Implantable Contraception

Abstract

Contraceptive implants are progestin-based, highly effective, and rapidly reversible methods of contraception that require little of the user and have few side effects. Over the past 35 years they have been approved in more than 60 countries and used by millions of women worldwide (Meirik et al., Hum Reprod Update 9(1):49–59, 2003). Their high efficacy along with ease of use makes them a good contraceptive option for women who require progestin-only methods, teens who find adherence to a contraceptive regime difficult, as well as healthy adult women who desire long-term protection. In most countries, two different contraceptive implants are available: the single-rod etonogestrel implant and the two-rod levonorgestrel system. The pharmacological profile and physical effects of all the implantable contraceptives are similar. While the etonogestrel implant is the only form of implantable contraception available in the United States (and the focus of this chapter), clinicians may encounter other systems in use worldwide.

Introduction

Contraceptive implants are progestin-based, highly effective, and rapidly reversible methods of contraception that require little of the user and have few side effects. Over the past 35 years they have been approved in more than 60 countries and used by millions of women worldwide [1]. Their high efficacy along with ease of use makes them a good contraceptive option for women who require progestin-only methods, teens who find adherence to a contraceptive regime difficult, as well as healthy adult women who desire long-term protection. In most countries, two different contraceptive implants are available: the single-rod etonogestrel implant and the two-rod levonorgestrel system. The pharmacological profile and physical effects of all the implantable contraceptives are similar. While the etonogestrel implant is the only form of implantable contraception available in the United States (and the focus of this chapter), clinicians may encounter other systems in use worldwide.

History of Implantable Contraception

Norplant, a six-capsule-implantable system containing 216 mg of levonorgestrel, was developed by the Population Council and first approved in 1983 in Finland, where it was manufactured. The United States Food and Drug Administration (US FDA) approved it in 1990, but the distributor withdrew it from the market in 2002. Over one million US women chose Norplant as their contraceptive. Norplant proved highly effective; over a 7-year duration of use, only about 1 % of users became pregnant [2]. Despite low rates of pregnancy and few serious side effects, limited supplies of the silastic components and unwarranted negative media coverage led to Norplant’s withdrawal from distribution in 2002, leaving no implant alternative for American women [3]. Production of Norplant was discontinued worldwide in 2008.

The 15-year experience with Norplant instigated further development and improvements in implant design. A two-rod levonorgestrel system (Jadelle) was also developed by the Population Council and manufactured in Finland. It was approved in the United States in 1998, but never marketed. Jadelle is effective for 5 years and was first registered for this length of use in the year 2000. Sino-implant (II) is a two-rod levonorgestrel implant system designed to imitate the performance of Jadelle. It is manufactured in China and is substantially less expensive than Jadelle (US$8 compared with US$23) [4]. This levonorgestrel implant has the potential to improve access to contraceptive implants in resource-poor settings.

In 2006, the US FDA approved Implanon, a single-rod etonogestrel implant. Implanon’s single rod provided great improvements over the previously available six capsule Norplant system in time and ease of insertion [5, 6]. The etonogestrel implant inserter is preloaded and disposable. Since only one rod is implanted, there is no chance of moving previously placed capsules out of position with insertion of additional ones. It is not necessary, as it was with Norplant, to create channels under the skin with local anesthetic, which made implants difficult to palpate right after insertion. In addition, ethylene vinyl acetate, the plastic from which Implanon is made, is less likely than Norplant’s silastic to form a fibrous sheath that can prolong removals [7]. These differences simplify the insertion and removal technique for the etonogestrel implant. For patients this simplicity means little discomfort at insertion or removal, an unobtrusive implant, and almost no scarring. For clinicians, it means simpler insertion and removal procedures of predictably short duration. The etonogestrel implant has subsequently been modified and marketed as Nexplanon. In December 2012, Merck stopped supplying Implanon to its distributors, whose supply was exhausted in early 2013. Implanon is no longer available for purchase in the United States. Implanon and Nexplanon are bioequivalent, but Nexplanon is radio-opaque and is preloaded into a simpler inserter that helps insure subdermal placement.

