DEFINITION AND PREVALENCE
Infertility is the inability to conceive after 12 months of unprotected sexual intercourse or after 6 months in women ≥35. This revised definition is based on data indicating that 50% of apparently normal couples will conceive within 3 months, 75–82% within 6 months, and 85–92% within 12 months, but recognizes the age-related decrease in fertility. In the United States, the overall rate of infertility in married women aged 15–44 is 6.7% based on the recent National Survey of Family Growth. The infertility rate has remained relatively stable over the past 30 years in most countries. However, the proportion of couples without children has risen, reflecting both higher numbers of couples in childbearing years and a trend to delay childbearing. This trend has important implications because of the age-related decrease in fecundability, the ability to conceive and carrying a baby to term; the incidence of primary impaired fecundability increases from ~15% between the ages of 15 and 29 to 18% between the ages of 30 and 35, and 40% between the ages of 35 and 44. It is estimated that 12% of women in the United States have received medical assistance for infertility, although this represents <50% of women with current fertility problems. Both infertility and the use of medical services increase with age and both are affected by race and ethnicity. There is increased infertility in non-Hispanic black women and lower use of fertility services among Hispanic and non-Hispanic black women, suggesting disparities in access to care.
The World Health Organization (WHO) considers infertility as a disability (an impairment of function) and thus access to health care for this indication falls under the Convention on the Rights of Persons with Disability. Thirty-four million women, predominantly from developing countries, have infertility resulting from maternal sepsis and unsafe abortion. In populations <60 years old, infertility is ranked the fifth highest serious global disability.
The spectrum of infertility ranges from reduced conception rates or the need for medical intervention to irreversible causes of infertility. Infertility can be attributed primarily to male factors in 20% of couples and female factors in 38% of couples and is unexplained in about 15% of couples (Fig. 389-1). Both male and female factors contribute to infertility in 25% of couples. Decreases in the ability to conceive as a function of age in women has led to recommendations that not only should women ≥34 years old seek attention sooner, but that they also receive an expedited workup and approach to treatment.
Causes of infertility. FSH, follicle-stimulating hormone; LH, luteinizing hormone.
APPROACH TO THE PATIENT Infertility INITIAL EVALUATION
In all couples presenting with infertility, the initial evaluation includes discussion of the appropriate timing of intercourse and discussion of modifiable risk factors such as smoking, alcohol, caffeine, and obesity. The range of required investigations should be reviewed as well as a brief description of infertility treatment options, including adoption. Initial investigations are focused on determining whether the primary cause of the infertility is male, female, or both. These investigations include a semen analysis in the male, confirmation of ovulation in the female, and, in the majority of situations, documentation of tubal patency in the female. In some cases, after an extensive workup excluding all male and female factors, a specific cause cannot be identified, and infertility may ultimately be classified as unexplained. PSYCHOLOGICAL ASPECTS OF INFERTILITY
Infertility is invariably associated with psychological stress related not only to the diagnostic and therapeutic procedures themselves but also to repeated cycles of hope and loss associated with each new procedure or cycle of treatment that does not result in the birth of a child. These feelings are often combined with a sense of isolation from friends and family. Counseling and stress-management techniques should be introduced early in the evaluation of infertility. Importantly, infertility and its treatment do not appear to be associated with long-term psychological sequelae. FEMALE CAUSES
Abnormalities in menstrual function constitute the most common cause of female infertility. These disorders, which include ovulatory dysfunction and abnormalities of the uterus or outflow tract, may present as amenorrhea or as irregular or short menstrual cycles. A careful history and physical examination and a limited number of laboratory tests will help to determine whether the abnormality is (1) hypothalamic or pituitary (low follicle-stimulating hormone [FSH], luteinizing hormone [LH], and estradiol with or without an increase in prolactin), (2) polycystic ovary syndrome (PCOS; irregular cycles, hyperandrogenism and/or polycystic ovarian pathology assessed by ultrasound in the absence of other causes of androgen excess), (3) ovarian (low estradiol with increased FSH), or (4) a uterine or outflow tract abnormality. The frequency of these diagnoses depends on whether the amenorrhea is primary or occurs after normal puberty and menarche (see Fig. 386-2).
