LARC methods

For most women, including adolescents and nulliparous women, LARC methods are considered first line . LARC methods include IUDs and the progestin-only subdermal implant. A large cohort trial enrolling close to 10,000 women found that the continuation and satisfaction rates were similar for all LARC methods, at 80%. At 3 years, the unplanned pregnancy rate was significantly lower in the LARC group when compared to pill, patch, and ring users (adjusted hazard ratio 21.8 (13.7–34.9)).

There are two types of IUD. The levonorgestrel (LNG) IUD contains progestin, which is largely confined to the uterus with minimal systemic drug absorption. The copper IUD is hormone-free. Thus, IUDs provide highly effective contraception for patients with either contraindication to or side effects from systemic hormones. In the past, concerns for infection and method failure made some health-care providers reluctant to recommend IUDs to transplant recipients. However, these patients are now considered appropriate candidates for IUD use by the CDC, transplantation experts, and the mycophenolate Risk Evaluation and Mitigation Strategy program.

In the modern literature, >200 solid organ transplant patients have been described using IUD (see Table 3 ). There are only two reported cases of method failure, both from 1981, and no reported cases of infection . IUDs rely on either copper or progestin as their primary mechanism of action. However, the additional immune-mediated mechanism of IUDs – altered humoral immunity at the level of the endometrium – would theoretically not be affected by modern transplant immunosuppression, which is primarily mediated by T cells . In addition, it has been convincingly demonstrated that IUDs are not associated with an increased risk of pelvic inflammatory disease (PID) or tubal infertility in the general population . Moreover, while similar studies have not been conducted in transplant recipients, there are extensive data from women with HIV infection that IUDs do not increase the risk of pelvic infection in an immunosuppressed population .

The two IUD types have different effects on menstrual bleeding. With the LNG IUD, most women continue to ovulate; however, the LNG IUD carries the dual Food and Drug Administration (FDA) indication for pregnancy prevention and treatment of heavy menstrual bleeding, and for most women menses are lighter and less frequent after the first 6 months of use. The copper IUD does not improve menses.

Subdermal progestin implants

The subdermal contraceptive implant is the most effective method of contraception ( Table 2 ). There are several brands of subdermal implant, and availability varies geographically. They contain a progestin, either LNG or etonogestrel (ENG), and thus do not increase a woman’s thrombogenic risk. There are no published reports of the subdermal implant among women with solid organ transplantation. Published reports of pregnancy with concomitant use of subdermal implant and efavirenz, an antiretroviral drug and a CYP450 inducer, suggests that the interaction may lead to a higher likelihood of contraceptive failure in the late second and third years of implant use . Until further evidence is published, it is reasonable to balance the proven high efficacy and safety among the general population with the theoretical yet understudied risk among patients taking CYP450-inducing medications.

Female sterilization

This method is chosen for its permanence, though it is less effective than some forms of reversible contraception. Efficacy can vary based on patient age and sterilization method, and younger patients have a higher regret rate . While tubal reversal is possible, it is not very effective and usually not covered under insurance. The options for female sterilization include a transcervical, hysteroscopic approach, laparoscopy, or laparotomy, all of which could be complicated by prior surgeries. If requested by the patient, sterilization can be carried out at the time of transplantation. Factors that can influence the choice of sterilization method can include patient history and anatomy, efficacy, ovarian cancer risk reduction, and surgical difficulty.

Combined hormonal contraception

Combined hormonal contraceptives (CHCs) contain both estrogen and progestin and include pill, patch, and ring formulations. Their convenience, familiarity, and advertising likely contribute to their common use despite relatively high typical-user failure rates. These methods have been described among small series of transplantation patients, but no study has been powered to address contraceptive effectiveness or safety.

One study of 26 renal transplantation patients reported no pregnancies and noted noncontraceptive benefits such as improved hematocrit after 18 months of use . Several women in this series required adjustment of their antihypertensive medications, and there was one case of deterioration of liver function in a previously stable patient. A study of 10 renal transplant patients using the transdermal patch shared similar favorable results . A retrospective study of 15 liver transplant patients using combined oral contraceptives (COCs) reported no adverse effects including no changes in liver function, glucose metabolism, blood pressure, body mass index (BMI), or rejection . Use of the contraceptive vaginal ring has been described in a prospective group of 17 renal and liver transplant patients. There were no cases of rejection, need to change immunosuppressive medication, or contraceptive failure . The COCs in these studies contain both 20 and 35 mcg of estradiol and a variety of progestins. Taken together, these studies, though small, reinforce safety relative to pregnancy in a transplant population and underscore the importance of exercising caution with the use of estrogen-containing methods in women with comorbidities.