Candidates for Implantable Contraception

Contraceptive implants are a good choice for women of reproductive age who are sexually active and desire long-term, continuous contraception. Implants should be considered for women who:

• 1. Desire a highly effective, long-term method of contraception.

• 2. Experience serious or minor estrogen-related side effects with estrogen-progestin contraception.

• 3. Prefer a method that does not require repeated adherence.

• 4. Desire a non-coitus-related method of contraception.

• 5. Have completed their childbearing but are not yet ready to undergo permanent sterilization.

• 6. Have a history of anemia with heavy menstrual bleeding.

• 7. Intend to breastfeed.

• 8. Have chronic illnesses, in which health will be threatened by pregnancy.

Most women are candidates for implantable contraception; there are few medical disorders where the risk of the method exceeds the benefit (e.g., current breast cancer). For clinicians in the United States, the Centers for Disease Control and Prevention (CDC) has listed these conditions on its Web site in the table, “United States Medical Eligibility Criteria (USMEC) for Contraceptive Use” [8]. Standard contraindications to use of hormonal contraceptives are:

• 1. Known or suspected pregnancy.

• 2. Current or past history of thrombosis or thromboembolic disorders.

• 3. Hepatic tumor or active liver disease.

• 4. Undiagnosed abnormal genital bleeding.

• 5. Known or suspected breast cancer or history of breast cancer.

• 6. Hypersensitivity to any component of the method.

Large epidemiologic studies have not identified an increased risk of stroke, myocardial infarction, or venous thromboembolism in users of progestin-only oral contraceptives [9–11] and none of these events occurred in any of the trials on which approval of implants was based [12]. For this reason, the World Health Organization (WHO) and the CDC have indicated progestin-only contraceptives represent a reasonable contraceptive choice for women with risk factors for, or a past history of, venous thromboembolic disease [8, 13]. Subsequently published data support this conclusion [14].

This recommendation differs from Nexplanon package labeling, which lists current or past thrombosis as a contraindication to use. Etonogestrel is the biologically active metabolite of the synthetic progestin desogestrel. Controversy remains as to whether desogestrel or its derivatives may be associated with an increased risk of venous thromboembolism compared with other progestins. Evidence of this increased risk comes from studies of oral contraceptives where desogestrel is administered in combination with ethinyl estradiol, rather than alone as in the implant [15].

Women with Chronic Medical Conditions

Implant contraceptives specifically can be a good choice for women with chronic illnesses because, aside from their need for highly effective contraception, there are no clinically significant metabolic changes associated with the sustained, low doses of progestin delivered by the implant. Studies of liver function, blood coagulation, immunoglobulin levels, serum cortisol levels, and blood chemistries have failed to detect changes outside of normal ranges and the etonogestrel implant has not been found to have important clinical effects on the lipoprotein profile, carbohydrate metabolism, thyroid and adrenal function, liver function, or the clotting mechanism [16]. A literature review concluded that the etonogestrel implant does not appear to have clinically significant effects on lipid metabolism or liver function, although there may be small changes in laboratory values [17]. These findings suggest that implant contraceptives are safe for woman at risk for metabolic, cardiovascular, or thromboembolic disorders.

For diabetics whose disease is well controlled by insulin or diet, implant contraceptives are a good choice. Although it is known that progestins can affect carbohydrate metabolism, most effects are seen with high doses of androgenic progestins, not the low doses found in implants nor with the less-androgenic etonogestrel used in Nexplanon.

Lactating Women

As progestin-only methods, the contraceptive implants are a good choice for breastfeeding women given that they do not interfere with breast milk production. Studies show no effects on breast milk quality or quantity, and infants of mothers with implants grow normally [18, 19]. Implants also seem to be a good choice for immediate postpartum administration. A small study comparing immediate postpartum insertion of the etonogestrel implant to depot medroxyprogesterone acetate at 6 weeks showed no impact on continuation of exclusive breastfeeding at 12 weeks and normal infant weight gain [20]. The World Health Organization (WHO) recently updated the recommendations on timing for postpartum initiation of progestin implants: Category 2 for < 6 weeks postpartum and category 1 for > 4 weeks postpartum [21]. The etonogestrel implant does not affect breastfeeding outcomes when placed in the immediate postpartum period (within 1–3 days of delivery) compared with delayed insertion (4–8 weeks) [22]. Immediate placement has also been found to be cost-effective when compared with delayed insertion [23, 24].

