 5 with robust inner cell mass (ICM) and trophectoderm scores. To prevent data leakage and ensure generalizability, the dataset was strictly partitioned into training and testing sets at the individual embryo/blastoid level rather than the image level. The framework integrates an ensemble of four fine-tuned convolutional neural networks (ResNet18, VGG16-BN, ResNet50, and EfficientNet-B0) for visual assessment, complemented by visual explainability via Grad-CAM and cognitive reasoning via the Gemini 2.5 Flash large language model (LLM). Quantitative evaluation revealed that the LLM meta-model achieved a weighted F1-score of 0.99, demonstrating functional equivalence to the statistical upper bound established by an XGBoost meta-model (F1-score: 1.00). Grad-CAM analysis confirmed that the models' decisions were biologically grounded, with high-quality predictions consistently correlating with high focus scores on the ICM. Furthermore, t-SNE visualization provided objective evidence of morphological similarity between clinical blastocysts and H9-derived blastoids. This hybrid framework establishes a new benchmark for objective, interpretable embryo grading and validates blastoids as a robust model system.</p><p><strong>Lay summary: </strong>In fertility clinics, selecting the best embryo for in vitro fertilization relies on visual inspection by experts, which can be subjective and inconsistent. In this study, 'clinical blastocysts' refers to early human embryos generated during ART procedures and imaged at the blastocyst stage before clinical decision-making. Scientists also use 'stem cell-derived blastoids', which are blastocyst-like structures generated from human stem cells in the laboratory. They are not embryos, but research models that reproduce selected structural features of early blastocysts and can help researchers study early human development under controlled laboratory conditions. To improve the evaluation of both clinical blastocysts and stem cell-derived blastoids, we developed an artificial intelligence system that acts like a panel of experts. First, the computer visually inspects thousands of images. Then, an advanced language model reviews these visual clues to agree on a final grad","PeriodicalId":101312,"journal":{"name":"Reproduction & fertility","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13482801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148458192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The effects of hormone changes over the menstrual cycle on elite athlete performance: meta-analysis and suggested standardised protocol.","authors":"Isla I Britton, W Colin Duncan","doi":"10.1530/RAF-25-0131","DOIUrl":"10.1530/RAF-25-0131","url":null,"abstract":"<p><strong>Abstract: </strong>Fluctuations in endogenous sex hormones across the menstrual cycle (MC) have been hypothesised to have physiological changes that could influence athletic performance. Due to the marginal nature of elite sport, even subtle physiological changes can meaningfully influence performance outcomes in elite female athletes. This systematic review and meta-analysis evaluated the effects of the menstrual cycle phase (MCP) on maximal oxygen uptake (VO2 max) in elite female athletes. Bibliographic databases were searched for studies that confirmed the MCP through serum or plasma hormone analysis and that involved elite or well-trained athletes. Meta-analyses compared VO2 max between early follicular (EF) and mid-luteal (ML) phases. Across five studies, no statistically significant differences were found in VO2 max between phases, although small, non-significant decreases in performance were observed in the EF phase. Despite null results, biological plausibility and athlete-reported experiences suggest that minor or individual-specific effects of MCP on performance may exist. Future research should use standardised protocols, larger cohorts and individualised sport-specific outcomes to better understand how MC dynamics influence an elite female athlete's performance. A suggested standardised protocol for conducting future research in this area was developed.</p><p><strong>Lay summary: </strong>Elite female athletes train and compete at the highest levels of sport, where even small changes in performance can make a difference between winning and losing. One possible under-researched influence on performance is the menstrual cycle (MC). During this monthly cycle, there are natural changes in hormone levels. We looked at all the published research to explore whether different MC stages affect sports performance in elite female athletes. No substantial evidence was found that endurance changes significantly across the cycle. However, a slight trend showed that performance might be negatively impacted during menstruation, when hormone levels are low. While these results suggest that the MC might not have a major impact overall, small changes could still matter in elite sport. More research with larger groups and better testing methods is needed to fully understand how the MC might affect an individual athlete's performance.</p>","PeriodicalId":101312,"journal":{"name":"Reproduction & fertility","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13427974/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148458150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Minte Ter Haar, Maral Shafei, Cecilia Arvidson, Anisa Assifi, Karin Emtell Iwarsson
