REVIEW

CURRENT
OPINION Fertility preservation options for transgender
and gender-nonconforming individuals
Molly B. Moravek

Purpose of review
To provide an overview of the current state of knowledge of fertility risks of gender-affirming therapy,
review fertility preservation options for transgender individuals and ways to minimize gender dysphoria
during fertility treatment, and identify gaps in knowledge.
Recent findings
Recent studies have corroborated older data that gender-affirming hormone therapy creates
histopathological changes in the gonads; however, the newer data suggests that some function of the
gametes may be preserved. One study in transgender men reported successful in-vitro maturation of
testosterone-exposed oocytes with normal spindle structures, and recent studies in transgender women
reveal early spermatogenesis in estradiol-exposed testes and some recovery of semen parameters following
cessation of hormones. Particular attention has recently been given to fertility preservation in transgender
adolescents, revealing unmet informational needs in this population and very few are actually pursuing
fertility preservation, even with counseling.
Summary
There is currently a paucity of data on the fertility effects of gender-affirming hormones, necessitating
fertility preservation counseling prior to initiation of therapy. Several modifications can be made to fertility
preservation protocols and procedures to decrease gender dysphoria or distress in transgender individuals,
but outcome data is still lacking. Achieving high-quality data collection will likely require cooperation
across multiple institutions.
Keywords
fertility preservation, gender-affirming hormones, transgender

INTRODUCTION recommend fertility preservation counseling prior

The Human Rights Campaign defines transgender as to starting any gender-affirming therapy, including
&&

‘an umbrella term for people whose gender identity
and/or expression is different from cultural expec-
tations based on the sex they were assigned at birth’
[1]. In the United States, it is estimated that approx-
imately 1.4 million adults identify as transgender,
with a 2 : 1 ratio of transgender women to transgen-
der men [2,3]. Worldwide, the transgender popula-
tion has been increasing over time, with subsequent
increased utilization of healthcare services [4,5 ].
&
Transgender people often seek out gender-affirming
medical or surgical treatment to better align their
physical appearance with that of their gender iden-
tity; however, many gender-affirming surgeries are
sterilizing and there is very little data on the effect of
gender-affirming hormone therapy on fertility. For
this reason, several professional medical organiza-
tions, including the World Professional Association
for Transgender Health, American Society for Repro-
ductive Medicine (ASRM), and Endocrine Society,
hormones [6,7,8 ]. Unfortunately, these guidelines
create a clinical dilemma for reproductive health
providers as there is currently very little high-quality
data to reference when counseling patients about
the possibility and extent of fertility risks, or with
which to make fertility preservation recommenda-
tions. The objective of this review is to provide an
overview of the current state of knowledge of fertil-
ity risks of gender-affirming therapy, review fertility
preservation options for transgender individuals
while highlighting ways to minimize gender
Division of Reproductive Endocrinology and Infertility, Department of
Obstetrics and Gynecology, University of Michigan, Ann Arbor, USA
Correspondence to Molly B. Moravek, MD, MPH, Center for Reproduc-
tive Medicine, 475 Market Place, Building 1 Suite B, Ann Arbor, MI
48108, USA. Tel: +1 734 232 9033; e-mail: mpenderg@med.umich.edu
Curr Opin Obstet Gynecol 2019, 31:170–176
DOI:10.1097/GCO.0000000000000537

www.co-obgyn.com Volume 31  Number 3  June 2019

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.