Adolescents

Adolescents are ideal candidates for contraceptive implants, as it is a method that does not require repeated adherence and offers a discrete method of highly effective contraception. Teens most frequently use methods with high failure rates, including condoms, withdrawal, and oral contraceptive pills [25]. Long-acting reversible contraception, including implants and intrauterine devices, has a high uptake among adolescents, with younger teens choosing the implant more commonly [26]. The etonogestrel implant is well accepted by postpartum teens as well [27]. Women under age 18 years have no medical contraindication to implantable contraception based on age alone and the American College of Obstetricians and Gynecologists recommends offering implants as a first-line method for teens seeking contraception [8, 28]. Despite the benefits and acceptability of implantable contraception, less than 1 % of current contraceptors and only 0.5 % of adolescents choose this method [29]. Recent studies indicate that use of implantable contraception has been increasing [30].

Pharmacology

The Nexplanon implant is 40 mm × 2.0 mm and consists of one nonbiodegradable rod of 40 % ethylene vinyl acetate and 60 % etonogestrel (the 3-keto derivative of desogestrel), covered with a rate-controlling ethylene vinyl acetate membrane 0.06 mm thick. The rod contains 68 mg etonogestrel that is slowly released over at least 3 years: initially at 60–70 mcg/day, decreasing to 35–45 mcg/day at the end of the first year, to 30–40 mcg/day at the end of the second year, and then to 25–30 mcg/day at the end of the third year (Fig. 9.1) [31]. The high initial rate of absorption is probably due to a significant amount of etonogestrel released from the uncovered ends of the implant. Peak serum concentrations (266 pg/mL) of etonogestrel are achieved within 1 day after insertion, suppressing ovulation, which requires only 90 or more pg/mL [32].

Fig. 9.1

Mean (±SD) serum concentration-time profile of etonogestrel after insertion of Nexplanon during 3 years of use

Etonogestrel is approximately 32 % bound to sex hormone binding globulin (SHBG) and 66 % bound to albumin in blood. Like other contraceptive steroids, serum levels of etonogestrel are reduced in women taking liver enzyme-inducing drugs such as rifampicin, griseofulvin, phenytoin, and carbamazepine, but are not affected by antibiotics. Steady release of etonogestrel into the circulation avoids first-pass effects on the liver. Bioavailability of etonogestrel remains nearly 100 % throughout 2 years of use. The elimination half-life of etonogestrel is 25 h, compared with 42 h for Norplant’s levonorgestrel. After implant removal, serum etonogestrel concentrations become undetectable within 1 week. Return of ovulation occurs in 94 % of women within 3–6 weeks after method discontinuation [32, 33]. Unlike Implanon or the levonorgestrel implants, the Nexplanon rod is radio-opaque so it can be detected by X-ray and thus does not require magnetic resonance imaging (MRI) for locating a malpositioned impalpable implant.

Mechanism of Action

Implants are highly effective progestin-only contraceptives that come in the form of one or more subdermally placed rods. The progestin diffuses from the implant into the surrounding tissues where it is absorbed by the circulatory system and distributed systemically, providing an initial level in the circulation that is lower than with oral or injected steroids. The release rate of the contraceptive implants is determined by total surface area and the density of the plastic (silastic or ethylene vinyl acetate) in which the progestin is contained. Implants are more effective than other methods because they do not require regular action by the user and because they have multiple modes of action.