{"title":"'For my own safety and peace of mind': views on contraception among young emergency contraception users: a qualitative study in Swedish pharmacies.","authors":"Minte Ter Haar, Maral Shafei, Cecilia Arvidson, Anisa Assifi, Karin Emtell Iwarsson","doi":"10.1530/RAF-26-0085","DOIUrl":"10.1530/RAF-26-0085","url":null,"abstract":"<p><strong>Introduction: </strong>Despite well-established contraceptive care services in Sweden, there remains an unmet need for contraception. Emergency contraceptive pills are provided over the counter in pharmacies without subsequent contraceptive counselling. Use is widespread, yet research on Swedish emergency contraceptive users is limited. Understanding their experiences is important for tailoring contraceptive care to their needs.</p><p><strong>Objective: </strong>To explore young emergency contraceptive pill users' experiences and perceptions on contraceptive decision-making and contraceptive use.</p><p><strong>Materials and methods: </strong>We performed a qualitative content analysis with an inductive approach on semi-structured interviews in 10 participants between 17 and 26 years old, who purchased emergency contraceptive pills in community pharmacies in Stockholm, Sweden.</p><p><strong>Results: </strong>The theme 'Navigating reproductive autonomy through perceptions, information and norms' was identified, supported by three categories: i) Emergency contraception at pharmacies facilitates reproductive autonomy, where participants shared their appreciation of easy access, ii) Internal perceptions and external information sources affect contraceptive use, considering factors such as one's personal situation and social media, and iii) Perceived social norms and their role in contraceptive experiences, where influences from social context and perceived stigma were mentioned.</p><p><strong>Conclusion: </strong>To support informed decision-making and reproductive autonomy, providers need to ensure easy access to contraception, while sustaining non-judgemental environments and actively countering myths and misconceptions with accurate, evidence-based information both offline and online.</p><p><strong>Lay summary: </strong>This is a qualitative study of 10 interviews with participants aged 17-26 years, who purchased emergency contraceptive pills in community pharmacies in Stockholm, Sweden. We explored experiences and perceptions of these young women on contraceptive decision-making and contraceptive use. Our findings show that community pharmacies play a role in facilitating reproductive autonomy and providing emergency contraceptive pills with minimal barriers to access. Contraceptive decision-making is shaped by internal perceptions, external information sources and different perspectives through friends, family and societal norms. Young women's views on contraception emphasise the wish for a personal approach suitable to their bodies and situational needs. They are navigating new information channels, in which social media plays a prominent role. Healthcare providers can play a role in creating a safe, supportive and non-judgemental environment, offline and online.</p>","PeriodicalId":101312,"journal":{"name":"Reproduction & fertility","volume":"7 3","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13548106/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148883114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhongxin Wang, Xuan Su, Ruonan Li, Yifei Wang, Nurul Akmal Jamaludin, Hana Chen
{"title":"Prevalence of sexual dysfunction and its association with fertility quality of life among infertile men in Henan, China.","authors":"Zhongxin Wang, Xuan Su, Ruonan Li, Yifei Wang, Nurul Akmal Jamaludin, Hana Chen","doi":"10.1530/RAF-25-0195","DOIUrl":"10.1530/RAF-25-0195","url":null,"abstract":"<p><strong>Abstract: </strong>Infertility is a global public health issue, with male factors contributing to about 50% of cases. Yet, studies on fertility quality of life (FertiQoL), sexual dysfunction (SD), and their interconnection remain understudied in China, especially in Henan Province. This study aimed to assess the prevalence of SD, measure FertiQoL, and examine their association among infertile men in Henan. A cross-sectional study was conducted among infertile men aged 18-54 years, recruited via quota and purposive sampling. Validated instruments such as the FertiQoL and the Arizona Sexual Experience Scale (ASEX) were used. Data were analyzed using chi-square tests and multivariable regression analysis. A total of 319 participants completed the survey. Overall, 69.9% had poor FertiQoL, and 24.8% experienced severe SD. The mean overall FertiQoL score was 33.5 ± 24.4, with similar mean scores across the emotional (33.8 ± 24.9), social (34.3 ± 26.0), and treatment-related (32.5-33.8) domains. Severe SD was independently associated with poor FertiQoL (AOR = 4.34, 95% CI = 2.37-7.97). Longer infertility duration (>10 years), middle age (35-44 years), and ART failure were also independently associated with poor FertiQoL. SD and poor FertiQoL are prevalent among infertile men in Henan, with all FertiQoL domains markedly affected. This study fills regional data gaps and highlights the need for targeted psychosocial screening and interventions in infertility care. Addressing sexual health and emotional support may improve the overall quality of life and treatment outcomes for infertile men in Henan.</p><p><strong>Lay summary: </strong>This study shows that sexual problems significantly affect the quality of life in infertile men, highlighting the need for comprehensive support beyond medical treatment.</p>","PeriodicalId":101312,"journal":{"name":"Reproduction & fertility","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13326717/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148240880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Assessing concordance of genetic parameters between trophectoderm and inner cell mass in morphologically scored day-5 embryos via NGS.","authors":"Nicole Salameh, Athina Theodosiou, Ludmila Kousoulidou, Ioannis Papaevripidou, Paola Evangelidou, Kyriaki Michailidou, Damianos Michaelides, Chloe Zoppou, Anna Agathangelou, Sozos Fasouliotis, Joanne Traeger-Synodinos, Periklis Makrythanasis, Carolina Sismani","doi":"10.1530/RAF-25-0157","DOIUrl":"10.1530/RAF-25-0157","url":null,"abstract":"<p><strong>Abstract: </strong>Preimplantation genetic testing for aneuploidy (PGT-A) is used for embryo selection, on a 5-10 cell biopsy from the trophectoderm (TE), which later forms the placenta. Whether this biopsy reflects the inner cell mass (ICM), which develops into the fetus, is still a subject of debate. Various parameters were previously evaluated, many of which have been proposed as potential biomarkers based on their observed associations, including the mitochondrial DNA (mtDNA) copy number. Here, we analysed thirty-two donated blastocysts, dissected into TE and ICM, with low-pass whole-genome sequencing. For 14 of these 32 embryos, PGT-A on TE biopsy was previously performed. Ploidy status, mtDNA copy number and the morphology of TE and ICM were evaluated. 