Human reproduction open最新文献

{"title":"Paternal age and neonatal outcomes: a population-based cohort study.","authors":"Wenxue Xiong, Xijia Tang, Lu Han, Li Ling","doi":"10.1093/hropen/hoaf006","DOIUrl":"10.1093/hropen/hoaf006","url":null,"abstract":"<p><strong>Study question: </strong>Is paternal age associated with neonatal outcomes?</p><p><strong>Summary answer: </strong>Paternal age is independently associated with preterm birth (PTB) and caesarean section.</p><p><strong>What is known already: </strong>Advanced maternal age has long been recognized as a major risk factor for adverse neonatal outcomes. However, the association between paternal age and neonatal outcomes are not well established, yet it is biologically plausible that an increasing number of genetic and epigenetic sperm abnormalities in older males may contribute to adverse neonatal outcomes.</p><p><strong>Study design size duration: </strong>This population-based cohort study was based on the National Free Preconception Checkups Project between 1 January 2014 and 31 December 2019 in Guangdong Province, China. Paternal age at the maternal last menstrual period was measured. The main outcomes included caesarean section, PTB, small for gestational age (SGA) and perinatal infant death (PID).</p><p><strong>Participants/materials setting methods: </strong>A total of 783 988 mother-neonate-father trios were included in this study. A modified Poisson regression model was employed to estimate relative risk (RR) and 95% CI and logistic regression models were used to analyse the relative importance of predictors. We used restricted cubic splines to flexibly model the non-linear dose-response association between paternal age and neonatal outcomes. We also assessed additive interactions between paternal and maternal age on neonatal outcomes.</p><p><strong>Main results and the role of chance: </strong>Neonates born to fathers aged 35-44 years had higher risks of caesarean section (RR: 1.07; 95% CI: 1.06-1.09) and PTB (RR: 1.15; 95% CI: 1.10-1.19) compared with neonates of fathers aged 25-34 years, after adjustment for confounders. The increased risks of PTB associated with paternal age appeared to be 'dose' dependent, with a J-shaped association curve (<i>P</i> for non-linearity<0.001). The relative importance of paternal age in predicting PTB and caesarean section was similar to, or even higher than, that of maternal age. The combined effects of advanced maternal and paternal age appeared to be less than additive joint effects (relative excess risk due to interaction<0). The association of paternal age with SGA or PID was not statistically significant (<i>P </i>><i> </i>0.05).</p><p><strong>Limitations reasons for caution: </strong>As with all observational studies, residual confounding could not be ruled out. Only couples who planned to conceive were included.</p><p><strong>Wider implications of the findings: </strong>In this population-based cohort study, paternal age was independently associated with caesarean section and PTB. These findings may be clinically useful in preconception counselling on parental age-related pregnancy risks. Our findings emphasize the need to further investigate the public health implications of increasing p","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 1","pages":"hoaf006"},"PeriodicalIF":8.3,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11878789/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143560188","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":"Clinical and ethical perspectives of ovarian stimulation and oocyte cryopreservation in adolescents: 6 years experience from a tertiary centre.","authors":"Sania Latif, Melanie Davies, Emily Vaughan, Dimitrios Mavrelos, Stuart Lavery, Ephia Yasmin","doi":"10.1093/hropen/hoaf005","DOIUrl":"10.1093/hropen/hoaf005","url":null,"abstract":"<p><strong>Study question: </strong>What are the clinical and ethical challenges of performing ovarian stimulation and oocyte cryopreservation in adolescents and the barriers to providing treatment?</p><p><strong>Summary answer: </strong>Our study shows that, in one of the largest case series to date in this population, post-pubertal adolescents as young as age 13 years can undergo ovarian stimulation and oocyte cryopreservation with a response comparable to adults.</p><p><strong>What is known already: </strong>Fertility preservation in adolescents has not been well studied, with little data available in the existing literature. Referrals for fertility preservation in adolescents are increasing due to developments in childhood cancer treatments, which have led to a growing population of children at risk of developing premature ovarian insufficiency. Those with certain benign conditions or gender incongruence also face this challenge. All established fertility preservation guidelines state that where there is a risk to fertility, oocyte cryopreservation should be offered to post-pubertal females. However, counselling and consenting young people about fertility decisions is an ethically complex area, and assessing capacity to consent in this age group is not straightforward.