Fertility Options for the Transgender and Gender Nonbinary Patient

Abstract

Comprehensive care for transgender and gender nonbinary patients has been a priority established by the World Professional Association for Transgender Health. Because pubertal suppression, gender-affirming hormone therapy, and antiandrogen therapy used alone or in combination during medical transition can affect gonadal function, understanding the effects these treatments have on fertility potential is important for practitioners caring for transgender and gender nonbinary patients. In this review, we outline the impacts of gender-affirming treatments on fertility potential and discuss the counseling and the treatment approach for fertility preservation and/or family building in transgender and gender nonbinary individuals.

Learning Points

1. Review impacts of gender-affirming medical treatments on gonadal function and future fertility.

2. Outline options for fertility preservation for transgender and gender nonbinary individuals.

3. Discuss the importance of early and regular counseling regarding future fertility and family-building in with transgender and gender nonbinary patient.

Case Presentation

Case 1

L.B. is a transgender male who initially presented after menarche at age 13 to discuss menstrual suppression and gender-affirming hormone therapy. He was counseled thoroughly on options for menstrual suppression, which he ultimately declined. At this initial visit, although testosterone was not initiated secondary to his age in conjunction with Endocrine Society guidelines and the expertise of his mental health provider, a care plan for gender-affirming hormone therapy was discussed and he was provided anticipatory guidance on risks and benefits of gender-affirming hormone therapy, including risks related to future fertility. He represented at age 15 with the support of his mental health care team for initiation of testosterone therapy. He and his parents were again counseled on the risks and benefits of treatment and were provided referrals for fertility preservation options. He elected to undergo oocyte cryopreservation and a successful retrieval of 28 oocytes occurred with one cycle of ovarian stimulation by the Reproductive Endocrinology and Infertility team. Following fertility preservation and within 2 months after presenting to discuss initiating treatment, testosterone was prescribed.

Case 2

C.T. is a transgender female who initially presented at age 13 to discuss pubertal suppression. At that visit, she was noted to be Tanner stage 3 and reported increasing pubertal changes such as voice cracking and penile growth. She was counseled thoroughly on options for pubertal suppression as well as the risks and benefits of this therapy. Additionally, she and her mother were counseled on future fertility in regard to the potential short-term impact of pubertal suppression as well as potential long-term impact of gender-affirming hormone therapy after pubertal suppression. They elected to pursue sperm cryopreservation, which was completed at an outside facility within 6 months of this counseling. Eight months after her initial counseling session and with support from her mental health team, a histrelin acetate implant was placed. Three months following initiation of pubertal suppression, estrogen therapy was initiated. Now, at age 16, she continues to present for routine follow-up and reports plans for gender-affirming surgery in the future.

Background

Historically, transgender and gender nonbinary individuals delayed gender-affirming therapy to complete childbearing, or these individuals considered themselves infertile at the initiation of gender-affirming care, even if they had not yet met their fertility goals (1). Many have reported that fertility is secondary to gender transition and cite a desire to not delay gender-affirming care as a reason to not undergo fertility preservation prior to gender transition (2). Some have even reported that loss of fertility with gender-affirming treatment is essential to consider gender transition complete or have reported that childbearing or the process of conceiving may exacerbate gender dysphoria (2, 3). Fertility and transgender care, therefore, have long been seen in silos, and even as patients and providers have begun to understand that the goals of gender transition and fertility are not mutually exclusive, often opportunities for fertility preservation have not been considered after initiation of gender-affirming therapy. Although still limited by small sample sizes or testing on nonhuman subjects, a growing body of evidence has provided better understanding of the potential effects of gender-affirming therapy on future fertility (4-6). This has allowed for more accurate and targeted counseling regarding expected fertility outcomes after initiating gender-affirming treatments. Additionally, recent advances in assisted reproductive technology (ART) have allowed transgender and gender nonbinary individuals to consider both reproductive and transition goals at initiation and throughout gender-affirming therapy.

This is important because fertility and family-building have been demonstrated to be valued by many transgender individuals (7-10). To assist transgender and gender nonbinary patients to meet goals both of family-building and gender transition, counseling regarding potential impacts of gender-affirming treatments on future fertility as well as fertility preservation options is important at initiation and throughout gender-affirming treatment. Many gender-diverse individuals report a desire for fertility counseling and, at a minimum, report considering fertility preservation (2, 7, 10). It is unclear how often patients are being offered this counseling, and when received, little is known about the breadth of counseling provided. For example, among transgender and gender nonbinary youth, as many as 79.5% of transgender teenagers reported never discussing future fertility with a health care provider (3). Of teenagers who reported discussions regarding fertility as part of medical transition, only half reported discussions about the impact of medical transition on fertility (3).