In summary, in a patient with stable graft function, CHC methods are reasonable contraceptive choices and tend to offer good menstrual cycle control. However, the estrogen-related risks combined with a relatively high typical-use failure are significant drawbacks to these methods.

Progestin-only pills

The use of POPs has not been described in a transplant population. These may be preferable in patients who have estrogen-related risks or side effects. Strict daily dosing is required, but this may be less of a burden in a transplant patient with excellent medication adherence. As with COC pills, the relatively high typical-user failure rate of this method is of concern, particularly in a transplant population.

Depot medroxyprogesterone acetate

DMPA is an injectable progestin-only contraceptive method dosed every 12 weeks. The initiation of therapy is often accompanied by irregular bleeding, but over time this improves and many women become amenorrheic. A “black box” warning from the FDA concerning the bone effects of DMPA with long-term use does not greatly concern family-planning experts who note the reversibility of bone changes in healthy adult women . However, there are no published reports of use in a transplant population in whom there is theoretical concern that the bone effects may not be transient.

Renal osteodystrophy, defined as disturbances in mineral metabolism combined with adynamic bone disease, is an important cause of morbidity and decreased quality of life in patients with chronic kidney disease. Additionally, transplant patients are often on lifelong glucocorticoid therapy, which is the most common form of secondary osteoporosis. In women with secondary osteoporosis, fracture can occur at higher bone mineral density (BMD) levels than in women with postmenopausal osteoporosis . When counseling transplantation patients regarding DMPA, the proven benefits of efficacy and improved bleeding should be balanced with the theoretical risk to bone health, especially among women younger than 25 years who are still building bone density.

Barrier methods

Barrier methods used alone do not provide high efficacy, and this is of particular concern in women with chronic disease or taking teratogenic medication. Barrier methods provide excellent protection from STIs and are a vital component of “dual protection” – combining barrier contraception with another method to increase efficacy.

Withdrawal and fertility awareness

These nonpharmacologic methods may be used by transplant patients due to less perceived risk when compared to other contraceptive methods. As discussed earlier, this ignores the risk of carrying a pregnancy, particularly when unplanned. In an observational study of women from Saudi Arabia post transplantation for HPV infection, withdrawal was the primary method of posttransplantation contraception; pregnancy rates were not reported . While these methods can be practiced with success among dedicated patients, there are several concerns. Due to underlying chronic illness or graft dysfunction, transplant patients may not have regular menstrual cycles, which are an important component of fertility awareness. It is unclear what effect chronic immunosuppression and glucocorticoid therapy have on cervical mucus or basal body temperature monitoring, used to predict ovulation. Lastly, behavior-based methods with high typical-user failure rates are not optimal for patients who have undergone transplantation or are taking teratogenic medications.

Emergency contraception

Emergency contraception (EC) is intended for use when a primary method fails, or contraception was not used. There are three options – the progestin LNG, the selective progestin receptor modulator (SPRM) ulipristal, and the copper IUD. The USMEC considers the two pharmacologic methods Category 1 in all medical conditions, as a single dose of EC is safe. The pharmacologic methods of EC work by inhibiting ovulation . The copper IUD as EC works by inhibiting fertilization, by interfering with sperm motility and function.

Contraception in adolescents

Health-care providers in the pediatric setting are accustomed to a high degree of parental involvement. Adolescents with complex medical conditions have the same needs and rights as all other adolescents to receive sexual and reproductive health care based on their own, not parental, consent. A confidential portion of the health-care visit is the standard of care for adolescents recommended by all major national medical organizations. Laws around consent for medical care by patients who have not yet reached the legal age of majority vary significantly by location; therefore, health-care providers should familiarize themselves with local laws.

Families sometimes express concern about whether the discussion or provision of contraception communicates tacit approval of or even promotes sexual activity in an adolescent who otherwise would abstain. There is no evidence that substantiates this concern. One randomized study of advanced provision of EC among 15–24-year-old patients did not show a difference in contraceptive or sexual behavior; the frequency of unprotected intercourse was high in intervention and control groups . A second trial of increased over-the-counter EC access again showed no change in routine contraceptive use or sexual risk behavior .

ACOG and the American Academy of Pediatrics have recommended LARC methods as first-line contraceptives among adolescents .