Purpose of Review
Hormonal and surgical treatments for transgender individuals can severely impact reproductive potential. In this review, we discuss the role of fertility preservation in both male-to-female and female-to-male transgender patients. We focus on the effects of hormone replacement therapy on the gonads and discuss current methods and techniques available for fertility preservation. Moreover, we review the current literature on patient attitudes toward fertility preservation and existing barriers to care.
The literature supports the notion that feminizing therapy negatively impacts spermatogenesis, as evidenced by impaired semen parameters. The degree of such decline lies on a spectrum and can be somewhat unpredictable. Similarly, masculinizing therapy with testosterone has variable effects on ovarian function, gynecologic organs, and future fertility potential. Further research is required to better elucidate the long-term effects of such therapies. Optimal timing for fertility preservation is in the postpubertal period prior to initiation of hormonal therapy. This is however not always possible. A multitude of barriers to pursuing fertility preservation exist, including lack of appropriate counseling, the potentially invasive nature of some fertility preservation methods, and the financial burden placed on the patients.
Fertility preservation in the transgender population remains poorly utilized. For transgender women, cryopreservation of sperm ideally is performed prior to initiation of hormone replacement therapy. Nonetheless, studies have shown that a degree of spermatogenesis is seen in some individuals without discontinuation of hormonal therapy. This could allow for less disruption, both physically and emotionally. Fertility preservation in transgender men remains invasive with oocyte retrieval as the main technique. Cessation of therapy, ovarian stimulation, and invasive testing has potential to be traumatic and enhance dysphoria. The possibility of fertility preservation at the time of gonadectomy is promising. Prepubertal fertility preservation is also on the horizon, though still experimental. Cost of preservation techniques and storage is currently prohibitive for many patients. Recent changes to state insurance mandates may soon make fertility preservation more accessible. Future research may demonstrate that fertility preservation is possible at the time of gender confirmation surgery, with the goal of being both effective and nontraumatic to the patient.
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Crissman HP, Berger MB, Graham LF, Dalton VK. Transgender demographics: a household probability sample of US adults, 2014. Am J Public Health. 2017;107(2):213–5.
Goodman M, Adams N, Cornell T, Kreukels B, Motmans J, Coleman E. Size and distribution of transgender and gender nonconforming populations: a narrative review. Endocrinol Metab Clin N Am. 2019;48(2):303–21.
Aydin D, Buk LJ, Partoft S, Bonde C, Thomsen MV, Tos T. Transgender surgery in Denmark from 1994 to 2015: 20-year follow-up study. J Sex Med. 2016;13(4):720–5.
Coleman E, et al. WPATH standards of care, World Prof. Assoc. Transgender Heal., 2012.
Committee E, Society A. Access to fertility services by transgender persons: an ethics committee opinion. Fertil Steril. 2015;104(5):1111–5.
Hembree WC, Cohen-Kettenis PT, Gooren L, Hannema SE, Meyer WJ, Murad MH, et al. Endocrine treatment of gender-dysphoric/gender-incongruent persons: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2017;102(11):3869–903.
Smith KP, Madison CM, Milne NM. Gonadal suppressive and cross-sex hormone therapy for gender dysphoria in adolescents and adults. Pharmacotherapy. 2014;34(12):1282–97.
Unger CA. Hormone therapy for transgender patients. Transl Androl Urol. 2016;5(6):877–84.
Rodriguez-rigau LJ, Tcholakian RK, Smith D. In vitro steroid metabolic studies in human testes. II: metabolism of cholesterol, pregnenolone, progesterone, androstenedione, and testosterone by testes of an estrogen-treated man. Steroids. 1977;30(6):729–39.
Dumasia K, Kumar A, Deshpande S, Balasinor NH. Estrogen, through estrogen receptor 1, regulates histone modifications and chromatin remodeling during spermatogenesis in adult rats. Epigenetics. 2017;12(11):953–63.
•• Schneider F, Kliesch S, Schlatt S, Neuhaus N. Andrology of male-to-female transsexuals: influence of cross-sex hormone therapy on testicular function. Andrology. 2017;5(5):873–80 This is a comprehensive review on the hormonal therapy available to the transgender woman as well as the resultant physiologic effects on the individuals body and reproductive organs.
Adeleye AJ, Reid G, Kao CN, Mok-Lin E, Smith JF. Semen parameters among transgender women with a history of hormonal treatment. Urology. 2019;124:136–41.
Kent MA, Winoker JS, Grotas AB. Effects of feminizing hormones on sperm production and malignant changes: microscopic examination of post orchiectomy specimens in Transwomen. Urology. 2018;121:93–6.
• Jiang DD, et al. Effects of Estrogen on Spermatogenesis in Transgender Women. Urology. 2019;132:117–22 This is a retrospective study examining the histology of orchiectomy specimens of transgender women who have undergone gender confirmation surgery. This study demonstrates the histologic effects that hormone replacement therapy can have on the architecture of the testicles and ultimately spermatogenesis.