Of those who receive counseling regarding fertility preservation, completion of fertility preservation procedures prior to initiating gender-affirming treatment remains low. For example, one study demonstrated that although 76.6% of transgender men and 76.1% of transgender women reported they had considered fertility preservation methods, only 3.1% of transgender men and 9.6% of transgender women had undergone any fertility preservation procedure (7). Similarly, in a study of transgender teenagers, 2 out of 72 who received fertility preservation counseling ultimately underwent fertility treatments; both of these individuals were transgender women (11). One study of Israeli teenagers demonstrated higher rates of usage of fertility preservation among young transgender women (45%); however, completion of fertility preservation transgender men remained low (6%) (12). It is unclear exactly why uptake of fertility preservation has been low in gender-diverse patients. Some suspect that ambivalence regarding future fertility in the setting of planned permanent gender transition may contribute to low uptake of fertility preservation options. Known barriers to transgender patients such as concern about discrimination and high treatment costs have also been cited as potential reasons for the low prevalence of fertility preservation among transgender and gender nonbinary individuals (3, 9, 11, 13).

Despite the potentially low use of fertility care among transgender and gender nonbinary individuals, thorough counseling regarding the impact of gender-affirming treatments and the options for fertility preservation remain important for every patient prior to and throughout medical and surgical transition. This is supported by the American Society of Reproductive Medicine, the Endocrine Society, and the World Professional Association for Transgender Health (WPATH) (14-16).

Impact of pubertal suppression on gonadal function

Depending on age at presentation for gender-affirming care, some patients may not have completed innate puberty following use of pubertal suppression with gonadotropin-releasing hormone (GnRH) agonists. GnRH agonists have traditionally been used in the care of children with central precocious puberty as a manner to reversibly suspend early puberty (17). In these patients, the data support little impact on future fertility potential, particularly for young females (18-21). The data for male patients are not as robust; however, small studies have demonstrated a minimal impact on pubertal function in boys after discontinuation of GnRH agonists (21, 22). However, these studies have been completed in patients who ultimately go on to complete innate puberty. For many transgender teenagers, GnRH agonists are also used to suspend puberty, but teenagers may never undergo innate puberty and instead may elect to proceed with gender-affirming hormone therapy following a period of pubertal suppression (16). Previous studies regarding the impact of GnRH agonists on fertility potential therefore may not be completely applicable to transgender or gender nonbinary patients who never complete innate puberty.

To date, there are no studies addressing fertility potential of gonads treated with pubertal suppression and subsequent gender-affirming hormone therapy, but significant concerns have been raised regarding the viability of fertility options for gonads that have not undergone puberty (23-25). This is particularly true in transgender men because oocytes undergo final maturation just prior to ovulation, thus requiring menarche to reach full fertility potential (26). Even with menarche, data have demonstrated both diminished fertility potential and egg quality for 1 to 3 years after menarche, indicating that menarche as well as maturation of the hypothalamic-pituitary-ovarian axis are necessary for fertility, which will not occur in transgender men who elect to suppress innate puberty (27). Conversely, spermarche can occur before puberty has been fully completed with evidence of spermatogenesis at testicular volumes as low as 5 mL and prior to completion of testicular growth or development of pubic hair (28, 29). Therefore, transgender women who have progressed to Tanner stage 2 or 3 prior to initiation of pubertal suppression may have the potential for successful fertility despite pubertal suppression. However, further long-term studies, particularly after the initiation of hormone therapy, are needed.

Impact of gender-affirming treatment on ovarian and uterine function

For transgender men who initiate testosterone after completion of puberty, several studies have demonstrated impacts on ovarian tissue and function, but long-standing impact or clinical consequences of this remains mixed (30-34). Although it is not considered an efficacious contraceptive, testosterone does induce anovulation (32, 35). However, data favor the reversibility of testosterone’s impact during breaks in treatment, particularly regarding attempted fertility or fertility preservation. In transgender men who have undergone fertility treatments, outcomes for ovarian stimulation and egg retrieval have been similar among transgender men who have never used hormone therapy, transgender men who have used hormone therapy, and cis-gendered women (36, 37). However, the length of time for a break in testosterone treatment necessary to resume normal ovarian function is unknown. For some, menstrual cycles have been demonstrated to return within 6 months of testosterone discontinuation although others have reported potential for longstanding and possible permanent amenorrhea following testosterone use (38, 39). Importantly, testosterone is considered teratogenic, but limited data exist to provide guidance for the timing of conception following testosterone discontinuation (40, 41).

