Human reproduction最新文献

{"title":"Bias due to non-consent in assisted reproductive treatment cohort studies: consent for disclosure to non-contact research in the Human Fertilisation and Embryology Authority register","authors":"Fiskani J M Kondowe, Matthew Gittins, Peter Clayton, Daniel R Brison, Stephen A Roberts","doi":"10.1093/humrep/deaf045","DOIUrl":"https://doi.org/10.1093/humrep/deaf045","url":null,"abstract":"STUDY QUESTION Is patient consent to research associated with the distribution of population characteristics and study outcomes in ART cohort studies? SUMMARY ANSWER The distribution of population characteristics in the patient consent subset differs from that in the non-consent subset and is not fully representative of the general ART population; thus, study results of population subsets requiring patient consent may be subject to bias. WHAT IS KNOWN ALREADY Non-consent in epidemiological studies may bias study results if the consent subset differs systematically from the non-consent subset and is thus not representative of the full study population. ART cohort datasets may be biased if they require patients to consent to use their data. As an example, from September 2009 onwards, ART patients in the UK have been asked for specific ‘consent to disclosure of identifying information’ (CD) for research studies. STUDY DESIGN, SIZE, DURATION This cohort study utilized an anonymized version of the Human Fertilisation and Embryology Authority (HFEA) dataset containing all CD and non-CD autologous ART treatment cycles (n = 819 512) conducted from 2004 to 2018 in the UK. A live birth (LB) subset of 155 986 singletons born during the same period was used to analyse child outcomes. Additionally, an aggregated version of the HFEA dataset was used to explore CD trends by clinic type (National Health Service [NHS], private, or both NHS and privately funded). PARTICIPANTS/MATERIALS, SETTING, METHODS The dataset containing all gamete cycles was used to explore factors associated with giving CD and to compare LB outcome trends (number of LBs per yearly treatment cycles started) between CD and non-CD cycles. The LB subset was used to compare the birthweight outcomes (low birthweight (LBW = birthweight < 2500 g or otherwise) and macrosomia (birthweight ≥4000 g or otherwise)) between CD and non-CD cycles. Logistic regression models explored the association between CD and population characteristics and the impact of CD on birthweight outcomes over the calendar years. Each regression model was adjusted for potential confounders: for all models (maternal age, ethnicity, previous IVF cycles, previous pregnancies, previous LBs, causes of infertility (tubal, endometriosis, male factor, ovulatory, unknown), and embryo transfer type and stage); for LB and birthweight models (ICSI, elective single embryo transfer, and ovarian stimulation); and additionally for birthweight models (child sex and gestation). MAIN RESULTS AND THE ROLE OF CHANCE During the study period, CD rates increased from 16% at its inception in 2009 to 64% in 2018. Fewer cycles from older patients (40–44 years old) and ethnic minorities (Black and Asian) gave CD. Cycles with previous ART treatments and LBs had lower rates of giving CD. CD was also associated with LB rates (higher in the CD group) and LBW (slightly more prevalent in the non-CD group). CD rates were consistently higher in NHS-only fun","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"71 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677716","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":"Pregnancy outcomes with increasing maternal age, greater than 40 years, in donor oocyte cycles.","authors":"Sabbagh Riwa, Meyers Alison, Korkidakis Ann, Heyward Quetrell, Penzias Alan, Sakkas Denny, Vaughan Denis, Toth Thomas","doi":"10.1093/humrep/deaf044","DOIUrl":"https://doi.org/10.1093/humrep/deaf044","url":null,"abstract":"<p><strong>Study question: </strong>Do IVF outcomes differ in patients over the age of 40 using donor oocytes?</p><p><strong>Summary answer: </strong>Even with the use of donor oocytes, maternal age appears to have an impact on live birth (LB) rate and perinatal outcomes.</p><p><strong>What is known already: </strong>Maternal age has a significant impact on the outcome of IVF, mainly attributed to age-related oocyte chromosomal factors.</p><p><strong>Study design, size, duration: </strong>This was a retrospective cohort study between 1 January 2015 and 31 December 2021.