Angiogénese como um alvo terapêutico para a endometriose

Copyright © Ordem dos Médicos 2014Introduction: Angiogenesis is a key factor for the successful establishment and growth of endometriotic lesions. Material and methods: We performed a literature search in PubMed and reviewed the most pertinent studies published until January 2014 and focused on the endometriosis-associated angiogenesis and/or anti-angiogenic strategies for the treatment of this gynecological disorder. Results: The present review provides a concise summary of the known molecular mechanisms that promote vascularization of endometriotic lesions and may serve as potential therapeutic targets. We also present a systematic overview of the inclusive and exclusive anti-angiogenic agents that have been already studied in cell cultures, animal models and/or endometriosis patients. Discussion and conclusion: The integration of anti-angiogenic approaches in the multimodal management strategies for endometriosis patients will be conditioned by the outcomes of future assessments regarding the effectiveness of such treatments, the risk of drug resistance development and the incidence of unacceptable side effects.info:eu-repo/semantics/publishedVersio

Somatic stem cells and their dysfunction in endometriosis

Copyright: © 2015 Djokovic and Calhaz-Jorge. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Emerging evidence indicates that somatic stem cells (SSCs) of different types prominently contribute to endometrium-associated disorders such as endometriosis. We reviewed the pertinent studies available on PubMed, published in English language until December 2014 and focused on the involvement of SSCs in the pathogenesis of this common gynecological disease. A concise summary of the data obtained from in vitro experiments, animal models, and human tissue analyses provides insights into the SSC dysregulation in endometriotic lesions. In addition, a set of research results is presented supporting that SSC-targeting, in combination with hormonal therapy, may result in improved control of the disease, while a more in-depth characterization of endometriosis SSCs may contribute to the development of early-disease diagnostic tests with increased sensitivity and specificity. Key message: Seemingly essential for the establishment and progression of endometriotic lesions, dysregulated SSCs, and associated molecular alterations hold a promise as potential endometriosis markers and therapeutic targets.info:eu-repo/semantics/publishedVersio

Modelo de ensino aprendizagem em grupos numa disciplina clínica do curso de Medicina