Uterine architecture is also altered by testosterone treatment, typically leading to endometrial atrophy, although some concern has been raised about the potential for endometrial hypertrophy under anovulatory conditions (32, 42). There are several reports of transgender men carrying pregnancies following discontinuation of testosterone treatment, indicating that previous gender-affirming hormone treatment may have little impact on the uterus’ ability to carry a pregnancy following discontinuation of treatment (38).

Impact of gender-affirming treatment on testicular function

For transgender women, the impact of estrogen on testicular function favors decreased spermatogenesis and poor parameters of semen quality but the data have been highly variable, ranging from slight alterations in sperm quality to azoospermia (43-47). One study, for example, found that in orchiectomy specimens of transgender women treated with estrogen therapy, more than 80% had germ cells and 40% had spermatids present in surgical specimens (48). Yet others have reported significant decreases in all semen analysis parameters for transgender women on estrogen, and similar outcomes have been reported for cis-gendered men undergoing trials of male contraception with estrogen, indicating significant subfertility. These findings are likely secondary to alterations in spermatogenesis with estrogen, but alterations or damage to testicular architecture with estrogen exposure are also a concern (46, 49-51). Once the semen analysis has been altered following estrogen therapy, little is known about reversibility and improvement in sperm quality with discontinuation of estrogen therapy (15). A small study of semen analyses of transgender women compared samples from transgender women who had currently, previously, or never used estrogen therapy and found that sperm concentrations and motility in transgender women who had previously used estrogen therapy were worse than those who had never used hormonal therapy but better than those currently treated with estrogen (47). However, this study was limited by sample size and variability in estrogen dosing and duration of treatment, demonstrating many residual unknowns regarding the impact of prolonged estrogen treatment on future fertility. Importantly, some alterations in sperm quality can be overcome with ART for insemination, except if spermatogenesis is completely inhibited.

Transgender women typically elect additional treatment with antiandrogens to combat the effects of circulating testosterone. Antiandrogen treatment most commonly can be in the form of a GnRH agonist, spironolactone, and cyproterone acetate or, rarely, finasteride or flutamide (16, 52). Given their antiandrogenic qualities, all may affect sperm quality (53-55). Additionally, although many of these options are considered reversible agents, long-term effects on sperm quality or testicular function have not been completely ruled out.

Decision to halt gender-affirming treatment to achieve fertility goals

Given the previously stated findings, for individuals who have already undergone gender-affirming hormone treatment and desire fertility, discontinuation of hormone therapy and/or antiandrogen therapy while pursuing fertility may be recommended. For those who undergo a treatment break, the duration off therapy is variable. For example, although it has been reported that some fertility clinics may allow for oocyte retrieval while on testosterone treatment, most published literature has reported a recommendation of 1 and 6 months off testosterone for transgender women undergoing fertility treatments (6, 52). However, there are no established standards for the time interval required for discontinuation of testosterone, estrogen, or antiandrogens to attempt fertility treatments, and results from small case series have been mixed (43, 47, 56). Additionally, for those who have undergone pubertal suppression and subsequent gender-affirming hormone therapy, a paucity of data exists regarding time off all treatment to allow for sufficient pubertal changes for fertility treatment. One potential algorithm for all patients who elect to halt therapy to maximize fertility potential is to check monthly serum estradiol, testosterone, luteinizing hormone, and follicle-stimulating hormone levels after discontinuation of cross-sex therapy until results trend toward innate hormonal levels. Routine pelvic ultrasound for assessment of antral follicle count or semen analysis to assess sperm quality would provide additional evidence for fertility potential, but these tests are invasive and could worsen anxiety or gender dysphoria. Thus, the decision regarding monitoring and timing of attempted fertility treatments should be individualized with an emphasis on shared decision making between the patient and provider.

