and vomiting (19% vs. 6%). However, because other ECPs are more effective, better tolerated, and more readily available, these alternatives are used infrequently.
Mifepristone as an ECP
One drug—mifepristone (RU 486)—can prevent pregnancy or cause abortion, depending on when it is taken. If mifepristone is taken within 5 days of unprotected intercourse, it will prevent pregnancy from occurring, and thus can be considered an ECP.
However, if mifepristone is taken after this time, it may terminate pregnancy that has already begun, and thus can be considered an abortifacient. When used as an ECP, mifepristone is 100%
effective. The drug is available in the United States but is not approved for EC.
The Copper IUD
Insertion of a copper IUD (ParaGard) within 5 days of unprotected intercourse can prevent pregnancy in most women. The method is more than 99.9% effective, allowing less than 1 pregnancy for every 1000 IUD recipients. IUD insertion has the additional benefit of providing ongoing contraception for up to 10 years.
Although using an IUD for EC is highly effective, the technique does have drawbacks: the IUD is expensive, not all women are candidates, and obtaining one quickly may be difficult.
CHAPTER 62 Birth Control
with methotrexate or mifepristone [RU 486]) is used early in pregnancy, as well as in the second trimester. Carboprost and dinoprostone are used in the second trimester only. With all three drugs, uterine contractions develop slowly.
As a result, about 18 hours must pass between dosing and expulsion of the fetus. Unlike other abortifacients, prostaglandins are not feticidal, and hence the aborted fetus may show transient signs of life. Following passage of the fetus and placenta, the patient should be examined for possible cervical or uterine laceration.
Control of Postpartum Hemorrhage. Carboprost is indicated for control of postpartum hemorrhage. The drug is reserved for bleeding that has been refractory to more conventional agents (oxytocin, ergot alkaloids). In these situations, carboprost may be lifesaving. Use of carboprost to control postpartum hemorrhage is discussed in Chapter 64.
Induction of Labor. Misoprostol has been used to induce labor. The regimen recommended by the American College of Obstetricians and Gynecolo-gists consists of 25 mcg vaginally repeated every 3 to 6 hours as needed.
Cervical Ripening. Dinoprostone and misoprostol can be used to initiate ripening of the cervix before induction of labor. This application is discussed in Chapter 64.
Adverse Effects
Gastrointestinal reactions are extremely common with dinoprostone and result from the ability of prostaglandins to stimulate smooth muscle of the alimentary canal. Vomiting and diarrhea occur in up to 62% of those treated. Nausea also occurs often. These responses can be reduced by pretreatment with antiemetic and antidiarrheal medications.
Intense uterine contractions can result in cervical or uterine laceration.
The patient should be examined thoroughly for trauma following expulsion of the fetus and placenta.
Fever is seen with dinoprostone. When hyperthermia develops, it is important to distinguish between drug-induced fever and pyrexia resulting from endometritis. With dinoprostone, there is a 10% incidence of headache, shivering, and chills.
Precautions and Contraindications
Prostaglandins are contraindicated for women with active disease of the heart, lungs, kidneys, or liver. Carboprost should be avoided in women with a history of asthma or hypertension.
Preparations, Dosage, and Administration
Dinoprostone. Dinoprostone [Prepidil, Cervidil, Prostin E2 ] is available in three formulations: (1) 20-mg vaginal suppositories, (2) 10-mg vaginal inserts, and (3) a 0.5-mg gel. Dinoprostone suppositories [Prostin E2 ] are used for abortion. The gel [Prepidil] and vaginal inserts [Cervidil]
are used for cervical ripening.
For induction of abortion (weeks 12 to 20), one 20-mg vaginal suppository is inserted initially, followed by one suppository every 3 to 5 hours as needed.
Carboprost Tromethamine. Carboprost tromethamine [Hemabate] is available in solution (250 mcg/mL) for IM administration. For induction of abortion (weeks 13 to 20), the dosage is 250 mcg initially followed by 250 mcg every 1.5 to 3.5 hours as needed. For control of postpartum bleeding, a single 250-mcg dose is injected.
Misoprostol. Misoprostol [Cytotec] is available in 100- and 200-mcg tablets. For induction of abortion in the first trimester, misoprostol is used in combination with mifepristone; dosing options for misoprostol include 400 mcg PO and 800 mcg vaginally. For induction of abortion in the second trimester, the dosage is 200 mcg administered vaginally every 6 to 12 hours until abortion occurs.
