Transgender Health

Volume 1.1, 2016

Transgender
DOI: 10.1089/trgh.2015.0010
Health

PERSPECTIVES Open Access

Preservation of Fertility Potential for Gender

and Sex Diverse Individuals
Emilie K. Johnson1–3,* and Courtney Finlayson4,5

Abstract
Gender and sex diverse individuals—transgender individuals and those with disorders of sex development (DSD)—
both face medical treatments that may impair biological fertility potential. Young DSD patients also often have ab-
normal gonadal development. Fertility preservation for these populations has historically been poorly understood
and rarely addressed. Future fertility should be discussed with gender and sex diverse individuals, particularly given
recent advances in fertility preservation technologies and evolving views of fertility potential. Key ethical issues in-
clude parental proxy decision-making and uncertainty regarding prepubertal fertility preservation technologies.
Many opportunities exist for advancing fertility-related care and research for transgender and DSD patients.
Key words: disorders of sex development; fertility preservation; gender dysphoria; transgender

Introduction be important to have the option of a biological child. Fer-

The term ‘‘gender and sex diversity’’ refers to (1) trans- tility preservation technologies (methods of storing eggs,
gender individuals for whom gender identity is incon- sperm, or precursor reproductive tissue for future use)
gruent with birth-assigned sex and (2) individuals with and societal attitudes toward ‘‘nontraditional’’ family
differences (disorders) of sex development (DSD), also structures have expanded significantly in recent years
known as intersex, for whom development of chromo- such that having a biological child is now possible for
somal, gonadal, or anatomic sex is atypical.1 In the many transgender adults and adults with DSD.
Lurie Children’s Gender and Sex Development Pro- The purpose of this perspectives article is to provide
gram, we have found that care for one group can inform an introduction and overview of preservation of biolog-
the other and patients benefit from specialists who are ical fertility potential for gender and sex diverse indi-
familiar with both. Although many distinctions exist be- viduals. We also propose next steps for advancing
tween transgender individuals and individuals with this new clinical and research focus.
DSD, an important area of commonality lies in the
area of fertility—the ability to have a biological child. Fertility Preservation for Transgender Patients
Many medical and surgical therapies available to trans- Loss of biological fertility was once thought to be a given
gender adolescents/young adults (AYA), and children consequence of gender transition.2 Transgender individ-
and AYA with DSD, can affect future fertility. Individuals uals and their healthcare teams have now begun to rec-
with DSD frequently also have subfertility related to their ognize that options for preserving reproductive potential
medical condition. Gender and sex diverse individuals exist. A majority of transgender adults believe that fertil-
often choose to build a family through options such as ity preservation should be discussed with and offered to
adoption or surrogacy. For some, however, it may also them.3,4 The Endocrine Society Guidelines recommend
1
Division of Urology, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, Illinois.
2
Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
3
Center for Healthcare Studies, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
4
Division of Endocrinology, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, Illinois.
5
Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois.

*Address correspondence to: Emilie K. Johnson, MD, MPH, Division of Urology, Ann & Robert H. Lurie Children’s Hospital of Chicago, 225 East Chicago Avenue, Box 24,
Chicago, IL 60611-2605, E-mail: [email protected]

ª Emilie K. Johnson et al. 2016; Published by Mary Ann Liebert, Inc. This Open Access article is distributed under the terms of the Creative Commons License
(http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original
work is properly credited.

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Johnson and Finlayson; Transgender Health 2016, 1.1 42
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counseling for transgender individuals regarding fertility hormone therapy. For transgender women, this involves
before initiating gender-affirming hormonal therapy.5 sperm preservation, with a sample typically obtained
Knowledge of the effects of medical treatments on fertil- through masturbation. When this is not possible due
ity, familiarity with available fertility preservation op- to anatomic, emotional, or physical maturity concerns,
tions, and an appreciation for potential ethical issues sperm can be retrieved directly from the testis using a sur-
are all necessary to effectively counsel patients. gical procedure, testicular sperm extraction (TESE). For
transgender men who have undergone female puberty,
Medical treatments—effects on fertility fertility preservation options include hormonal stimula-
Pubertal suppression with gonadotropin releasing ago- tion followed by oocyte or embryo cryopreservation.
nists (GnRH-a) not only prevents development of po- Ovarian tissue cryopreservation (OTC), an experimen-
tentially distressing secondary sex characteristics but tal procedure in which prepubertal ovarian tissue is har-
also suspends germ cell maturation. Puberty appears vested and preserved, is offered to women with cancer.14
to progress normally after discontinuation.6 However, OTC is a potential area of future investigation for peripu-
many transgender individuals initiate gender-affirming bertal affirmed males, as it does not require hormonal
hormone therapy concurrently with pubertal suppres- stimulation. Similarly, testicular cryopreservation may
sion,7 and thus, germ cells never fully mature. This offer fertility potential for peripubertal affirmed females.
highlights the need for discussion of fertility options Prepubertal tissue cryopreservation protocols for oncol-
before initiating GnRH-a treatment. ogy patients could be expanded to transgender individuals
Gender-affirming hormones produce impairments in the future. Although the technology is still developing,
in gonadal histology that can cause infertility. Estrogen fertility experts expect that precursor egg and sperm cells
use by transgender women results in impaired sper- will soon be able to be matured and used with assisted re-
matogenesis and an absence of Leydig cells in the tes- productive technologies to produce a biological child.15–17
tis.8,9 Testosterone use by transgender men causes
ovarian stromal hyperplasia10,11 and follicular atresia.10 Ethics
Gonadal effects of gender-affirming hormones are A primary ethical concern regarding fertility preservation
thought to be at least partially reversible. For example, for transgender AYA is that parents must make decisions
pregnancy has been reported in transgender men who about fertility preservation if it is to occur before initiation
have previously used testosterone.12,13 Thresholds have of pubertal suppression and/or gender-affirming hormone
not been established for the amount and duration of therapy. Although this is done with patient assent, children
exogenous testosterone or estrogen exposure necessary are often not intellectually or emotionally mature enough
to have a permanent negative effect on fertility. to predict their future desires or understand the implica-
For patients who elect surgical transition, gonadec- tions of their present decisions. This results in transgenera-
tomy will render them permanently sterile. Thus, this tional fertility decision-making, which may not align with
is the last opportunity for fertility preservation for pa- future patient desires; disagreement between the patient
tients who choose gender reassignment surgery that and parent regarding fertility preservation may also arise.
includes gonadal removal. In addition, there may be patient distress associated with
procurement processes, given that the gamete type is not
Fertility preservation options congruent with gender identity. Furthermore, peripubertal
Table 1 summarizes current fertility preservation tech- tissue cryopreservation is experimental. It is unknown if
niques, stratified by pubertal status. Transgender individ- and when assisted reproductive technologies will be avail-
uals who have undergone spontaneous biological puberty able to mature germ cells. Thus, patients are potentially in-
consistent with their birth-assigned sex may elect for fer- curring surgical risk and storing gonadal tissue without the
tility preservation before initiation of gender-affirming guarantee of future fertility.

