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      Current global status of male reproductive health

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          Abstract

          BACKGROUND

          The widespread interest in male reproductive health (MRH), fueled by emerging evidence, such as the global decline in sperm counts, has intensified concerns about the status of MRH. Consequently, there is a pressing requirement for a strategic, systematic approach to identifying critical questions, collecting pertinent information, and utilizing these data to develop evidence-based strategies. The methods for addressing these questions and the pathways toward their answers will inevitably vary based on the variations in cultural, geopolitical, and health-related contexts. To address these issues, a conjoint ESHRE and Male Reproductive Health Initiative (MRHI) Campus workshop was convened.

          OBJECTIVE AND RATIONALE

          The three objectives were: first, to assess the current state of MRH around the world; second, to identify some of the key gaps in knowledge; and, third, to examine how MRH stakeholders can collaboratively generate intelligent and effective paths forward.

          SEARCH METHODS

          Each expert reviewed and summarized the current literature that was subsequently used to provide a comprehensive overview of challenges related to MRH.

          OUTCOMES

          This narrative report is an overview of the data, opinions, and arguments presented during the workshop. A number of outcomes are presented and can be summarized by the following overarching themes: MRH is a serious global issue and there is a plethora of gaps in our understanding; there is a need for widespread international collaborative networks to undertake multidisciplinary research into fundamental issues, such as lifestyle/environmental exposure studies, and high-quality clinical trials; and there is an urgent requirement for effective strategies to educate young people and the general public to safeguard and improve MRH across diverse population demographics and resources.

          LIMITATIONS, REASONS FOR CAUTION

          This was a workshop where worldwide leading experts from a wide range of disciplines presented and discussed the evidence regarding challenges related to MRH. While each expert summarized the current literature and placed it in context, the data in a number of areas are limited and/or sparse. Equally, important areas for consideration may have been missed. Moreover, there are clear gaps in our knowledge base, which makes some conclusions necessarily speculative and warranting of further study.

          WIDER IMPLICATIONS

          Poor MRH is a global issue that suffers from low awareness among the public, patients, and heathcare professionals. Addressing this will require a coordinated multidisciplinary approach. Addressing the significant number of knowledge gaps will require policy makers prioritizing MRH and its funding.

          STUDY FUNDING/COMPETING INTEREST(S)

          The authors would like to extend their gratitude to ESHRE for providing financial support for the Budapest Campus Workshop, as well as to Microptic S.L. (Barcelona) for kindly sponsoring the workshop. P.B. is the Director of the not-for-profit organization Global Action on Men’s Health and receives fees and expenses for his work, (which includes the preparation of this manuscript). Conflicts of interest: C.J.D.J., C.L.R.B., R.A.A., P.B., M.P.C., M.L.E., N.G., N.J., C.K., AAP, M.K.O., S.R.-H., M.H.V.-L.: ESHRE Campus Workshop 2022 (Travel support—personal). C.J.D.J.: Cambridge University Press (book royalties—personal). ESHRE Annual Meeting 2022 and Yale University Panel Meeting 2023 (Travel support—personal). C.L.R.B.: Ferring and IBSA (Lecture), RBMO editor (Honorarium to support travel, etc.), ExSeed and ExScentia (University of Dundee), Bill & Melinda Gates Foundation (for research on contraception). M.P.C.: Previously received funding from pharmaceutical companies for health economic research. The funding was not in relation to this work and had no bearing on the contents of this work. No funding from other sources has been provided in relation to this work (funding was provided to his company Global Market Access Solutions). M.L.E.: Advisor to Ro, Doveras, Next, Hannah, Sandstone. C.K.: European Academy of Andrology (Past president UNPAID), S.K.: CEO of His Turn, a male fertility Diagnostic and Therapeutic company (No payments or profits to date). R.I.M.: www.healthymale.org.au (Australian Government funded not for profit in men’s health sector (Employed as Medical Director 0.2 FET), Monash IVF Pty Ltd (Equity holder)). N.J.: Merck (consulting fees), Gedeon Richter (honoraria). S.R.-H.: ESHRE (Travel reimbursements). C.N.: LLC (Nursing educator); COMMIT (Core Outcomes Measures for Infertility Trials) Advisor, meeting attendee, and co‐author; COMMA (Core Outcomes in Menopause) Meeting attendee, and co‐author; International Federation of Gynecology and Obstetrics (FIGO) Delegate Letters and Sciences; ReproNovo, Advisory board; American Board of Urology Examiner; American Urological Association Journal subsection editor, committee member, guidelines co‐author Ferring Scientific trial NexHand Chief Technology Officer, stock ownership Posterity Health Board member, stock ownership. A.P.: Economic and Social Research Council (A collaborator on research grant number ES/W001381/1). Member of an advisory committee for Merck Serono (November 2022), Member of an advisory board for Exceed Health, Speaker fees for educational events organized by Mealis Group; Chairman of the Cryos External Scientific Advisory Committee: All fees associated with this are paid to his former employer The University of Sheffield. Trustee of the Progress Educational Trust (Unpaid). M.K.O.: National Health and Medical Research Council and Australian Research Council (Funding for research of the topic of male fertility), Bill and Melinda Gates Foundation (Funding aimed at the development of male gamete-based contraception), Medical Research Future Fund (Funding aimed at defining the long-term consequences of male infertility). M.H.V.-L.: Department of Sexual and Reproductive Health and Research (SRH)/Human Reproduction Programme (HRP) Research Project Panel RP2/WHO Review Member; MRHI (Core Group Member), COMMIT (member), EGOI (Member); Human Reproduction (Associate Editor), Fertility and Sterility (Editor), AndroLATAM (Founder and Coordinator).

