Reproduction & fertility最新文献

{"title":"Clinical validity of Midway PGT-A: a comparative study with traditional PGT-A and analysis of fertilization strategies.","authors":"Jiujie Dou, Zhan Hu, Boya Zhao, Senlin Shi","doi":"10.1530/RAF-25-0128","DOIUrl":"10.1530/RAF-25-0128","url":null,"abstract":"<p><strong>Graphical abstract: </strong></p><p><strong>Abstract: </strong>Infertile patients initially undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) with fresh embryo transfer often lack baseline indications for preimplantation genetic testing for aneuploidy (PGT-A); however, after multiple failed transfers, they may become eligible for PGT-A, which can be performed on residual vitrified-thawed embryos (a strategy termed 'Midway PGT-A'), whose clinical value remains unconfirmed. This study aimed to assess the clinical utility of Midway PGT-A and whether fertilization methods (IVF vs ICSI) affect its chromosomal testing results and clinical outcomes. A 2020-2023 retrospective cohort study analyzed 463 PGT-A cycles, comprising 202 Midway PGT-A cycles (132 IVF and 70 ICSI subcycles) and 261 traditional PGT-A cycles, with comparisons made regarding blastocyst aneuploidy profiles and clinical pregnancy outcomes. The results showed that compared with traditional PGT-A, Midway PGT-A was associated with fewer biopsied blastocysts (P < 0.05), a higher rate of numerical chromosomal abnormalities (P < 0.05), and a lower rate of structural chromosomal abnormalities (P < 0.05). In the Midway PGT-A group, IVF and ICSI subcycles had similar euploidy and aneuploidy rates, but the IVF subcycle exhibited a significantly higher clinical pregnancy rate (P < 0.05) and implantation rate (P < 0.05). Multivariable logistic regression confirmed that ICSI was independently associated with a lower clinical pregnancy rate compared with IVF. In summary, Midway PGT-A delivers equivalent outcomes compared with traditional PGT-A. IVF does not alter the chromosomal detection results of Midway PGT-A and may further optimize clinical reproductive performance, validating the clinical value of Midway PGT-A for patients with post-transfer PGT-A eligibility.</p><p><strong>Lay summary: </strong>Many people undergoing fertility treatments do not need embryo genetic testing initially. However, after repeated failed pregnancies, miscarriages, or having a baby with birth defects, they may need this test later. We tested the genetic health of their leftover frozen embryos - a strategy we call 'Midway testing'. Our study of 463 cycles found that Midway testing worked as well as standard testing done earlier. The number of embryos tested was lower for Midway testing, but it found more whole-chromosome issues and fewer chromosome structure issues. Fertilization methods did not change test results, but one method led to higher pregnancy and implantation rates. This testing offers a valuable option for people who need genetic embryo checks after failed fertility cycles, helping them use existing frozen embryos effectively.</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/PMC13482791/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148611660","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 genetics of primary dysmenorrhoea: a systematic review.","authors":"Ella Heger, Miriam Szabo, Rachel Reid-McCann, Ioana-Wilhelmina Lucinescu, Nura Fitnat Topbas Selcuki, Krina T Zondervan, Katy Vincent","doi":"10.1530/RAF-26-0004","DOIUrl":"10.1530/RAF-26-0004","url":null,"abstract":"<p><strong>Abstract: </strong>Dysmenorrhoea is the most common gynaecological condition in women of reproductive age. Approximately 90% of cases are primary dysmenorrhoea (PDM), which is not associated with an underlying pathology. Dysmenorrhoea can have a substantial impact on quality of life, yet current therapies do not provide adequate relief to everyone. Family history (FHx) is a known risk factor that suggests genetic involvement. We therefore aimed to synthesise the literature describing the genetics of PDM. Three databases (MEDLINE, Embase and Web of Science) were searched for studies published up to November 2025. Key search terms included 'dysmenorrhea', 'polymorphism' and 'SNP'. Articles were screened independently by two researchers, and data were extracted and presented in a narrative format. Quality assessment was conducted using the Newcastle-Ottawa Scale and STREGA guidelines. Fifteen articles were included in the review (n = 7 case-control; n = 4 cross-sectional; and n = 4 genome-wide association studies (GWASs)). Candidate gene studies identified seven polymorphisms and two combined genotypes that were associated with PDM. One significant positive association was replicated in two studies (ESR1 PvuII). GWASs highlighted loci near the NGF, ZMIZ1, IL1A and IL1B genes. The NGF and IL1 loci support what is known about the involvement of inflammatory pathways in PDM pathogenesis. However, they are also known endometriosis loci. The current literature is limited by a lack of adequate secondary dysmenorrhoea case exclusion, limited ethnic populations and low quality. Further research in multiple ancestries is essential to increase generalisability, while thorough diagnostic protocols will reduce misclassification, improve understanding of PDM pathogenesis and thus help inform new treatment development.