April 6, 2022
By Christina Fleckenstein, Drexel University College of Medicine

Intro

Transgender individuals face unique health care difficulties surrounding family planning and fertility preservation (FP). The term “transgender” refers to people whose gender identity is different from the gender they were assigned at birth. Clinical treatment for these individuals includes puberty suppression, gender-affirming hormone therapy or gender-affirming surgical procedures.¹ These treatments are all indications for fertility preservation.¹ It is recommended for clinicians to discuss family planning with all transgender patients, and ideally these patients should see fertility specialists prior to starting gender-affirming treatment. About half of transgender individuals want biological children, and over a third of transgender people would have considered fertility preservation, if all options had been presented to them.^2,3 Yet survey data indicates that only 12-13% of transgender adolescents see a fertility specialist and fewer than 5% completed FP procedures.^1,3 This article addresses the effect of gender-affirming therapy on fertility, different fertility preservation options, and the discrepancy between desired biological parenthood and low rates of FP among transgender individuals.

Fertility in Trans Women

Medication

Gender-affirming medications for trans women include cyproterone acetate, GnRH agonists, spironolactone and supplemental estrogens.^1,3 Spironolactone and cyproterone acetate have anti-androgenic properties. The effect of spironolactone on spermatogenesis has not been well studied. In comparison, data suggests that as little as 5 mg of Cyproterone acetate daily for two to four months impacts sperm mobility, morphology and quantity, with variably recovery of spermatogenesis.¹ Transgender women are normally prescribed 25-50 mg daily for androgen suppression. GnRH agonists reduce gonadotropin production in the brain and can cause testicular atrophy at high or long doses, irreversibly impairing fertility and spermatogenesis.^1,3 Estrogen has variable effects on spermatogenesis, including possible testicular atrophy and permanent sterilization. When used in combination with anti-adrenergic drugs, more significant fertility impairment can occur.

Fertility Preservation

For trans women who have undergone puberty (and therefore spermarche), the standard fertility preservation includes cryopreservation (preservation of sperm).¹ Semen samples are obtained by masturbation, using vibratory or electrical stimulation if necessary. In cases where gender-affirming medications or gender dysphoria make erection and ejaculation impossible, surgical sperm retrieval (SSR) can be performed at the time of gender-affirming surgery. However, SSR has been primarily studied among post-chemotherapy patients, with unknown success rates in transgender patients. Testicular tissue and spermatogonium stem cell cryopreservation is currently experimental, and represents a future avenue for fertility preservation.

Barriers to Fertility Preservation

Several unique barriers to fertility preservation exist among trans women beyond the lack of adequate counseling and referral previously mentioned. First, patients must discontinue medical therapy several months prior to semen collection to prevent azoospermia.^1,4 This can induce physical changes that can be psychologically distressing. The act of masturbation itself for semen collection can cause significant distress. Further, erection and ejaculation may be difficult or impossible second to gender-affirming estrogen or ant-androgenic medications, even if discontinued before sampling.¹

Some data also suggests that semen ejaculate is less viable among trans women compared to cis men, for incompletely understood reasons. A meta-analysis compared sperm analysis from the ejaculate of 141 healthy cisgender men and 78 transgender individuals, excluding those previously or currently on gender-affirming medication, and found significantly lower ejaculatory volume, total motile sperm count, post-thaw sperm count and post-thaw sperm motility among trans women.⁵ Fear of unsuccessful cryopreservation or the potential to need to provide multiple samples may discourage trans women from pursuing cryotherapy.

Lastly, cryopreservation is only possible in patients who have undergone spermarche, which occurs around age 13, and samples are more viable when collected several years after spermarche. Success of cryopreservation is 91% among 15- to 18-year-old cis men and 95% among 18- to 20-year-old cis men.¹ This presents a challenging decision for young trans-girls between early gender-affirming therapy to prevent or delay puberty and biological parenthood.

Fertility in Trans Men

Medications

Testosterone, in a variety of preparations, is the standard gender-affirming medication for trans men. It induces virilization by acting directly on end-organs.¹ Interestingly, testosterone causes endometrial proliferation in 48-83% of trans men, from peripheral testosterone-to-estrogen conversion and unopposed estrogen stimulation.¹ Testosterone does not affect the ovarian pool, nor does it induce PCOS, as was historically thought. Testosterone may inhibit ovulation, but unintentional pregnancy in trans men on testosterone has been reported.^1,4 For this reason, it is recommended that these individuals use barrier protection to prevent conception or discontinue testosterone therapy six months prior to trying for conception, due to testosterone’s teratogenic effects. For these reasons, conversations regarding fertility should be had prior to treatment start.

Fertility Preservation

The standard fertility preservation procedures for trans men include oocyte cryopreservation and embryo cryopreservation.^1,4 Both options require oocyte retrieval after controlled ovarian hyperstimulation (COH), which is accomplished with high dose-gonadotropins and GnRH analogues. This process requires daily monitoring of hormone levels and serial transvaginal ultrasound to monitor oocyte growth. Egg retrieval occurs about two weeks after COH initiation, under ultrasound-guided aspiration of the follicular fluid. Oocytes are preserved or fertilized with sperm to develop an embryo for preservation.