The approach to further evaluation of these disorders is described in detail in Chap. 386. Ovulatory Dysfunction
In women with a history of regular menstrual cycles, evidence of ovulation should be sought (Chap. 385). Even in the presence of ovulatory cycles, evaluation of ovarian reserve is recommended for women age >35 years if they are interested in fertility. Measurement of FSH on day 3 of the cycle (an FSH level <10 IU/mL on cycle day 3 predicts adequate ovarian oocyte reserve) is the most cost-effective test. Other tests antral follicle count on ultrasound, and anti-müllerian hormone (AMH; <0.5 ng/mL predicts reduced ovarian reserve although there is variability between labs). Importantly, tests of ovarian reserve help to predict the response to exogenous gonadotropins but do not predict ability to conceive. Tubal Disease
Tubal dysfunction may result from pelvic inflammatory disease (PID), appendicitis, endometriosis, pelvic adhesions, tubal surgery, previous use of an intrauterine device (IUD), and a previous ectopic pregnancy. However, a cause is not identified in up to 50% of patients with documented tubal factor infertility. Because of the high prevalence of tubal disease, evaluation of tubal patency by hysterosalpingogram (HSG) or laparoscopy should occur early in the majority of couples with infertility. Subclinical infections with Chlamydia trachomatis may be an underdiagnosed cause of tubal infertility and require the treatment of both partners. Endometriosis
Endometriosis is defined as the presence of endometrial glands or stroma outside the endometrial cavity and uterine musculature. Its presence is suggested by a history of dyspareunia (painful intercourse), worsening dysmenorrhea that often begins before menses, or a thickened rectovaginal septum or deviation of the cervix on pelvic examination. Mild endometriosis does not appear to impair fertility; the pathogenesis of the infertility associated with moderate and severe endometriosis may be multifactorial with impairments of folliculogenesis, fertilization, and implantation, as well as adhesions. Endometriosis is often clinically silent, however, and can only be excluded definitively by laparoscopy. MALE CAUSES
Known causes of male infertility include primary testicular disease, genetic disorders (particularly Y chromosome microdeletions), disorders of sperm transport, and hypothalamic-pituitary disease resulting in secondary hypogonadism (See also Chap. 384). However, the etiology is not ascertained in up to one-half of men with suspected male factor infertility. The key initial diagnostic test is a semen analysis. Testosterone levels should be measured if the sperm count is low on repeated examination or if there is clinical evidence of hypogonadism. Gonadotropin levels will help to determine a gonadal versus a central cause of hypogonadism.
In addition to addressing the negative impact of smoking on fertility and pregnancy outcome, counseling about nutrition and weight is a fundamental component of infertility and pregnancy management. Both low and increased body mass index (BMI) are associated with infertility in women and with increased morbidity during pregnancy. Obesity has also been associated with reduced fertility in men. The treatment of infertility should be tailored to the problems unique to each couple. In many situations, including unexplained infertility, mild-to-moderate endometriosis, and/or borderline semen parameters, a stepwise approach to infertility is optimal, beginning with low-risk interventions and moving to more invasive, higher risk interventions only if necessary. After determination of all infertility factors and their correction, if possible, this approach might include, in increasing order of complexity: (1) expectant management, (2) clomiphene citrate or an aromatase inhibitor (see below) with or without intrauterine insemination (IUI), (3) gonadotropins with or without IUI, and (4) in vitro fertilization (IVF). The time used for evaluation, correction of problems identified, and expectant management can be longer in women age <30 years, but this process should be advanced rapidly in women aged >35 years. In some situations, expectant management will not be appropriate. OVULATORY DYSFUNCTION
Treatment of ovulatory dysfunction should first be directed at identification of the etiology of the disorder to allow specific management when possible. Dopamine agonists, for example, may be indicated in patients with hyperprolactinemia (Chap. 373); lifestyle modification may be successful in women with low body weight, a history of intensive exercise or obesity.