</p><p><strong>Participants/materials, setting, methods: </strong>This study included all patients who had a single embryo transfer cycle using donor oocytes during the study period. The study was conducted at a single university-affiliated fertility center. Data on BMI, paternal age, and type of cycle (natural vs programmed) were evaluated in relation to miscarriages and LBs when comparing age groups of 40-44, 45-49, and ≥50. Generalized estimating equation (GEE) models with logit functions were used to control for confounding variables.</p><p><strong>Main results and the role of chance: </strong>A total of 1660 single embryo transfer cycles using donor oocytes in patients ≥40 years were performed during the study period. Of these, 969 were in patients aged 40-44, 607 in patients 45-49, and 84 in patients ≥50 years of age. The presence of an LB was significantly lower in patients 45-49 compared to those 40-44 (P = 0.023). The LB rate remained lower in patients >50 but was not statistically significant. This relationship persisted after adjusting for BMI, paternal age, cycle type, and type of oocyte donor (fresh vs frozen oocyte donor) (P = 0.016). Moreover, the birthweight was lower in the older age groups (45-49 and ≥50) compared to the reference group of patients aged 40-44 (P = 0.004).</p><p><strong>Limitations, reasons for caution: </strong>The presence of an LB was lower in patients aged 45-49 and ≥50 compared to 40-44; however, this finding was not statistically significant for the ≥50 age group, likely due to the smaller sample size compared to the other two age groups. The use of preimplantation genetic testing for aneuploidy (PGT-A) was not included since only a minority of patients using donor oocytes underwent PGT-A. The inclusion of both fresh and frozen donor oocytes may also be deemed a limitation, as some studies have indicated better outcomes from fresh compared to frozen donor oocytes.</p><p><strong>Wider implications of the findings: </strong>Maternal age, beyond its relation to oocyte quality, was shown to affect the achievement of an LB. This is an important finding to include in patient counseling, particularly for those proceeding with donor oocytes.</p><p><strong>Study funding/competing interest(s): </strong>No authors report conflicts of interest or disclosures. There was no study funding.</p><p><strong>Trial registration number: </strong>N/A.</p>","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669135","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":"Plasma metabolites associated with endometriosis in adolescents and young adults","authors":"Nan Lin, Oana A Zeleznik, Allison F Vitonis, Ashley Laliberte, Amy L Shafrir, Julian Avila-Pacheco, Clary Clish, Kathryn L Terry, Stacey A Missmer, Naoko Sasamoto","doi":"10.1093/humrep/deaf040","DOIUrl":"https://doi.org/10.1093/humrep/deaf040","url":null,"abstract":"STUDY QUESTION What are the plasma metabolomics profiles associated with endometriosis in adolescents and young adults? SUMMARY ANSWER Our findings show dysregulation of plasma metabolomic profiles in adolescents and young adults with endometriosis, revealing systemic elevation of fatty acyls and ceramides in endometriosis cases compared to controls. WHAT IS KNOWN ALREADY Endometriosis is a gynecologic disease often presenting with severe pelvic pain impacting around 200 million reproductive-aged women worldwide. However, little is known about the pathophysiology and molecular features of endometriosis diagnosed during adolescence and young adulthood. STUDY DESIGN, SIZE, DURATION We conducted a cross-sectional analysis including 190 laparoscopically confirmed endometriosis cases and 120 controls who participated in The Women’s Health Study: From Adolescence to Adulthood, which enrolled participants from 2012 to 2018. Control participants were females without a diagnosis of endometriosis enrolled from the same clinics as the cases or recruited from the general population. Among the cases, 81 had blood samples collected before and after surgery. PARTICIPANTS/MATERIALS, SETTING, METHODS Plasma metabolites were measured in blood collected at enrollment using liquid chromatography–tandem mass spectrometry, and a total of 430 known metabolites were evaluated in our analysis. We used linear regression adjusting for age at blood draw, BMI, hormone use, and fasting status at blood draw. Metabolite set enrichment analysis (MSEA) was used to identify metabolite classes. Number of effective tests (NEF) and false discovery rate (FDR) were used for multiple testing correction. MAIN RESULTS AND THE ROLE OF CHANCE The median age was 17 years for endometriosis cases and 22 years for controls. The majority of endometriosis cases had rASRM