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Medical Eligibility Criteria (MEC) for contraceptive use outlines the benets and
risks of contraceptive methods when used in the setting of various medical condi-
tions, including solid organ transplantation [25] (Table13.5).
The most effective forms of reversible contraception are the copper intrauter-
ine device (IUD), levonorgestrel containing IUDs, and etonogestrel implant,
with fewer than 1in 100 users becoming pregnant with typical use. These meth-
ods are generally safe to use after a transplant if there have been no complica-
tions, and may also be the preferred non-estrogen containing forms of
contraception given the known risks of estrogen use that may overlap with
underlying comorbidities in SOT recipients, such as hypertension and hyperco-
agulability. If there have been graft complications such as acute or chronic graft
failure, the CDC MEC categorizes initiation of the copper or levonorgestrel
IUDs as category 2, meaning the advantages generally outweigh the risks. If an
IUD is already in place at the time of graft failure, it is considered safe to con-
tinue use (Table 13.5). While there was previously concern about method failure
and risk of infection with IUDs, these concerns have not been substantiated and
IUDs are considered safe and among the most effective forms of contraception
for transplant recipients [26].
Depot medroxyprogesterone (DMPA) has been associated with a reversible
decrease in bone density [27]. Given the prevalence of renal osteodystrophy and
other bone disease in patients with chronic kidney disease leading to kidney
transplant, and the common use of chronic corticosteroids, the benets of using
DMPA should be balanced with the theoretical impact on bone health (see
Chap. 11).
Combined hormonal contraceptive (CHC) methods such as the pill, patch, or
ring contain both estrogen and progesterone and have a failure rate of about 9%.
These methods are considered safe to use when there have been no graft com-
plications after transplant and there are no contraindications to estrogen use,
including migraine with aura, history of arterial or venous thrombosis, or his-
tory of an estrogen sensitive cancer. If using the CHC pill or patch, consider
starting with a lower estrogen dose formulation and if there are bothersome
symptoms related to low- dose estrogen such as abnormal uterine bleeding, then
the estrogen dose can be increased. However, if there have been graft complica-
tions, or if the indication for liver transplantation was Budd-Chiari syndrome,
estrogen use is contraindicated and CHCs are not recommended (Table 13.5).
Additionally, estradiol and norethindrone have the potential to decrease tacroli-
mus levels. While these are not anticipated to be large effects, it would be rea-
sonable to coordinate with the transplant team and recheck tacrolimus levels
2–4weeks after starting CHCs.
Progestin only pills (POP) have about the same contraceptive efcacy as
CHCs and can be used by patients who have a contraindication to estrogen use
whether or not there are graft complications. Regardless of transplant status, it
is important to counsel patients on taking POPs at the same time every day to
13 Gynecologic and Reproductive Health Considerations in the Adult Solid Organ…
388
Table 13.4
Acceptable
contraception options when
taking mycophenolic acid
medications
1. IUD (hormonal or copper) alone
2. Permanent sterilization
3. A barrier method plus a hormonal contraceptive other than
the IUD
4. Two different barrier methods
maximize efcacy since one of the main mechanisms for contraception is the
short-term thickening of cervical mucous, in addition to variable ovulation
suppression.
Barrier methods such as male and female condoms and the diaphragm, and topi-
cal methods such as spermicide or vaginal pH modulators are less effective contra-
ception options with typical use failure rates ranging from 18% to 21%. Because
barrier methods may provide inadequate contraception, it is suggested that they are
used as an adjunct to a more effective method, such as an IUD or progestin implant
or the birth control pill [5]. This is especially relevant for mycophenolate containing
medications, which are regulated under the Food and Drug Administration’s Risk
Evaluation and Mitigation Strategies (REMS) program. In addition to the increased
risk of teratogenicity, mycophenolate interacts with serum estrogen and progester-
one and could theoretically reduce combined hormonal contraceptive efcacy. Per
the REMS program, patients are recommended to use one of the acceptable contra-
ception options listed in Figure Table13.4 while taking mycophenolic acid medica-
tions. If using a reversible contraceptive method, then it should be continued for
6weeks after discontinuation of a mycophenolic acid-containing medication [12].