KEY POINTS
 Transgender people are just as interested in having
children as their cisgender counterparts.
 Although there is evidence of effects on reproductive
organs from gender-affirming hormone therapy, the
effect on actual fertility, and the reversibility of such
effects, is currently unknown.
 Transgender individuals should be offered fertility
preservation prior to starting gender-affirming therapy,
both because of the current lack of knowledge on
fertility following hormone therapy and to possibly
prevent reoccurrence of gender dysphoria following
transition.
 Fertility preservation options are the same for
transgender individuals as cisgender individuals, but
protocols and procedures may need to be tailored to
minimize patient distress and gender dysphoria.
 There are abundant opportunities for research
surrounding fertility and fertility preservation in
transgender populations, but acquiring high-quality
data may require modeling and multiinstitutional
cooperation.
dysphoria during fertility treatment, and identify
gaps in knowledge with suggestions of how best to
further the field.
BRIEF OVERVIEW OF GENDER-AFFIRMING
THERAPY
It is important to recognize that not all transgender
people will pursue gender-affirming medical or surgi-
cal treatments. Additionally, not all transgender or
gender-nonconforming people presenting for treat-
ment will identify as the opposite sex from that which
they were assigned at birth, and may instead identify
as gender fluid or nonbinary. As such, the goals of
gender-affirming therapy is different for each indi-
vidual, and often requires multidisciplinary involve-
ment. Generally speaking, however, the overarching
goal of gender-affirming hormone therapy is to
induce secondary sex characteristics congruent with
&&
an individual’s gender identity [8 ,9,10]. For trans-
masculine individuals, hormone therapy consists of
exogenous testosterone administration to suppress
serum estradiol levels and increase serum testoster-
&&
one to typical male-range levels [8 ,9]. For transfe-
minine individuals, estradiol is usually administered
in conjunction with an antiandrogen, such as spiro-
nolactone or a 5-alpha reductase inhibitor, to sup-
press testosterone levels and achieve serum estradiol
&&
levels in normal female ranges [8 ,10]. In adoles-
cents, gonadotropin-releasing hormone (GnRH)
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Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
Fertility preservation for transgender patients Moravek
agonists may be started at Tanner stage 2 and 3, to
halt puberty and prevent development of incongru-
ent secondary sex characteristics, as well as prolong
the period during which the adolescent can further
explore their gender identity before starting gender-
&&
affirming hormones [8 ]. Gender-affirming surgical
options range from minor cosmetic procedures to
&&
major genital reconstruction [8 ].
PARENTING DESIRES IN TRANSGENDER
ADULTS AND YOUTH
Studies report that anywhere from 40 to 54% of
transgender adults desire future parenthood [11–
13]. In one of these studies, almost half of participants
said they specifically wanted genetically related off-
spring [12]. Two of these studies asked explicitly
about fertility preservation, and 51% transgender
women and 38% transgender men told researchers
that they would have considered sperm or oocyte
cryopreservation had it been offered prior to initia-
tion of gender-affirming treatment [11,13]. Addition-
ally, many transgender adults surveyed think that
medical professionals should be offering fertility pres-
ervation prior to the initiation of gender-affirming
hormones [13,14]. Parenthood has also been shown
to improve quality of life and mental health in trans-
gender adults [11,15], and having children was found
to decrease suicide risk in transgender women [15].
In transgender youth, studies estimate that 24–
36% desire future genetically related children; how-
ever, many more of the participants in these studies
were unsure whether they would ultimately desire
& &
genetically related offspring [16 ,17 ]. One of these
studies also reported that more than half of parents of
transgender youth wanted more information about
fertility preservation and hoped that their child
would consider fertility preservation prior to starting
&
hormone therapy [17 ]. Nonetheless, even in clinics
with high rates of documented fertility preservation
counseling, utilization rates are still low, with cost,
delay of gender-affirming treatment, and invasive-
ness of procedures all identified as barriers [18 ,19 ].
& &
EFFECT OF GENDER-AFFIRMING
HORMONE THERAPY ON FERTILITY
Although the reproductive consequences of gender-
affirming surgery that removes gonads or other
reproductive organs is evident, the fertility effects
(if any) of long-term gender-affirming hormone
therapy is much less clear. The existing data comes
from observational studies that often present con-
flicting results, most likely secondary to inconsis-
tent durations and doses of gender-affirming
hormones.
www.co-obgyn.com 171
Fertility, IVF and reproductive genetics
Masculinizing medical treatment
Studies on the effect of testosterone on ovarian his-
tology in transgender men date back to 1986, and
mostly consist of observational case series. The
majority of these studies report a phenotype similar