Loverro G, Resta L, Dellino M, Edoardo DN, Cascarano MA, Loverro M, et al. Uterine and ovarian changes during testosterone administration in young female-to-male transsexuals. Taiwan J Obstet Gynecol. 2016;55(5):686–91.
Grynberg M, Fanchin R, Dubost G, Colau JC, Brémont-Weil C, Frydman R, et al. Histology of genital tract and breast tissue after long-term testosterone administration in a female-to-male transsexual population. Reprod BioMed Online. 2010;20(4):553–8.
Urban RR, Teng NNH, Kapp DS. Gynecologic malignancies in female-to-male transgender patients: the need of original gender surveillance. Am J Obstet Gynecol. 2011;204(5):e9.
Caanen MR, Schouten NE, Kuijper EAM, van Rijswijk J, van den Berg M, van Dulmen-den Broeder E, et al. Effects of long-term exogenous testosterone administration on ovarian morphology, determined by transvaginal (3D) ultrasound in female-to-male transsexuals. Hum Reprod. 2017;32(7):1457–64.
• De Roo C, et al. Ovarian tissue cryopreservation in female-to-male transgender people: insights into ovarian histology and physiology after prolonged androgen treatment. Reprod BioMed Online. 2017;34(6):557–66 This study assessed the effects of prolonged testosterone on the ovaries in transgender men. They demonstrated surprisingly normal cortical follicle distribution. They were also able to demonstrate in-vitro maturation potential of cumulus-oocyte complex (COC) after androgen therapy. Anti-Mullerian hormone levels were well correlated to the number of COCs identified. Such findings assist with counseling regarding ovarian function and fertility potential after hormone replacement therapy.
Yaish I, et al. OR11-3 evidence for preserved ovarian reserve in transgender men receiving testosterone therapy: anti-Mullerian hormone serum levels decrease modestly after one year of treatment. J Endocr Soc. 2019;3(Suppl 1):OR11–3.
Vander Borght M, Wyns C. Fertility and infertility: Definition and epidemiology. Clin Biochem. 2018;62(March):2–10.
Hamada A, et al. Semen characteristics of transwomen referred for sperm banking before sex transition: a case series. Andrologia. 2015;47(7):832–8.
• Mattawanon N, Spencer JB, Schirmer DA, Tangpricha V. Fertility preservation options in transgender people: a review. Rev Endocr Metab Disord. 2018;19(3):231–42 This detailed review discusses fertility preservation options ranging from semen cryopreservation for transgender women to oocyte cryopreservation for transgender men. The article explains the process necessary for all methods and touches upon experimental methods for prepubertal patients.
Schneider F, et al. Options for fertility treatments for trans women in Germany. J Clin Med. 2019;8(5):730.
Matoso A, Khandakar B, Yuan S, Wu T, Wang LJ, Lombardo KA, et al. Spectrum of findings in orchiectomy specimens of persons undergoing gender confirmation surgery. Hum Pathol. 2018;76:91–9.
Wierckx K, Stuyver I, Weyers S, Hamada A, Agarwal A, de Sutter P, et al. Sperm freezing in transsexual women. Arch Sex Behav. 2012;41(5):1069–71.
Cobo A, Garcia-Velasco JA, Coello A, Domingo J, Pellicer A, Remohi J. Oocyte vitrification as an efficient option for elective fertility preservation. Fertil Steril. 2016;105(3):755–64.
Maxwell S, Noyes N, Keefe D, Berkeley AS, Goldman KN. Pregnancy outcomes after fertility preservation in transgender men. Obstet Gynecol. 2017;129(6):1031–4.
Armuand G, Dhejne C, Olofsson JI, Rodriguez-Wallberg KA. Transgender men’s experiences of fertility preservation: a qualitative study. Hum Reprod. 2017;32(2):383–90.
• Lierman S, et al. Fertility preservation for trans men: frozen-thawed in vitro matured oocytes collected at the time of ovarian tissue processing exhibit normal meiotic spindles. J Assist Reprod Genet. 2017;34(11):1449–56 This study sought to assess the developmental competency of oocytes obtained at the time oophorectomy for gender-confirming surgery in transgender men on hormone therapy. Cumulus-oocyte complexes (COCs) were collected and subjected to in-vitro maturation followed by vitrification. They found normal spindle structure and chromosomal alignment in-vitro matured COCs. Such findings are promising for the possibility of fertility preservation to be performed at the time of gonadectomy, utilizing in-vitro maturation of hormone exposed ovarian tissue.
Rienzi L, Gracia C, Maggiulli R, LaBarbera A, Kaser DJ, Ubaldi FM, et al. Oocyte, embryo and blastocyst cryopreservation in ART: systematic review and meta-analysis comparing slow-freezing versus vitrification to produce evidence for the development of global guidance. Hum Reprod Update. 2017;23(2):139–55.
Giudice MG, de Michele F, Poels J, Vermeulen M, Wyns C. Update on fertility restoration from prepubertal spermatogonial stem cells: how far are we from clinical practice? Stem Cell Res. 2017;21:171–7.