Lastly, when counseling SOT recipients about contraception and sexual health, it is
important to also highlight the added benet of male and female condoms in reduc-
ing the risk of sexually transmitted infections.
Patients can opt for permanent contraception methods such as vasectomy or
tubal sterilization if they are certain they do not desire a future pregnancy.
Vasectomies are often performed as a simple procedure in the clinic, whereas tubal
sterilization is a more involved outpatient procedure that generally includes laparo-
scopic surgery and general anesthesia. Patients should be counseled that permanent
contraception can be surgically reversed only in rare instances.
The copper IUD, COC, oral levonorgestrel, and ulipristal acetate are listed in the
CDC MEC as emergency contraception options for transplant recipients when used
within the rst 3–5days after unprotected intercourse [25]. More recently, the levo-
norgestrel IUD was found to be non-inferior to the copper IUD for emergency con-
traception in the rst month after IUD placement and is also thought to be an
effective option for SOT recipients [28, 29] (Table13.5).
N. Tan and A. H. McClintock
389
Table 13.5
Contraceptive efcacy and safety [25, 30, 31]
% of users with an unintended
pregnancy in the rst year of use
CDC MEC Category
a
No graft
failure Graft failure
b
Cu-IUD 0.8% 1 2 (initiation)
1 (continuation)
LNG-IUD 0.2% 1 2 (initiation)
1 (continuation)
Implant 0.05% 2 2
DMPA 6% 2/3 2/3
POP 9% 2 2
CHC 9% 2 4
Condom 18% (male)
21% (female)
1 1
Diaphragm with
spermicide
12% 1 1
Cu-IUD
c
N/A 1 2
UPA
c
N/A 1 1
LNG pill
c
N/A 1 1
COC
c
N/A 1 1
LNG IUD
c
N/A Not listed in
MEC
Not listed in
MEC
Cu-IUDcopper intrauterine device, LNGlevonorgestrel, DMPAdepot medroxyprogesterone ace-
tate, POPprogestin only pills, CHCcombined hormonal contraceptive, U PA ulipristal acetate,
COC combined oral contraceptive
a
CDC MEC Categories:
1—No restriction for the use of the contraceptive method
2—Advantages of using the method generally outweigh the theoretical or proven risks
3—Theoretical or proven risks usually outweigh the advantages of using the method
4—Unacceptable health risk if the contraceptive method is used
b
Acute and chronic graft failure, graft rejection and cardiac allograft vasculopathy
c
Emergency contraceptive method
13.4 Abortion Care forSolid Organ Transplant Recipients
Safe access to abortion services is an important aspect of reproductive healthcare
and especially so for transplant recipients. As mentioned earlier in this chapter, up
to half of pregnancies in solid organ transplant recipients are unplanned. Due to the
use of immunosuppressive medications and common comorbidities, there is an
increased risk of complications in the health of the pregnant recipient, the fetus, and
the transplanted organ. If a pregnancy is considered prohibitively risky for the recip-
ient’s health, if there is acute allograft rejection, if there is a spontaneous miscar-
riage, or if malformation or abnormal development of the fetus is noted on screening,
restrictive legislative policies may limit access to abortion and/or miscarriage care
that is medically indicated. However, it is important to note that both medication
and procedural abortion can be safe for transplant recipients [5]. In the general
population, risks of a serious infection, hospital admission, or need for transfusion
13 Gynecologic and Reproductive Health Considerations in the Adult Solid Organ…
390
range from 0.01% to 0.5% [32]. Data regarding abortion in transplant recipients is
sparse, though one meta-analysis of pregnancy outcomes in kidney transplant recip-
ients indicated that the induced abortion rate in this population worldwide is approx-
imately 12.4% [33].
If a transplant recipient seeks abortion care, we recommend a timely multidisci-
plinary discussion with obstetrics/gynecology, transplant specialists, and the
patient’s other medical specialists to discuss the benets and risks of medical and
procedural abortion options. The appropriateness and feasibility of either option
will depend on the patient’s preference, duration of gestation, medical comorbidi-
ties, provider experience, and access to services.