It is important to note that gender-affirming hormone and antiandrogen breaks may raise concerns for some patients regarding regression of desired secondary sex characteristics or return of menstrual bleeding, particularly in patients who desire fertility but do not wish to carry a pregnancy themselves (6, 57). Breaks from gender-affirming medications can lead to anxiety and increasing gender dysphoria, especially when regression of desired secondary sex characteristics is at risk. Moreover, development of some secondary sex characteristics, such as hair or breast growth, may be irreversible without surgical or dermatologic treatment, which can result in worsened gender dysphoria and/or additional financial costs associated with these treatments.

It is important to counsel patients about the potential need for a treatment break when pursuing fertility and provide targeted mental health counseling and support throughout the fertility preservation process, particularly if gender-affirming treatment breaks are necessary.

Assessment

Initial visit

Given the potential effects of treatment on gonadal function, the ideal timing for fertility counseling is prior to initiation of gender-affirming care. However, understanding that a patient’s wishes and understanding of his or her own fertility may change with age, psychosocial development or relationship status is also important for ongoing counseling (3, 5, 58). Visits for fertility counseling should start with a thorough history of gender-affirming treatment. It is important to know whether pubertal suppression in the form of a GnRH agonist was used, and if so, the patient’s pubertal stage at initiation and the duration of pubertal suppression should be documented. If applicable, age, pubertal staging, and dose at initiation of gender-affirming hormone treatment should be requested as well as duration of gender-affirming hormone therapy, current dosage, and length of time on the current dosage of hormone therapy. Antiandrogen therapy used in conjunction with estrogen therapy for transgender women should also be documented along with the dosage and duration of this treatment. Menstrual history for transgender men as well as methods used for menstrual suppression should be recorded. Gender-affirming surgical treatments should be reviewed, particularly those that may alter gonadal tissue.

Because family-building can occur in many varieties, fertility goals should be assessed. Patients should be asked if they desire to grow their family with children who share their genetic makeup, thus assessing the importance of retrieval of sperm or oocytes from the patient. For those who have initiated or completed hormonal transition, assessment of willingness to halt treatment for the duration of fertility care is needed. For those individuals who are less interested in fertility preservation but are actively considering growing their family, discussions regarding plans for a sperm or egg donor (partner or bank) as well as plans for a gestational carrier should be assessed. Some transgender men who have not completed surgical transition, for example, may consider carrying a pregnancy (38). Others may rely on partners or surrogates for embryo transfer. Understanding a patient’s anatomy as well as his or her fertility goals in relation to that anatomy is paramount prior to fertility workup and counseling.

For transgender youth and their parents, a validated questionnaire has been developed to assess attitudes toward future fertility (59). Similar validated assessments for transgender adults have not been established.

Physical examination

The physical examination should evaluate pubertal development. Tanner staging of breasts, testicles (if applicable), and pubic hair should be completed. This examination is particularly important for transgender women who underwent pubertal suppression, because Tanner staging with measurement of testicular volume may predict ability to undergo sperm cryopreservation (29). Additional physical exam findings, outside evidence of gender-affirming surgical treatment, are unlikely to alter counseling regarding fertility care.

Laboratory evaluation

Laboratory assessment of gonadotropins and sex hormones can provide some evidence of gonadal function; however, these studies can be altered by active use of gender-affirming hormones or antiandrogens (60, 61). Antimüllerian hormone (AMH) is typically used to assess ovarian reserve, but is not always an accurate predictor of fertility potential in women (62). For transgender men, studies have been mixed regarding alterations in AMH by testosterone and, thus, AMH levels may not add value in fertility counseling for these patients (63, 64).

However, if a transgender male presents for fertility counseling prior to gender-affirming treatment or during a gender-affirming treatment break, follicle-stimulating hormone, and estradiol drawn between days 2 and 4 of the menstrual cycle, progesterone drawn 1 week before expected menses, as well as AMH levels drawn at any time throughout the menstrual cycle may be obtained by a reproductive endocrinology and infertility specialist to assess physiologic hormonal changes throughout the menstrual cycle and guide medication regimens for fertility treatment (65).

Imaging

Evaluating the ovaries on ultrasound for ovarian volume and antral follicle count can assist with decision making regarding medication regimens for fertility treatment. Typically, transvaginal ultrasonography is the preferred method for ovarian imaging and antral follicle counts, although transabdominal and transrectal imaging of ovaries is possible (66). Given the discomfort that some transgender men may experience with imaging of female structures or placement of a transvaginal probe, completion of ultrasounds for fertility purposes should be reserved for reproductive endocrinology and infertility specialists to minimize repetition and frequency of imaging.