Medications used for ovulation induction include agents that increase FSH through alteration of negative feedback, gonadotropins, and pulsatile GnRH. Clomiphene citrate is a nonsteroidal estrogen antagonist that increases FSH and LH levels by blocking estrogen negative feedback at the hypothalamus. The efficacy of clomiphene for ovulation induction is highly dependent on patient selection. It induces ovulation in ~60% of women with PCOS and has traditionally been the initial treatment of choice. Combination with agents that modify insulin levels such as metformin does not appear to improve outcomes. Clomiphene citrate is less successful in patients with hypogonadotropic hypogonadism. Aromatase inhibitors are also used for treatment of infertility. Studies suggest they may have advantages over clomiphene in some populations. Estrogen receptor blockade using Tamoxifen has been used in conjunction with gonadotropins in breast cancer patients undergoing in vitro fertilization (IVF) for embryo banking. Gonadotropins are highly effective for ovulation induction in women with hypogonadotropic hypogonadism and PCOS and are used to induce the development of multiple follicles in unexplained infertility and in older reproductive-age women. Disadvantages include a significant risk of multiple gestation and the risk of ovarian hyperstimulation, particularly in women with polycystic ovaries, with or without other features of PCOS. Careful monitoring and a conservative approach to ovarian stimulation reduce these risks. Currently available gonadotropins include urinary preparations of LH and FSH, highly purified FSH, and recombinant FSH. Although FSH is the key component, LH is essential for steroidogenesis in hypogonadotropic patients, and LH or human chorionic gonadotropin (hCG) may improve results through effects on terminal differentiation of the oocyte. These methods are commonly combined with IUI.
None of these methods are effective in women with premature ovarian failure, in whom donor oocyte or adoption are the methods of choice. TUBAL DISEASE
If hysterosalpingography suggests a tubal or uterine cavity abnormality or if a patient is aged ≥35 at the time of initial evaluation, laparoscopy with tubal lavage is recommended, often with a hysteroscopy. Although tubal reconstruction may be attempted if tubal disease is identified, it is generally being replaced by the use of IVF. These patients are at increased risk of developing an ectopic pregnancy. ENDOMETRIOSIS
Although 60% of women with minimal or mild endometriosis may conceive within 1 year without treatment, laparoscopic resection or ablation appears to improve conception rates. Medical management of advanced stages of endometriosis is widely used for symptom control but has not been shown to enhance fertility. In moderate and severe endometriosis, conservative surgery is associated with pregnancy rates of 50 and 39%, respectively, compared with rates of 25 and 5% with expectant management alone. In some patients, IVF may be the treatment of choice. MALE FACTOR INFERTILITY
The treatment options for male factor infertility have expanded in recent years (Chap. 384). Secondary hypogonadism is highly amenable to treatment with gonadotropins or pulsatile gonadotropin-releasing hormone (GnRH) where available. In vitro techniques have provided new opportunities for patients with primary testicular failure and disorders of sperm transport. Choice of initial treatment options depends on sperm concentration and motility. Expectant management should be attempted initially in men with mild male factor infertility (sperm count of 15 to 20 × 106/mL and normal motility). Moderate male factor infertility (10–15 × 106/mL and 20–40% motility) should begin with IUI alone or in combination with treatment of the female partner with ovulation induction, but it may require IVF with or without intracytoplasmic sperm injection (ICSI). For men with a severe defect (sperm count of <10 × 106/mL, 10% motility), IVF with ICSI or donor sperm should be used. If ICSI is performed because of azoospermia due to congenital bilateral absence of the vas deferens, genetic testing for CFTR gene mutations and counseling should be provided because of the risk of cystic fibrosis. ASSISTED REPRODUCTIVE TECHNOLOGIES
The development of assisted reproductive technologies (ARTs) has dramatically altered the treatment of male and female infertility. IVF is indicated for patients with many causes of infertility that have not been successfully managed with more conservative approaches. IVF or ICSI is often the treatment of choice in couples with a significant male factor or tubal disease, whereas IVF using donor oocytes is used in patients with premature ovarian failure and in women of advanced reproductive age. Success rates are influenced by cause of infertility and age, varying between 48% in women <35 to ≤10% in women >40. Success rates are highest in anovulatory women and lowest in women with decreased ovarian reserve. In the United States, success rates are higher in white than in black, Asian, or Hispanic women. Although often effective, IVF is costly and requires careful monitoring of ovulation induction and the use of invasive techniques, including the aspiration of multiple follicles. IVF is associated with a significant risk of multiple gestation, particularly in women age <35, in whom the rate can be as high as 30%. However, improved techniques and recognition of the risk associated with even twin pregnancies has led to adoption of age-specific guidelines by many clinics and a significant decline in the rate of twins (<25%) and very few higher order multiple births.