In medical education there is a long experience of small group teaching and learning (mainly problem-centred). This methodology requires a considerable number of teachers/tutors and seems more adequate for a coherent introduction of clinical elements during basic sciences learning than in the clinical years. Its use in a pure clinical setting demands specific modifications.In the academic year of 2006-2007 a new model for theoretical-practical sessions in Gynaecology was established for the students of Obstetrics and Gynaecology: discussion of a short clinical case (including a list of possible diagnosis, adequate clinical investigation and treatment proposals) in groups of 8 to 10 students followed by discussion among groups, after which the teacher produced a synthesis of the case. The total number of students involved in this program was divided in three groups throughout the year. A Likert-type questionnaire was used to assess how the students responded to the new methodology and to compare the acceptance with that of the established model used in the theoretical-practical sessions of Obstetrics. The correlation between the results of the written summative evaluation related to the experimental model and the global quantitative assessment of the discipline was also studied. More than 90% of the students rated as either “Very useful” or “Extremely useful” the possibility to study on clinical “real” situations, the final discussion with the teacher and the possibility to check and discuss the results of their group with those of the other groups in the class. A little more than 61% of the students showed preference for the new model. The evaluation of the answers of the three groups showed that the first one had, in general, the worst results. In the whole group of students, a positive significant correlation was found between the results of the specific written evaluation concerning the theoretical-practical sessions in Gynaecology and the overall written assessment of the discipline. Within-group analysis showed that the correlation was statistically significant only in one of the groups. In conclusion, this thesis was based on a pilot study applying an educational model for groups learning in a real situation. The response of the students to the model was very positive but there was not a clear preference for this methodology when compared to the one traditionally used in the discipline. The detailed implications of the results are discussed and some issues of the undergraduate curriculum in Medicine course are approached in a reflexive manner.Na educação médica há uma experiência longa de ensino e aprendizagem em pequenos grupos (essencialmente para resolução de problemas). Essa metodologia, além de requerer número considerável de docentes-tutores, parece mais adequada à introdução coerente de elementos clínicos na aprendizagem das ciências básicas do que ao ciclo clínico da formação pré-graduada. A sua aplicação às disciplinas clínicas impõe adaptações específicas. Para os alunos da disciplina de Obstetrícia e Ginecologia da Faculdade de Medicina de Lisboa no ano lectivo de 2006-2007 foi estabelecido um novo modelo de aulas teórico-práticas de Ginecologia: discussão de uma história clínica breve (com elaboração de hipóteses diagnósticas, subsequente investigação e propostas terapêuticas) em grupos de 8 a 10 alunos seguida de discussão entre os grupos e integração final pelo docente. O total dos alunos do curso foi distribuído por três blocos aproximadamente iguais ao longo do ano. A avaliação da adesão dos alunos à metodologia e a comparação com o modelo clássico de aulas teórico-práticas usado nas aulas de Obstetrícia foram efectuadas através de questionário essencialmente com perguntas fechadas (tipo escala de Likert). Foi também avaliada a correlação entre o resultado da avaliação específica das aulas teórico-práticas de Ginecologia e o resultado da avaliação teórica global da cadeira. Mais de 90% dos alunos consideraram “Muito útil“ ou “Extremamente útil“ a possibilidade de estudar sobre casos concretos, a resolução final dos casos discutida como docente e a possibilidade de conferir os resultados do seu grupo com os dos outros grupos. Cerca de 61% dos alunos disseram preferir o novo modelo, em relação ao clássico. A avaliação dos resultados dos três grupos mostra globalmente uma pior adesão no primeiro bloco de alunos. No grupo total de alunos encontrou-se uma correlação positiva significativa entre o resultado da avaliação específica das aulas teórico-práticas de Ginecologia e o resultado da avaliação global da disciplina. Analisando separadamente os grupos, essa correlação foi estatisticamente significativa apenas num dos blocos. Em conclusão, esta investigação-piloto desenvolvida em situação real teve grande adesão dos alunos ao modelo, embora não fosse nítida uma preferência por esta estratégia educativa quando comparada com a mais usual na disciplina. As implicações detalhadas dos resultados são discutidas ao longo do texto, sendo também abordados, de modo reflexivo, alguns aspectos do ensino pré-graduado da Medicina

Impacto do índice de massa corporal na histerectomia totalmente laparoscópica

Total laparoscopic hysterectomy: impact of body mass index on outcomesOverviewand aims: Hysterectomy is one of the most common gynecological surgical procedures and several studies have demonstrated the multiple advantages of laparoscopic approach in general. Obesity was initially considered to be a contraindication for laparoscopy. However, this historical perspective has been disputed. The aim of this study was to assess the effect of the body mass index (BMI) on intra-operative parameters and intra and post-operative complication rates of total laparoscopic hysterectomy (TLH). Study design: A retrospective, observational, descriptive and analytic study. Population: AllTLH performed in our department, by the same surgical team, between April 2009 and March 2014,were evaluated. Methods:Medicalrecordswere reviewed for patient characteristics(BMI, age, medical and surgical history),surgical characteristics (surgical indication and concomitant procedure, uterine weight, operating time, post-operative hemoglobin variation, length of hospitalstay), and intra and post-operative complications.The datawere analyzed according to patients’BMI. Results: The study population was divided in normal BMI (n=145), overweight (n=119) and obese (n=54). Obese patients were older, more frequently postmenopausal and with more medical pathology than normal BMI patients.More than 50% of the patients had history of at least one previous abdominopelvic surgery with no differences among the groups. No significant differences were found in terms of uterine weight (217.7 ± 154.8 vs. 257.5 ± 176.1 vs. 225.4 ± 151.0 g; p> 0.05), post-operative hospital stay (1.6 ± 0.9 vs. 1.5 ± 1.0 vs. 1.5 ± 0.9 days; p> 0.05), operating time (72.2 ± 25.3 vs.77.5 ± 25.8 vs. 83.6 ± 35.3 minutes; p> 0.05) or complication rates (12.4% vs. 14.3% vs. 13.0%). Conclusions: This study demonstrates that, in qualified hands, obesity did not increase the operating time and the intra or post-operative complication rates associated with TLH. Thus, high BMI should not be considered a contraindication for this procedur