81% of blastocysts showed full ploidy concordance, and 19% showed partial concordance between their ICM and TE. Out of the 14 embryos with previous PGT-A results, 86% showed full concordance, and 14% showed partial concordance. Non-euploid blastocysts showed a significantly higher mtDNA copy number in both ICM and TE. Interestingly, among euploid blastocysts, the higher rates of mtDNA were observed in those with the best morphology of the TE alone. These results suggest that TE ploidy correctly reflects ICM, and a TE biopsy is suitable for embryo status prediction. A high mtDNA copy number in TE or ICM alone may also be indicative of aneuploidy, but a euploid embryo with a high mtDNA copy number could be suggestive of a better implantation potential. Our data support the clinical utility of PGT-A, especially when combined with additional biomarkers.</p><p><strong>Lay summary: </strong>Genetic testing before implantation is a technique used after in vitro fertilisation to check whether an embryo has the correct number of chromosomes, by testing a few cells from the outside layer that will form the placenta. One common concern is whether these cells accurately represent the actual cells that will develop into the baby. Here, we compared these two cell groups and observed a high consistency. We also investigated the amount of DNA copies in the cell's energy-producing parts. Embryos with abnormal chromosome number were found to have a higher number of DNA copies than embryos with normal chromosome number. Among embryos in the latter group, those with the healthiest external appearance had the highest number of DNA copies in these energy-producing regions. These findings suggest that genetic testing before implantation is helpful and that choosing the best embryos could be further improved by considering additional biological factors.</p>","PeriodicalId":101312,"journal":{"name":"Reproduction & fertility","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13317831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148240323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fatima Aljassim, Charlotte H Rigby, Josephine A Drury, Rafah Alnafakh, Corie Rushworth, Alison Maclean, Dharani K Hapangama, Christopher J Hill
{"title":"Hydrosalpinx perturbs the tubal and endometrial immune environment.","authors":"Fatima Aljassim, Charlotte H Rigby, Josephine A Drury, Rafah Alnafakh, Corie Rushworth, Alison Maclean, Dharani K Hapangama, Christopher J Hill","doi":"10.1530/RAF-25-0204","DOIUrl":"10.1530/RAF-25-0204","url":null,"abstract":"<p><strong>Abstract: </strong>Hydrosalpinx is a chronic pathological manifestation seen in approximately 30% of tubal disease cases. In addition to contributing to infertility and pelvic pain, hydrosalpinx has been associated with early pregnancy loss and reduced implantation in assisted reproductive technology. Though not fully understood, previous studies have demonstrated altered immunological activity in those with hydrosalpinx, which has been suggested to impact endometrial receptivity. To validate these findings and to explore the pathogenesis of tubal disease, the aim of this study was to identify and quantify the immune cell population in tubes with hydrosalpinx and in the endometrium from the same patients. This observational study included patients in the secretory phase of the menstrual cycle undergoing salpingectomy/salpingo-oophorectomy with/without hysterectomy for benign gynaecological conditions. The number and type of immune cells present in endometrial and fallopian tube tissue sections were investigated using immunostaining for CD45, CD3, CD4, CD8, CD56 and CD68. We show that T cells are more abundant in the endometrium of women with hydrosalpinx and that cytotoxic T cell numbers are lower in diseased tubes. Uterine natural killer cells and macrophages are significantly elevated in both tubal and endometrial tissues in hydrosalpinx, demonstrating a disruption in the normal uterine immune cell microenvironment that may affect endometrial receptivity, with implications for tubal disease-associated subfertility.</p><p><strong>Lay summary: </strong>Hydrosalpinx is a common condition characterised by inflammation, distortion and fluid accumulation in the fallopian tubes. Hydrosalpinx is a leading cause of subfertility; however, the mechanisms that cause this problem are not fully understood. We studied the immune cells present in both the fallopian tubes and uterine lining (endometrium) of women with hydrosalpinx and compared them to samples from women without tubal disease. The samples were collected in the second half of the menstrual cycle, when the uterine lining is prepared for implantation of a fertilised embryo. We quantified the total immune cell numbers and specific immune cell subtypes (these are immune cells with specific roles in the body, such as destroying harmful bacteria or regulating the immune system) in the different tissues and compared them between the hydrosalpinx and control groups. We found that hydrosalpinx is associated with both tubal and endometrial immune cell changes, which may contribute to infertility by affecting the normal physiological processes that allow the endometrium to accept an embryo and establish a pregnancy.</p>","PeriodicalId":101312,"journal":{"name":"Reproduction & fertility","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13317832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148240753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}