</p><p><strong>Study design size duration: </strong>This was a retrospective observational cohort study of 182 referrals for fertility preservation counselling to a specialist unit, and we present outcomes for the 33 adolescents who underwent 36 cycles of ovarian stimulation and oocyte cryopreservation between January 2018 and January 2024.</p><p><strong>Participants/materials setting methods: </strong>We included patients aged 13-18 years who underwent ovarian stimulation and oocyte cryopreservation for fertility preservation due to high or intermediate risk of gonadotoxicity from medical or surgical treatment at a public-funded specialist unit. The primary outcome was oocyte yield; secondary outcomes included oocyte maturity rate, complications, and dropout rate. Data were retrieved from a prospectively managed database.</p><p><strong>Main results and the role of chance: </strong>There was a total of 182 referrals received, and of these, 33 patients underwent 36 cycles of ovarian stimulation and oocyte cryopreservation. Indications for fertility preservation included malignancy <i>n</i> = 19/36 (54%), ovarian cyst surgery <i>n</i> = 7/36 (19%), immunological disorders <i>n</i> = 4/36 (11%), benign haematological disease <i>n</i> = 2/36 (6%), gender reassignment treatment <i>n</i> = 3/36 (8%), and genetic conditions <i>n</i> = 1/36 (3%). The youngest child who underwent ovarian stimulation was aged 13 years and 10 months at the time of egg collection; the minimum time from menarche to ovarian stimulation was 4 months, the median AMH (anti-Müllerian hormone) was 16.7 pmol/l (range 2.8-36.9 pmol/l), and the antral follicle count (AFC) was 11 (3-36). The median number of cryoprese","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 1","pages":"hoaf005"},"PeriodicalIF":8.3,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11825388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143434439","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":"Trial characteristics, geographic distribution, and selected methodological issues of 1425 infertility trials published from 2012 to 2023: a systematic review.","authors":"Qian Feng, Wanlin Li, James Crispin, Salvatore Longobardi, Thomas D'Hooghe, Ben W Mol, Wentao Li","doi":"10.1093/hropen/hoaf004","DOIUrl":"10.1093/hropen/hoaf004","url":null,"abstract":"<p><strong>Study question: </strong>What are the trial characteristics, geographic distribution, and selected methodological issues of randomized controlled trials (RCTs) in infertility published from 2012 to 2023?</p><p><strong>Summary answer: </strong>Of the 1425 infertility RCTs, over two-thirds focused on IVF, nearly two-fifths did not use pregnancy or live birth as the primary outcome, a third lacked a primary outcome, a half were unregistered, and just over half were conducted in China (22%), Iran (20%), or Egypt (10%).</p><p><strong>What is known already: </strong>RCTs are the main source of evidence on the effectiveness of interventions. Knowledge about RCTs in infertility from the recent past will help to pinpoint research gaps and prioritize the future research agenda. Here, we aim to present a descriptive analysis of trial characteristics, geographic distribution, and selected methodological issues in infertility trials published in the last decade.</p><p><strong>Study design size duration: </strong>This is a systematic review. We systematically searched Embase, Medline, and Cochrane Central for RCTs in infertility from January 2012 to August 2023. RCTs involving subfertile women and women who reported pregnancy endpoints were eligible, while conference abstracts or secondary analyses were not. We did not limit our search based on the language of the articles.</p><p><strong>Participants/materials setting methods: </strong>The full articles were text-mined and manually extracted for the description of trials' characteristics (e.g. sample size, blinding method, types of intervention), the country where the patients were recruited, and methodological issues (trial registrations and specification of primary outcomes). We extracted funding statements from Dimensions, a literature database chosen for its comprehensive and robust metadata. Gross domestic product (GDP) data were obtained from the United Nations' official website. The accuracy of extracted data was validated in a random sample of 50 articles, and false positivity and false negativity were all at or below 8%. We used descriptive statistics, including frequencies and percentages to illustrate the overall and temporal trends.</p><p><strong>Main results and the role of chance: </strong>Among 8757 records, we found 1425 eligible RCTs, with a median sample size of 140, and 33.3% had a sample size <100. Most (69.6%) of the trials focused on IVF, with the rest focusing on ovulation induction (12.4%), intrauterine insemination (10.6%), surgeries (4.8%), or other interventions (2.6%). Regarding the geographic distribution, China (n = 310), Iran (n = 284), and Egypt (n = 138) contributed to 51% of the RCTs, followed by Turkey (n = 82), India (n = 71), and the USA (n = 69); mainland Europe produced 343 trials. Ranked by publications of trials per trillion GDP, Greece had the most papers with 4.6, followed by Iraq at 3.9, and Iran at 2.5. Regarding trial registration, 47.8% of trials were u","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 