stage I or II (&amp;gt;95%). We identified 63 plasma metabolites associated with endometriosis (NEF &amp;lt; 0.05). Endometriosis cases had higher levels of plasma metabolites associated with proinflammatory response [e.g. eicosatrienoic acid (β = 0.61, 95% CI = 0.37, 0.86)], increased oxidative stress response [e.g. xanthine (β = 0.64, 95% CI = 0.39, 0.88)], and downregulation of metabolites related to apoptosis [glycocholic acid (β = −0.80, 95% CI = −1.04, −0.56)]. MSEA revealed increased fatty acyls (FDR = 2.3e−4) and ceramides (FDR = 6.0e−3) and decreased steroids and steroid derivatives (FDR = 1.3e−4) in endometriosis cases compared to controls. When we examined the changes in plasma metabolite profiles before and after surgery among endometriosis cases, 55 endometriosis-associated metabolites significantly changed from before to after surgery. MSEA revealed steroids and steroid derivatives (FDR = 8.1e−4) significantly increased after surgery, while fatty acyls (FDR = 1.2e−4) significantly decreased after surgery. Ceramides did not change from pre- to post-surgery and were elevated in post-surgical blood compared to controls","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"56 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143661360","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":"Clinical presentation of congenital hypogonadotropic hypogonadism in males with delayed puberty according to genetic etiology: a systematic review and meta-analysis after reclassification of gene variants","authors":"Sebastián Castro, Franco G Brunello, Gabriela Sansó, Agustín Izquierdo, Jonathan Zaiat, Mariela Urrutia, Marcelo Martí, Rodolfo A Rey, Mariana L Tellechea, Romina P Grinspon","doi":"10.1093/humrep/deaf041","DOIUrl":"https://doi.org/10.1093/humrep/deaf041","url":null,"abstract":"STUDY QUESTION Which phenotypes can be confidently linked to a genetic etiology in males with congenital hypogonadotropic hypogonadism (CHH) resulting in absent or arrested puberty? SUMMARY ANSWER In this systematic review and reclassification of the disease-causing potential of gene variants using the recommendations of the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP), we found that absent or arrested puberty in males with CHH was linked to 93 genes, of which 29 were unequivocally disease-causing. WHAT IS KNOWN ALREADY The number of genes and phenotype characterizations associated with CHH in males has rapidly increased since the advent of next-generation sequencing technologies; however, the quality of the evidence for the interpretation of the causal relationship of gene variants is limited due to the lack of systematic criteria applied to the assessment of the pathogenic potential of the variants. STUDY DESIGN, SIZE, DURATION We performed a systematic review of original articles indexed in PubMed until 5 October 2022 and using the search terms ‘((‘hypogonadotropic hypogonadism’ OR Kallmann) AND (sequencing OR mutation OR variant))’ limited to ‘Humans’ and ‘English’. PARTICIPANTS/MATERIALS, SETTING, METHODS After two investigators undertook the literature search independently, titles and abstracts of all records were reviewed by four of the authors to identify those articles to be included in the full-text review. Clinical data and the association with gene variants were extracted from males with delayed or arrested puberty due to CHH according to the article authors’ criteria. Raw sequence variant information was used to reevaluate their pathogenic potential applying the ACMG/AMP guidelines for variant classification with InterVar. Subsequently, we considered the phenotype specificity criteria for sequence variant pathogenicity classification, based on curated genes associated with CHH, and classified patients into three categories: with monogenic disease-causing variants in genes associated with CHH, with variants in genes whose causality is unclear, and with variants that are not disease-causing. MAIN RESULTS AND THE ROLE OF CHANCE From a total of 1083 records, we included 245 publications with 775 male patients with CHH resulting in absent or arrested puberty, carrying 1001 variants in 93 genes. Gene variants were detected by Sanger sequencing in 61.8% of the cases and by next-generation sequencing (NGS) technologies in the rest. After variant reclassification of causality, 278 individuals were not considered to have a bona fide disease-causing gene variant, and 497 patients were reclassified as carrying at least one disease-causing variant associated with CHH. They carried 503 different disease-causing variants in 29 genes. Spontaneous