Progestin-containing implants have two primary mechanisms of action: inhibition of ovulation and restriction of sperm penetration through cervical mucus [34]. Antiestrogenic actions of the progestins affect the cervical mucus, making it viscous, scanty, and impenetrable by sperm thus inhibiting fertilization [35]. At high doses, progestins also inhibit gonadotropin secretion, thereby inhibiting follicular maturation and ovulation [36]. This dual effect allows contraceptive efficacy to be maintained even though ovulation is not consistently inhibited in etonogestrel implant users toward the end of the 3-year period of use. Even if follicles grow during use of progestin implants, oocytes are not fertilized. If the follicle ruptures, the abnormalities of the ovulatory process prevent release of a viable egg. Although progestins suppress endometrial activity, which makes the endometrium unreceptive to implantation, this is not a contraceptively important effect since the major mechanisms of action prevent fertilization [37]. No signs of embryonic development have been found among implant users, indicating that progestin implants have no abortifacient properties.

Efficacy

General Population

The etonogestrel implant is among the most effective contraceptives available (Table 9.1) and is as good as or better than sterilization procedures [36].

Table 9.1 Percentage of women experiencing an unintended pregnancy during the first year of typical use and the first year of perfect use of contraception and the percentage continuing use at the end of the first year (United States)

An analysis of 11 clinical trials in which 942 women enrolled for 2–4 years showed the etonogestrel implant was well tolerated and effective: no pregnancies occurred while women were using this method of contraception [12]. Six pregnancies have been reported during the first 14 days after implant removal. The manufacturer cites a Pearl Index of 0.38 pregnancies per 100 women-years of use, which is similar to that of other long-acting methods of contraception. New data indicate that the etonogestrel implant’s efficacy at pregnancy prevention continues for 5 years (Table 9.2) [37]. Method failure pregnancies may be intrauterine or extrauterine [38]. An important reason for the etonogestrel implant’s high efficacy in actual use is the nature of the delivery system itself, requiring little effort on the part of the user. Because compliance does not require frequent resupply or instruction in use, as with oral contraception, the actual or typical use effectiveness is very close to the theoretical (lowest expected) effectiveness.

Table 9.2 Efficacy of implantable contraception at 36, 48, and 60 months

Overweight and Obese Women

The etonogestrel implant is not contraindicated in obese women. Although the effectiveness of the etonogestrel implant has not been adequately studied in women more than 130 % of their ideal body weight (body mass index [BMI] >30 kg/m²), available data show no decrease in contraceptive efficacy even though etonogestrel concentration is affected by weight. Etonogestrel concentrations do not decline below contraceptive levels as body weight increases, nor is there an increased risk of difficult insertions or removals with increasing BMI [39].

Drug Interactions Impacting Efficacy

Contraceptive efficacy may be decreased in women taking medications that affect the metabolism of etonogestrel. One case report of contraceptive failure occurred in a woman on carbamazepine for a seizure disorder who had had an etonogestrel implant in place for 25 months [40]. Another case report described contraceptive failure in two human immunodeficiency virus (HIV)-positive women using the etonogestrel implant and on antiretroviral therapy (efavirenz-zidovudine-lamivudine in one woman and efavirenz-emtricitabine-tenofovir in the other) [41]. Both implants appeared to be correctly positioned and there was no obvious reason for the contraceptive failures other than a possible decrease of etonogestrel efficacy related to administration of hepatic enzyme-inducing antiretroviral medications. Although it is not currently possible to assess the magnitude of the risk of contraceptive failure in this setting, prospective users taking antiretrovirals should be informed that effavirenz use accelerates etonogestrel metabolism and greatly increases implant failure rates. This risk does not preclude use of implants as they remain highly effective for most women on antiretroviral and antiseizure drugs. Furthermore, HIV-positive women are typically advised to use condoms to protect against transmission of HIV and other sexually transmitted infections; thus they typically have backup contraceptive protection.

Counseling

Irregular Bleeding

Unscheduled bleeding is a common side effect, which may or may not decrease with continued use. Because implants allow for follicular development but not ovulation, endogenous estrogen production is nearly normal, and unlike the combined estrogen-progestin contraceptives, progestin is not regularly withdrawn to allow endometrial sloughing. Consequently, the endometrium sheds at unpredictable intervals and menstrual bleeding patterns can be highly variable among users of implant contraception. Changes include alterations in the interval between bleeding, the duration and volume of menstrual flow, and spotting.