</p><p><strong>Lay summary: </strong>Period pain is extremely common in menstruating women and has a major impact on their lives, yet we still do not have a full understanding of its biological causes or how to treat all women effectively. Research shows that period pain can run in families; therefore, we conducted this review to highlight which genes appear to be related to period pain (specifically period pain that is not caused by an existing condition, such as endometriosis or fibroids). After searching three academic databases, we found 15 studies that met our criteria. Three genes were highlighted across two or more studies; these genes are known to be involved in pain processing and how the body deals with immune responses and oestrogen (a female hormone). From this review, we know that we need more research on this topic as there are still likely to be more genes involved in period pain and these might vary in different ethnic populations.</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/PMC13452037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148458118","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":"Mouse oocyte phenotypes differ in blastocyst response to resveratrol and vitamin B12.","authors":"Hyung Min Kim, Kyungmi Juhn, Eunhye Jung, Hyejeong Park, Juhee Jin, Jinho Lim, Hyejun Lee, Jeong Yoon","doi":"10.1530/RAF-26-0036","DOIUrl":"10.1530/RAF-26-0036","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Abstract: &lt;/strong&gt;This experimental laboratory study examined whether associations between culture condition and blastocyst formation differed across radiomics-defined oocyte clusters and age groups. Mouse oocytes (n = 2,061) were assigned to control or five supplementation groups: resveratrol (0.1, 0.5, 1.0 μM) and vitamin B12 (50, 200 pM). The primary outcome was blastocyst formation across morphological clusters and age subgroups. Three clusters with distinct baseline blastocyst formation rates were identified: Cluster 1, 28.2% (44/156); Cluster 2, 42.4% (156/368); and Cluster 3, 34.9% (105/301). Cluster 2 comprised the largest and most spherical oocytes with heterogeneous cytoplasmic texture. Cluster 3 represented the smallest, brightest phenotype with the most uniform intensity profile, whereas Cluster 1 showed intermediate size, irregular contours, and high internal contrast. Associations between culture condition and blastocyst formation differed across radiomics-defined clusters. In Cluster 1, blastocyst formation increased from 28.2 to 45.1% with resveratrol 1.0 μM and to 48.7% with vitamin B12 200 pM. In Cluster 3, blastocyst formation increased from 34.9 to 60.4% with vitamin B12 50 pM and to 50.0% with resveratrol 0.1 μM. Cluster 2 showed a non-significant increase from 42.4 to 57.9% with resveratrol 0.5 μM. Older oocytes exhibited lower developmental competence than younger oocytes. Selecting the best performing medium for each cluster-age combination increased overall blastocyst formation from 36.97% (305/825) to 56.00% (126/225). These findings indicate associations among radiomics-defined clusters, culture conditions, and blastocyst formation. Prospective cluster-stratified studies are required to determine whether cluster-guided culture-condition selection improves developmental outcomes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Lay summary: &lt;/strong&gt;Not all eggs have the same ability to develop into embryos, and they may respond differently to the conditions in which they are cultured. In this study, we analysed images of more than 2,000 mouse eggs to determine whether features visible in the images could identify groups of eggs with different developmental potential. We first used eggs grown under standard culture conditions to define three groups based on their image characteristics. We then examined how eggs in these groups developed under standard conditions or with different amounts of resveratrol, an antioxidant, or vitamin B12 added to the special fluid used to support embryo development. The three groups differed in their rates of development to the blastocyst stage, an early stage of embryo development, and the relationship between culture condition and blastocyst development also varied between groups and between younger and older mice. These findings suggest that egg image characteristics may help us understand why eggs respond differently to their culture environment. However, further prospective experiments are needed before these","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/PMC13615864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148914832","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":"Exploring