puberty was absent in 85.5% and arrested in 14.5% of the 497 individuals with CHH carrying bona fide disease-causing variants. In males with abs","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"90 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143653330","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":"Is it justified to offer intrauterine infusion of autologous PRP in women with repeated implantation failure?","authors":"Evangelia T Katsika, Christos A Venetis, Julia K Bosdou, Efstratios M Kolibianakis","doi":"10.1093/humrep/deaf014","DOIUrl":"https://doi.org/10.1093/humrep/deaf014","url":null,"abstract":"<p><p>In recent years, an increased interest in the efficacy of intrauterine infusion of autologous platelet-rich plasma (PRP) in women with repeated implantation failure (RIF) has resulted in the publication of 13 randomized controlled trials (RCTs) and 11 meta-analyses. Although these meta-analyses support an increase in pregnancy rates after intrauterine infusion of autologous PRP, the low quality of the available original clinical studies along with concerns regarding their trustworthiness seriously questions their internal validity and does not allow for definitive conclusions to be drawn. In addition, the variability in the definition of RIF used in the individual studies limits their external validity, renders the pooling of the results problematic, and, overall, complicates the extrapolation of the results published. The variability in the definition of RIF has been recently addressed by the ESHRE, which published an evidence-based definition of RIF to facilitate the evaluation of interventions in these patients. Taking into consideration this definition, which identifies a real clinical problem, evaluation of intrauterine infusion of PRP in the published literature has not so far been performed explicitly in patients with RIF. The potential of intrauterine infusion of autologous PRP to improve outcomes for women with RIF remains an important area of research in ART. However, the current evidence is insufficient to inform clinical practice, highlighting the need for well-designed studies to provide clearer guidance.</p>","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143648280","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":"From hope to hesitation: why couples fail to return for infertility treatment after the first consultation","authors":"Camilla Scognamiglio, Federico Cirillo, Camilla Ronchetti, Matteo Secchi, Andrea Busnelli, Emanuela Morenghi, Carlo Alviggi, Paolo Emanuele Levi-Setti","doi":"10.1093/humrep/deaf012","DOIUrl":"https://doi.org/10.1093/humrep/deaf012","url":null,"abstract":"STUDY QUESTION What are the key factors that influence couples’ decision not to return for fertility treatment after their first consultation? SUMMARY ANSWER Advanced maternal age, lower ovarian reserve, and eligibility for heterologous fertilization are primary determinants of non-return among couples. WHAT IS KNOWN ALREADY Previous research highlights the psychological, financial, and demographic reasons behind high dropout rates in IVF, yet a comprehensive understanding of the factors driving non-return, particularly at the first consultation, is still lacking and warrants further study. STUDY DESIGN, SIZE, DURATION This single-center observational study, incorporating both retrospective and prospective components, analyzed couples consulting at Humanitas Research Hospital from 2012 to 2021. The retrospective review spanned 24 773 couples from 2012 to 2021, among whom 6174 did not return. The prospective cohort included 986 couples who failed to return out of a total of 3214 couples who had their first consultation in 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS Participants included couples seeking their first fertility consultation at a specialized fertility center. Retrospective data were extracted from internal records to assess personal, demographic, and biological factors (anti-Mullerian hormone [AMH] and FSH levels) contributing to non-return, while non-returning patients in the prospective arm completed a telephone questionnaire in addition to data extraction from internal records. MAIN RESULTS AND THE ROLE OF CHANCE Between 2012 and 2021, 24.92% of couples did not return after the initial consultation, with older age and diminished ovarian reserve as significant predictors. Of 3214 couples in 2021, 986 (30.68%) did not return after their first consultation. All 986 patients were contacted, and the response rate was 85.1%. Non-returning women were significantly older (37.1 vs. 35.6 