Human reproduction open最新文献

{"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}

{"title":"Independent factors associated with intracytoplasmic sperm injection outcomes in patients with complete azoospermia factor c microdeletions.","authors":"Yangyi Fang, Zhe Zhang, Yinchu Cheng, Zhigao Huang, Jiayuan Pan, Zixuan Xue, Yidong Chen, Vera Y Chung, Li Zhang, Kai Hong","doi":"10.1093/hropen/hoae071","DOIUrl":"10.1093/hropen/hoae071","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Which independent factors influence ICSI outcomes in patients with complete azoospermia factor c (AZFc) microdeletions?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;In patients with complete AZFc microdeletions, the sperm source, male LH, the type of infertility in women, and maternal age are the independent factors associated with ICSI outcomes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;AZF microdeletions are the second most prevalent factor contributing to infertility in men, with AZFc microdeletions being the most frequently affected locus, accounting for 60-70% of all cases. The primary clinical phenotypes are oligoasthenozoospermia and azoospermia in patients with complete AZFc microdeletions. These patients can achieve paternity through ICSI using either testicular (T-S) or ejaculated (E-S) spermatozoa. With aging in men with AZFc microdeletions, oligoasthenozoospermia or severe oligozoospermia may gradually progress to azoospermia.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;In this retrospective cohort study, the independent factors associated with the outcomes of 634 ICSI cycles in 634 couples with the transfer of 1005 embryos between February 2015 and December 2023 were evaluated. The analysis included 398 ICSI cycles in 398 couples using E-S and 236 ICSI cycles in 236 couples using T-S; all men had complete AZFc microdeletions.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;The inclusion criteria were as follows: (i) men had complete AZFc microdeletions and (ii) the couple underwent ICSI treatment using T-S or E-S. The exclusion criteria were as follows: (i) cycles involving frozen-thawed oocytes; (ii) cycles in which all fresh embryos were frozen and not transferred; (iii) cycles lost to follow-up; and (iv) multiple ICSI cycles, apart from the first cycle for each couple. The primary outcome was the cumulative live birth rate per ICSI cycle, whereas the secondary outcomes were the clinical pregnancy rate per ICSI cycle, fertilization rate, and the no-embryo-suitable-for-transfer cycle rate (NESTR). Moreover, the maternal and neonatal outcomes were analyzed. Continuous variables showing non-normal distributions were expressed as median and interquartile range and were analyzed using the Kruskal-Wallis test. Categorical variables were expressed as percentages and were analyzed using the χ&lt;sup&gt;2&lt;/sup&gt; or Fisher's exact test. Linear and logistic regression models were constructed to assess the independent factors associated with ICSI outcomes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;The T-S group exhibited inferior ICSI outcomes than the E-S group, marked by significantly reduced rates of cumulative live birth, clinical pregnancy, fertilization, high-quality embryos, blastocyst formation, and implantation, with higher NESTRs. However, the miscarriage rate and neonatal outcomes did not significantly differ between the groups. Multivariate linear regression analysi","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 4","pages":"hoae071"},"PeriodicalIF":8.3,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11652272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142857140","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":"AI predictive models and advancements in microdissection testicular sperm extraction for non-obstructive azoospermia: a systematic scoping review.","authors":"Hossein Jamalirad, Mahdie Jajroudi, Bahareh Khajehpour, Mohammad Ali Sadighi Gilani, Saeid Eslami, Marjan Sabbaghian, Hassan Vakili Arki","doi":"10.1093/hropen/hoae070","DOIUrl":"10.1093/hropen/hoae070","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;How accurately can artificial intelligence (AI) models predict sperm retrieval in non-obstructive azoospermia (NOA) patients undergoing micro-testicular sperm extraction (m-TESE) surgery?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;AI predictive models hold significant promise in predicting successful sperm retrieval in NOA patients undergoing m-TESE, although limitations regarding variability of study designs, small sample sizes, and a lack of validation studies restrict the overall generalizability of studies in this area.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;Previous studies have explored various predictors of successful sperm retrieval in m-TESE, including clinical and hormonal factors. However, no consistent predictive model has yet been established.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;A comprehensive literature search was conducted following PRISMA-ScR guidelines, covering PubMed and Scopus databases from 2013 to 15 May 2024. Relevant English-language studies were identified using Medical Subject Headings (MeSH) terms. We also used PubMed's 'similar articles' and 'cited by' features for thorough bibliographic screening to ensure comprehensive coverage of relevant literature.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;The review included studies on patients with NOA where AI-based models were used for predicting m-TESE outcomes, by incorporating clinical data, hormonal levels, histopathological evaluations, and genetic parameters. Various machine learning and deep learning techniques, including logistic regression, were employed. The Prediction Model Risk of Bias Assessment Tool (PROBAST) evaluated the bias in the studies, and their quality was assessed using the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD) guidelines, ensuring robust reporting standards and methodological rigor.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;Out of 427 screened articles, 45 met the inclusion criteria, with most using logistic regression and machine learning to predict m-TESE outcomes. AI-based models demonstrated strong potential by integrating clinical, hormonal, and biological factors. However, limitations of the studies included small sample sizes, legal barriers, and challenges in generalizability and validation. While some studies featured larger, multicenter designs, many were constrained by sample size. Most studies had a low risk of bias in participant selection and outcome determination, and two-thirds were rated as low risk for predictor assessment, but the analysis methods varied.