emerging concepts in the pathophysiology of PCOS: microbiome dysbiosis and immunological dysregulation.","authors":"Parijot Kumar, Michael W O'Reilly, Karen McGowan, Conor Harrity","doi":"10.1530/RAF-25-0187","DOIUrl":"10.1530/RAF-25-0187","url":null,"abstract":"<p><strong>Abstract: </strong>Polycystic ovary syndrome (PCOS) is a complex yet common endocrine disorder, affecting 5-20% of reproductive-age women, characterised by a combination of hyperandrogenism, anovulation, and metabolic dysfunction. This combination of factors has traditionally been assumed to be the causative factors for the subfertility associated with PCOS, but significant microbial dysbiosis and alterations in immune function are identified in women with PCOS, suggesting a more complicated multifactorial impact on reproduction. Microbiome alterations vary between different PCOS subtypes, suggesting that hyperandrogenism and insulin resistance can impact microbial communities. The immunological implications of these microbiome changes are still poorly understood, along with their impact on reproductive outcomes, such as implantation, miscarriage, and assisted reproduction success rates. Although therapeutic interventions are chosen based on their endocrine and metabolic effects, many of these also target the microbiome and have immunomodulatory effects. Understanding these microbiome-host interactions and immunological factors provides new insights into the complex spectrum of PCOS pathophysiology and provides the potential for novel therapeutic approaches.</p><p><strong>Lay summary: </strong>Polycystic ovary syndrome (PCOS) is a common hormonal condition affecting up to one in five women of reproductive age. It can cause irregular periods, excess hair growth, acne, and difficulties with fertility. Recent research suggests that PCOS not only is a hormonal disorder but also involves changes in the body's bacteria, known as the microbiome, and disturbances in the immune system. These changes may contribute to inflammation, insulin resistance, and hormone imbalance. Understanding how the microbiome and immune system interact in PCOS could lead to new ways to diagnose and treat the condition. Future therapies may focus on restoring a healthy microbiome to improve metabolic and reproductive health.</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/PMC13470631/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148364641","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":"Fertilization time and oocyte spindle integrity: implication for embryo ploidy.","authors":"Irena Kratochvilova, Olga Tepla, Anna Pšeničková, Jan Kybic, Denis Baručić, Kateřina Veselá, Gabriela Tauwlinklová, Katerina Komrskova, Jaromír Mašata","doi":"10.1530/RAF-26-0016","DOIUrl":"10.1530/RAF-26-0016","url":null,"abstract":"<p><strong>Graphical abstract: </strong></p><p><strong>Abstract: </strong>The aim of this retrospective study in assisted reproductive technology was to provide new evidence that i) the visibility of the meiotic spindle (MS) in human oocytes with an extruded first polar body predicts not only nuclear maturation but also embryo ploidy and ii) the interval between ovulation triggering and ICSI-mediated fertilization affects the chromosomal status of embryos. MS visibility was assessed using polarized light microscopy, and the trigger-to-fertilization interval was adjusted accordingly to increase the likelihood of complete oocyte nuclear maturation. Extending the trigger-fertilization interval based on MS status significantly increased the proportion of mature oocytes (displaying both MS and polar body) from 79 to 92% (P < 0.05), indicating ongoing spindle assembly. Of 1,879 oocytes examined under polarized light, 462 (24.5%) developed into embryos undergoing PGT-A. Embryos derived from immature oocytes (without visible MS or with a spindle bridge to the polar body) had a euploidy rate of 14%, compared with 42% in embryos from mature (visible MS) oocytes (P < 0.05). Differences in embryo euploidy were also associated with the interval between ovulation trigger and ICSI fertilization. Cycles with a trigger-ICSI interval of 40-44 h had a significantly higher likelihood of euploidy (47%) compared with cycles in which the trigger-ICSI interval was 36-39 h (33%) (P < 0.05). For example, in women of advanced maternal age, who exhibit an increased risk of embryonic aneuploidy, spindle-guided assessment of oocyte maturation and quality may improve the prediction of subsequent embryo ploidy.