No imaging is indicated for transgender women prior to fertility counseling or treatment.

Treatment

There are currently no standard guidelines for fertility preservation or reproductive care of transgender and gender nonbinary individuals (23).

Gamete cryopreservation

For cis-gendered women undergoing potentially gonadotoxic therapies, oocyte and embryo cryopreservation are considered standard of care for fertility preservation for postpubertal patients (67). Because testosterone may not affect ovarian function and future fertility irreversibly or to the same degree as other gonadotoxic treatments, such as chemotherapy or radiation, the risks and benefits of oocyte and embryo cryopreservation may be weighed differently in transmasculine individuals compared to cis-gendered individuals receiving other gonadotoxic therapies. However, given that hormonal therapies for gender transition have the potential to affect ovarian function, oocyte and embryo cryopreservation should be discussed with transgender men who have undergone innate puberty. Unfortunately, little success has been achieved for ART of immature oocytes, thus oocyte cryopreservation cannot be offered to premenarchal patients. For cryopreservation, oocytes are removed under sedation via transvaginal aspiration. It is important to note that the process of ovarian stimulation required for oocyte retrieval can take several weeks and requires multiple injections of gonadotropins and GnRH agonists as well as serial transvaginal ultrasounds, all of which can be traumatic or undesired by transgender males (6). Typically, multiple cycles may be recommended depending on the yield of mature oocytes with each retrieval and an individual’s family-building goals; suggestions range from 8 to 26 mature oocytes to increase the probability of future pregnancy, which for some can be achieved with one retrieval and for others requires additional stimulation and retrieval attempts (68, 69). Following retrieval, oocytes can be cryopreserved separately or fertilized with sperm. Embryo cryopreservation has been preferred for cryopreservation; however, given potential legal, ethical, and religious considerations regarding embryo cryopreservation and advancement in cryopreservation techniques yielding improved pregnancy outcomes from oocyte cryopreservation alone, both can be considered (67). Among cis-gendered women, pregnancy outcomes following oocyte cryopreservation have been favorable (70). Data for transgender men are not as robust presumably because of the low uptake of oocyte cryopreservation; however, successful pregnancies have been reported (71).

For transgender women, sperm cryopreservation can be completed. This can be attempted as long as patients have progressed to Tanner stage 2 of pubertal development or with testicular volumes as low as 5 mL (28, 29). The youngest age of reported successful specimen collection is age 11 (72). Sperm quality may be affected in specimens from those who have not completed puberty; however, sperm cryopreservation should be completed regardless of the sample quality given because some ART techniques can lead to successful oocyte fertilization despite abnormalities in semen analysis. The same is true for older transgender women who may have negative effects on sperm quality from gender-affirming medications (39).

Medically, the least invasive method of recovering sperm for cryopreservation is via masturbation. For individuals who cannot produce a specimen or experience significant psychologic stress with masturbation, electroejaculation or penile vibratory stimulation can be used (6, 55). Typically, more than one specimen collection is recommended to yield sufficient sperm concentration for use with ART; however, the number of recommended collections depends on sperm quantity and quality in the specimen and intended ART use (intrauterine insemination requires higher sperm concentrations that in vitro fertilization) (73). If an individual completes multiple collections, typically he or she should allow 2 to 5 days between collections (73). Percutaneous epididymal sperm aspiration and surgical sperm retrieval via testicular biopsies are additional, but more invasive, manners of sperm extraction. This has typically been reserved for those who fail ejaculatory collection; however, recent data have shown some success with this method in the transgender population, in whom it was previously used at the time of gender-affirming orchiectomy (5, 6, 13, 55).

Given this, although concerns about delaying treatment are cited by transgender individuals as reasons to not pursue fertility preservation, it is important to note that one cycle of sperm cryopreservation can be completed in 24 to 48 hours and one cycle of oocyte cryopreservation can be completed in 1 to 2 weeks (2).