Medication abortion uses mifepristone and misoprostol, or misoprostol alone.
Mifepristone is a selective progesterone receptor modulator and at higher doses also
has glucocorticoid receptor antagonist properties. There is a theoretical risk of mife-
pristone interfering with prednisone activity—therefore, for patients taking chronic
corticosteroids, consideration of mifepristone should be discussed with the trans-
plant team prior to use. Contraindications to mifepristone include adrenal insuf-
ciency, ectopic pregnancy, coagulopathy or anticoagulation use, inherited porphyria,
or allergy to mifepristone [15]. In these cases, a misoprostol alone regimen can be
used to induce abortion, though may be slightly less effective. In the rare event
(1–4% of cases) that a medication abortion leads to an incomplete termination, a
dilation and evacuation may be recommended.
Procedural abortion can include aspiration and/or dilation and evacuation
depending on the duration of gestation and is the preferred method for patients with
contraindications to medication abortion. There are no known increased risks asso-
ciated with procedural abortions in transplant recipients, but there is a paucity
of data.
13.5 Pregnancy
Many solid organ transplant recipients can successfully and safely conceive and
become parents with appropriate risk assessment and medical optimization.
Transplant Pregnancy Registry International (TPRI) recorded over 2700 pregnan-
cies in female SOT recipients in the US, including Puerto Rico, in 2022, though this
may be an underestimate given that the registry data is reported by healthcare pro-
viders or self-reported by patients [34]. The majority of pregnancies are in those
with kidney (57.6%) and liver (37.8%) transplants, with a much smaller number of
heart (4.4%) and lung (0.1%) transplants [35]. This follows the general trend in
prevalence of transplanted organ, with the kidney being the most commonly trans-
planted organ, followed by the liver. The low number of pregnancies in lung trans-
plant recipients likely reects the recommendation from some transplant centers to
avoid pregnancy altogether [1].
It is important to note that the rate of live births and pregnancy loss among SOT
recipients are similar to those among the general population, and pregnancy does
N. Tan and A. H. McClintock
391
Table 13.6
Pregnancy outcomes by transplanted organ [1, 34, 36, 39]
Kidney
[1, 34]
Liver
[1, 34]
Kidney-
pancreas [1,
34]
Heart
[1, 34]
Lung
[1, 34]
No transplant
[36, 39]
Hypertension requiring
medication therapy
48% 21% 52% 47% 53% 16%
Preeclampsia 30% 20% 37% 26% 14% 5–7%
Insulin treated diabetes 8% 8% 3% 8% 32% 5–9%
Live birth 75% 73% 69% 69% 64% 67%
Loss
a
[39] 23% 26% 30% 27% 35% 20%
Preterm delivery
(<37weeks)
52% 35% 76% 43% 64% 10.38%
Low birthweight (<
2500g)
52% 35% 83% 46% 81% 8.6%
Rejection during
pregnancy
3% 5% 5% 7% 10% N/A
Graft loss within
2years of delivery
5.5% 2.6% 10.3% 2.4% 8.8% N/A
a
Includes miscarriage or spontaneous abortion, ectopic pregnancy, and stillbirth or fetal death
not seem to impact long-term survival among recipients [1]. Additionally, there is
no clear data that pregnancy leads to graft loss, though there is evidence that worse
transplant function (e.g., elevated serum creatinine in kidney transplant) prior to
pregnancy is associated with graft loss [1]. Although many primary care providers
are not directly involved in obstetrical care, they can counsel patients on the risks of
pregnancy for the birth parent, the fetus, and the graft, and refer early for pre-
conception planning as discussed above.
Some of the risks associated with pregnancy after SOT are listed in Table13.6.