years) and exhibited lower AMH levels (1.87 vs. 2.83 ng/ml) and higher FSH levels (13.13 vs. 8.19 mIU/ml). Primary reasons for non-return included eligibility for gamete donation (34.09%), spontaneous pregnancy (29.20%), and transferring treatment to another center (18.71%). Other contributing factors were existing parenthood (11.43%), psychological distress (9.65%), and dissatisfaction with the doctor (7.39%). These findings highlight the multifaceted nature of treatment discontinuation and underscore the importance of comprehensive support to mitigate non-return risk. LIMITATIONS, REASONS FOR CAUTION This study is limited by its single-center design: generalizability may vary based on differences in patient demographics and healthcare settings across regions and countries. Additionally, the prospective analysis may be affected by selection bias, as those non-returning patients who could not be reached might have provided meaningfully different answers. WIDER IMPLICATIONS OF THE FINDINGS These findings align with current literature while providing new ins","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":"15 1","pages":""},"PeriodicalIF":6.1,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143641068","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":"The major phytocannabinoids, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), affect the function of CatSper calcium channels in human sperm.","authors":"Lydia Wehrli, Hannah Altevogt, Christoph Brenker, Fanny Zufferey, Michel F Rossier, Timo Strünker, Serge Nef, Rita Rahban","doi":"10.1093/humrep/deaf020","DOIUrl":"https://doi.org/10.1093/humrep/deaf020","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Do the main psychoactive phytocannabinoid delta-9-tetrahydrocannabinol (THC) and its non-psychoactive analog cannabidiol (CBD) affect human sperm function?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;THC and CBD affect the sperm-specific Ca2+ channel CatSper, suppress activation of the channel by progesterone (P4) and prostaglandin E1 (PGE1), and THC also alters human sperm function in vitro.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;Marijuana (Cannabis sativa) is one of the most commonly used recreational drugs worldwide. Although the effects of phytocannabinoids on semen parameters have been studied, there is no evidence of a direct impact of THC and CBD on human sperm.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design, size, duration: &lt;/strong&gt;We investigated the effects of the major psychoactive phytocannabinoid, THC, its non-psychoactive analog, CBD, and their major metabolites on Ca2+ influx via CatSper in human spermatozoa. THC and CBD were selected to further evaluate their action on P4-, PGE1-, and pH-induced activation of CatSper. The effects of THC and CBD on sperm motility, penetration into viscous media, and acrosome reaction (AR) were also assessed.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials, setting, methods: &lt;/strong&gt;The effects of phytocannabinoids on CatSper activity were investigated on semen samples from healthy volunteers and men with homozygous deletion of the CATSPER2 gene using kinetic Ca2+ fluorimetry and patch-clamp recordings. Motility was assessed by computer-assisted sperm analysis (CASA). Sperm penetration into viscous media was assessed using a modified Kremer test. The AR was evaluated by flow cytometry using Pisum sativum agglutinin-stained spermatozoa.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;Both THC and CBD increased the intracellular calcium concentration with CBD inducing a greater increase compared to THC. These Ca2+ signals were abolished in men with homozygous deletion of the CATSPER2 gene demonstrating that they are mediated through CatSper. THC suppressed the P4- and the PGE1-induced Ca2+ increase with a half-maximal inhibitory concentration (IC50) of 1.88 ± 1.15 µM and 0.98 ± 1.10, respectively. CBD also suppressed the P4- and PGE1-induced Ca2+ signal with an IC50 of 2.47 ± 1.12 µM and 6.14 ± 1.08 µM, respectively. The P4 and PGE1 responses were also suppressed by THC and CBD metabolites, yet with greatly reduced potency and/or efficacy. THC and CBD were found to inhibit the Ca2+ influx evoked by intracellular alkalization via NH4Cl, with THC featuring a higher potency compared to CBD. In conclusion, THC and CBD inhibit both the ligand-dependent and -independent activation of CatSper in a dose-dependent manner. This indicates that these phytocannabinoids are genuine CatSper inhibitors rather than P4 and PGE1 antagonists. Finally, THC, but not CBD, impaired sperm hyperactivation and penetration into viscous media and induced a small increase in AR.