</p><p><strong>Lay summary: </strong>This IVF study investigated whether giving human eggs more time to mature before fertilization can improve embryo quality. Eggs showing clear signs of full maturity under the polarization microscope were more likely to develop into embryos with the correct number of chromosomes. Having the correct chromosome number is important for healthy embryo development and a successful pregnancy. Eggs that were given a few extra hours to mature before fertilization were more likely to produce healthy embryos with the correct number of chromosomes. The best results were seen when fertilization took place 40-44 h after the hormone injection, rather than 36-39 h later. Fertilization was carried out using a procedure in which a single sperm is injected directly into an egg. These findings suggest that careful assessment of egg maturity and optimization of fertilization timing may help improve IVF outcomes.</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/PMC13452034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148582005","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":"Letter regarding Griffiths et al. \"anti-Müllerian hormone decreased in women with superficial peritoneal endometriosis and associated with an elevated inflammatory profile\".","authors":"Jasper Verguts, Tanne Daniels","doi":"10.1530/RAF-26-0127","DOIUrl":"10.1530/RAF-26-0127","url":null,"abstract":"","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/PMC13482790/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148671932","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":"Localisation of immune cell populations during human fetal testicular development.","authors":"Samira Hosseini, Davor Jezek, Marina Kos, Benedict Nathaniel, Ewa Rajpert-De Meyts, Mark P Hedger, Hans-Christian Schuppe, Kate L Loveland, Daniela Fietz","doi":"10.1530/RAF-25-0189","DOIUrl":"10.1530/RAF-25-0189","url":null,"abstract":"<p><strong>Graphical abstract: </strong></p><p><strong>Abstract: </strong>This study addresses the limited knowledge of immune cells and their origins in the human fetal testis. By identifying and localising macrophages, T cells, neutrophils, and mast cells, evidence of their potential roles in testicular and epididymal development is provided. Macrophages (CD68+), T cells (CD3+), neutrophils (CD66b+), and mast cells (tryptase+ and chymase+) were identified using immunohistochemistry and immunofluorescence in 20 formalin-fixed fetal testes (and epididymides, when present) collected at autopsy from stillborn fetuses (gestational weeks, GW14-41). Immune cell transcripts were compiled from published scRNA-seq datasets from human embryonic (GW6-8) and fetal (GW12-16) testes. CD68+ macrophages were abundant in interstitial, testis border, and perivascular regions, increasing adjacent to cords from GW23 onward. Interstitial CD3+ T cells were rare in second trimester but more frequent in the third. CD66b+ neutrophils were extremely rare. Chymase+ mast cells were absent, while tryptase+ mast cells were present near the capsule and vessels. scRNA-seq identified CD68-expressing cells as the predominant immune population from GW6-16. This first description of multiple immune cell types in the human fetal testis reveals similarities to murine testes; in both species, early macrophage abundance, preceding bone marrow haematopoiesis, suggests yolk sac and/or liver origins, while later-appearing immune cells are likely bone marrow-derived. The near-complete absence of Ly6G+ neutrophils in the later gestation stages differs from observations in mouse. These findings highlight potential developmental windows vulnerable to immune-related disruption and reinforce the value of mouse models for understanding human testis development.</p><p><strong>Lay summary: </strong>This study examines how the immune system helps the testicles to form before birth. In animals, immune cells called macrophages are important for early testis development, but their roles and those of other immune cells in humans were unclear. We studied tissues from 20 stillborn babies between 14 and 41 weeks of pregnancy to identify immune cells in developing testes and compared our results with existing genetic data. We found that macrophages were the most common immune cells, appearing early and increasing in number as the testis grew. Other immune cells, including T cells and mast cells, appeared later. Our findings suggest that macrophages come from early sources, such as the yolk sac or fetal liver, and play a key role in building the testis. Understanding these processes could reveal how factors affecting immune cell functions before birth could impair male fertility in men.