In the analysis of 11 clinical trials, unscheduled bleeding was the primary reason for discontinuation, with a rate of 14.8 % in the United States and Europe, but only 3.7 % in Southeast Asia, Chile, and Russia [12]. United States users were more likely to discontinue because of prolonged or heavy bleeding than women from other countries (7.0 vs. 4.3 %). The mean number of bleeding and spotting days per 90-day reference period was 7.3 and 10.4 days, respectively. One third of 90-day reference periods had fewer than three bleeding/spotting episodes; one fifth had no bleeding/spotting (amenorrhea); 17 % had a bleeding episode that lasted more than 14 days; and 6 % had more than five bleeding/spotting episodes. The number of unscheduled bleeding days was highest in the first 3 months of use, decreased during the first year of use, and then plateaued for the second and third years of use. However, this decrease may have resulted from patients discontinuing as a result of a bleeding irregularity, leaving for analysis those less likely to experience bleeding. Although amenorrhea occurs in approximately 20 % of women in the first year of use, the rates of amenorrhea actually decline with duration of use to 13 % by year 3 [42].

Women who experienced more days of bleeding were more likely to discontinue, especially if the bleeding was prolonged. For example, the mean number of bleeding/spotting days in women who discontinued and who continued implant use during a 90-day reference period was 45.2 and 16.5 days, respectively. Frequent or prolonged bleeding/spotting was reported in about 90 % of women who discontinued the implant but in only 22 % of those who continued its use [43].

Management of Irregular Bleeding

Treatment of unscheduled bleeding is not necessary, but since bleeding disturbances are the principal cause of discontinuation, several approaches to their treatment have been used. For women who have no contraindications to estrogen, prolonged bleeding may be treated with a short course of oral estrogen: conjugated estrogens, 1.25 mg, or estradiol, 2 mg, administered daily for 7 days [44]. An alternative approach is to administer an estrogen-progestin oral contraceptive for 1–3 months. Studies have also shown some benefit with mifepristone, doxycycline, and NSAIDs but estrogen is probably the most effective treatment. A pragmatic approach to the management of unscheduled bleeding is outlined in Table 9.3 [43].

Table 9.3 A pragmatic approach to manage unscheduled bleeding in women using the etonogestrel implant

Other Side Effects

The most common adverse events besides unscheduled bleeding that were deemed possibly, probably, or definitely related to the etonogestrel implant included headache (16 %), weight gain (12 %), acne (12 %), breast tenderness (10 %), emotional lability (6 %), and abdominal pain (5 %) [12].

The etonogestrel implant does not induce bone loss. In contrast, depot medroxyprogesterone acetate (DMPA), another progestin-only contraceptive that reduces estrogen levels, is associated with a decrease in bone mineral density.

There is conflicting evidence about whether or not DMPA increases the risk of human immunodeficiency virus (HIV) acquisition and transmission compared to noncontraceptive users [45, 46]. There is no evidence that other contraceptive progestins at lower doses, such as the etonogestrel implant, have similar effects.

A large epidemiologic study using registry data from Denmark did not find an increased risk of arterial events among 24,954 implant users compared with over 9 million nonusers of hormonal contraception [14]. For thrombotic stroke, there were three events among users, incidence 12/100,000 person years, RR 0.88, 95 % CI 0.28–2.72; for myocardial infarction, there were three events among users, incidence 12/100,000 person years, RR 2.14, 95 % CI 0.69–6.65.

Sexually Transmitted Infections

Sexually active women are exposed to the risk of pregnancy as well as to the risk of sexually transmitted infections (STIs), such as HIV, hepatitis B, human papillomavirus, Chlamydia trachomatis, syphilis, and gonorrhea, whose sequelae may be life threatening. Implantable contraceptives neither increase the risk of nor offer protection against STIs [47]. Women counseled about contraception should also be informed about the risks of STIs. They should be advised that use of condoms concomitantly with an effective method of pregnancy prevention is the best means of protection against unintended pregnancy and STIs. It seems likely that the etonogestrel implant, like oral contraceptive pills and DMPA, reduces the risk of pelvic upper tract infection (PID), probably because of progestin effects on cervical mucus.