Preparations, Dosage, and Administration
Mifepristone [Mifeprex] is supplied in single-dose packets containing three 200-mg tablets. The dosage is 600 mg taken all at once—followed in 2 days by 400 mcg of misoprostol (if mifepristone did not induce complete abortion by itself). Mifepristone is available only through qualified physicians; it is not sold in pharmacies.
FDA-Approved Protocol for Abortion
Under the FDA-approved protocol, induction of abortion with mifepristone/
misoprostol requires two visits to a qualified physician. To dispense mifepristone, a physician must be qualified to determine pregnancy duration and to diagnose ectopic pregnancy. In addition, the physician must either (1) be able to perform surgical abortion (in the event mifepristone/misoprostol fails) as well as curettage (in the event of severe bleeding) or (2) have a commitment from a colleague to perform these procedures.
Prostaglandins: Misoprostol, Carboprost, and Dinoprostone
Prostaglandins are synthesized in all tissues of the body, where they act as local hormones. Unlike true hormones, which travel to distant sites to produce their effects, prostaglandins act on the very tissues in which they are made;
degradation of prostaglandins is so rapid that they rarely escape their tissue of origin intact. Although the prostaglandins produce a broad spectrum of physiologic effects, their clinical use is limited. In obstetrics, prostaglandins are indicated for induction of abortion, cervical ripening before labor induction, and control of postpartum hemorrhage. The use of prostaglandins for abortion is discussed here. Their use for cervical ripening and control of postpartum hemorrhage is discussed in Chapter 64.
Nomenclature
Nomenclature regarding the prostaglandins can be confusing and hence deserves clarification. Each prostaglandin has three names: a traditional name, an official generic name, and a brand name. Misoprostol, carboprost, and dinoprostone are generic names. For carboprost, the traditional name is 15-methyl-prosta-glandin F2 alpha and the brand name is Hemabate. For dinoprostone, the traditional name is prostaglandin E2; brand names are Cervidil, Prepidil, and Prostin E2 . For misoprostol, a synthetic analog of prostaglandin E1, the brand name is Cytotec.
Physiologic and Pharmacologic Effects
Uterine Stimulation. Prostaglandins increase the force, frequency, and duration of uterine contractions. In the early months of pregnancy, the uterus is more responsive to prostaglandins than to oxytocin. During the second and third trimesters, prostaglandins can induce contractions of sufficient strength to cause complete evacuation of the uterus.
Like oxytocin, prostaglandins appear to have a physiologic role as promoters of uterine contraction, spontaneous labor, and delivery. Observations supporting this statement include: (1) Exogenous prostaglandins can induce uterine contractions that are very similar in frequency and duration to contractions that occur spontaneously; (2) the ability of the uterus to synthesize prostaglandins increases at term; (3) the prostaglandin content of amniotic fluid, umbilical blood, and maternal blood increases at term and during labor; and (4) labor is delayed and prolonged by agents that inhibit prostaglandin synthesis.
Cervical Softening. Local application of prostaglandins produces cervical softening. This softening results from breakdown of collagen and hence mimics the process by which natural cervical ripening occurs. Softening of the cervix does not depend on uterine stimulation.
Therapeutic Uses
Abortion. All three prostaglandins—misoprostol, carboprost, and dinoprostone—can be used to induce abortion. Misoprostol (in combination
KEY POINTS
■ The most effective methods of birth control are etono-gestrel subdermal implants [Nexplanon], intramuscular medroxyprogesterone acetate [Depo-Provera], IUDs, and sterilization. OCs and transdermal patches are a close second.
■ Sterilization is the most common form of birth control.
OCs and male condoms come next.
■ A long-term method of birth control (e.g., Nexplanon, Depo-Provera, IUD) is a good choice when adherence is a problem.
Continued
Summary of Major Nursing Implications
aCOMBINATION ORAL CONTRACEPTIVES Preadministration Assessment
Therapeutic Goal
Prevention of unwanted pregnancy.
Baseline Data
Assess for a history of hypertension, diabetes, thrombophle-bitis, thromboembolic disorders, cerebrovascular disease, coronary artery disease, breast carcinoma, estrogen-dependent neoplasm, and benign or malignant liver tumors.