Total laparoscopic hysterectomy: retrospective analysis of 262 cases

Introdução: A histerectomia é a cirurgia ginecológica major mais frequentemente realizada nos países desenvolvidos, considerando- -se três principais vias de abordagem: vaginal, abdominal e laparoscópica. Apesar de múltiplas vantagens, a histerectomia totalmente laparoscópica tem-se associado a controvérsia relativamente à taxa de complicações. Objectivos: Análise da nossa casuística de histerectomia totalmente laparoscópica e avaliação da taxa de complicações. Material e Métodos: Análise retrospetiva dos processos clínicos das doentes submetidas a histerectomia totalmente laparoscópica no nosso departamento, pela mesma equipa cirúrgica, entre abril de 2009 e março de 2013 (n = 262). Resultados: As doentes tinham em média 48,9 ± 9 anos e 49,2% tinha antecedentes de cirurgia abdomino-pélvica. O índice de massa corporal médio era 26,5 ± 4,5 kg/m2 , sendo que 42% eram obesas ou tinham excesso de peso. O tempo operatório médio para realiza- ção da histerectomia totalmente laparoscópica foi 77,7 ± 27,5 minutos, diminuindo significativamente com o aumento da experiência da equipa cirúrgica. O peso médio da peça operatória foi 241 ± 168,4g e a duração média do internamento após a cirurgia foi 1,49 ± 0,9 dias. A diferença entre a hemoglobina pré e pós-operatória foi 1,5 ± 0,8g/dL. A morbilidade major foi 1,5% (n = 4) e a minor 11,5% (n = 30). Salienta-se um caso de conversão para laparotomia e dois casos de deiscência da cúpula vaginal. Não ocorreu nenhuma lesão urinária ou gastrointestinal grave. Conclusões: Esta série demonstra que, se realizada por uma equipa cirúrgica adequadamente treinada, a histerectomia totalmente laparoscópica é segura e associada a baixa taxa de complicações.INTRODUCTION: Hysterectomy is one of the most common gynecological procedures and may be performed either by vaginal approach, laparotomy or laparoscopy. Although total laparoscopic hysterectomy has multiple advantages, conflicting major complication rates have been previously reported. OBJECTIVES: To describe our experience performing TLH and to evaluate complication rates. MATERIAL AND METHODS: A retrospective observational study of all total laparoscopic hysterectomy performed in our department, by the same surgical team, between April 2009 and March 2013 (n = 262), was conducted. Medical records were reviewed for patient characteristics, operating time, uterine weight, post-operative hemoglobin variation, length of hospital stay, and intra and postoperative complications. RESULTS: Patient average age was 48.9 ± 9.0 years and 49.2% had previous abdominopelvic surgery. The average body mass index was 26.5 ± 4.5 kg/m(2) and 42% of women were either overweight or obese. The mean operating time during the total study period was 77.7 ± 27.5 minutes, but it decreased significantly as the surgical team's training increased. Average uterine weight was 241.0 ± 168.4 g and average hospital stay was 1.49 ± 0.9 days. The mean postoperative hemoglobin variation was -1.5 ± 0.8 g/dL. The major and minor complication rates were 1.5% (n = 4) and 11.5% (n = 30), respectively. One procedure was converted to laparotomy and two women had a vaginal vault dehiscence. No important urinary tract or bowel injuries occurred. CONCLUSIONS: This study demonstrates that, in experienced hands, total laparoscopic hysterectomy is safe and with low complications rates

Validação da versão portuguesa do questionário EHP-30 (The endometriosis health profile-30)