Only 15% of married couples in the United States report having unprotected sexual intercourse in the past 3 months. Although recent statistics indicate a decrease in unintended pregnancy in the United States, 45% of births are still the result of unintended pregnancy; approximately one-third of these result from incorrect use or failure of contraceptives, and >50% result in induced abortion. Unintended pregnancy is higher in Latina than white women with black women having the highest rates. Teenage pregnancies continue to represent a serious public health problem in the United States, with >1 million unintended pregnancies each year—a significantly greater incidence than in other industrialized nations. However, changes in teen behaviors are occurring, with an increase in contraceptive use at both first and most recent sexual encounter.
The use of contraception in women aged 15–49 years who were married or in a union doubled worldwide from 36% in 1970 to 64% in 2015. The absolute number of married women who use contraception is projected to increase to nearly 800 million by 2030. However, there remains an unmet need for family planning in at least 10% of the population in most regions of the world.
Of the contraceptive methods available (Table 389-1), a reversible form of contraception is used by >50% of couples with a significant increase in the use of long-acting forms such IUDs in the past decade. Sterilization (male or female) is used as a permanent form of contraception by over one-third of couples. Pregnancy termination is relatively safe when directed by health care professionals but is rarely the option of choice.
TABLE 389-1Effectiveness of Different Forms of Contraception ||Download (.pdf) TABLE 389-1 Effectiveness of Different Forms of Contraception
|Method of Contraception ||Theoretical Effectiveness (%) ||Actual Effectiveness (%) ||Continued Use at 1 Year (%) ||Use of Method by U.S. Women at Risk of Unintended Pregnancy (%) |
|No Method ||15 ||15 || ||10 |
|Fertility Awareness ||96 ||76 ||47 ||1.2 |
|Withdrawal ||96 ||78 ||46 ||4.4 |
|Barrier Methods || || || || |
| Condoms ||98 ||82 ||43 ||13.7 |
| Diaphragm ||94 ||82 ||57 ||2 |
|Spermicides ||82 ||72 ||43 ||1 |
|Sterilization || || || || |
| Female ||99.5 ||99.5 ||100 ||22.6 |
| Male ||99.5 ||99.9 ||100 ||7.4 |
|Intrauterine Device || || || ||9.3 |
| Copper T ||99.4 ||99.8 ||85 || |
| Progestin-containing ||99.8 ||99.8 ||88 || |
|Hormonal Contraceptives || || || || |
| Combined and Progestin only ||99.7 ||91 ||67 ||23.3 |
| Transdermal Patch ||99.7 ||91 ||67 ||0.5 |
| Vaginal Ring ||99.7 ||91 ||67 ||1.8 |
|Implant || || || ||1.2 |
| Depot Provera ||99.8 ||94 ||56 || |
| Nexplanon ||99.5 ||99.5 ||84 || |
|Emergency Contraception || || || ||0.3 |
No single contraceptive method is ideal, although all are safer than carrying a pregnancy to term. The effectiveness of a given method of contraception does not just depend on the efficacy of the method itself. Discrepancies between theoretical and actual effectiveness emphasize the importance of patient education and adherence when considering various forms of contraception (Table 389-1). Contraceptive use is stratified by race/ethnicity with higher oral contraceptive use in white women and greater use of long-acting reversible contraceptive (LARC) methods in Latina women. For oral contraceptives, discontinuation rates are highest among Black women whereas there is no racial/ethnic differences for LARC methods. Knowledge of the advantages and disadvantages of each contraceptive is essential for counseling an individual about the methods that are safest and most consistent with his or her lifestyle. The WHO has extensive family planning resources for the clinician and patient that can be accessed online. Similar resources for determining medical eligibility are available through the Centers for Disease Control and Prevention (CDC). Considerations for contraceptive use in obese patients and after bariatric surgery are discussed below.