Whole gonadal cryopreservation

Ovarian tissue cryopreservation (OTC) is the only available option for individuals assigned female at birth who have not yet undergone innate puberty and who wish to preserve fertility prior to receiving any gender-affirming treatment (74). This procedure involves surgical removal, typically via laparoscopy, of a portion of the cortex of the ovary or one entire ovary. The ovarian cortex, the location of oocytes within the ovary, is then cryopreserved in small sections and implanted back into the body at the time of desired fertility. To date there have been no successful pregnancies from in vitro maturation of oocytes in patients who have undergone OTC. Live birth has been achieved in this manner for cancer patients (74-77). However, although few reported births have occurred in those who have cryopreserved tissue prior to menarche, the majority of reported births are from tissue removed in postpubertal patients (76, 77). Because of this small number of studies, ongoing research is needed to support the efficacy in ovaries removed prior to puberty. OTC was considered experimental until 2020 (74). Prior to this change in distinction made by the American Society of Reproductive Medicine, OTC was rarely offered to transgender and gender nonbinary patients given strict experimental protocols. It is unclear how readily available this procedure will be for transgender and gender nonbinary patients following these changes. Additionally, studies comparing fertility and pregnancy outcomes from cryopreserved ovarian tissue vs from testosterone-treated ovarian tissue are needed.

Testicular tissue cryopreservation is considered experimental and can be completed only at institutions with experimental protocols. Despite promising evidence that this may be a future alternative for fertility preservation, no established protocols for tissue reimplantation or in vitro maturation of gametes have been developed and no live births have been reported to date (74, 78, 79). Given the experimental nature of this procedure, it is not regularly offered as an option for fertility preservation in transgender women; however, some have advocated for the option for testicular tissue cryopreservation, if desired, at the time of gonadectomy (5, 55). Importantly, however, many advocate for gonadectomy after age 18 given concerns regarding sterilization of minors, and WPATH recommends hormone transition for at least 1 year prior to surgical transition, thus many patients are likely to initiate hormone therapy prior to gonadectomy (16). Some have suggested that instead of considering testicular cryopreservation, sperm freezing from testicular specimens may be a preferred option for fertility preservation at the time of orchiectomy (80).

Pregnancy

During discussions of oocyte and sperm retrieval, it is important discuss plans for the carrier of a future embryo. Some transgender men may desire to carry a pregnancy (15, 38). Others do not desire for reimplantation into their own womb because they feel that this would not match their gender identity (9). Some cannot undergo reimplantation secondary to gender-affirming hysterectomy (15). Transgender women may elect to use the womb of the individual contributing an oocyte. However, transgender and gender nonbinary individuals vary in elected partners, and thus it is important to remember that a couple hoping to expand their family may require assistance from a gestational carrier to complete their pregnancy goals (81). Uterine transplant, while possible, remains experimental and carries significant medical risks, and, thus should not be readily discussed as an alternative to gestational carrier at the present time, but with continued advancement may be a potential option for transgender women (39, 82, 83).

Adoption

Many transgender individuals report an interest in family building via adoption (3, 9). In a study of adult transgender individuals who had already undergone transition and self-identified as having a desire to become parents in the future, more than one-third reported a desire to use adoption as the manner for family building; for transgender women specifically, 75% reported a desire to parent via adoption (9). Transgender teenagers, too, see adoption as a viable option for family building. In one study of teens counseled on fertility preservation options prior to gender-affirming therapy, 45% of those who declined fertility preservation reported declining because they planned to adopt children in the future (11).

Controversies and Areas of Uncertainty

Cost of fertility care

Financial limitations are a regularly cited concern for transgender families undergoing fertility treatments (5, 9, 82). Depending on where the patient lives, insurance providers may not cover some or all fertility treatments, thus it is important for patients to be aware of the financial implications of each of these treatments. Even for those who have coverage benefits for fertility care, out-of-pocket costs vary by insurance, country, region, state, fertility provider, and/or procedure. Typical fertility costs specific to those in the United States have been outlined in previous literature that can be loosely used for reference; however, for those interested in pursuing fertility treatments, often a realistic assessment of anticipated cost can be obtained during an initial consultation with a fertility specialist (5). There are a few organizations that offer financial assistance to transgender or gender nonbinary individuals undergoing fertility treatments that are outlined and updated regularly at https://www.familyequality.org/resources/lgbtq-family-building-grants/.