1","pages":"hoaf004"},"PeriodicalIF":8.3,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842059/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143470181","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":"FAP+ activated fibroblasts are detectable in the microenvironment of endometriosis and correlate with stroma composition and infiltrating CD8+ and CD68+ cells.","authors":"Franziska Kellers, Ulf Lützen, Frederik Verburg, Annett Lebenatus, Karolin Tesch, Fatih Yalcin, Moritz Jesinghaus, Valentina Stoll, Hanna Grebe, Christoph Röcken, Dirk Bauerschlag, Björn Konukiewitz","doi":"10.1093/hropen/hoaf003","DOIUrl":"10.1093/hropen/hoaf003","url":null,"abstract":"<p><strong>Study question: </strong>Do activated fibroblasts expressing fibroblast activation protein-α (FAP) - which is traceable in positron emission topography/computed topography (PET/CT) - play a role in the microenvironment of endometriosis?</p><p><strong>Summary answer: </strong>Activated fibroblasts expressing FAP are detectable in endometriotic lesions and correlate with iron and collagen content and infiltrating CD8-positive cytotoxic T cells and CD68-positive macrophages in the microenvironment endometriotic lesions.</p><p><strong>What is known already: </strong>FAP-positive activated fibroblasts are found in various fibrosis-related pathologies and in the desmoplastic stroma of solid tumours; they can be traced in PET/CT but have not been investigated in the context of endometriosis, a chronic disease involving hormone-mediated repetitive tissue remodelling and fibrosis.</p><p><strong>Study design size duration: </strong>We analysed a cohort of endometriosis patients (n = 159) who had undergone surgery with removal of endometriotic foci at our University Hospital (tertiary care centre) between 2018 and 2024. All patients provided written informed consent. The median age of the patients was 34 years. In total, 245 samples from different locations were analysed retrospectively.</p><p><strong>Participants/materials setting methods: </strong>We investigated the expression of FAP and its relation to stroma composition and the immune microenvironment of endometriosis in 245 specimens from peritoneal lesions, ovarian endometriomas, deep infiltrating endometriosis, and extra-abdominal lesions using conventional histology and immunohistochemistry followed by digital image analysis. Tissue within a radius of 500 µm of ectopic endometrium-like epithelium was analysed. To measure FAP expression in the perilesional stroma, a histoscore (H-score) was calculated. Masson trichrome staining was used to determine collagen content. Prussian blue staining for iron was used for age-dating of lesions. The abundance of CD68-positive macrophages and CD8-positive cytotoxic T cells within the microenvironment of ectopic endometriotic glands was analysed. Extra-lesional tissue served as controls.</p><p><strong>Main results and the role of chance: </strong>Distinct FAP expression (H-score >10) was observed in 84% of endometriotic lesions and in only 4% of extra-lesional controls. FAP expression was significantly higher in endometriotic lesions (mean H-score 61.8) than in extra-lesional tissue (mean H-score 3.8, <i>P</i> < 0.0001). There was a significant (<i>P</i> < 0.05) association with collagen content when comparing samples with low (H-score <100) and high (H-score ≥100) FAP expression, and a significant difference in FAP expression correlating with the tissue iron content when comparing strong staining intensity and negative samples (<i>P</i> < 0.0005) or samples with weak staining intensity (<i>P</i> < 0.005). Moreover, the abundance of CD8-positive and CD","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 1","pages":"hoaf003"},"PeriodicalIF":8.3,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11829078/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143434441","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":"Hormone receptor profile of ectopic and eutopic endometrium in adenomyosis: a systematic review.","authors":"Alison Maclean, Laura Tipple, Emily Newton, Dharani K Hapangama","doi":"10.1093/hropen/hoaf002","DOIUrl":"10.1093/hropen/hoaf002","url":null,"abstract":"<p><strong>Study question: </strong>What is the hormone receptor profile of adenomyosis lesions in comparison to correctly located endometrium?</p><p><strong>Summary answer: </strong>Adenomyosis lesions exhibit increased oestrogen receptor (ER) expression compared to the eutopic endometrium; there are conflicting results regarding progesterone receptor (PR) expression and a lack of studies on androgen receptor (AR) expression.</p><p><strong>What is known already: </strong>Adenomyosis lesions express hormone receptors indicating an influence from ovarian steroid hormones. However, hormone treatments are often ineffective in controlling adenomyosis symptoms, which suggests alternate hormonal responses and, potentially, a distinct hormone receptor expression profile within adenomyosis lesions compared to the eutopic endometrium.