Barrier contraceptives (such as condoms, diaphragms, and cervical caps) and spermicides are easily available, reversible, and have fewer side effects than hormonal methods. However, their effectiveness is highly dependent on adherence and proper use (Table 389-1). A major advantage of barrier contraceptives is the protection provided against sexually transmitted infections (STIs) (Chap. 131). Consistent use is associated with a decreased risk of HIV, gonorrhea, nongonococcal urethritis, and genital herpes, probably due in part to the concomitant use of spermicides. Natural membrane condoms may be less effective than latex condoms for prevention of sexually transmitted diseases, and petroleum-based lubricants can degrade condoms and decrease their efficacy for preventing HIV infection. Barrier methods used by women include the diaphragm, cervical cap, and contraceptive sponge. There is some evidence that the diaphragm is more effective when used in conjunction with a spermicide. The cervical cap and sponge are less effective than the diaphragm, and there have been rare reports of toxic shock syndrome with the diaphragm and contraceptive sponge.
Sterilization procedures are highly effective for both men and women (Table 389-1) and are commonly chosen by fertile men and multiparous women >30 years old. Sterilization refers to a procedure that prevents fertilization by surgical interruption of the fallopian tubes in women or the vas deferens in men. Although tubal ligation and vasectomy are potentially reversible, these procedures should be considered permanent and should not be undertaken without patient counseling.
Tubal ligation methods are highly effective with a 10-year cumulative pregnancy rate of 1.85 per 100 women with both postpartum or interval procedures. However, when pregnancy does occur, the risk of ectopic pregnancy may be as high as 30%. The success rate of tubal reanastomosis depends on the method of ligation used, but even after successful reversal, the risk of ectopic pregnancy remains high. The use of salpingectomy has increased to 33% with emerging evidence that ovarian cancer originates from dysplastic cells in the fallopian tube. Hysteroscopic sterilization has been used, particularly in women with pelvic adhesions or other co-morbidities. Essure is the most commonly used commercially available product and involves insertion of a nickel-titanium double coil which results in tubal fibrosis. Data indicate very low unintended pregnancy rates (1.5 per 1000 women) with ultrasound and/or HSG confirmation of correct placement. Although still available, the U.S. Food and Drug Administration (FDA) issued a black box warning in 2015 due to post-marketing reports of long-term pain, abnormal bleeding, and allergic reactions. Intrauterine quinacrine is also effective and has been used for many years in resource-poor settings. Vasectomy is a highly effective and low risk outpatient surgical procedure. The no-scalpel technique, which is used in the United States, results in fewer complications, but has not been accepted worldwide. The development of azoospermia may be delayed for 2–6 months, and other forms of contraception must be used until two sperm-free ejaculations provide proof of sterility. Current data indicate that reanastomosis may restore fertility in 50–70% of men, but the success rate declines with time after vasectomy and may be influenced by factors such as the development of antisperm antibodies which occurs in 60–80% of men.
IUDs inhibit pregnancy through a spermicidal effect (copper IUDs) or by inhibiting ovulation (progestin containing devices). IUDs provide a high level of efficacy in the absence of systemic metabolic effects, and ongoing motivation is not required to ensure efficacy once the device has been placed. IUD use is greatest in Europe and Canada (33%) but is increasing in other parts of the world, including the United States. An IUD should not be used in women at high risk for development of STI or in women at high risk for bacterial endocarditis. Progestin-containing IUDs are contraindicated in women with breast cancer. The IUD may not be effective in women with uterine leiomyomas because they alter the size or shape of the uterine cavity. IUD use is associated with increased menstrual blood flow, although this is less pronounced with the progestin-releasing IUD.