Introduction: Endometriosis Health Profile Questionnaire-30 is currently the most used questionnaire for quality of life measurement in women with endometriosis. The aim of this study is to evaluate the psychometric properties and to validate the Portuguese Endometriosis Health Profile Questionnaire-30 version. MATERIAL AND METHODS A sequential sample of 152 patients with endometriosis, followed in a Portugal reference center, were asked to complete a questionnaire on social and demographic features, the Portuguese version of the Endometriosis Health Profile Questionnaire-30 and of the Short Form Health Survey 36 Item â version 2. Appropriate statistical analysis was performed using descriptive statistics, factor analysis, internal consistency, item-total correlation and convergent validity. RESULTS Factorial analysis confirmed the validity of the five-dimension structure of the Endometriosis Health Profile Questionnaire-30 core questionnaire, which explained 83.2% of the total variance. All item-total correlations presented acceptable results and high internal consistency, with Cronbach's alpha ranging between 0.876 and 0.981 for the core questionnaire and between 0.863 and 0.951 for the modular questionnaire. Significant negative associations between similar scales of Endometriosis Health Profile Questionnaire-30 and Short Form Health Survey 36 Item â version 2 were demonstrated. Data completeness achieved was high for all dimensions. The emotional well-being scale in the core questionnaire and the infertility scale in the modular section had the highest median scores, and therefore the most negative impact on the quality of life of participating women. DISCUSSION The test-retest reliability and responsiveness of the questionnaire should be evaluated in future studies. CONCLUSION The present study demonstrates that the Portuguese version of the Endometriosis Health Profile Questionnaire-30 is a valid, reliable and acceptable tool for evaluating the health-related quality of life of Portuguese women with endometriosis.Introdução: O Endometriosis Health Profile Questionnaire-30 é atualmente o questionário mais utilizado para avaliação da qualidade de vida em mulheres com endometriose. O objetivo do presente estudo é avaliar as propriedades psicométricas e validar a versão portuguesa do Endometriosis Health Profile Questionnaire-30. Material e Métodos: Amostra sequencial de conveniência, constituída por 152 doentes com endometriose, de um centro de referência no país, que autopreencheram um questionário sociodemográfico, a versão portuguesa do Endometriosis Health Profile Questionnaire-30 e do Short Form Health Survey 36 Item–versão 2. Procedeu-se a análise estatística apropriada, com estatística descritiva, análise fatorial, avaliação da consistência interna, correlação item-total e validade convergente (usando o Short Form Health Survey 36 Item–versão 2). Resultados: A análise fatorial confirmou a validade da estrutura em cinco dimensões do questionário central, explicando uma variância total de 83,2%. A correlação item-total apresentou resultados aceitáveis em todos os itens e a consistência interna foi elevada, com α Cronbach variando de 0,876 a 0,981 nas dimensões do questionário central, e de 0,863 a 0,951 no modular. Demonstrou-se associação negativa significativa entre as dimensões similares do Endometriosis Health Profile Questionnaire-30 e do Short Form Health Survey 36 Item–versão 2. A taxa de preenchimento do questionário foi elevada para todas as dimensões. A perda do bem-estar emocional (no questionário central) e a infertilidade (no modular) apresentaram as pontuações médias mais elevadas e, consequentemente, impacto mais negativo sobre a qualidade de vida. Discussão: São necessários estudos para avaliar a fiabilidade teste-reteste e a sensibilidade à mudança desta versão portuguesa do Endometriosis Health Profile Questionnaire-30. Conclusão: Este estudo demonstra que a versão portuguesa do Endometriosis Health Profile Questionnaire-30 é um instrumento adaptado, validado e bem aceite para a avaliação da qualidade de vida das mulheres portuguesas com endometriose

Good practice recommendations for information provision for those involved in reproductive donation(dagger)

© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact [email protected] question: What information and support should be offered to donors, intended parents and donor-conceived people, in general and in consideration of the availability of direct-to-consumer genetic testing and matching services? Summary answer: For donors, intended parents and donor-conceived offspring, recommendations are made that cover information needs and informed consent, psychosocial implications and disclosure. What is known already: Trends indicate that the use of donor-assisted conception is growing and guidance is needed to help these recipients/intended parents, the donors and offspring, navigate the rapidly changing environment in which donor-assisted conception takes place. Study design size duration: A working group (WG) collaborated on writing recommendations based, where available, on evidence collected from a literature search and expert opinion. Draft recommendations were published for stakeholder review and adapted where relevant based on the comments received. Participants/materials setting methods: Papers retrieved from PUBMED were included from 1 January 2014 up to 31 August 2020, focusing on studies published since direct-to-consumer genetic testing has become more widespread and accessible. The current paper is limited to reproductive donation performed in medically assisted reproduction (MAR) centres (and gamete banks): donation outside the medical context was not considered. Main results and the role of chance: In total, 32 recommendations were made for information provision and support to donors, 32 for intended parents and 27 for donor-conceived offspring requesting information/support. Limitations reasons for caution: The available evidence in the area of reproductive donation is limited and diverse with regards to the context and types of donation. General conclusions and recommendations are largely based on expert opinion and may need to be adapted in light of future research. Wider implications of the findings: These recommendations provide guidance to MAR centres and gamete banks on good practice in information provision and support but should also be considered by regulatory bodies and policymakers at a national and international level to guide regulatory and legislative efforts towards the protection of donors and donor-conceived offspring. Study funding/competing interests: The development of this good practice paper was funded by European Society of Human Reproduction and Embryology (ESHRE), covering expenses associated with the WG meetings, the literature searches and dissemination. The WG members did not receive any payment. The authors have no conflicts of interest to declare. Disclaimer: This document represents the views of ESHRE, which are the result of consensus between the relevant ESHRE stakeholders and where relevant based on the scientific evidence available at the time of preparation. The recommendations should be used for informational and educational purposes. They should not be interpreted as setting a standard of care, or be deemed inclusive of all proper methods of care nor exclusive of other methods of care reasonably directed to obtaining the same results. They do not replace the need for application of clinical judgement to each individual presentation, nor variations based on locality and facility type. †ESHRE pages content is not externally peer reviewed. The manuscript has been approved by the Executive Committee of ESHRE.info:eu-repo/semantics/publishedVersio

Characterizing partial AZFc deletions of the Y chromosome with amplicon-specific sequence markers

BACKGROUND: The AZFc region of the human Y chromosome is a highly recombinogenic locus containing multi-copy male fertility genes located in repeated DNA blocks (amplicons). These AZFc gene families exhibit slight sequence variations between copies which are considered to have functional relevance. Yet, partial AZFc deletions yield phenotypes ranging from normospermia to azoospermia, thwarting definite conclusions on their real impact on fertility. RESULTS: The amplicon content of partial AZFc deletion products was characterized with novel amplicon-specific sequence markers. Data indicate that partial AZFc deletions are a male infertility risk [odds ratio: 5.6 (95% CI: 1.6–30.1)] and although high diversity of partial deletion products and sequence conversion profiles were recorded, the AZFc marker profiles detected in fertile men were also observed in infertile men. Additionally, the assessment of rearrangement recurrence by Y-lineage analysis indicated that while partial AZFc deletions occurred in highly diverse samples, haplotype diversity was minimal in fertile men sharing identical marker profiles. CONCLUSION: Although partial AZFc deletion products are highly heterogeneous in terms of amplicon content, this plasticity is not sufficient to account for the observed phenotypical variance. The lack of causative association between the deletion of specific gene copies and infertility suggests that AZFc gene content might be part of a multifactorial network, with Y-lineage evolution emerging as a possible phenotype modulator