to polycystic ovary syndrome, although others report
similar follicle counts between testosterone-exposed
&&
ovaries and controls [20–25,26 ]. Of note, the lon-
gest median duration of testosterone treatment
among these studies was 4 years, so the results do
not necessarily reflect the effect of longer term tes-
tosterone therapy. The most recent of these studies,
&&
published by De Roo et al. [26 ] not only studied the
histology of the ovaries from testosterone-treated
transgender men, but also isolated cumulus–oocyte
complexes for in-vitro maturation and spindle anal-
ysis. Interestingly, they found a normal spindle pat-
tern in 94% of MII oocytes obtained, and a normal
&&
chromosome pattern in 87% [26 ]. The authors also
noted no relationship between duration of testoster-
one therapy and number of observed follicles, but the
mean duration of testosterone therapy in this study
&&
was only 58 weeks [26 ]. There are two studies that
compare serum antimu € llerian hormone (AMH) levels
in transgender men before and after initiation of
testosterone therapy, with one study reporting a
decrease in AMH [27], and the other no change
[28], but participants in both studies were adminis-
tered additional hormone-modifying medications,
such as GnRH agonist or progestins, so neither
reflects the effect of isolated testosterone therapy,
as is most commonly prescribed in the United States
[27,28]. Finally, Caanen et al. published a study in
2017 comparing the appearance of the ovaries on
three-dimensional, transvaginal ultrasound between
56 testosterone-treated transgender men and 80 con-
trol cisgender women. The authors reported no dif-
ference in the incidence of polycystic ovarian
morphology (defined as 12 antral follicles in at least
one ovary) between the two groups [29]. Importantly,
none of the aforementioned studies evaluated
whether any of the observed ovarian changes had a
direct effect on fertility or if they were reversible
following testosterone cessation.
Despite conflicting data on the histopatholog-
ical effects of testosterone on the reproductive sys-
tem of transgender men, both the popular press and
the medical literature support the fact that it is at
least possible for transgender men to conceive fol-
lowing testosterone therapy. In a survey study of
transgender men who had a live birth, 80% of
participants who had been on testosterone resumed
menses within 6 months of cessation, 84% used
their own oocytes for conception, and 32% actually
conceived while still on testosterone [30]. Of note,
duration of testosterone treatment was less than
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Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
2 years for over half of study participants, so results
may not be generalizable to individuals who have
been on testosterone for longer durations. Unfortu-
nately, there are no studies of transgender men
attempting pregnancy after testosterone, so overall
fecundity and fertility rates are unknown. There are
also no studies on the health of offspring conceived
from testosterone-exposed oocytes.
Feminizing medical treatment
Similar to the data on the reproductive consequences
of masculinizing hormone therapy, the existing data
on the effects of feminizing therapy on fertility con-
sist mostly of older, observational studies with incon-
sistent results [31]. A recent retrospective cohort
study of transgender women compared semen
parameters between those who had never been
exposed to gender-affirming hormones, those who
were previously on gender-affirming hormones (dis-
continuation period 3–6.5 months), and those cur-
&&
rently on gender-affirming hormones [32 ]. Though
was a trend toward worsening semen parameters in
the prior hormone exposure group compared with
the never exposure group, only the current user group
had parameters outside the WHO reference range,
and three of seven current users were azoospermic
&&
[32 ]. Of note, there were only three previous gender-
affirming hormone users and seven current users
included in the study, making it difficult to draw
any conclusions about the effect of duration of expo-
&&
sure or cessation [32 ]. Other recent studies have
looked at testicular histology at the time of gender-
affirming surgery, and found that estradiol exposure
leads to smaller seminiferous tubules, abnormal
appearance of the sertoli and leydig cells, and fatty
&
degeneration in the connective tissue [33,34 ]. Addi-
tionally, examination of the testes at the time of
orchiectomy has also revealed impaired spermato-
genesis (maturation arrest), regardless of whether
patients were on estradiol only or estradiol with an
antiandrogen, although the stage of maturation
arrest and incidence of azoospermia differed among
& &
studies [33,34 ,35 ]. Interestingly, there are also
reports of an increased incidence of semen abnormal-
ities (count, motility, and morphology) even in trans-
gender women who have never been exposed to
&&
hormones [36,37 ], although the physiology behind
this observation has not yet been elucidated.
Gonadotropin-releasing hormone agonist in
peripubertal adolescents
There is abundant evidence to suggest that repro-
ductive changes from isolated GnRH agonist expo-
sure in men or women for other indications are
Volume 31  Number 3  June 2019