</p><p><strong>Study design size duration: </strong>This systematic review with a thematic analysis retrieved studies from the PubMed, Ovid Medline, Embase, Scopus, and Cochrane Library databases, and searches were conducted from inception through to May 2024. Human studies were included and identified using a combination of exploded MeSH terms ('adenomyosis') and free-text search terms ('oestrogen receptor', 'progesterone receptor', 'androgen receptor', 'hormone receptor').</p><p><strong>Participants/materials setting methods: </strong>This review was reported in accordance with the PRISMA guidelines. All studies reporting original data concerning hormone receptors in adenomyosis lesions compared to eutopic endometrium in adenomyosis were included. Studies that did not report original data or provide a review of the field were excluded. Bias analysis was completed for each study using the Newcastle-Ottawa scoring system.</p><p><strong>Main results and the role of chance: </strong>There were 1905 studies identified, which were screened to include 12 studies that met the eligibility criteria, including 11 proteomic studies and one transcriptional study, with a total of 555 individual participants. ER expression was consistently increased in adenomyosis lesions compared to the eutopic endometrium, specifically in the secretory phase. When endometrial subregion was considered, this difference was specific to the endometrial functionalis only. When different isoforms were considered, this increase in ER expression was specific to ERα rather than ERβ. There were conflicting results on PR expression, with most studies showing no significant difference or reduced levels in adenomyosis lesions compared to the eutopic endometrium. There is a paucity of data on AR expression in adenomyosis lesions, with only one study of small sample size included.</p><p><strong>Limitations reasons for caution: </strong>A high risk of bias arose from studies grouping endometrial samples across different menstrual cycle phases for analysis. The coexistence of gynecological conditions like endometriosis may also confound the hormone receptor profile of t","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 1","pages":"hoaf002"},"PeriodicalIF":8.3,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11810641/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143400819","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":"Now is the time to introduce new innovative assisted reproduction methods to implement accessible, affordable, and demonstrably successful advanced infertility services in resource-poor countries.","authors":"Willem Ombelet, Jonathan Van Blerkom, Gerhard Boshoff, Carin Huyser, Federica Lopes, Geeta Nargund, Hassan Sallam, Koen Vanmechelen, Rudi Campo","doi":"10.1093/hropen/hoaf001","DOIUrl":"10.1093/hropen/hoaf001","url":null,"abstract":"<p><p>Nearly 200 million people worldwide suffer from infertility. Disparities exist between developed and developing countries due to differences in the availability of infertility care, different reimbursement policies and socio-cultural differences surrounding procreation. In low- and middle-income countries, specialized infertility centres are either scarce or non-existent, mostly in private settings, and accessible only to the fortunate few who can afford them. The success and sustainability of ARTs will depend on our ability to optimize these techniques in terms of availability, affordability, and effectiveness. A low-cost, simplified IVF system has been developed and shown to be safe, cost-effective, and widely applicable to low-resource settings. Combined with inexpensive mild ovarian stimulation protocols, this could become a truly effective means of treating infertility and performing assisted reproduction at affordable prices, but only if such programmes are sincerely desired and supported by all relevant stakeholders. A receptive political, governmental, and clinical community is essential.</p>","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 1","pages":"hoaf001"},"PeriodicalIF":8.3,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11810638/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143400878","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":"Birth defects reporting and the use of dydrogesterone: a disproportionality analysis from the World Health Organization pharmacovigilance database (VigiBase).","authors":"Alexandra Henry, Pietro Santulli, Mathilde Bourdon, Chloé Maignien, Charles Chapron, Jean-Marc Treluyer, Jean Guibourdenche, Laurent Chouchana","doi":"10.1093/hropen/hoae072","DOIUrl":"10.1093/hropen/hoae072","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Is there an association between dydrogesterone exposure during early pregnancy and the reporting of birth defects?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;This observational analysis based on global safety data showed an increased reporting of birth defects, mainly hypospadias and congenital heart defects (CHD), in pregnancies exposed to dydrogesterone, especially when comparing to progesterone.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;Intravaginal administration of progesterone is the standard of care to overcome luteal phase progesterone deficiency induced by ovarian stimulation in ART. In recent years, randomized controlled clinical trials demonstrated that oral dydrogesterone was non-inferior for pregnancy rate at 12 weeks of gestation and could be an alternative to micronized vaginal progesterone. Safety profiles in both mother and child were similar. However, concerns have been raised regarding an association between dydrogesterone usage during early pregnancy and CHD in offspring.