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Limitations, reas","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143614756","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":"Case Report: Androgenetic/biparental chimera with two biparental cell lines leading to placental mesenchymal dysplasia: a possible novel mechanism of formation.","authors":"Mar Xunclà, María Ángeles Sánchez-Durán, Natàlia Rey, María Serrano, Pedro Antonio Martínez, Lourdes Trobo, Jessica Camacho Soriano, Alberto Plaja, Neus Castells-Sarret, Maria Àngels Rigola, Elena García-Arumí, Eduardo Fidel Tizzano","doi":"10.1093/humrep/deaf038","DOIUrl":"https://doi.org/10.1093/humrep/deaf038","url":null,"abstract":"<p><p>Placental mesenchymal dysplasia (PMD) is a rare placental pathology that may be associated with Beckwith-Wiedemann features in the fetus and may be due to the presence of an androgenetic cell line. Many of the reported PMD cases describe the presence of a biparental and an isodisomic androgenetic cell line. The proposed mechanism of formation is by fertilization of a haploid ovum by a haploid sperm and duplication of the male pronucleus. We present a case with evidence of the participation of three different haploid gametes, one ovum and two spermatozoa, which led to an androgenetic/biparental chimera (ABC) in which three fetal cell lines were detected: two biparental, genetically different, cell lines but with the same maternal contribution, and one heterodisomic androgenetic cell line. To our knowledge, this is the first described case of ABC with two different biparental cell lines. We propose a novel mechanism based on the heterogoneic division of the tripronucleated zygote to explain the formation of this rare ABC.</p>","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596843","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":"Cumulative live birth rates of 31 478 untested embryos from 11 463 women challenge traditional recurrent implantation failure definitions.","authors":"L Dhaenens, R Colman, I De Croo, H Verstraelen, P De Sutter, D Stoop","doi":"10.1093/humrep/deaf036","DOIUrl":"https://doi.org/10.1093/humrep/deaf036","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Is there evidence of a plateau in the cumulative live birth rate (cLBR) after a certain number of consecutive transfers of untested embryos?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;In our cohort of 11 463 women, the cLBR continues to increase with each additional transfer of an untested embryo, reaching 68.3% after six blastocyst transfers and 78.0% after 10 blastocyst transfers.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;While cumulative success rates in ART are rising, implantation failure remains a persistent challenge. The actual frequency of recurrent implantation failure (RIF) and whether RIF surpasses the inherent implantation potential of transferred embryos remains a matter of debate. A recent study reported a cLBR of 98% after five euploid blastocyst transfers, suggesting that most implantation failures are likely embryonic rather than endometrial. However, it remains unclear how these findings can be extrapolated to patients who did not undergo preimplantation genetic testing for aneuploidy (PGT-A). While theoretical models estimate cumulative implantation probabilities based on published blastocyst euploidy rates by female age, real-world data on cumulative success in routine clinical practice remain limited.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design, size, duration: &lt;/strong&gt;This non-interventional retrospective cohort study included records of all completed IVF/ICSI cycles (including thus fresh and frozen-thawed transfers of one oocyte retrieval cycle) in women who underwent IVF/ICSI at the Ghent University Hospital between January 2010 and December 2022. After excluding treatments involving PGT, oocyte donation and surrogacy, or a mix of cleavage stage and blastocyst stage transfers, our dataset consisted of 11 463 women who underwent a total of 19 378 IVF/ICSI cycles, resulting in a total of 31 478 embryo transfers.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials, setting, methods: &lt;/strong&gt;The number of embryos transferred ('time') until achieving live birth ('event') was analysed using a Kaplan-Meier approach with inverse probability weighting (IPW). Additionally, logistic regression analysis was conducted to assess the predictive value of the number of previously transferred embryos on the live birth rates (LBRs) of the second and subsequent transfers, adjusting for female age, quality of previously transferred embryos, and stage of embryos transferred (cleavage stage versus blastocyst stage).