Identifying High-Risk Patients
Absolute contraindications to OC use are thromboembolic disorders, cerebrovascular disease, coronary occlusion, abnormal liver function, known or suspected breast carcinoma, undiagnosed abnormal genital bleeding, known or suspected pregnancy, and smokers older than 35. Relative contraindica-tions are diabetes, hypertension, cardiac disease, history of cholestatic jaundice of pregnancy, gallbladder disease, uterine leiomyoma, epilepsy, and migraine.
Women anticipating elective surgery in which postoperative immobilization increases the risk of thrombosis should stop OCs before surgery.
Implementation: Administration Dosing Schedule
Provide the patient with the following dosing instructions:
• Initiate dosing on the first day of menses, or the first Sunday after the onset of menses.
• For most combination OCs, the approved dosing schedule consists of 21 days of active drug followed by 7 days off
(for the 7 “off” days, the manufacturer may provide inert tablets, iron-containing tablets, or no tablets).
• For all OCs, take pills at the same time each day (e.g., with a meal, at bedtime).
Responding to Missed Doses
For women using a 28-day-cycle combination OC—except Natazia—provide the following instructions regarding missed doses:
• If 1 or more pills are missed in the first week, take 1 pill as soon as possible and then continue with the pack. Use an additional form of contraception for 7 days.
• If 1 or 2 pills are missed during the second or third week, take 1 pill as soon as possible and then continue with the active pills in the pack—but skip the placebo pills and go straight to a new pack once all the active pills have been taken.
• If 3 or more pills are missed during the second or third week, follow the same instructions given for missing 1 or 2 pills, but use an additional form of contraception for 7 days.
Note: The response to a missed dose of Natazia is more complex than with other combination OCs. Consult the package insert for details.
Inform women using an extended-cycle or continuous OC that once the pills have been taken daily for at least 3 weeks, up to 7 days can be missed with little or no increased risk of pregnancy.
Postpartum Use
Inform the patient that OCs can be initiated 2 weeks after delivery if breast-feeding is not intended. (For breast-feeding
progestin-only OCs (aka minipills).
■ Almost all combination OCs use the same estrogen:
ethinyl estradiol. In contrast, eight different progestins are employed.
■ Combination OCs act primarily by inhibiting ovulation.
■ Although combination OCs can cause a variety of adverse effects, serious events are rare.
■ Thrombotic events with combination OCs are caused by the progestin as well as the estrogen.
■ The risk of thrombotic events is lowest with combination OCs that (1) have a low dose of estrogen and (2) contain a first-generation progestin. Conversely, risk is high with OCs that contain drospirenone or desogestrel.
■ The risk of thrombotic events is increased in women who smoke and in those with thrombophilias.
■ When used by nonsmoking women with normal cardio-vascular function, OCs produce no greater mortality than other active forms of birth control.
■ Combination OCs protect against ovarian and endometrial cancer and do not increase the risk of breast cancer.
■ OCs are contraindicated during pregnancy, not because they are dangerous, but because they have no legitimate use during pregnancy. If accidental pregnancy occurs, OCs should be discontinued.
nobarbital, St. John’s wort).
■ Because they lack estrogen, progestin-only OCs are safer than combination OCs—but are less effective and cause more menstrual irregularity.
■ Progestin-only OCs prevent pregnancy by causing produc-tion of thick, sticky mucus (which creates a barrier to migration of sperm) and by suppressing endometrial growth (which discourages nidation).
■ Subdermal etonogestrel implants [Nexplanon] are active for 3 years and are among the most effective contraceptives available.
■ Nexplanon has the same mechanism as progestin-only pills:
production of thick, sticky mucus and involution of the endometrium.
■ Injectable medroxyprogesterone acetate [Depo-Provera]
is active for 3 months and is one of the most effective contraceptives available.
■ Depo-Provera prevents pregnancy mainly by suppressing ovulation. In addition, it thickens cervical mucus and alters the endometrium such that nidation is discouraged.
Please visit http://evolve.elsevier.com/Lehne for chapter-specific NCLEX® examination review questions.
CHAPTER 62 Birth Control
patients, the progestin-only minipill can be started immediately postpartum.)
Promoting Adherence
Counsel the patient about the importance of taking OCs as prescribed. Encourage the patient to read the package insert provided with combination OCs.