ART in Europe, 2017: results generated from European registries by ESHRE

© The Author(s) 2021. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.Study question: What are the data on ART and IUI cycles, and fertility preservation (FP) interventions reported in 2017 as compared to previous years, as well as the main trends over the years? Summary answer: The 21st ESHRE report on ART and IUI shows the continual increase in reported treatment cycle numbers in Europe, with a decrease in the proportion of transfers with more than one embryo causing an additional slight reduction of multiple delivery rates (DR) as well as higher pregnancy rates (PR) and DR after frozen embryo replacement (FER) compared to fresh IVF and ICSI cycles, while the number of IUI cycles increased and their outcomes remained stable. What is known already: Since 1997, ART aggregated data generated by national registries, clinics or professional societies have been gathered and analyzed by the European IVF-monitoring Consortium (EIM) and communicated in a total of 20 manuscripts published in Human Reproduction and Human Reproduction Open. Study design size duration: Data on European medically assisted reproduction (MAR) are collected by EIM for ESHRE on a yearly basis. The data on treatments performed between 1 January and 31 December 2017 in 39 European countries were provided by either National Registries or registries based on personal initiatives of medical associations and scientific organizations. Participants/materials setting methods: Overall, 1382 clinics offering ART services in 39 countries reported a total of 940 503 treatment cycles, including 165 379 with IVF, 391 379 with ICSI, 271 476 with FER, 37 303 with preimplantation genetic testing (PGT), 69 378 with egg donation (ED), 378 with IVM of oocytes, and 5210 cycles with frozen oocyte replacement (FOR). A total of 1273 institutions reported data on 207 196 IUI cycles using either husband/partner's semen (IUI-H; n = 155 794) or donor semen (IUI-D; n = 51 402) in 30 countries and 25 countries, respectively. Thirteen countries reported 18 888 interventions for FP, including oocyte, ovarian tissue, semen and testicular tissue banking in pre- and postpubertal patients. Main results and the role of chance: In 21 countries (20 in 2016) in which all ART clinics reported to the registry, 473 733 treatment cycles were registered for a total population of approximately 330 million inhabitants, allowing a best-estimate of a mean of 1435 cycles performed per million inhabitants (range: 723-3286).Amongst the 39 reporting countries, the clinical PR per aspiration and per transfer in 2017 were similar to those observed in 2016 (26.8% and 34.6% vs 28.0% and 34.8%, respectively). After ICSI the corresponding rates were also similar to those achieved in 2016 (24% and 33.5% vs 25% and 33.2% in 2016). When freeze all cycles were removed, the clinical PRs per aspiration were 30.8% and 27.5% for IVF and ICSI, respectively.After FER with embryos originating from own eggs the PR per thawing was 30.2%, which is comparable to 30.9% in 2016, and with embryos originating from donated eggs it was 41.1% (41% in 2016). After ED the PR per fresh embryo transfer was 49.2% (49.4% in 2016) and per FOR 43.3% (43.6% in 2016).In IVF and ICSI together, the trend towards the transfer of fewer embryos continues with the transfer of 1, 2, 3 and ≥4 embryos in 46.0%, 49.2%, 4.5% and in 0.3% of all treatments, respectively (corresponding to 41.5%, 51.9%. 6.2% and 0.4% in 2016). This resulted in a reduced proportion of twin DRs of 14.2% (14.9% in 2016) and stable triplet DR of 0.3%. Treatments with FER in 2017 resulted in a twin and triplet DR of 11.2% and 0.2%, respectively (vs 11.9% and 0.2% in 2016).After IUI, the DRs remained similar at 8.7% after IUI-H (8.9% in 2016) and at 12.4% after IUI-D (12.4.0% in 2016). Twin and triplet DRs after IUI-H were 8.1% and 0.3%, respectively (in 2016: 8.8% and 0.3%) and 6.9% and 0.2% after IUI-D (in 2016: 7.7% and 0.4%). Amongst 18 888 FP interventions in 13 countries, cryopreservation of ejaculated sperm (n = 11 112 vs 7877 from 11 countries in 2016) and of oocytes (n = 6588 vs 4907 from eight countries in 2016) were the most frequently reported. Limitations reasons for caution: As the methods of data collection and levels of reporting vary amongst European countries, interpretation of results should remain cautious. Some countries were unable to deliver data about the number of initiated cycles and deliveries. Wider implications of the findings: The 21st ESHRE report on ART, IUI and FP interventions shows a continuous increase of reported treatment numbers and MAR-derived livebirths in Europe. Being already the largest data collection on MAR in Europe, efforts should continue to optimize data collection and reporting with the perspective of improved quality control, transparency and vigilance in the field of reproductive medicine. Study funding/competing interests: The study has received no external funding and all costs are covered by ESHRE. There are no competing interests.info:eu-repo/semantics/publishedVersio

Immune and spermatogenesis-related loci are involved in the development of extreme patterns of male infertility.