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;Kaplan-Meier estimates using an IPW approach showed cLBRs increasing from 51.1% (95% CI: 49.2-53.0%) after a third, up to 68.3% (95% CI: 64.6-72.0%) after a sixth and even as high as 78.0% (95% CI: 69.5-86.5%) after a tenth blastocyst transfer, respectively. As maternal age increases, higher numbers of blastocysts are required to achieve the same cLBR. Moreover, no age category achieves an 80% cLBR until after the transfer of eight blastocysts. Maternal age has a cons","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143596844","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":"High serum estradiol levels on the day of frozen blastocyst transfer are associated with increased early miscarriage rates in artificial cycles using transdermal estrogens.","authors":"Chloé Maignien, Timon Jobin, Mathilde Bourdon, Léa Melka, Louis Marcellin, Christelle Laguillier-Morizot, Ahmed Chargui, Catherine Patrat, Charles Chapron, Pietro Santulli","doi":"10.1093/humrep/deaf037","DOIUrl":"https://doi.org/10.1093/humrep/deaf037","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Do serum estradiol (E2) levels on the day of frozen blastocyst transfer (FBT) affect pregnancy outcomes in hormonal replacement therapy (HRT) cycles using transdermal estrogens?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;E2 levels ≥313 pg/ml on the day of FBT are associated with increased early miscarriage rates (EMRs), but do not significantly impact the live birth rate (LBR).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;E2 plays a crucial role in endometrial receptivity and placentation. The effect of serum E2 levels measured around the time of FBT in HRT cycles remains debated, with some studies indicating a negative impact of high E2 levels and others finding no significant difference. Currently, no studies focus exclusively on HRT cycles using transdermal estrogens, which are considered safer regarding thromboembolic complications.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design, size, duration: &lt;/strong&gt;This retrospective cohort study analyzed 2364 patients undergoing HRT-FBT cycles at a university hospital between January 2019 and December 2022. Each patient was included only once during the study period.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials, setting, methods: &lt;/strong&gt;The study involved patients undergoing single autologous FBT under HRT with transdermal estrogens and vaginal micronized progesterone. Serum E2 levels were measured in the morning of the FBT at a single laboratory. Primary outcomes included the LBR, with secondary outcomes encompassing clinical pregnancy rates, EMRs, and neonatal outcomes (birth weight and term of delivery). Patients were categorized into three groups based on E2 levels: &lt;25th centile (&lt;122 pg/ml), between 25th and 75th centile (122-312 pg/ml), and &gt;75th centile (≥313 pg/ml), and analyzed using univariate and multivariate logistic regression models.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;Of the 2364 patients, 590 were in the '&lt;122 pg/ml' group, 1184 in the '122-312 pg/ml' group, and 590 in the '≥313 pg/ml' group. The median (interquartile range) E2 level in the entire study population was 195.3 pg/ml (122.1-312.8). The LBRs across the E2 level groups were 33.7%, 31.6%, and 31.0%. Crude and adjusted odds ratios (ORs) showed no significant differences in LBR between the '&lt;122 pg/ml' and '≥313 pg/ml' groups compared to the '122-312 pg/ml' reference group (adjusted OR 0.9, 95% CI 0.72-1.14 and 0.9, 95% CI 0.69-1.09, respectively). The EMRs for the groups were 25.5%, 24.6%, and 30.3%, respectively. While crude analysis showed no differences between the groups, the multivariable analysis indicated that the '≥313 pg/ml' group had a significantly higher risk of early miscarriage compared to the reference group (adjusted OR 1.5, 95% CI 1.06-2.18). No significant differences were observed in clinical pregnancy rates or neonatal outcomes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Limitations, reasons for caution: &lt;/strong&gt;The primary limitation is the study's retrospective design, which introduces risks of selecti","PeriodicalId":13003,"journal":{"name":"Human reproduction","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572929","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}