Because of their ease of use and efficacy, oral contraceptive pills are the most widely used form of hormonal contraception. They act by suppressing ovulation, changing cervical mucus, and altering the endometrium. The current formulations are made from synthetic estrogens and progestins. The estrogen component of the pill consists of ethinyl estradiol or mestranol, which is metabolized to ethinyl estradiol. Multiple synthetic progestins are used. Norethindrone and its derivatives are used in many formulations. Low-dose norgestimate and the more recently developed (third-generation) progestins (desogestrel, gestodene, drospirenone) have a less androgenic profile; levonorgestrel appears to be the most androgenic of the progestins and should be avoided in patients with hyperandrogenism. The three major formulations of oral contraceptives are (1) fixed-dose estrogen-progestin combination, (2) phasic estrogen-progestin combination, and (3) progestin only. Each of these formulations is administered daily for 3 weeks followed by a week of no medication during which menstrual bleeding generally occurs. Two extended oral contraceptives are approved for use in the United States; Seasonale is a 3-month preparation with 84 days of active drug and 7 days of placebo, whereas Lybrel is a continuous preparation. Current doses of ethinyl estradiol range from 10 to 50 μg. However, indications for the 50-μg dose are rare, and the majority of formulations contain 20–35 μg of ethinyl estradiol. The reduced estrogen and progestin content in the second- and third-generation pills has decreased both side effects and risks associated with oral contraceptive use (Table 389-2). At the currently used doses, patients must be cautioned not to miss pills due to the potential for ovulation and this may be particularly important in obese women. Side effects, including breakthrough bleeding, amenorrhea, breast tenderness, and weight gain, often respond to a change in formulation. Oral contraceptive use is associated with a decreased risk of endometrial, ovarian and colon cancer. However, even the lower dose oral contraceptives have been associated with an increased risk of breast cancer, cardiovascular disease (myocardial infarction, stroke, venous thromboembolism [VTE]), but the absolute excess risk is extremely low. VTE risk is higher with the third-generation than the second-generation progestins, and the risk of stroke and VTE is also higher with drospirenone (although not cyproterone). Again, the absolute excess risk is small. In addition to their use as highly effective contraceptives, estrogen-progestin combinations are used for treatment of amenorrhea and oligoamenorrhea and continuous formulations are commonly used for treatment of premenstrual syndrome and premenstrual dysphoric disorder, menstrual migraine, leiomyomas, and endometriosis.
TABLE 389-2Oral Contraceptives: Contraindications and Disease Risk ||Download (.pdf) TABLE 389-2 Oral Contraceptives: Contraindications and Disease Risk
Women age >35 years who smoke ≥15 cigarettes per day
Known ischemic heart disease or multiple risk factors for cardiovascular disease (older age, smoking, diabetes, and hypertension)
Previous thromboembolic event, stroke or known thrombogenic mutations
Complicated valvular heart disease
Complicated solid organ transplantation
Hypertension (systolic ≥160 mmHg or diastolic ≥100 mmHg)
Systemic lupus erythematous (positive or unknown antiphospholipid antibodies
Cirrhosis, hepatic adenoma or hepatoma
Pregnancy and early postpartum (<21 days)
Undiagnosed abnormal uterine bleeding
Hypertension (adequately controlled or systolic 140–159 or diastolic 90–99)
Women receiving anticonvulsant drug therapy
Women following bariatric surgery (malabsorptive procedure)
Coronary heart disease—increased in smokers >35; no relation to progestin type
Hypertension—relative risk 1.8 (current users) and 1.2 (previous users)
Venous thrombosis—relative risk ~4; may be higher with third-generation progestin, drospirenone, and patch; compounded by obesity (tenfold increased risk compared with nonobese, no OCP); markedly increased with factor V Leiden or prothrombin gene mutations
Stroke—slight increase; unclear relation to migraine headache
Cerebral vein thrombosis—relative risk ~13–15; synergistic with prothrombin gene mutation
Cervical cancer—relative risk 2–4
Breast cancer—may increase risk, particularly in carriers of BRCA1 and possibly BRCA2
Ovarian cancer—50% reduction in risk
Endometrial cancer—40% reduction in risk
The microdose progestin-only minipill is less effective as a contraceptive, having a pregnancy rate of 2–7 per 100 women-years. However, it may be appropriate for women at increased risk for cardiovascular disease or for women who cannot tolerate synthetic estrogens.