Rates of hypertensive disorders of pregnancy such as gestational hypertension, pre-
eclampsia, preterm birth, and low birth weight in pregnant SOT recipients are about
three to six times higher than without SOT [34–37]. Hypertensive disorders of preg-
nancy can lead to fetal growth restriction, low birth weight, and medically indicated
preterm birth, all of which are also observed at higher rates among SOT recipients
compared to the general population. Though there is low quality evidence, the
SMFM guidelines strongly recommend daily low-dose aspirin prophylaxis to
reduce the risk for preeclampsia in pregnant SOT recipients, and to reduce the risk
of renal allograft failure in renal transplant recipients since the benets appear to
outweigh the risks [1].
The SMFM guidelines recommend a low threshold to work up any changes to
baseline allograft function during and after pregnancy [1]. Reports of the incidence
of allograft rejection during pregnancy or subsequent graft loss during or after preg-
nancy among SOT recipients vary in the literature. The 2022 TPRI reports rates of
acute rejection during pregnancy range from 3% to 10% depending on the trans-
planted organ, whereas a meta-analysis by Yo etal. that included studies from 2004
to 2023 reported the pooled incidence of acute allograft rejection in kidney, liver,
lung, and heart transplants was 2.39% [34, 35]. Yo etal. reported a 1.55% pooled
13 Gynecologic and Reproductive Health Considerations in the Adult Solid Organ…
392
incidence of graft loss during pregnancy, and the TPRI reported rates of graft loss
within 2 years of delivery ranged from 2.4% to 10.3% depending on the trans-
planted organ [34, 35]. However, again, with normal pre-pregnancy graft function,
there is no clear data to suggest that pregnancy increases the risk of allograft loss [1].
Although transplant often leads to return to fertility, some SOT recipients may
experience difculty becoming pregnant. There are only a few studies reporting
pregnancy outcomes in SOT recipients after using assisted reproductive technology
(ART) such as in vitro fertilization (IVF). In a study of 33 kidney transplant recipi-
ents, 86% of pregnancies resulted in a live birth and graft survival rates were similar
to pregnancies conceived without ART [34]. A small study of invitro fertilization in
patients with chronic liver disease or liver transplantation found a live birth rate of
50% among the 11 females with a liver transplant who had undergone a total of 14
rounds of IVF between 1990 and 2019 [38]. General risks of ART include ovarian
hyperstimulation syndrome which can lead to liver dysfunction and increased risk
of thrombosis, multiple births, and low birth weight. As data continues to emerge,
patients who are interested in ART should be referred to reproductive endocrinolo-
gists and maternal–fetal medicine specialists to discuss timing and other consider-
ations in conjunction with their multidisciplinary healthcare team.
13.6 Menopause
Menopausal hormone therapy (MHT) refers to the use of estrogen and progesterone or
estrogen alone after natural or iatrogenic menopause. Indications for MHT include treat-
ment of moderate to severe vasomotor symptoms, moderate to severe vulvovaginal
symptoms, prevention of osteoporosis in postmenopausal females, and treatment of pre-
mature hypoestrogenism (e.g., premature ovarian insufciency or bilateral oophorec-
tomy) [40]. Data regarding MHT use in transplant recipients is sparse. Postmenopausal
SOT recipients with contraindications to oral and transdermal estrogen including hyper-
tension, history of stroke or coronary artery disease, increased risk of thromboembo-
lism, active liver disease, history of estrogen sensitive cancer, or unexplained vaginal
bleeding should be counseled against the use of MHT [40]. These contraindications
generally do not apply to low-dose vaginal estrogen therapy (note that there are two
types of estrogen-containing vaginal ring, low-dose and high-dose).
One prospective study from 1998 evaluated 32 female liver transplant recipients
between 46 and 70years old who used a combination of transdermal estradiol and
oral progesterone while taking corticosteroids, azathioprine, and/or cyclosporine
for immunosuppression and found no change in liver enzyme activity, liver synthe-
sis function and coagulation factors up to 6months after initiation [41]. A small
retrospective case-control study of heart transplant recipients using MHT did not
reveal signicant differences in 5-year survival, graft complications, thrombosis,
cancer, or non-fatal major adverse cardiac events [42]. Given these data, meno-
pausal hormone therapy could be considered for postmenopausal SOT recipients
after weighing the risks and benets and following discussion with their multidisci-
plinary care team.