completely reversible [38–40]. However, to this
author’s knowledge, there are no published data
on reproductive function after halting puberty with
GnRH agonist, then transitioning directly into gen-
der-affirming hormone therapy. Data are also lack-
ing on the fertility effects of decades of gender-
affirming hormones started in adolescence, even
without pretreatment with GnRH agonist, as
opposed to the relatively short-term exposure stud-
ies mentioned above. Therefore, it is currently
unknown whether fertility can be regained, either
naturally or with exogenous gonadotropin admin-
istration, in transgender adults who initiated gen-
der-affirming medical therapy as adolescents.
FERTILITY PRESERVATION OPTIONS FOR
TRANSGENDER INDIVIDUALS
Fertility preservation options for transgender individ-
uals are the same as they are for cisgender individuals;
however, some considerations should be made to try
to reduce gender dysphoria during the process of
fertility preservation. It is important that patients
also understand what interventions will be required
to use their cryopreserved gametes in the future and,
for those that do not elect fertility preservation, what
their future options for genetically related offspring
may be, which depends largely on if and with whom
they are partnered (Table 1). Additionally, fertility
preservation counseling in transgender men should
not be influenced by their inclination to carry a
pregnancy, as some patients may have a partner with
a uterus who will carry the pregnancy or they may
decide to use a gestational carrier.
Transgender men
Oocyte and/or embryo cryopreservation are estab-
lished methods of fertility preservation for
Table 1. Options for genetically related offspring for transgender individuals
Transgender men
Partner with sperm:
Willing/able to carry pregnancy – intercourse/IUI
Not willing/able to carry pregnancy – IVF with gestational carrier
No partner with sperm:
Willing/able to carry pregnancy – donor insemination
Not willing/able to carry pregnancy – IVF to fertilize own eggs
(donor sperm) and have partner or gestational carrier carry
pregnancy
Fertility preservation only:
Oocyte cryopreservation (postpubertal)
Ovarian tissue cryopreservation (prepubertal or postpubertal)
IUI, intrauterine insemination; IVF, in-vitro fertilization.
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Fertility preservation for transgender patients Moravek
postpubertal individuals assigned female at birth
[41]. As live birth rates from frozen oocytes now
approach that of fresh oocytes [42–44], there is no
need to fertilize oocytes with partner or donor
sperm, unless the patient desires. Patients should
be forewarned that ovarian stimulation will increase
their serum estradiol levels, and that transvaginal
ultrasound monitoring may be necessary, as both of
these aspects of the process may be distressing to
transgender men. Strategies to decrease this distress
include the concomitant use of aromatase inhibitors
during stimulation to minimize estradiol elevations,
which has already been shown not to compromise
outcomes in breast cancer patients undergoing ovar-
ian stimulation for fertility preservation [45]. Addi-
tionally, transabdominal ultrasound monitoring
should be performed whenever feasible.
There are currently no data with which to coun-
sel transgender men who have already been on
testosterone therapy about the success of ovarian
stimulation for current or future fertility relative to
individuals without high-dose testosterone expo-
sure. There is a single case report of a transgender
men with a 26-month history of testosterone
administration who successfully fertilized his
oocytes with donor sperm and transferred two blas-
tocysts into his cisgender wife, who had an ongoing
&
pregnancy at the time of publication [46 ]. Of note,
in this case, testosterone was discontinued for 3
months, followed by 2 weeks of oral contraceptive
&
pills prior to ovarian stimulation [46 ]. The two
existing reports of oocyte cryopreservation in trans-
gender men only include patients who pursued
fertility preservation prior to testosterone therapy
[47,48]. There is also a case series of transgender
youth who pursued oocyte cryopreservation for fer-
tility preservation, but ovarian stimulation occurred
prior to initiation of any hormones in all of the cases
&
[49 ]. A small qualitative study of transgender men
Transgender women
Partner with ovaries/uterus:
Partner willing to carry pregnancy – intercourse/IUI
Partner not willing/able to carry pregnancy –
IVF with gestational carrier
No partner with ovaries/uterus:
Egg donation with gestational carrier
Fertility preservation only:
Sperm banking (postpubertal)
Testicular tissue cryopreservation (prepubertal)
www.co-obgyn.com 173
Fertility, IVF and reproductive genetics
who underwent ovarian stimulation for fertility
preservation revealed that there were many aspects
of the process, including pelvic exams, cessation of
testosterone, and return of menses, that were dis-
tressing to participants, but medical outcomes were
not reported [50]. Thus, there are currently no
guidelines instructing clinicians how long testoster-
one needs to be stopped – or if it needs to be stopped
at all – prior to initiating ovarian stimulation. There
are also no data on the success of ovarian stimula-
tion in transgender men who previously had