</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/PMC13452043/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148538002","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":"Influence of sire fertility on the metabolism of in vitro produced embryos.","authors":"Quinn A Hoorn, Elena O'Callaghan, David A Kenny, Sean Fair, Patrick Lonergan, Constantine A Simintiras","doi":"10.1530/RAF-26-0028","DOIUrl":"10.1530/RAF-26-0028","url":null,"abstract":"<p><strong>Abstract: </strong>Bull field fertility varies greatly and is largely influenced by differences in early embryo survival rather than fertilization failure alone. We, therefore, investigated whether sire fertility status is reflected in the metabolomic profile of embryo-conditioned culture media. Six Holstein-Friesian bulls were selected from a population of 840 sires and classified using an adjusted sire fertility index. Mean (±SD) values were 4.27 ± 0.61% for highly fertile bulls (HF, n = 3) and -13.1 ± 1.85% for sub-fertile bulls (SF, n = 3). Cumulus-oocyte complexes were fertilized using frozen-thawed semen from individual bulls. On day 7 post-fertilization, grade 1 blastocysts (pools of n = 15 per bull; n = 3 replicates) were transferred to fresh culture medium for 24 h. On day 8, embryo-conditioned media from both fertility treatments and unconditioned media were collected, snap-frozen, and subjected to high-throughput untargeted metabolomic profiling. A total of 149 metabolites were detected. Unsupervised analysis revealed substantial overlap between HF and SF sire-derived embryo-conditioned media, while both differed from unconditioned media. The relative abundance of 30 metabolites was altered by embryo presence, irrespective of sire fertility. Direct comparison of HF vs SF sire-derived embryo-conditioned media identified only three differentially abundant metabolites. However, multivariate machine learning analysis identified a panel of eight N-acetylated amino acids, which discriminated embryos derived using semen from bulls of divergent fertility status with high accuracy (AUROC = 0.903). In conclusion, sire fertility status imparts a subtle but detectable metabolic imprint on the early embryo, which can be exploited to non-invasively discriminate embryos according to potential developmental competence.</p><p><strong>Lay summary: </strong>Reproductive efficiency is fundamental to productive and profitable cattle farming. Even bulls that pass routine fertility assessments can achieve very different pregnancy rates. Understanding the biological basis of this variation has important practical implications. We studied whether differences in early embryo metabolism might help explain why some bulls consistently outperform others in fertility. We created embryos in the laboratory using sperm from highly fertile and sub-fertile bulls. Then, we analyzed hundreds of small molecules that reflect metabolic activity in the fluid surrounding the embryo, and we detected very few differences between the two groups. However, using a machine learning approach, we identified a panel of eight molecules that distinguished embryos by sire fertility status with high accuracy. These findings suggest that a bull's fertility leaves a subtle but detectable metabolic imprint on early embryos, with potential future applications in non-invasive embryo quality assessment.</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/PMC13386233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148304431","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":"Gonadotropin-releasing hormone agonists during cyclophosphamide for ovarian protection in systemic lupus erythematosus.","authors":"Mauro Francesco Pio Maiorano, Gennaro Cormio, Vera Loizzi, Brigida Anna Maiorano, Giacomo Corrado, Erica Silvestris","doi":"10.1530/RAF-25-0191","DOIUrl":"10.1530/RAF-25-0191","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Abstract: &lt;/strong&gt;This study aimed to assess whether co-treatment with gonadotropin-releasing hormone agonists during cyclophosphamide therapy protects ovarian function and preserves fertility in women with systemic lupus erythematosus. We performed a systematic review and meta-analysis of comparative cohort studies including premenopausal women with systemic lupus erythematosus treated with intravenous cyclophosphamide with or without gonadotropin-releasing hormone agonists. The primary outcome was primary ovarian insufficiency, with pregnancy and serious adverse events as secondary outcomes. Two reviewers independently selected studies, extracted data, and assessed risk of bias. Pooled risk ratios with 95% confidence intervals were calculated using fixed-effect models. Five cohort studies including 162 women (93 with gonadotropin-releasing hormone agonists and 69 controls) met the inclusion criteria; no randomized controlled trials were available. Premature ovarian insufficiency occurred in 5 of 93 women receiving gonadotropin-releasing hormone agonists and in 28 of 69 controls, corresponding to a risk ratio of 0.16 (95% confidence interval (CI): 0.07-0.37). Pregnancy was more frequent after gonadotropin-releasing hormone agonist co-treatment (19 of 87 versus 6 of 60 women; risk ratio: 1.82, 95% CI: 0.86-3.86), although this difference did not reach statistical significance. The incidence of serious adverse events was similar between groups (10 of 36 versus 10 of 34 women; risk ratio: 0.99; 95% CI: 0.50-1.93). In premenopausal women with systemic lupus erythematosus receiving cyclophosphamide, co-treatment with gonadotropin-releasing hormone agonists markedly reduces the risk of primary ovarian insufficiency without evidence of added serious toxicity and may increase subsequent pregnancy. However, the absence of randomized controlled trials represents a major limitation, and larger prospective randomized or well-controlled studies with a standardized long-term reproductive follow-up are needed to confirm these findings.