We conducted a genome-wide association study in a large population of infertile men due to unexplained spermatogenic failure (SPGF). More than seven million genetic variants were analysed in 1,274 SPGF cases and 1,951 unaffected controls from two independent European cohorts. Two genomic regions were associated with the most severe histological pattern of SPGF, defined by Sertoli cell-only (SCO) phenotype, namely the MHC class II gene HLA-DRB1 (rs1136759, P = 1.32E-08, OR = 1.80) and an upstream locus of VRK1 (rs115054029, P = 4.24E-08, OR = 3.14), which encodes a protein kinase involved in the regulation of spermatogenesis. The SCO-associated rs1136759 allele (G) determines a serine in the position 13 of the HLA-DRβ1 molecule located in the antigen-binding pocket. Overall, our data support the notion of unexplained SPGF as a complex trait influenced by common variation in the genome, with the SCO phenotype likely representing an immune-mediated condition.We thank the National DNA Bank Carlos III (University of Salamanca, Spain) for supplying part of the control DNA samples from Spain and all the participants for their essential collaboration. This work was supported by the Spanish Ministry of Science through the Spanish National Plan for Scientific and Technical Research and Innovation (refs. SAF2016-78722-R and PID2020-120157RB-I00), the Andalusian Plan for Research and Innovation (PAIDI 2020) (ref. PY20_00212), and the R+D+i Projects of the FEDER Operational Programme 2020 (ref. B-CTS-584-UGR20). F.D.C. was supported by the “Ramón y Cajal” programme (ref. RYC-2014-16458), and L.B.C. was supported by the Spanish Ministry of Economy and Competitiveness through the “Juan de la Cierva Incorporación” programme (ref. IJC2018-038026-I, funded by MCIN/AEI /10.13039/501100011033), all of them including FEDER funds. A.G.J. was funded by MCIN/AEI /10.13039/501100011033 and FSE “El FSE invierte en tu futuro” (ref. FPU20/02926). IPATIMUP integrates the i3S Research Unit, which is partially supported by the Portuguese Foundation for Science and Technology (FCT), financed by the European Social Funds (COMPETE-FEDER) and National Funds (projects PEstC/SAU/LA0003/2013 and POCI-01-0145-FEDER-007274). A.M.L. is funded by the Portuguese Government through FCT (IF/01262/2014). P.I.M. is supported by the FCT post-doctoral fellowship (SFRH/BPD/120777/2016), financed from the Portuguese State Budget of the Ministry for Science, Technology and High Education and from the European Social Fund, available through the Programa Operacional do Capital Humano. ToxOmics—Centre for Toxicogenomics and Human Health, Genetics, Oncology and Human Toxicology, Nova Medical School, Lisbon, is also partially supported by FCT (Projects: UID/BIM/00009/2013 and UIDB/UIDP/00009/2020). SLarriba received support from “Instituto de Salud Carlos III” (grant DTS18/00101], co-funded by FEDER funds/European Regional Development Fund (ERDF)—a way to build Europe), and from “Generalitat de Catalunya” (grant 2017SGR191). SLarriba is sponsored by the “Researchers Consolidation Programme” from the SNS-Departament de Salut Generalitat de Catalunya (Exp. CES09/020). The German cohort was recruited within the Male Reproductive Genomics (MERGE) study and supported by the German Research Foundation Clinical Research Unit ‘Male Germ Cells’ (DFG CRU326, grants to F.T. and J.G.). This article is related to the Ph.D. Doctoral Thesis of Miriam Cerván-Martín (grant ref. BES-2017-081222 funded by MCIN/AEI/10.13039/501100011033 and FSE “El FSE invierte en tu futuro”)