CME

Reproductive planning for women after solid-organ transplant

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Release date: September 1, 2017
Expiration date: August 31, 2018
Estimated time of completion: 1 hour

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ABSTRACT

Women who receive transplants require contraception counseling because of the teratogenicity of immunosuppressant medications and the risks posed by pregnancy after transplant. Fortunately, pregnancy can succeed with careful planning and monitoring.

KEY POINTS

  • The number of solid-organ transplants in US women of childbearing age has increased over the past 20 years.
  • Women should wait at least 1 year after receiving a solid-organ transplant before attempting to become pregnant, and then should do so only when cleared by the transplant team and obstetrician, with close monitoring.
  • The various types of contraception can be grouped by their effectiveness and by the medical eligibility criteria set by the US Centers for Disease Control and Prevention.
  • Transplant recipients of childbearing age should use 2 contraceptive methods concurrently, one of which should be condoms.

 

References

Increasing numbers of women of childbearing age are receiving solid-organ transplants. All need counseling on how to prevent pregnancy while they are taking immunosuppressive agents. Some want to become pregnant after their transplant and thus require counseling and follow-up to maintain good health during pregnancy (Table 1).1

Counseling topics for women of childbearing age after solid-organ transplant

Primary care physicians can assist with basic contraception counseling and pregnancy planning for their patients who have had solid-organ transplants. In this review, we describe contraceptive options and pregnancy planning for these women.

TRANSPLANTS IN WOMEN ARE INCREASING

Over the past 20 years, the number of solid-organ transplants in US women has increased steadily. Since 1988, 38% of the 634,000 transplants performed were in women, and 47% of these women were of childbearing age (ages 18 to 49).2 Kidneys accounted for 60% of solid-organ transplants,2 and kidney transplant is now commonly performed in women of childbearing age. In 2012, of 176,000 patients with a functioning renal graft, 40.5% were women, and recipients between ages 20 and 44 composed the second-largest age group.3

FERTILITY IN WOMEN WITH END-STAGE RENAL DISEASE

Women in their reproductive years who have end-stage renal disease have lower fertility rates than women in the general population. In women undergoing peritoneal dialysis or hemodialysis, conception rates decrease to around 0.5% per year.4 This lower rate is most likely related to hypothalamic-pituitary-gonadal dysfunction, leading to reduced or total impairment of ovulation, menstrual irregularities, and infertility.5

Fertility often returns within a few months after transplant,1,6 and reported posttransplant pregnancy rates range from 3.3% to 18%,7–9 with up to one-third of pregnancies being unintended.6,10 These numbers are likely an underestimate because they do not reflect all pregnancies that are terminated, as many women do not voluntarily report having had an abortion.

Fertility is also severely diminished in women with end-stage liver disease. After liver transplant, sex hormone levels return to normal for many women, and menses soon resume.11

In 2005, the National Transplantation Pregnancy Registry reported 1,418 pregnancies in 919 female recipients of solid-organ transplants. In 2010, this number had increased to 1,940 pregnancies in 1,185 recipients, of whom 75% were kidney transplant recipients.12

A successful pregnancy outcome is most likely when a minimum of 1 year intervenes between transplant and conception.12,13

TERATOGENICITY OF IMMUNOSUPPRESSANTS

Immunosuppressant drugs commonly used for maintenance therapy after solid-organ transplant include the following:

  • Calcineurin inhibitors (eg, cyclosporine,  tacrolimus)
  • Antiproliferative and antimetabolite agents (eg, mycophenolate mofetil, azathioprine)
  • Corticosteroids
  • Mammalian target of rapamycin inhibitors (eg, sirolimus, everolimus)
  • T-cell costimulation blockers (eg, belatacept).14

The US Food and Drug Administration (FDA) previously classified mycophenolate mofetil and azathioprine in pregnancy risk category D (positive evidence of human fetal risk). The teratogenic risk of mycophenolate mofetil is well established in studies documenting specific congenital malformations and fetal loss in the first trimester.13,15 The teratogenic risk of azathioprine, on the other hand, is estimated to be minimal to small.16 Many of the associated fetal abnormalities may be related to the complexity of the underlying medical condition of the mother rather than to the medication.16

Pregnancy and lactation considerations of common immunosuppresant drugs

In June 2015, the FDA’s new Pregnancy and Lactation Labeling Rule went into effect, which removes the pregnancy letter categories A, B, C, D, and X from labeling.17 This rule was designed to help providers counsel their patients regarding the specific risks and benefits of a drug when used by pregnant or nursing women. However, the ABCDX categories are still commonly used. Table 2 shows information about the risks during pregnancy and lactation posed by the immunosuppressive drugs commonly used by posttransplant patients.18

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