Table 1. Current Fertility Preservation Options

Gamete type Pre- or peripubertal options Postpubertal options

a
Oocyte Ovarian tissue cryopreservation Ovarian stimulation, with oocyte retrieval and cryopreservation of oocyte or embryo
Spermatozoa Testicular tissue cryopreservationa Sperm banking, with sample obtained through masturbation or surgical biopsy
a
Experimental.
Johnson and Finlayson; Transgender Health 2016, 1.1 43
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Table 2. DSD Fertility Effects, Research Needs, and Fertility Preservation Techniques

Applicable fertility
Characteristic Fertility effect Research needs preservation technique

Abnormal gonads (streak, dysgenetic) Congenital and/or progressive Establish presence and Cryopreserve testicular
gonadal failure quality of germ cells or ovarian tissuea
by age
Risk of gonadal malignancy Gonadectomy traditionally -Malignancy risk- If gonadectomy required
performed stratification by condition -Postpubertal: preserve sperm
-Surveillance protocols or oocytes
if gonads retained -Prepubertal: cryopreserve
nonmalignant tissue
Abnormal hormone production Abnormal sperm and Determine fertility rates Existing assisted reproductive
oocyte production techniques: ovarian
stimulation, testicular
sperm extraction
Discordance between gender identity Reframing view allows for Patient/parent N/A
and germ cell type biological fertility potential perspectives needed
a
Experimental.
DSD, disorders of sex development.

Fertility Preservation for Patients with DSD genital adrenal hyperplasia, and 5-alpha reductase
As for transgender patients, infertility or sterility has deficiency. These diverse DSD conditions differ in eti-
often been assumed for many DSD patients. The ap- ology and fertility potential. DSD patients are at risk
proach to DSD care has shifted in the last few decades for potential infertility or sterility due to the following:
from the assumption that individuals were psychosex- (1) abnormal gonadal development, (2) gonadectomy
ually neutral and early sex reassignment surgery was for malignancy risk, (3) abnormal hormonal function,
preferred, without concern for future fertility, to one and (4) discordance between gonadal type and gender
in which it is acknowledged that the formation of gen- identity. These often overlapping etiologies are out-
der identity is poorly understood and that irreversible lined in Table 2, along with description of further re-
surgeries should be avoided or performed only with quired advances in research to better predict fertility
great caution and counseling. In current practice, the potential and applicable preservation techniques.
future fertility potential is considered and discussed,
but there remain little evidence and infrequent coun- Fertility preservation options
seling about fertility preservation. Currently, the treatment for infertility in DSD is lim-
ited. General options for pre and postpubertal fertility
DSD conditions—fertility effects preservation are the same as for transgender patients
The term DSD refers to a diverse group of conditions (Table 1). However, the inherent gonadal abnormalities
that result in atypical sex development. This includes faced by DSD patients make the possibility of fertility
sex chromosome abnormalities, including Turner and preservation less certain. Most reports of success in
Klinefelter syndrome, disorders of gonadal development, achieving biological offspring are in males, resulting
including complete and partial gonadal dysgenesis, and from TESE and/or intracytoplasmic sperm injection;
disorders of androgen synthesis or action—complete this has been reported in Klinefelter syndrome, PAIS,
and partial androgen insensitivity (CAIS, PAIS), con- and 5-alpha reductase deficiency.18–21

Table 3. Comparison of Fertility-Related Issues for Individuals with Transgender Versus DSD Conditions

Transgender DSD

Inherent gonadal abnormality No Frequent

Medical treatments leading to infertility Frequent Infrequent
Surgical treatments leading to infertility Generally only in adulthood Frequent in childhood
Parental proxy decision-making Yes Yes
Medically ‘‘unnecessary’’ surgery for pre- Yes Rare
or peripubertal fertility preservation
Concern about transmission of a genetic condition No more than the general population Yes
Gonadal type discordant with gender identity Always Sometimes
Johnson and Finlayson; Transgender Health 2016, 1.1 44
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Author Disclosure Statement Cite this article as: Johnson EK, Finlayson C (2016) Preservation of
fertility potential for gender and sex diverse individuals, Transgender
No competing financial interests exist. Health 1:1, 41–44, DOI: 10.1089/trgh.2015.0010.

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