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;We performed a disproportionality analysis, also called case-non-case study, similar in concept to case-control studies, using the WHO global safety database, VigiBase. The study cohort consisted of individual pregnancy-related safety reports, using the &lt;i&gt;ad hoc&lt;/i&gt; standardized query (SMQ 'Pregnancy and neonatal topics'). Cases of birth defects consisted of safety reports containing terms related to the 'congenital, familial and genetic disorders' System Organ Class from the Medical Dictionary for Regulatory Activities. Non-cases consisted of safety reports containing any other adverse event, in pregnancy-related safety reports.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;Considering reports since database inception to 31 December 2021, we first compared the reporting of birth defects with dydrogesterone to that of any other drug on the database, then to any other drug used for ART. Secondly, we performed a comparison on the reporting of birth defects for dydrogesterone with progesterone. Results are presented as reporting odds ratio (ROR) and their 95% CI. For each comparison, two sensitivity analyses were performed. Finally, a case-by-case review was performed to further characterize major birth defects and sort anomalies according to classification of EUROCAT.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;Study cohort consisted of 362 183 safety reports in pregnant women, among which 50 653 reports were related to the use of drugs for ART, including 145 with dydrogesterone and 1222 with progesterone. Of these, 374 (0.7%) were cases of birth defects: 60 with dydrogesterone and 141 with progesterone, including 48 and 92 cases compatible with major birth defect cases according to EUROCAT classification, respectively. Major birth defects reported with dydrogesterone were mainly genital defects such as hypospadias and CHD. A significantly hi","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 1","pages":"hoae072"},"PeriodicalIF":8.3,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11726828/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142980906","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 interplay between mitochondrial DNA genotypes, female infertility, ovarian response, and mutagenesis in oocytes.","authors":"Annelore Van Der Kelen, Letizia Li Piani, Joke Mertens, Marius Regin, Edouard Couvreu de Deckersberg, Hilde Van de Velde, Karen Sermon, Herman Tournaye, Willem Verpoest, Frederik Jan Hes, Christophe Blockeel, Claudia Spits","doi":"10.1093/hropen/hoae074","DOIUrl":"10.1093/hropen/hoae074","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Is there an association between different mitochondrial DNA (mtDNA) genotypes and female infertility or ovarian response, and is the appearance of variants in the oocytes favored by medically assisted reproduction (MAR) techniques?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;Ovarian response was negatively associated with global non-synonymous protein-coding homoplasmic variants but positively associated with haplogroup K; the number of oocytes retrieved in a cycle correlates with the number of heteroplasmic variants in the oocytes, principally with variants located in the hypervariable (HV) region and rRNA loci, as well as non-synonymous protein-coding variants.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;Several genes have been shown to be positively associated with infertility, and there is growing concern that MAR may facilitate the transmission of these harmful variants to offspring, thereby passing on infertility. The potential role of mtDNA variants in these two perspectives remains poorly understood.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;This cohort study included 261 oocytes from 132 women (mean age: 32 ± 4 years) undergoing ovarian stimulation between 2019 and 2020 at an academic center. The oocyte mtDNA genotypes were examined for associations with the women's fertility characteristics.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;The mtDNA of the oocytes underwent deep sequencing, and the mtDNA genotypes were compared between infertile and fertile groups using Fisher's exact test. The impact of the mtDNA genotype on anti-Müllerian hormone (AMH) levels and the number of (mature) oocytes retrieved was assessed using the Mann-Whitney &lt;i&gt;U&lt;/i&gt; test for univariate analysis and logistic regression for multivariate analysis. Additionally, we examined the associations of oocyte maturation stage, infertility status, number of ovarian stimulation units, and number of oocytes retrieved with the type and load of heteroplasmic variants using univariate analysis and Poisson or linear regression analysis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;Neither homoplasmic mtDNA variants nor haplogroups in the oocytes were associated with infertility status or with AMH levels. Conversely, when the relationship