Ongoing Evaluation and Interventions Minimizing Adverse Effects
Thrombotic Disorders. Combination OCs slightly increase the risk of thrombosis and thromboembolism. To minimize the risk of a thrombotic event, (1) use OCs of low estrogen content, (2) avoid OCs that contain drospirenone or desogestrel, (3) avoid OCs in women with known risk factors for thrombotic disorders, and (4) discontinue OCs at least 4 weeks before elective surgery in which postoperative thrombosis might be expected. Inform the patient about symptoms of thrombosis and thromboembolism (e.g., leg tenderness or pain, sudden chest pain, shortness of breath, severe headache, sudden visual disturbance), and instruct her to notify the prescriber if these develop.
Hypertension. Perform periodic determinations of blood pressure. If hypertension is detected, discontinue OCs. Blood pressure usually normalizes. However, for women with chronic hypertension, OCs can be used as long as the blood pressure is normal.
Abnormal Uterine Bleeding. During initial use, combina-tion OCs may cause breakthrough bleeding or spotting. This usually resolves with continued use. Bleeding is less likely with low-estrogen OCs.
Instruct the patient to notify the prescriber if two consecu-tive periods are missed; the possibility of pregnancy must be evaluated.
Instruct the patient to notify the prescriber if bleeding irregularities persist; an alternative OC may be tried.
Inform the patient that once OCs are discontinued, menses quickly return to normal.
Use in Pregnancy and Lactation. OCs are contraindi-cated during pregnancy, not because they are dangerous, but because they have no therapeutic role. Pregnancy should be ruled out before OC use. Instruct the patient to discontinue OC use if accidental pregnancy should occur.
Inform the patient that OCs can reduce milk production early in lactation. Once the milk supply is established, OC use can be resumed.
Stroke in Women With Migraine. When used by women with migraine, OCs may increase the risk of thrombotic stroke.
To minimize risk, OCs should be reserved for migraineurs who are under age 35, don’t smoke, are generally healthy, and have migraine without aura.
Hyperkalemia. Combination OCs that contain drospi-renone (e.g., YAZ) pose a risk of hyperkalemia and hence should not be used by (1) women with conditions that pre-dispose to hyperkalemia (e.g., renal insufficiency, adrenal insufficiency, liver disease) or by (2) women taking drugs that can increase potassium levels (see Drugs That Elevate Potassium, later).
Summary of Major Nursing Implications
a—cont’d
aPatient education information is highlighted as blue text.
Minimizing Adverse Interactions
Agents That Reduce OC Levels. Levels of OCs can be reduced by agents that induce hepatic drug-metabolizing enzymes (e.g., phenobarbital, phenytoin, troglitazone, rifampin, ritonavir, St. John’s wort). Advise women who are taking these agents to be alert for indications of reduced OC levels (e.g., breakthrough bleeding, spotting) and to notify the prescriber if these occur. An increase in OC dosage or the use of an alternative method of birth control may be required.
Drugs Whose Effects Are Reduced by OCs. OCs can reduce the effects of some drugs, including warfarin, insulin, and some oral hypoglycemics. When combined with OCs, these drugs may require a greater-than-normal dosage.
Drugs Whose Effects Are Increased by OCs. OCs can increase blood levels of several drugs, including theophylline and imipramine. Women using these drugs in combination with OCs should be alert for signs of toxicity; dosage reduction for theophylline or imipramine may be required.
Drugs That Elevate Potassium. Drugs that elevate serum potassium (e.g., potassium supplements, potassium-sparing diuretics, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers) should be avoided by women using OCs that contain drospirenone, which promotes potassium retention.
PROGESTIN-ONLY ORAL CONTRACEPTIVES Preadministration Assessment
Therapeutic Goal
Prevention of unwanted pregnancy.
Implementation: Administration Dosing Schedule
Instruct the patient to initiate the minipill on day 1 of the menstrual cycle and to take 1 pill every day thereafter. Pills should be taken at the same time each day (e.g., with a meal, at bedtime).
Responding to Missed Doses
Provide the patient with the following instructions regarding missed doses:
• If 1 pill is missed, take it as soon as the omission is remem-bered. Use a backup form of contraception for 2 days.
• If 2 pills are missed, take 2 pills as soon as the omission is remembered, and use a backup form of contraception for 2 days.
• If 3 pills are missed, the minipill should be stopped. Do not resume use until menstruation occurs or until pregnancy has been ruled out.
Ongoing Evaluation and Interventions Minimizing Adverse Effects
Menstrual Irregularities. Breakthrough bleeding, spotting, amenorrhea, inconsistent cycle length, and variations in the amount and duration of monthly flow are common and unavoid-able. Forewarn the patient of these effects.