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          Most cited references113

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          Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

          This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.
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            Disruption of histone methylation in developing sperm impairs offspring health transgenerationally.

            A father's lifetime experiences can be transmitted to his offspring to affect health and development. However, the mechanisms underlying paternal epigenetic transmission are unclear. Unlike in somatic cells, there are few nucleosomes in sperm, and their function in epigenetic inheritance is unknown. We generated transgenic mice in which overexpression of the histone H3 lysine 4 (H3K4) demethylase KDM1A (also known as LSD1) during spermatogenesis reduced H3K4 dimethylation in sperm. KDM1A overexpression in one generation severely impaired development and survivability of offspring. These defects persisted transgenerationally in the absence of KDM1A germline expression and were associated with altered RNA profiles in sperm and offspring. We show that epigenetic inheritance of aberrant development can be initiated by histone demethylase activity in developing sperm, without changes to DNA methylation at CpG-rich regions.
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              Changes in sexual attitudes and lifestyles in Britain through the life course and over time: findings from the National Surveys of Sexual Attitudes and Lifestyles (Natsal)

              Summary Background Sexual behaviour and relationships are key components of wellbeing and are affected by social norms, attitudes, and health. We present data on sexual behaviours and attitudes in Britain (England, Scotland, and Wales) from the three National Surveys of Sexual Attitudes and Lifestyles (Natsal). Methods We used a multistage, clustered, and stratified probability sample design. Within each of the 1727 sampled postcode sectors for Natsal-3, 30 or 36 addresses were randomly selected and then assigned to interviewers. To oversample individuals aged 16–34 years, we randomly allocated addresses to either the core sample (in which individuals aged 16–74 years were eligible) or the boost sample (in which only individuals aged 16–34 years were eligible). Interviewers visited all sampled addresses between Sept 6, 2010, and Aug 31, 2012, and randomly selected one eligible individual from each household to be invited to participate. Participants completed the survey in their own homes through computer-assisted face-to-face interviews and self-interview. We analysed data from this survey, weighted to account for unequal selection probabilities and non-response to correct for differences in sex, age group, and region according to 2011 Census figures. We then compared data from participants aged 16–44 years from Natsal-1 (1990–91), Natsal-2 (1999–2001), and Natsal-3. Findings Interviews were completed with 15 162 participants (6293 men, 8869 women) from 26 274 eligible addresses (57·7%). 82·1% (95% CI 81·0–83·1%) of men and 77·7% (76·7–78·7%) of women reported at least one sexual partner of the opposite sex in the past year. The proportion generally decreased with age, as did the range of sexual practices with partners of the opposite sex, especially in women. The increased sexual activity and diversity reported in Natsal-2 in individuals aged 16–44 years when compared with Natsal-1 has generally been sustained in Natsal-3, but in men has generally not risen further. However, in women, the number of male sexual partners over the lifetime (age-adjusted odds ratio 1·18, 95% CI 1·08–1·28), proportion reporting ever having had a sexual experience with genital contact with another woman (1·69, 1·43–2·00), and proportion reporting at least one female sexual partner in the past 5 years (2·00, 1·59–2·51) increased in Natsal-3 compared with Natsal-2. While reported number of occasions of heterosexual intercourse in the past 4 weeks had reduced since Natsal-2, we recorded an expansion of heterosexual repertoires—particularly in oral and anal sex—over time. Acceptance of same-sex partnerships and intolerance of non-exclusivity in marriage increased in men and women in Natsal-3. Interpretation Sexual lifestyles in Britain have changed substantially in the past 60 years, with changes in behaviour seeming greater in women than men. The continuation of sexual activity into later life—albeit reduced in range and frequency—emphasises that attention to sexual health and wellbeing is needed throughout the life course. Funding Grants from the UK Medical Research Council and the Wellcome Trust, with support from the Economic and Social Research Council and the Department of Health.
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                Author and article information