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Lay summary: &lt;/strong&gt;Systemic lupus erythematosus is an autoimmune disease that often affects young women. When the disease is severe, the drug cyclophosphamide, which can damage the ovaries and cause early menopause and infertility, may be used. With our study, we wanted to assess whether adding injections of gonadotropin-releasing hormone agonists, drugs that temporarily switch off the ovaries, can protect fertility. We combined results from five studies including 162 women with systemic lupus erythematosus who received cyclophosphamide with or without these hormone injections. Early permanent loss of ovarian function occurred in 5 of 93 women who received the injections, compared with 28 of 69 women who did not. More women in the injection group later became pregnant (19 of 87 versus 6 of 60). Serious side effects were similar in both groups. These findings suggest that temporary ovarian suppression","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/PMC13539409/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148595482","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":"Late-stage vacuolization as a compaction-dependent prognostic marker for day 4 embryo selection.","authors":"Yasong Geng, Aixin Yang, Fangfang Dai, Haoyang Dai, Linlin Tao, Guozhen Li, Chun He, Lingyin Kong, Jing Ma, Bo Zheng, Fang Wang","doi":"10.1530/RAF-26-0008","DOIUrl":"10.1530/RAF-26-0008","url":null,"abstract":"<p><strong>Graphical abstract: </strong></p><p><strong>Abstract: </strong>This study aimed to evaluate the prognostic value of late-stage vacuolization in day 4 embryos relative to compaction status. We retrospectively analyzed 9,779 embryos from 2,409 patients undergoing fresh D4 transfers between 2018 and 2024. Embryos were stratified by compaction status (full, partial, and non-compaction) and assessed for vacuolization. Predictive performance for blastocyst formation was evaluated using ROC curves and logistic regression. The results showed that late-stage vacuolization correlated with higher maternal and paternal age, increased gonadotropin (Gn) dosage, and lower anti-Müllerian hormone (AMH)/estradiol (P < 0.001), but comparable oocyte yield and intracytoplasmic sperm injection (ICSI) rates (P > 0.05). False-compaction subgroup (77.6% of vacuolized embryos) showed reduced transferable blastocyst (38.7 vs 53.3%, P = 0.021), high-quality blastocyst (9.8 vs 23.4%, P = 0.001), and day 5 blastocyst rates (20.6 vs 35.1%, P = 0.007). A significant interaction was observed between late-stage vacuolization and compaction status affecting both transferable and high-quality blastocyst formation (P for interaction < 0.001). In particular, late-stage vacuolization significantly increased the rates of transferable (OR = 3.34, 95% CI: 2.54-4.39, P < 0.001) and high-quality blastocyst formation (OR = 2.51, 95% CI: 1.60-3.96, P < 0.001) in the non-compacted subgroup. Conversely, it decreased the high-quality blastocyst formation rate in the fully compacted subgroup (OR = 0.37, 95% CI: 0.15-0.89, P = 0.026), while showing no significant effect on transferable blastocyst formation in this group (OR = 0.83, 95% CI: 0.28-2.48, P = 0.740). In conclusion, late-stage vacuolization is a compaction-dependent prognostic marker, detrimental in compacted embryos yet potentially beneficial in non-compacted ones. We hypothesize that its effects may be mediated through mechanical stress-induced pseudo-compaction, suggesting that it should be integrated into D4 embryo grading systems in a context-specific manner.</p><p><strong>Lay summary: </strong>This study looked at over 9,700 embryos used in IVF. We found that tiny, bubble-like structures (called 'vacuolization') inside a 4-day-old embryo can be either good or bad news, depending on whether the embryo's cells are tightly or loosely packed together. In tightly packed embryos, these bubbles are harmful and reduce the chance of forming a high-quality embryo. In loosely packed embryos, the same bubbles can be helpful and increase the chance of successful development. This is different from other embryo problems, which are always bad. By checking for these bubbles and how packed the cells are, we can predict which embryo is most likely to lead to a baby 10% more accurately than before. To use this new method, embryos need to be grown for 4 days instead of 3 days.</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/PMC13427979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148304475","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}