between the number of oocytes retrieved and different mtDNA genotypes was examined, a positive association was observed between the number of metaphase (MII) oocytes (&lt;i&gt;P&lt;/i&gt; = 0.005) and haplogroup K. Furthermore, the presence of global non-synonymous homoplasmic variants in the protein-coding region was significantly associated with a reduced number of total oocytes and MII oocytes retrieved (&lt;i&gt;P&lt;/i&gt; &lt; 0.001 for both). Regarding the type and load of heteroplasmic variants in the different regions, there were no significant associations according to maturation stage of the oocyte or to fertility status; however, the number of oocytes retrieved correlated positively w","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 1","pages":"hoae074"},"PeriodicalIF":8.3,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11739621/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017655","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":"Unmasking the risk: clinical trials <i>versus</i> real-world evidence on dydrogesterone and birth defects.","authors":"Fabio Parazzini, Anna Cantarutti, Giovanna Esposito","doi":"10.1093/hropen/hoae073","DOIUrl":"10.1093/hropen/hoae073","url":null,"abstract":"","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 1","pages":"hoae073"},"PeriodicalIF":8.3,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11726824/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142980908","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":"Evidence-based guideline: premature ovarian insufficiency<sup />.","authors":"Nick Panay, Richard A Anderson, Amy Bennie, Marcelle Cedars, Melanie Davies, Carolyn Ee, Claus H Gravholt, Sophia Kalantaridou, Amanda Kallen, Kimberly Q Kim, Micheline Misrahi, Aya Mousa, Rossella E Nappi, Walter A Rocca, Xiangyan Ruan, Helena Teede, Nathalie Vermeulen, Elinor Vogt, Amanda J Vincent","doi":"10.1093/hropen/hoae065","DOIUrl":"10.1093/hropen/hoae065","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;How should premature/primary ovarian insufficiency (POI) be diagnosed and managed based on the best available evidence from published literature?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;The current guideline provides 145 recommendations on symptoms, diagnosis, causation, sequelae, and treatment of POI.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;Premature ovarian insufficiency (POI) presents a significant challenge to women's health, with far-reaching implications, both physically and emotionally. The potential implications include adverse effects on quality of life; fertility; and bone, cardiovascular, and cognitive health. Although hormone therapy (HT) can mitigate some of these effects, many questions still remain regarding the optimal management of POI.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;The guideline was developed according to the structured methodology for development of ESHRE guidelines. Key questions were determined by a group of experts and informed by a scoping survey of women and health care professionals. Literature searches and assessments were then performed. Papers published up to 30 January 2024 and written in English were included in the guideline. An integrity review was conducted for the randomized controlled trials (RCTs) on POI included in the guideline.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;Based on the collected evidence, recommendations were formulated and discussed within the guideline development group until consensus was reached. Women with lived experience of POI informed the recommendations in general, and particularly on those on provision of care. A stakeholder review was organized after finalization of the draft. The final version was approved by the guideline development group and the ESHRE Executive Committee.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;New data indicate a higher prevalence of POI, 3.5%, than was previously thought. This guideline aims to help health care professionals to apply best practice care for women with POI. The recent update of the POI guideline covers 40 clinical questions on diagnosis of the condition, the different sequelae, including bone, cardiovascular, neurological and sexual function, fertility and general well-being, and treatment options, including HT. The list of clinical questions was expanded from the previous iteration of the guideline (2015) based on the scoping survey and appreciation of emerging knowledge of POI. Questions were added on the role of anti-Müllerian hormone (AMH) in the diagnosis of POI, fertility preservation, muscle health, and specific considerations for HT in iatrogenic POI. Additionally, the topic on complementary treatments was extended with specific focus on non-hormonal treatments and lifestyle management options. Significant changes from the previous 2015 guideline include the recommendations that only one elevated FSH &gt;25 IU is required for diagnosis of P","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 4","pages":"hoae065"},"PeriodicalIF":8.3,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631070/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142808392","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}