Additional barriers to fertility care

Individuals who do not meet heteronormative standards have often met significant stigma regarding family building. Legislation, for example, has historically limited access to family building and ART for many lesbian, gay, bisexual, transgender, questioning (LQBTQ+) individuals and families. And, although access to these services by LGBTQ+ individuals has increased more recently, many transgender and gender nonbinary individuals still face barriers to this care (84-86). In fact, a study published in 2017 found that almost 70% of fertility clinics listed in the Society for Assisted Reproductive Technology database did not include information on the care of transgender individuals on their websites, which may dissuade transgender or gender nonbinary individuals from seeking care at those institutions (87). Moreover, transgender patients have reported refusal of services from ART clinics on disclosure as transgender (86).

These barriers are not limited to ART, but also exist for those families seeking adoption for family building. Legal barriers can also limit the ability of a nonchildbearing parent or a parent who is not genetically related to a child to seek parenting or custody rights in a variety of LGBTQ+ families (88). It is important that transgender and gender nonbinary patients acknowledge the potential for barriers to fertility care and family building to make an informed family-planning decision.

The most commonly cited concern for withholding ART from transgender and gender nonbinary individuals is child welfare. Importantly, this claim has not been upheld in limited studies (82). Many professional societies have not supported this claim (14, 89).

Additionally, regarding the care of transgender adolescents, many have cited concerns about patient maturity and ability for teenage patients to effectively weigh their desire for family building (23, 84). Some have suggested that low uptake of fertility preservation in the adolescent population may be due to lack of developmental ability to make decisions about future fertility (23). Others have reported that fertility concerns are less important to teenage patients and parents, falling behind priorities like pubertal suppression, gender transition, mental health concerns, and feeling safe and accepted in the community and by family members, which may limit their desire to discuss and pursue fertility preservation options (90). Additionally, given that age 18 is typically considered the legal age of consent (although this may vary depending on the state or country), providers have cited parental involvement and consent for fertility preservation as a potentially confounding factor in decision making for fertility preservation among transgender adolescents (23, 82). For patients who are not yet of age to provide consent, legal consent for procedures is typically required from one parent with legal guardianship. Consent from both parents, although often not legally required, is, of course, strongly recommended, particularly when there is parental disagreement or joint legal custody (91).

Finally, the role that regret regarding fertility preservation as well as regret regarding hormone therapy or desire to retransition plays in decisions regarding fertility preservation (particularly in adolescents) is difficult to assess and has not been evaluated. The decision to undergo fertility preservation is complex and not only involves weighing known risks of medical treatment on future fertility, but also includes a personal evaluation of fecundity, family building, and moral or ethical beliefs about artificially storing, using, or potentially discarding unused genetic tissue. Studies have been completed in cis-gendered patients receiving gonadotoxic treatments and have demonstrated a low incidence of regret for fertility preservation decisions among those who are thoroughly counseled about risks and options prior to medical treatments regardless of their decision to forgo or pursue fertility preservation prior to treatment (92, 93). It is unknown whether incidence of regret regarding fertility preservation among transgender or nonbinary patients is similar. Moreover, the topic of regret regarding gender-affirming therapy and desire to retransition has not been well studied to date, and it is unknow what role this plays in decisions regarding fertility preservation.

Back to the Cases

Our cases outline experiences of 2 transgender teenagers, both of whom ultimately underwent fertility preservation prior to initiating gender-affirming treatment. Although this is not the case for every transgender and gender nonbinary patient, it is important to highlight these cases because they demonstrate a potential path for maximizing goals of future fertility and gender-affirming care. Data regarding fertility outcomes before, during, and after gender transition remain limited and mixed. Ongoing research in this field, particularly with assessment of pregnancy outcomes, is needed. However, despite these limitations, it is important that regardless of where a patient is in his, her, or their transition, assessment of fertility goals and counseling on fertility options occurs early, often, and throughout gender transition. This counseling should include a comprehensive review of all available options based on past and current gender-affirming treatments and place a large emphasis on shared patient-provider decision making. For transgender and gender nonbinary patients with gonadal tissue in situ who desire future fertility, evidence supports that it is never too early or too late to discuss fertility goals and fertility options to maximize future fertility in conjunction with—and not opposition to—gender transition.

Glossary

Abbreviations

AMH

antimüllerian hormone

ART

assisted reproductive technology

GnRH

gonadotropin-releasing hormone

LQBTQ+

lesbian gay bisexual transgender questioning

OTC

ovarian tissue cryopreservation

WPATH

World Professional Association for Transgender Health

Additional Information

Disclosure Summary: The authors are employees of the Division of Intramural Research at the National Institute of Child Health and Human Development.

Data Availability

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.