N. Tan and A. H. McClintock
393
For patients requiring systemic menopausal hormone therapy, transdermal formula-
tions of estrogen may be preferred over oral formulations given their association with a
lower risk of venous thromboembolism, possibly because transdermal administration of
estrogen bypasses the hepatic rst-pass effect. Oral progesterone or off-label use of the
levonorgestrel IUD should be used concurrently with systemic estrogen if the patient
has not had a hysterectomy, given the higher risk of endometrial hyperplasia and cancer
with unopposed estrogen exposure. If a patient has localized vulvovaginal symptoms
such as frequent UTIs, incontinence, dyspareunia, and vulvar/vaginal irritation, without
indications for systemic MHT, a low- dose topical vaginal estrogen may provide relief
with the benet of minimal systemic absorption. The different formulations include
creams, tablets, and rings. Of note, there is a ring with higher, systemic levels of estrogen
that would not be used as a low-dose option for topical vaginal estrogen.
13.7 Osteoporosis
End-organ disease prior to transplant and medications used post-transplant increase
the risk of osteoporosis and fracture in SOT recipients, which is further compounded
by postmenopausal status [43]. Osteoporosis screening recommendations for SOT
recipients are discussed further in Chap. 14.
13.8 Gynecologic Cancers
HPV-associated gynecologic cancers occur at increased rates in solid organ trans-
plant recipients compared to the general population. Risk of these cancers is dis-
cussed in Chap. 10, and screening is discussed in Chap. 14.
13.9 Conclusion
Primary care providers play an important role in the reproductive and gynecologic
health of SOT recipients. Although there are increased risks involved, with dedi-
cated counseling, planning, and coordination with other transplant care providers,
many SOT recipients can achieve their pregnancy and family planning goals and
manage the menopausal transition safely and effectively. Additionally, as the num-
ber of transplants increases, primary care providers can encourage patients who are
interested to enroll in transplant registries to contribute to research efforts about
obstetric and gynecologic health outcomes for recipients of reproductive age.
13 Gynecologic and Reproductive Health Considerations in the Adult Solid Organ…
394
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397© 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_14
Chapter 14
Preventive Health intheAdult Solid Organ
Transplant Recipient
RebeccaS.Gold andLeahMarcotte
14.1 Cancer Screening inSolid Organ Transplant Recipients
Cancer is one of the leading causes of death in solid organ transplant (SOT) recipi-
ents, in addition to cardiovascular disease and infections. Overall, solid organ trans-
plant recipients have a twofold increased incidence of all types of cancers and a
two- to three-fold increased rate of cancer mortality, as compared to the general
population. The most extensive cohort study involving 175,732 solid organ trans-
plant recipients (58.4% kidney, 21.6% liver, 10% heart, and 4% lung) in the United
States (US) showed a cancer standardized incidence ratio of 2.1 [1]. The risk was
increased for a total of 32 different malignancies. The cancers with the highest risk
relative to the general population included Kaposi sarcoma (KS); non-Hodgkin
lymphoma; lip, nonmelanoma skin, vulvar, anal, and kidney; and liver mostly
among liver transplant recipients. Immunosuppression is associated with an
increased incidence in human papilloma virus (HPV)-related cancers (vulva, vagina,
cervix, and anus) [2]. Skin cancers are the most frequent overall malignancy seen in
the solid organ transplant population, accounting for more than 40% of post-
transplant malignancies [3]. (See Chap. 10, Table 10.3.)
The risk of specic malignancies varies according to the organ transplanted.
Lung transplant recipients have a twofold increase in non-Hodgkin lymphoma com-
pared to other solid transplant recipients [1]. Lung cancer is more common in lung
and heart transplant recipients than in kidney or liver recipients. Liver and kidney
cancers are more common in liver and kidney transplant recipients, respectively.
Solid organ transplant recipients with primary sclerosing cholangitis are at increased
R. S. Gold (*) · L. Marcotte
Division of General Internal Medicine, Department of Medicine, University of Washington,
Seattle, WA, USA
e-mail: goldr@uw.edu; leahmar@uw.edu