puberty halted with GnRH agonist, followed
directly by testosterone administration.
Given that ovarian stimulation entails a rise in
gender incongruent hormones and potentially inva-
sive monitoring and procedures, there is also great
interest in the possibility of ovarian tissue cryopres-
ervation (OTC) for fertility preservation in transgen-
&&
der men [26 ,51]. OTC is an experimental
procedure during which all or part of the ovary is
surgically removed and strips of the ovarian cortex
&&
are cryopreserved [26 ,52]. An advantage of OTC is
that it can theoretically be performed at the time of
gender-affirming surgery, following careful counsel-
ing about the lack of data on the reproductive effects
of testosterone. OTC is also currently the only avail-
able option for prepubertal transgender boys pursu-
ing fertility preservation, although not all providers
agree it is an appropriate intervention in this setting
[53]. More than 130 live births following re-trans-
plantation of cryopreserved ovarian tissue have
been reported in cisgender women, including two
patients that were either prepubertal or peripubertal
when the ovary was removed [54–58]. However, in
all of these cases, the ovarian tissue was re-trans-
planted into the individual it originally came from,
which may not be ideal for many transgender men.
Fortunately, there continues to be strides toward
successful in-vitro maturation of oocytes in the
scientific literature, including in transgender men
[51,59,60].
Transgender women
Semen cryopreservation is an established method of
fertility preservation for postpubertal individuals
assigned male at birth and should be offered prior
to the initiation of gender-affirming hormones or
surgery. The most common means of semen collec-
tion is via masturbation; however, some transgender
women may find masturbation or ejaculation dis-
tressing, or may have erectile or ejaculatory dysfunc-
&&
tion secondary to hypoandrogenism [8 ,36]. For
these patients, options such as penile vibratory
stimulation or electroejaculation should be consid-
ered [61]. Testicular sperm aspiration or
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Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.
microsurgical sperm extraction are also options in
patients for whom ejaculation is unacceptable, or in
patients with oligospermia or azoospermia, but is
more invasive and costly. There are currently no
studies evaluating the acceptability or success rates
of the different options for sperm collection specifi-
cally in transgender women. Furthermore, for trans-
gender women who are already on estradiol and/or
antiandrogens, it is unclear how long hormones
need to be stopped before resumption of normal
spermatogenesis (if it occurs at all), during which
time testosterone production will resume and may
cause unwanted masculinizing effects.
For prepubertal transgender girls, testicular tis-
sue cryopreservation (TTC) is currently the only
fertility preservation option. TTC is an experimental
procedure that consists of surgical removal and
cryopreservation of testicular tissue. It is important
to note that no spermatogenic recovery has been
reported from TTC to date. Thus, families choosing
this option are relying on the successful develop-
ment of future technologies enabling spermatogo-
nial stem cells to be matured into sperm, which are
currently only being studied in animal models [62].
CONCLUSION
As is evidenced above, there are very little data in the
existing literature on the reproductive effects of
gender-affirming hormone therapy, which means
that current clinical guidelines presume a loss of
fertility when recommending fertility preservation
counseling prior to initiation of hormone therapy.
More importantly, the extent to which any repro-
ductive effects are reversible following cessation of
hormones is completely unknown, as most of the
current data comes from examination of gonads at
the time of gender-affirming surgery. Given that
individual centers may not see enough reproduc-
tive-age patients interested in both gender-affirming
hormones and fertility to address these questions in
a timely fashion, future studies will likely require
animal models and/or pooling of data across multi-
ple institutions and clinics. Even if reproductive
effects of hormones are found to be completely
reversible, some individuals may still desire fertility
preservation prior to initiating gender-affirming
therapy so as not to reintroduce gender dysphoria
later in life. Therefore, in addition to gathering more
data on clinical effects, much work remains to be
done to further explore the best fertility preserva-
tion options to offer transgender individuals. Par-
ticularly in transgender men who have previously
been on testosterone, the management of testoster-
one before and during ovarian stimulation, as well
as stimulation protocols, need to be more
Volume 31  Number 3  June 2019

thoroughly studied. Until these studies are done,
patients should be counseled that current practice is
based off of expert opinion, small case series, and
extrapolation from cisgender populations.
Acknowledgements
None.
Financial support and sponsorship
None.
Conflicts of interest
There are no conflicts of interest.
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Volume 31  Number 3  June 2019