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381© The Author(s), under exclusive license to Springer Nature
Switzerland AG 2025
C. J. Wong (ed.), Primary Care of the Solid Organ Transplant Recipient,
https://doi.org/10.1007/978-3-031-98076-3_13
Chapter 13
Gynecologic andReproductive Health
Considerations intheAdult Solid Organ
Transplant Recipient
NinaTan andAdelaideH.McClintock
13.1 Introduction
From family planning considerations to menopause, gynecologic and reproductive
health counseling is an essential part of comprehensive primary care for the solid
organ transplant (SOT) recipient. Prior to transplant, many SOT recipients of repro-
ductive age are unable to conceive because of the effects of end-organ disease on
reproductive function, often leading to oligo or anovulation. Fortunately, solid organ
transplantation can facilitate return to fertility for those interested in becoming par-
ents. However, studies have shown that many recipients of reproductive age are not
aware of this return to fertility, are not counseled on the use of contraception, and
that up to half of pregnancies in SOT recipients are unplanned [1–5]. Given the
increased risks of pregnancy-related complications and use of immunosuppressive
medications that can be harmful in pregnancy, it is important for the health of the
patient, fetus, and transplanted organ to discuss reproductive and gynecologic health
early and often with SOT recipients, and to discuss the nuances of contraception and
pregnancy planning with a multidisciplinary healthcare team including maternal–
fetal medicine providers, transplant specialists, and pharmacists. Given the risks
associated with unplanned pregnancies in SOT recipients, primary care providers
should also feel comfortable counseling recipients about abortion care if medically
necessary or desired.
N. Tan (*) · A. H. McClintock
Division of General Internal Medicine, Department of Medicine, University of Washington,
Seattle, WA, USA
e-mail: ninat@uw.edu; ahearst@uw.edu
382
13.2 Pre-conception Counseling
Pre-conception counseling and family planning discussions are an important aspect
of preventive care for all patients. Given the medical complexity and intensity of
resources in transplant care, it is especially important in this population. For SOT
recipients of reproductive age, pre-conception counseling is typically initiated dur-
ing the pretransplant evaluation period and readdressed at least yearly during child-
bearing years [1]. The recipient’s reproductive health goals should be elicited and
supported within an interdisciplinary context including primary care providers,
maternal–fetal medicine specialists, and transplant specialists. The interdisciplinary
team should review contraception, fetal and maternal risks of pregnancy after trans-
plant, potential impacts of pregnancy on graft organ function, timing of pregnancy,
and medication management before, during and after pregnancy.
13.2.1 Pregnancy Timing
Chronic end-stage organ dysfunction is often associated with increased rates of
infertility and menstrual cycle irregularities. Ovulation and return to fertility can
occur within months after transplantation and is often viewed as a benet to trans-
plant. This timing, however, coincides with the acute post-transplant period which
is associated with a higher risk of maternal, fetal, and graft complications and risk
of infection [6], leading the Society for Maternal Fetal Medicine (SMFM), the
American Society of Transplantation (AST), and the International Society for Heart
and Lung Transplantation (ISHLT) to recommend deferring pregnancy for at least
1year after transplant [1, 5, 7]. In the case of lung transplantation, the recommenda-
tion is to defer pregnancy for at least 2years due to higher rates of allograft rejection
and more intensive immunosuppressive medication regimens [5]. Some transplant
centers in the United States (US) discourage pregnancy at any time post lung trans-
plant due to the increased risks of preterm birth and neonatal mortality compared to
individuals with abdominal solid organ transplants, and incomplete or conicting
data on allograft function and risk of acute cellular rejection in the year following
pregnancy [1]. Other clinical factors to consider when discussing pregnancy timing
are listed in Table13.1.
