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      Markers of vitality in ovaries of transmen after long-term androgen treatment: a prospective cohort study

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          Abstract

          Background

          Gender-affirming hormone therapy has been hypothesized to reduce the patient’s reproductive potential in transmen, although the exact long-term effects on future fertility are unknown.

          Methods

          In this prospective cohort study we aimed to evaluate ovaries of 20 transmen by using hormone serum levels, histomorphological analysis and fluorescence activated cells sorting (FACS) analysis – in order to assess the amount of vital cells.

          Results

          The median total number of follicles per field of view was 39 (IQR 12–122). Of all follicles ( n = 1661), the vast majority was primordial ( n = 1505, 90.6%), followed by primary ( n = 76, 4.6%), abnormal ( n = 63, 3.8%) and secondary follicles ( n = 17, 1.0%). FACS analysis was available for 13 samples (65.0%) and the median frequency of vital cells was 87.5% (IQR, 77.7–95.4%). Both a higher age ( p = 0.032) and a lower BMI ( p = 0.003) were significantly associated with a higher frequency of vital cells.

          Conclusion

          The majority of ovarian cells after long-term androgen treatment were vital in FACS analysis and histomorphological evaluation revealed a normal cortical follicle distribution. These results are currently exploratory, but might be promising for issues on fertility preservation.

          Trial registration

          The study was approved by the ethics committee of the Medical University of Vienna (EK 2240/2016) and was retrospectively registered in the Current Controlled Trials Register (registration number NCT03649087, date of registration: 28.08.2018).

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          Most cited references40

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          Oocyte–somatic cell interactions in the human ovary—novel role of bone morphogenetic proteins and growth differentiation factors

          BACKGROUND Initially identified for their capability to induce heterotopic bone formation, bone morphogenetic proteins (BMPs) are multifunctional growth factors that belong to the transforming growth factor β superfamily. Using cellular and molecular genetic approaches, recent studies have implicated intra-ovarian BMPs as potent regulators of ovarian follicular function. The bi-directional communication of oocytes and the surrounding somatic cells is mandatory for normal follicle development and oocyte maturation. This review summarizes the current knowledge on the physiological role and molecular determinants of these ovarian regulatory factors within the human germline-somatic regulatory loop. OBJECTIVE AND RATIONALE The regulation of ovarian function remains poorly characterized in humans because, while the fundamental process of follicular development and oocyte maturation is highly similar across species, most information on the regulation of ovarian function is obtained from studies using rodent models. Thus, this review focuses on the studies that used human biological materials to gain knowledge about human ovarian biology and disorders and to develop strategies for preventing, diagnosing and treating these abnormalities. SEARCH METHODS Relevant English-language publications describing the roles of BMPs or growth differentiation factors (GDFs) in human ovarian biology and phenotypes were comprehensively searched using PubMed and the Google Scholar database. The publications included those published since the initial identification of BMPs in the mammalian ovary in 1999 through July 2016. OUTCOMES Studies using human biological materials have revealed the expression of BMPs, GDFs and their putative receptors as well as their molecular signaling in the fundamental cells (oocyte, cumulus/granulosa cells (GCs) and theca/stroma cells) of the ovarian follicles throughout follicle development. With the availability of recombinant human BMPs/GDFs and the development of immortalized human cell lines, functional studies have demonstrated the physiological role of intra-ovarian BMPs/GDFs in all aspects of ovarian functions, from follicle development to steroidogenesis, cell–cell communication, oocyte maturation, ovulation and luteal function. Furthermore, there is crosstalk between these potent ovarian regulators and the endocrine signaling system. Dysregulation or naturally occurring mutations within the BMP system may lead to several female reproductive diseases. The latest development of recombinant BMPs, synthetic BMP inhibitors, gene therapy and tools for BMP-ligand sequestration has made the BMP pathway a potential therapeutic target in certain human fertility disorders; however, further clinical trials are needed. Recent studies have indicated that GDF8 is an intra-ovarian factor that may play a novel role in regulating ovarian functions in the human ovary. WIDER IMPLICATIONS Intra-ovarian BMPs/GDFs are critical regulators of folliculogenesis and human ovarian functions. Any dysregulation or variations in these ligands or their receptors may affect the related intracellular signaling and influence ovarian functions, which accounts for several reproductive pathologies and infertility. Understanding the normal and pathological roles of intra-ovarian BMPs/GDFs, especially as related to GC functions and follicular fluid levels, will inform innovative approaches to fertility regulation and improve the diagnosis and treatment of ovarian disorders.
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            Reproductive wish in transsexual men.

            Hormonal therapy and sex reassignment surgery (SRS) in transsexual persons lead to an irreversible loss of their reproductive potential. The current and future technologies could create the possibility for female-to-male transsexual persons (transsexual men) to have genetically related children. However, little is known about this topic. The aim of this study is to provide information on the reproductive wishes of transsexual men after SRS. METHODS A self-constructed questionnaire was presented to 50 transsexual men in a single-center study.
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              Female-to-male transgender quality of life.

              We evaluated health-related quality of life in female-to-male (FTM) transgender individuals, using the Short-Form 36-Question Health Survey version 2 (SF-36v2). Using email, Internet bulletin boards, and postcards, we recruited individuals to an Internet site (http://www.transurvey.org), which contained a demographic survey and the SF36v2. We enrolled 446 FTM transgender and FTM transsexual participants, of which 384 were from the US. Analysis of quality of life health concepts demonstrated statistically significant (p<0.01) diminished quality of life among the FTM transgender participants as compared to the US male and female population, particularly in regard to mental health. FTM transgender participants who received testosterone (67%) reported statistically significant higher quality of life scores (p<0.01) than those who had not received hormone therapy. FTM transgender participants reported significantly reduced mental health-related quality of life and require additional focus to determine the cause of this distress. Providing this community with the hormonal care they request is associated with improved quality of life.
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                Author and article information

                Contributors
                julian.marschalek@meduniwien.ac.at
                detlef.pietrowski@meduniwien.ac.at
                sabine.dekan@meduniwien.ac.at
                marie-louise.marschalek@muv.ac.at
                max.brandstetter@live.at
                johannes.ott@meduniwien.ac.at
                Journal
                Mol Med
                Mol. Med
                Molecular Medicine
                BioMed Central (London )
                1076-1551
                1528-3658
                5 September 2020
                5 September 2020
                2020
                : 26
                : 83
                Affiliations
                [1 ]GRID grid.22937.3d, ISNI 0000 0000 9259 8492, Department of Obstetrics and Gynecology, Clinical Division of Gynecologic Endocrinology and Reproductive Medicine, , Medical University of Vienna, ; Spitalgasse 23, 1090 Vienna, Austria
                [2 ]GRID grid.22937.3d, ISNI 0000 0000 9259 8492, Clinical Institute of Pathology, , Medical University of Vienna, ; Spitalgasse 23, 1090 Vienna, Austria
                Author information
                http://orcid.org/0000-0002-2761-5262
                Article
                214
                10.1186/s10020-020-00214-x
                7487795
                32891132
                9c34d252-4e19-4a84-a162-a5082e5ad3fc
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 30 April 2020
                : 28 August 2020
                Funding
                Funded by: Medical Scientific Fund of the Mayor of the City Vienna
                Award ID: n/a
                Award Recipient :
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2020

                transgender,transmen,fertility,histomorphology,fluorescence activated cells sorting (facs)

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