63 Drug Therapy for Infertility
Infertility: Causes and Treatment Strategies, p. 770 Female Infertility, p. 770
Male Infertility, p. 771
Drugs Used to Treat Female Infertility, p. 771 Drugs for Controlled Ovarian Stimulation,
p. 771
Dopamine Agonists for Hyperprolactinemia, p. 774
Drugs for Endometriosis, p. 775 Key Points, p. 776
Summary of Major Nursing Implications, p. 776
and growth and development of the conceptus. These events can take place only if the ovaries, uterus, hypothalamus, and pituitary are functioning properly. If the activity of any of these structures is disturbed, fertility can be impaired.
Anovulation and Failure of Follicular Maturation In the absence of adequate hormonal stimulation, ovarian follicles will not ripen and ovulation will not take place.
Frequently, these causes of infertility can be corrected with drugs. The agents used to promote follicular maturation and/
or ovulation are clomiphene, menotropins, follitropins (e.g., urofollitropin), and human chorionic gonadotropin (hCG).
Clomiphene induces follicular maturation and ovulation by promoting release of FSH and LH from the pituitary gland;
in some cases, induction of ovulation requires co-treatment with hCG. Menotropins and follitropins are used in conjunction with hCG: Menotropins and follitropins act directly on the ovary to promote follicular development; after follicles have matured, hCG is given to induce ovulation. Because hCG acts on mature follicles to cause ovulation, the drug is used only after follicular maturation has been induced with another agent (menotropins, a follitropin, or clomiphene). The pharmacology of clomiphene, menotropins, follitropins, and hCG is discussed later in this chapter.
Unfavorable Cervical Mucus
In the periovulatory period, the cervical glands normally secrete large volumes of thin, watery mucus. These secretions, which are produced under the influence of estrogen, facilitate passage of sperm through the cervical canal. If the cervical mucus is scant or of inappropriate consistency (thick, sticky), sperm will be unable to pass through to the uterus. Production of unfavorable mucus may occur spontaneously or as a side effect of clomiphene.
Cervical mucus can be restored to its proper volume and consistency by administering estrogen. Two regimens have been employed. In one, ethinyl estradiol is given beginning early in the menstrual cycle (on day 6, 7, or 8) and continued through day 12 or 13; dosages range from 20 to 80 mcg/day.
In the other regimen, conjugated estrogens are administered from day 5 through day 15 of the cycle; dosages range from 2.5 to 5 mg/day. When used to counteract the effects of clo-miphene on the cervical mucus, estrogens are administered for 10 days beginning 1 day after the last clomiphene dose.
Hyperprolactinemia
Elevation of prolactin levels may be caused by a pituitary adenoma or by disturbed regulation of the healthy pituitary gland. Amenorrhea, galactorrhea, and infertility may all occur in association with excessive prolactin. The mechanism by which hyperprolactinemia impairs fertility is unknown. Hyper-prolactinemia can be treated with cabergoline, bromocriptine, and other dopamine agonists.
Infertility (subfertility) is defined as a decrease in the ability to reproduce. This contrasts with sterility, which is the complete absence of reproductive ability. About 10% of couples attempt-ing to have children experience infertility. Failure to conceive may be due to reproductive dysfunction of the male partner, the female partner, or both. When medical treatment is imple-mented, approximately one-half of infertile couples achieve pregnancy. So far, drug therapy of female infertility has been considerably more successful than drug therapy of male infertility.
In treating infertility, the chances of success are greatly enhanced by accurate diagnosis. A thorough history of both partners is essential, including information on frequency and timing of coitus and the use of drugs that might lower fertility.
Routine evaluation should include a semen analysis, determina-tion of fallopian tube patency, and assessment of ovuladetermina-tion. If the patient reports regular menstrual cycles, ovulation is presumed, and hence there is no need to determine estrogen and progesterone levels.
In this chapter, we discuss infertility in two stages. First, we discuss the underlying causes of reproductive dysfunction.
Second, we discuss the fertility-promoting drugs. As preparation to study these agents, you should review Chapter 61 for information on the menstrual cycle and information on the biosynthesis and physiologic and pharmacologic effects of estrogens and progestins. Pay special attention to the roles of gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH).
INFERTILITY: CAUSES AND TREATMENT STRATEGIES Female Infertility
Female infertility can result from dysfunction in all phases of the reproductive process. The most critical phases are follicular maturation, ovulation, transport of the ovum through the fal-lopian tubes, fertilization of the ovum, nidation (implantation),