Table 13.1 Factors to consider in pregnancy timing for solid organ transplant recipients [1, 5, 7]
Stable and adequate graft function: most guidelines recommend delaying pregnancy for at least
1-year post-transplantation; for lung transplant at least 2years or indenitely
No history of rejection in the past year
No evidence of acute infections
Stable maintenance dosing of immunosuppressive medications
Management of comorbid conditions is optimized
N. Tan and A. H. McClintock
383
Table 13.2
Medical evaluation prior to pregnancy for solid organ transplant recipients
Multidisciplinary consultation with transplant subspecialists, maternal–fetal medicine, and
other providers involved in the patient’s chronic disease management, if applicable
Complete medical history
Indication for transplant
History of rejection
History of infection, including opportunistic
Other medical conditions
a
Evaluation of medications
Identify teratogenic risk
Assess stability of immunosuppressant dosing
Assessment of vaccination status and provision of indicated vaccines
Vital sign assessment and complete physical exam
Baseline lab evaluation: complete metabolic panel, CBC, hemoglobin A1c
Assessment of allograft function
b
Type and screen due to risk of post-transplant red blood cell alloimmunization
Evaluation of psychosocial status and social supports if needed
From [1], reprinted with permission
a
See Chap. 11, Metabolic Complications in the Adult Solid Organ Transplant Recipient
b
See Chaps. 4, 5, 6 and 7 for organ-specic assessment of graft function
13.2.2 Medical Evaluation Prior toPregnancy
Prior to pregnancy, the SMFM recommends the evaluation outlined in Table13.2
for individuals with a solid organ transplant. There are also organ-specic guide-
lines and expert consensus statements for pre-conception and pregnancy care from
the American Association for the Study of Liver Diseases [8], International Society
for Heart and Lung Transplantation [5], and Kidney Disease: Improving Global
Outcomes [9].
In addition to the transplant-specic considerations highlighted here, standard
pre-conception counseling principles are applicable. This includes optimizing
comorbid chronic conditions such as diabetes or hypertension for both the birth par-
ent and their partner (if applicable), ensuring adequate folic acid intake, up to date
cancer and infectious disease screenings, mental health screenings, and appropriate
immunizations including the TdaP vaccine between 27 and 36weeks of pregnancy
for neonatal protection, and the SARS-CoV-2 vaccine. Immunizations for solid
organ transplant recipients are reviewed more comprehensively in Chap. 14.
13.2.3 Medication Management
Prior to pregnancy, potentially teratogenic medications should be transitioned to
safer options or discontinued entirely, if appropriate. Commonly used medications
such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers,
13 Gynecologic and Reproductive Health Considerations in the Adult Solid Organ…
384
and antimicrobials (e.g., sulfamethoxazole/trimethoprim, uconazole) are among
those that can cause harm to the fetus. While it is important to continue immunosup-
pressive medications during pregnancy to help maintain graft function and prevent
rejection, not all immunosuppressive therapies are considered safe in pregnancy.
Commonly used post-transplant medications such as azathioprine, calcineurin
inhibitors, and low-dose prednisone are considered to be safe for use in pregnancy.
However, mycophenolic acid-containing medications, including mycophenolate
mofetil, are antiproliferative agents with teratogenic effects and are associated with
pregnancy loss, preterm birth, and graft failure [10, 11]. See the “Contraception”
section below for further discussion about pregnancy planning while taking these
medications [12]. Ideally, patients are transitioned off mycophenolate at least
6weeks prior to attempting to conceive, though a longer period may be benecial
to ensure stability on a new immunosuppressive regimen. See Table13.3 for a list of
commonly used immunosuppressive medications and their effect on pregnancy,
fetal development, and lactation.
There has been no clear evidence of increased risk of pregnancy complications
or teratogenic effects related to male SOT recipients’ use of immunosuppressive
medications [13, 14]. However, FDA labeling indicates that genotoxic effects have
been observed in animal studies using higher doses of mycophenolate exposure, so
Table 13.3 Considerations for pregnancy with commonly used maintenance immunosuppressive
therapies [1, 4–6, 12, 17, 18]
Effect on pregnancy Teratogenicity Lactation
Calcineurin
inhibitors
(cyclosporine,
tacrolimus)
Increased risk of preterm
birth and intrauterine
growth restriction (IUGR)
Dose-dependent adverse
effects include
hypertension, acute kidney
injury, hyperglycemia,
electrolyte abnormalities,
seizures
Likely requires dosage
adjustment in pregnancy
(binds to albumin and
erythrocytes)
No clear evidence for
increased risk of
teratogenicity
Ok to use
Antiproliferative and
antimetabolite agents
Mycophenolic acid
products
Contraindicated during
pregnancy
Increased risk of
spontaneous abortion
Increased risk of preterm
birth and IUGR
Signicantly increased risk
of central nervous system
(CNS) malformations, cleft
lip and palate abnormalities,
anomalies in cardiac, renal,
limb and gastrointestinal
development
Generally
avoided
(limited
data)
Azathioprine Increased risk of preterm
birth and IUGR
No clear evidence for
increased risk of
teratogenicity
Ok to use
(continued)
N. Tan and A. H. McClintock
385
Table 13.3
(continued)
Effect on pregnancy Teratogenicity Lactation
Corticosteroids Increased risk of preterm
premature rupture of
membranes (PPROM),
IUGR and preeclampsia
Dose-dependent adverse
effects include adrenal
suppression, hypertension,
hyperglycemia, peptic
ulcer disease, loss of bone
density
Possible increased risk of
fetal oral clefts (limited data)
Ok to use
Mammalian target of
rapamycin (mTOR)
inhibitors (sirolimus,
everolimus)
No clear evidence for
increased risk of
pregnancy complications
(limited data). Some
reports of increased risk of
preterm delivery and
IUGR
No clear evidence for
increased risk of
teratogenicity (limited data)
May be ok
to use
(limited
data)
IUGRintrauterine growth restriction, PPROMpreterm premature rupture of membranes
effective contraception is recommended for sexually active male patients while they
are taking mycophenolate and for 90days after discontinuation [15]. Sirolimus may
affect male fertility through its effects on spermatogenesis leading to decreased
sperm counts and decreased motile sperm, though there is a lack of robust data to
support this [16]. Although male SOT recipients commonly experience hypogonad-
ism and erectile dysfunction both before and after transplant, fertility generally
improves after transplantation and many males will go on to conceive a child.