A weekly contraceptive patch (Ortho Evra) is available and has similar efficacy to oral contraceptives. Approximately 2% of patches fail to adhere, and a similar percentage of women have skin reactions. Efficacy is lower in women weighing >90 kg. The amount of estrogen delivered may be comparable to that of a 40-μg ethinyl estradiol oral contraceptive, raising the possibility of increased risk of VTE, which must be balanced against potential benefits for women not able to successfully use other methods. A monthly contraceptive estrogen/progestin injection (Lunelle) is highly effective, with a first-year failure rate of <0.2%, but it may be less effective in obese women. Its use is associated with bleeding irregularities that diminish over time. Fertility returns rapidly after discontinuation. A monthly vaginal ring (NuvaRing) that is intended to be left in place during intercourse is also available for contraceptive use. It is highly effective, with a 12-month failure rate of 0.7%. Ovulation returns within the first recovery cycle after discontinuation.
Long-Term Hormonal Contraceptives
There are two forms of long-acting hormonal contraceptives in addition to the progestin-containing IUD, both of which act by inhibiting ovulation and causing changes in the endometrium and cervical mucus that result in decreased implantation and sperm transport. Depot medroxyprogesterone acetate (Depo-Provera, DMPA) is effective for 3 months when administered SC or IM, but return of fertility after discontinuation may be delayed for up to 12–18 months. Irregular bleeding is common initially with amenorrhea in almost 70% of users at 2 years. Two percent of women discontinue use due to weight gain. Nexplanon is a hormonal implant that slowly releases the progestin, etonogestrel, and is approved by the FDA for 3 years of use. It is associated with unscheduled bleeding but has very favorable continuation rates, and is associated with rapid return of ovulation after removal. Both forms of contraception may be particularly good for women in whom an estrogen-containing contraceptive is contraindicated (e.g., migraine exacerbation, sickle cell anemia, fibroids). DMPA can induce bone loss and may be contraindicated in areas of high HIV prevalence because of potential negative effects on both immunologic regulation and genital track permeability. Neither of these side effects occur with use of the progestin implant. DMPA and Nexplanon are contraindicated in women with current breast cancer because of theoretical concerns about the adverse effects of progestins on breast cancer.
The probability of pregnancy without relation to time of the month is 8%, but the probability varies significantly in relation to proximity to ovulation and may be as high has 30%. In order of efficacy, methods of postcoital contraception include the following:
Copper IUD insertion within a maximum of 5 days has a reported efficacy of 99–100% and prevents pregnancy by its spermicidal effect; insertion is frequently available through family planning clinics, but may be associated with a higher risk of abdominal pain compared with other methods.
Oral antiprogestins (ulipristal acetate, 30 mg single dose, available worldwide, or mifepristone, 600 mg single dose, not available for this indication in the United States) prevent pregnancy by delaying or preventing ovulation; when administered, ideally within 72 h but up to 120 h after intercourse, they have an efficacy of 98–99%; require a prescription.
Levonorgestrel (1.5 mg as a single dose) delays or prevents ovulation and is not effective after ovulation; should be taken within 72 h of unprotected intercourse, and has an efficacy that varies between 60 and 94%; it is available over the counter.
Combined estrogen and progestin regimens have lower efficacy and are no longer recommended. A pregnancy test is not necessary before the use of oral methods, but pregnancy should be excluded before IUD insertion. Risk factors for failure of oral regimens include close proximity to ovulation and unprotected intercourse after use. In addition, there is an increased risk of pregnancy in obese and overweight women using levonorgestrel for postcoital contraception and an increased risk in obese women using an antiprogestin.
IMPACT OF OBESITY ON CONTRACEPTIVE CHOICE
Approximately one-third of adults in the United States are obese. Although obesity is associated with some reduction in fertility, the vast majority of obese women can conceive. The risk of pregnancy-associated complications is higher in obese women. Intrauterine contraception may be more effective than oral or transdermal methods for obese women. The WHO guidelines provide no restrictions (class 1) for the use of intrauterine contraception, DMPA, and progestin-only pills for obese women (BMI ≥30) in the absence of coexistent medical problems, whereas methods that include estrogen (pill, patch, ring) are considered class 2 (advantages generally outweigh theoretical or proven risks) due to the increased risk of thromboembolic disease. There are no restrictions to the use of any contraceptive methods following restrictive bariatric surgery procedures, but both combined and progestin-only pills are relatively less effective following procedures associated with malabsorption.