                Contributors
                Journal
                Hum Reprod Open
                Hum Reprod Open
                hropen
                Human Reproduction Open
                Oxford University Press
                2399-3529
                2024
                12 April 2024
                12 April 2024
                : 2024
                : 2
                : hoae017
                Affiliations
                Department of Urology, University of Minnesota Medical Center, University of Minnesota , Minneapolis, MN, USA
                Division of Systems Medicine, School of Medicine, Ninewells Hospital and Medical School, University of Dundee , Dundee, UK
                Discipline of Biological Sciences, School of Environment and Life Sciences, College of Engineering, Science and Environment, University of Newcastle , Newcastle, Australia
                MRC Centre for Reproductive Health, University of Edinburgh , Edinburgh, UK
                Global Action on Men’s Health , UK
                Assisted Reproductive Technology Unit, Department of Obstetrics and Gynaecology, Faculty of Medicine, The Chinese University of Hong Kong , Shatin, China
                Health Economics, Global Market Access Solutions LLC , Mooresville, NC, USA
                University Medical Center Groningen , Groningen, The Netherlands
                Department of Urology and Obstetrics & Gynecology, Stanford University , Stanford, CA, USA
                IVIRMA Global Research Alliance, IVI Foundation, Instituto de Investigación Sanitaria La Fe (IIS La Fe) , Valencia, Spain
                Department of Growth and Reproduction and International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen , Copenhagen, Denmark
                Department of Pharmacology and Therapeutics, Faculty of Medicine, McGill University , Montreal, QC, Canada
                Centre de Recherche du Centre Hospitalier de l’Université de Montréal , Montréal, QC, Canada
                Département de Pathologie et Biologie Cellulaire, Université de Montréal , Montréal, QC, Canada
                Department of Experimental and Clinical Biomedical Sciences, ‘Mario Serio’, University of Florence, University Hospital of Careggi (AOUC) , Florence, Italy
                Hudson Institute of Medical Research, Monash University , Melbourne, Australia
                Monash IVF Group , Cremorne, Australia
                Clarence C. Department of Urology, University of Illinois Chicago (UIC), College of Medicine, Department of Bioengineering, UIC College of Engineering, Chicago, IL, USA
                School of BioSciences and Bio21 Institute, The University of Melbourne, Parkville , Australia
                Faculty of Biology, Medicine and Health, Core Technology Facility, University of Manchester , Manchester, UK
                Department of Growth and Reproduction and International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Rigshospitalet, University of Copenhagen , Copenhagen, Denmark
                Fertility Europe , Evere, Belgium
                The International Islamic Center for Population Studies and Research, Al-Azhar University , Maadi, Cairo, Egypt
                Egyptian IVF Center , Maadi, Cairo, Egypt
                Faculty of Medical Sciences, Biosciences Institute, Newcastle University , Newcastle upon Tyne, UK
                School of Medicine, Johns Hopkins University , Baltimore, MD, USA
                Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas de Argentina—Fundación IBYME , Buenos Aires, Argentina
                Author notes
                Correspondence address. Instituto de Biología y Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Fundación IBYME (FIBYME), Vuelta de Obligado 2490 (C1428ADN) Buenos Aires, Argentina. Tel: +5411-4783-2869 ext1248/1271; Fax: +5411-4786-2564; E-mail mhvazquez@ 123456ibyme.conicet.gov.ar ; mhvazl@ 123456gmail.com
                Author information
                https://orcid.org/0000-0002-4083-5833
                https://orcid.org/0000-0003-0062-9979
                https://orcid.org/0000-0002-9152-156X
                https://orcid.org/0000-0002-7495-518X
                https://orcid.org/0000-0002-4736-8262
                https://orcid.org/0000-0002-1886-745X
                https://orcid.org/0000-0001-5482-0141
                https://orcid.org/0000-0003-4827-0838
                https://orcid.org/0000-0002-0168-7233
                https://orcid.org/0000-0001-6748-8918
                https://orcid.org/0000-0001-7298-4940
                https://orcid.org/0000-0002-4387-8871
                https://orcid.org/0000-0002-9152-1893
                https://orcid.org/0000-0002-3218-8250
                https://orcid.org/0000-0002-4463-6532
                Article
                hoae017
                10.1093/hropen/hoae017
                11065475
                38699533
                ed25222e-80ce-40c0-8e74-49e5f7823b51
                © The Author(s) 2024. 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 ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 08 September 2023
                : 22 February 2024
                : 11 March 2024
                : 02 May 2024
                Page count
                Pages: 16
                Funding
                Funded by: Budapest Campus Workshop;
                Categories
                Review
                AcademicSubjects/MED00905

                male infertility,male reproductive health,andrology,fertility,contraception,genetics,epigenetics,education,economics,policy

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