13.2.4 Cytomegalovirus (CMV) Infection Prevention
Cytomegalovirus (CMV) is the most common opportunistic infection among SOT
recipients and should be ruled out prior to pregnancy (Table13.2) [19]. CMV pro-
phylaxis is given for any transplant recipient who is positive for CMV to prevent
reactivation, and to recipients who are CMV negative and receive an organ from a
CMV positive donor to prevent primary infection.
In cohort analyses, the rates of neonatal infections in SOT recipients were
similar to pregnant individuals without a transplant [1, 20]. However, when
present, CMV can be vertically transmitted in up to 70% of pregnancies affected
in the general population, leading to abnormalities in fetal development such as
microcephaly, and longer-term sequelae such as hearing loss and developmental
delay [21]. There are only limited, small studies assessing the safety of antiviral
medication administration in pregnancy to treat CMV infection [22]. Therefore,
13 Gynecologic and Reproductive Health Considerations in the Adult Solid Organ…
386
it is recommended that prophylactic therapy or preemptive treatment is com-
pleted prior to conception to prevent CMV disease for the health of both the
birth parent and the fetus [1].
There are two main options for CMV prevention after SOT.The rst is universal
prophylaxis which generally involves treatment with antiviral medications (e.g.,
valganciclovir or ganciclovir) for 3–12months in the immediate post-transplant
period, depending on the type of organ transplanted and the patient and donor
serostatus [19]. Prophylaxis is recommended as the preferred CMV prevention ther-
apy for heart and lung transplants, and is not recommended for CMV- seronegative
recipients who received a transplant from a CMV-seronegative donor [19]. The sec-
ond option is a preemptive strategy where antiviral medications are administered
only if surveillance labs reveal early subclinical CMV replication [19]. This is an
option for CMV-seropositive recipients of kidney, liver, pancreas, and heart trans-
plants, or for CMV-seronegative recipients of seropositive liver and kidney
transplants.
13.3 Contraception
In 2023, there were 18,077 solid organ transplants in recipients’ assigned female
at birth and over 54% of them (9781) were in recipients of reproductive age
between 18 and 49years old [23]. Unfortunately, many solid organ transplant
recipients report not being informed of the possibility of return to fertility and
pregnancy after transplant. In one survey of 309 female solid organ transplant
recipients, it was found that 44% were unaware that they could become pregnant
after transplant [2]. Another study of 217 female solid organ transplant recipi-
ents aged 18–45 found that 33% were unaware of the recommendation to use
contraception within the rst year after transplantation [3]. Furthermore, vari-
ous data suggests that up to half of pregnancies among heart, lung, kidney, and
liver transplant recipients are unplanned [1, 4, 5]. Given the successful return to
fertility for many SOT recipients, increased risks associated with pregnancy
early in the post-transplant period, teratogenicity of commonly used immuno-
suppressive medications, and difculty accessing even medically necessary
abortion care for many, it is imperative that contraception is discussed early and
consistently with transplant recipients and their partners.
Contraception is recommended before or soon after receiving the transplanted
organ. For estrogen-containing methods, it is recommended to discuss timing with
the transplant team, with most experts recommending deferring initiation to at least
6-weeks post-transplant due to the increased risk of post-operative thromboembo-
lism [24]. When discussing contraceptive options, the patient’s preferences and
their reproductive goals should be elicited and integrated into the decision, in addi-
tion to counseling regarding pregnancy timing. The Centers for Disease Control
N. Tan and A. H. McClintock