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Limitations reasons for caution: &lt;/strong&gt;The limitations of this review include the heterogeneity of the included research, potential publication bias and reliance on only two databases (PubMed and Scopus), which may limit the scope of the findings. Additionally, the absence of a meta-analysis prevents quantit","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2025 1","pages":"hoae070"},"PeriodicalIF":8.3,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11700607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069933","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":"A comprehensive study of common and rare genetic variants in spermatogenesis-related loci identifies new risk factors for idiopathic severe spermatogenic failure.","authors":"Andrea Guzmán-Jiménez, Sara González-Muñoz, Miriam Cerván-Martín, Nicolás Garrido, José A Castilla, M Carmen Gonzalvo, Ana Clavero, Marta Molina, Saturnino Luján, Samuel Santos-Ribeiro, Miguel Ángel Vilches, Andrea Espuch, Vicente Maldonado, Noelia Galiano-Gutiérrez, Esther Santamaría-López, Cristina González-Ravina, Fernando Quintana-Ferraz, Susana Gómez, David Amorós, Luis Martínez-Granados, Yanira Ortega-González, Miguel Burgos, Iris Pereira-Caetano, Ozgur Bulbul, Stefano Castellano, Massimo Romano, Elena Albani, Lluís Bassas, Susana Seixas, João Gonçalves, Alexandra M Lopes, Sara Larriba, Rogelio J Palomino-Morales, F David Carmona, Lara Bossini-Castillo","doi":"10.1093/hropen/hoae069","DOIUrl":"10.1093/hropen/hoae069","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Study question: &lt;/strong&gt;Can genome-wide genotyping data be analysed using a hypothesis-driven approach to enhance the understanding of the genetic basis of severe spermatogenic failure (SPGF) in male infertility?&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Summary answer: &lt;/strong&gt;Our findings revealed a significant association between SPGF and the &lt;i&gt;SHOC1&lt;/i&gt; gene and identified three novel genes (&lt;i&gt;PCSK4&lt;/i&gt;, &lt;i&gt;AP3B1&lt;/i&gt;, and &lt;i&gt;DLK1&lt;/i&gt;) along with 32 potentially pathogenic rare variants in 30 genes that contribute to this condition.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;What is known already: &lt;/strong&gt;SPGF is a major cause of male infertility, often with an unknown aetiology. SPGF can be due to either multifactorial causes, including both common genetic variants in multiple genes and environmental factors, or highly damaging rare variants. Next-generation sequencing methods are useful for identifying rare mutations that explain monogenic forms of SPGF. Genome-wide association studies (GWASs) have become essential approaches for deciphering the intricate genetic landscape of complex diseases, offering a cost-effective and rapid means to genotype millions of genetic variants. Novel methods have demonstrated that GWAS datasets can be used to infer rare coding variants that are causal for male infertility phenotypes. However, this approach has not been previously applied to characterize the genetic component of a whole case-control cohort.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Study design size duration: &lt;/strong&gt;We employed a hypothesis-driven approach focusing on all genetic variation identified, using a GWAS platform and subsequent genotype imputation, encompassing over 20 million polymorphisms and a total of 1571 SPGF patients and 2431 controls. Both common (minor allele frequency, MAF &gt; 0.01) and rare (MAF &lt; 0.01) variants were investigated within a total of 1797 loci with a reported role in spermatogenesis. This gene panel was meticulously assembled through comprehensive searches in the literature and various databases focused on male infertility genetics.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants/materials setting methods: &lt;/strong&gt;This study involved a European cohort using previously and newly generated data. Our analysis consisted of three independent methods: (i) variant-wise association analyses using logistic regression models, (ii) gene-wise association analyses using combined multivariate and collapsing burden tests, and (iii) identification and characterisation of highly damaging rare coding variants showing homozygosity only in SPGF patients.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Main results and the role of chance: &lt;/strong&gt;The variant-wise analyses revealed an association between SPGF and &lt;i&gt;SHOC1&lt;/i&gt;-rs12347237 (&lt;i&gt;P &lt;/i&gt;=&lt;i&gt; &lt;/i&gt;4.15E-06, odds ratio = 2.66), which was likely explained by an altered binding affinity of key transcription factors in regulatory regions and the disruptive effect of coding variants within the gene. Three additional genes (&lt;i&gt;PCSK4&lt;/i&gt;, &lt;i&gt;AP3B1&lt;/i&gt;, and &lt;i&gt;DLK1&lt;/i&gt;) were identified as novel relevan","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 4","pages":"hoae069"},"PeriodicalIF":8.3,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11645127/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142830969","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":"Reply: Birth rate decline, COVID-19 pandemic, and vaccination programmes.","authors":"Tomáš Sobotka, Maria Winkler-Dworak, Kryštof Zeman","doi":"10.1093/hropen/hoae068","DOIUrl":"10.1093/hropen/hoae068","url":null,"abstract":"","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 4","pages":"hoae068"},"PeriodicalIF":8.3,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11590250/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142735208","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 rate decline, COVID-19 pandemic, and vaccination programmes.","authors":"Hinpetch Daungsupawong, Viroj Wiwanitkit","doi":"10.1093/hropen/hoae067","DOIUrl":"10.1093/hropen/hoae067","url":null,"abstract":"","PeriodicalId":73264,"journal":{"name":"Human reproduction open","volume":"2024 4","pages":"hoae067"},"PeriodicalIF":8.3,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11590251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142735206","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}