Ovarian tissue cryopreservation (OTC), via ovarian biopsy and freezing, is an option at a handful of institutions across the country. It can be performed at the time of gender-affirming surgery and is the preferred option for pre-pubertal youth when COH may be inappropriate.

Barriers to Fertility Preservation

There are similarly unique barriers to trans men undergoing fertility preservation. Unlike with trans women, pre-pubertal FP is possible in trans boys, as oogenesis occurs in utero for XX people assigned female at birth. As mentioned, OTC is preferred in these patients.

Despite FP options for patients of all ages, multiple cycles of COH and egg retrieval may be required, as 15 or greater oocytes predict a 85.2% success of pregnancy in patients under 25 years old.¹ Egg retrieval is less efficacious in patients over 35 years old, due to reduced cortical follicles. For these reasons, FP procedures and egg retrieval goals should be discussed between providers and patients prior to starting FP procedures and any gender-affirming care.

Cryopreservation in trans men can provoke significant gender dysphoria, as patients must discontinue testosterone therapy, which can lead to unwanted physical changes and the resumption of menses.⁴ Patients also must undergo invasive, serial gynecological examinations and transvaginal ultrasound, which can be psychological distressing.¹ Additionally, clinical staff unfamiliar with the care of trans patients may use gendered words, such as vagina, uterus, labia and the like, which can cause distress.^1,4 For this reason, clinicians are encouraged to ask patients how they prefer their body parts be called before starting an examination or procedure.

Further, trans men must also consider carrying a pregnancy originated via in vitro fertilization or intrauterine insemination, or pursuing surrogacy at the time that they desire parenthood, a multifaceted decision. There are also unique considerations for all couples pursuing embryo cryopreservation, such as preservation protocol should partners split in the future or change their minds about parenthood.¹

General Limitations

In addition to the barriers mentioned, both trans men and trans women face a fear of discrimination when pursuing FP. Historically, “it has been argued that transgender people are mentally unfit to parent” and should have limited access to reproductive services.⁴ In fact, sterilization procedures are promoted for these individuals in some countries, only propagating this harmful, discriminatory and untrue stigma.⁴ A 2020 survey of 116 transgender people who were assigned female at birth found that 32.6% of participants feared discrimination as a transgender parent.^1,2 Clinician inexperience and provider bias contribute to this statistic, as well as clinical environments related to conception and pregnancy that cater to feminine and female-identifying patients (i.e., “Women’s Center,” feminine-only propaganda, intake forms assuming female sex).

Another major barrier to FP services is cost. A survey found that 73.9% of transgender patients who were assigned female at birth who desired future fertility cited cost of obtaining and freezing genetic material as a major barrier. One fertility treatment center’s website lists one stimulation cycle and egg retrieval as $5,200 and one egg freezing cycle as $6,000.6 These costs do not even reflect consultation, shipments and long-term storage costs.

Discussion

Transgender people face numerous barriers to fertility preservation. Not all individuals are adequately counseled by their physicians or referred to fertility specialists prior to starting gender-affirming care. Fertility preservation may not be possible in individuals who have undergone extensive medical or surgical gender-affirming care, or those who are prepubescent, such as young trans girls. Fertility preservation procedures are intensive, invasive and gendered, which can cause significantly gender dysphoria. Plus, our health care system is overwhelmingly cisgender-oriented, which may be exclusionary or explicitly discriminatory toward transgender patients. Lastly, the steep cost associated with FP presents a major barrier. These limitations partially account for the disparity between the large number of transgender people who desire biological parenthood and the very few who pursue FP. This review aims to spark conversation and insight into ways we can restructure our practice to be increasingly inclusive, and to increase access to equitable fertility preservation resources for transgender people.

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Sources/Resources:

1. Mattawanon, N., Spencer, J. B., Schirmer, D. A., & Tangpricha, V. (2018). Fertility preservation options in transgender people: a review. Reviews in Endocrine and Metabolic Disorders, 19(3), 231-242.
2. Defreyne, J., Van Schuylenbergh, J., Motmans, J., Tilleman, K. L., & T’Sjoen, G. G. R. (2020). Parental desire and fertility preservation in assigned female at birth transgender people living in Belgium. Fertility and Sterility, 113(1), 149-157.
3. Transgender youth face barriers to fertility preservation (2017, March 29). Ann & Robert H. Lurie Children’s Hospital of Chicago. https://www.luriechildrens.org/en/news-stories/transgender-youth-face-major-barriers-to-fertility-preservation/.
4. Cheng, P. J., Pastuszak, A. W., Myers, J. B., Goodwin, I. A., & Hotaling, J. M. (2019). Fertility concerns of the transgender patient. Translational Andrology and Urology, 8(3), 209.
5. Li, K., Rodriguez, D., Gabrielsen, J. S., Centola, G. M., & Tanrikut, C. (2018). Sperm cryopreservation of transgender individuals: trends and findings in the past decade. Andrology, 6(6), 860-864.
6. How much does it cost to freeze your eggs at Advanced Fertility Center of Chicago? (Accessed 2022, January 23). Advanced Fertility Center of Chicago. https://advancedfertility.com/fertility-treatment/affording-care/egg-freezing-cost/.

 
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