Clermont Y. Kinetics of spermatogenesis in mammals: seminiferous epithelium cycle and spermatogonial renewal. Physiol Rev. 1972;52(1):198–236.
Takashima S, Shinohara T. Culture and transplantation of spermatogonial stem cells. Stem Cell Res. 2018;29:46–55.
Sadri-Ardekani H, Akhondi MA, van der Veen F, Repping S, van Pelt AMM. In vitro propagation of human prepubertal spermatogonial stem cells. JAMA. 2008;36(23):1–5.
Nickkholgh B, et al. Genetic and epigenetic stability of human spermatogonial stem cells during long-term culture. Fertil Steril. 2014;102(6):1700–1707.e1.
Ntemou E, Kadam P, van Saen D, Wistuba J, Mitchell RT, Schlatt S, et al. Complete spermatogenesis in intratesticular testis tissue xenotransplants from immature non-human primate. Hum Reprod. 2019;34(3):403–13.
Wallace WHB, Kelsey TW, Anderson RA. Fertility preservation in pre-pubertal girls with cancer: the role of ovarian tissue cryopreservation. Fertil Steril. 2016;105(1):6–12.
Donnez J, Dolmans M-M. Fertility preservation in women. N Engl J Med. 2017;377(17):1657–5.
Demeestere I, Simon P, Dedeken L, Moffa F, Tsépélidis S, Brachet C, et al. Live birth after autograft of ovarian tissue cryopreserved during childhood. Hum Reprod. 2015;30(9):2107–9.
Donnez J, Dolmans MM. Ovarian cortex transplantation: 60 reported live births brings the success and worldwide expansion of the technique towards routine clinical practice. J Assist Reprod Genet. 2015;32(8):1167–70.
Uzelac PS, Delaney AA, Christensen GL, Bohler HCL, Nakajima ST. Live birth following in vitro maturation of oocytes retrieved from extracorporeal ovarian tissue aspiration and embryo cryopreservation for 5 years. Fertil Steril. 2015;104(5):1258–60.
Tornello SL, Bos H. Parenting intentions among transgender individuals. LGBT Health. 2017;4(2):115–20.
De Sutter P, Verschoor A, Hotimsky A, Kira K. The desire to have children and the preservation of fertility in transsexual women: a survey. Int J Transgend. 2002;6(3).
•• Chen D, et al. Attitudes toward fertility and reproductive health among transgender and gender-nonconforming adolescents. J Adolesc Health. 2018;63(1):62–8 This study identified that transgender adolescents have interest in family building, via either adoption or biological parenthood, though it is not always recognized. The article also sheds some light on the thought process patients may experience when arriving to the decision of whether or not to pursue fertility preservation.
Chiniara LN, Viner C, Palmert M, Bonifacio H. Perspectives on fertility preservation and parenthood among transgender youth and their parents. Arch Dis Child. 2019:1–6.
Chen D, Simons L, Johnson EK, Lockart BA, Finlayson C. Fertility preservation for transgender adolescents. J Adolesc Health. 2017;61(1):120–3.
•• Nahata L, Tishelman AC, Caltabellotta NM, Quinn GP. Low fertility preservation utilization among transgender youth. J Adolesc Health. 2017;61(1):40–4 This article highlights the concern that many transgender adolescents decline fertility preservation even when it is presented as an option. The authors discuss the need to better understand the family planning goals of transgender adolescents and ensure that they are sufficiently informed to understand the impact of their decision-making.
Auer MK, Fuss J, Nieder TO, Briken P, Biedermann SV, Stalla GK, et al. Desire to have children among transgender people in Germany: a cross-sectional multi-center study. J Sex Med. 2018;15(5):757–67.
Walter JR, Xu S, Woodruff TK. A call for fertility preservation coverage for breast cancer patients: the cost of consistency. J Natl Cancer Inst. 2017;109(5):1–5.
Mitu K. Transgender reproductive choice and fertility preservation. AMA J Ethics. 2016;18(11):1119–25.
Learmonth C, Viloria R, Lambert C, Goldhammer H, Keuroghlian AS. Barriers to insurance coverage for transgender patients. Am J Obstet Gynecol. 2018;219(3):272.e1–4.
Kyweluk MA, Reinecke J, Chen D. Fertility preservation legislation in the United States: potential implications for transgender individuals. LGBT Health. 2019;6(7):331–4.
State Legislation, Alliance for Fertility Preservation, 2019. [Online]. Available: http://www.allianceforfertilitypreservation.org/advocacy/state-legislation. Accessed 21 Oct 2019.
Chen D, et al. Factors affecting fertility decision-making among transgender adolescents and young adults. LGBT Heal. 2019;6(3):107–15.
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Bearelly, P., Rague, J.T. & Oates, R.D. Fertility Preservation in the Transgender Population. Curr Sex Health Rep (2020). https://doi.org/10.1007/s11930-020-00238-8
- Gender dysphoria