Initiation

For healthy women, no physical examination or laboratory tests are indicated before insertion of an etonogestrel implant [48]. Although some medical conditions represent contraindications to hormone use [8], the low prevalence of these conditions in asymptomatic reproductive age women does not warrant screening for these conditions by physical examination or laboratory testing for the safe initiation of implants.

The possibility of early pregnancy can generally be assessed by review of the woman’s menstrual, sexual, and contraceptive history. The absence of pregnancy can be reasonably inferred if she meets any of the criteria in (Box 1). An appropriately timed pregnancy test (at least 2 weeks after the last episode of sex) can be obtained if the absence of pregnancy is uncertain. There is no evidence that the etonogestrel implant or other hormonal contraceptives have caused abnormal fetal development. Most of the few pregnancies reported among etonogestrel implant users were present before insertion.

The implant can be inserted at any time as long as the clinician is reasonably certain that the patient is not pregnant. Women who are postabortion (either medical or surgical) or postpartum (even if breastfeeding) can have the implant inserted immediately after termination of pregnancy or delivery [8].

Backup Contraception

Abstinence or backup contraception is suggested for the first 7 days after insertion if the implant is inserted more than 5 days since the beginning of the patient’s last menstrual period [8, 46] although data to support this need is lacking [49]. This conservative approach is recommended because changes in cervical mucus are probably complete within 36 h of insertion. Options for backup contraception include use of condoms or continued use of the woman’s previous method of contraception. For women who are more than 3 weeks postpartum, not exclusively breastfeeding, and have not resumed menses, backup contraception is suggested. For women who are postpartum, exclusively breastfeeding, and have not resumed menses, backup contraception is suggested for those who are more than 6 months postpartum. For women who are postabortion, 7 days of backup contraception is also recommended if the implant is not placed on the day of the abortion.

If the woman has been using an intrauterine device (IUD) and is switching to the implant, she may have residual sperm in her reproductive tract, which could result in fertilization and implantation if the IUD is removed. Options include:

• Advise the woman to retain the IUD for at least 7 days after the implant is inserted and then return for IUD removal.

• Advise the woman to abstain from sexual intercourse or use barrier contraception for 7 days before removing the IUD and switching to the implant. Adding backup contraception for 7 days is suggested if the implant is inserted more than 5 days since the beginning of the patient’s last menstrual period.

• Advise the woman to use emergency contraception at the time of IUD removal and use backup contraception for 7 days if the implant is inserted more than 5 days since the beginning of the patient’s last menstrual period.

Box 1 How to be reasonably certain that a woman is not pregnant

A health-care provider can be reasonably certain that a woman is not pregnant if she has no symptoms or signs of pregnancy and meets any one of the following criteria:

• Is ≤7 days after the start of normal menses.

• Has not had sexual intercourse since the start of last normal menses.

• Has been correctly and consistently using a reliable method of contraception.

• Is ≤7 days after spontaneous or induced abortion.

• Is within 4 weeks postpartum.

• Is fully or nearly fully breastfeeding (exclusively breastfeeding or the vast majority [≥85 %] of feeds are breastfeeds),* amenorrheic, and <6 months postpartum.

*Source: Labbok M, Perez A, Valdez V, et al. The Lactational Amenorrhea Method (LAM): a postpartum introductory family planning method with policy and program implications. Adv Contracept 1994;10:93–109.

Insertion

Insertion of Nexplanon is a brief office procedure performed under local anesthesia. A clinician who has been trained in the technique can do it in less than 1 min [50]. The US Food and Drug Administration (FDA) and Nexplanon’s maker, Merck, agreed that Implanon and Nexplanon would be distributed only to clinicians who have received 3 h of training in patient selection, counseling, insertion, and removal. Those already trained for Implanon can take an online course to qualify for use of Nexplanon (www.nexplanon-usa.com). Questions regarding training can be answered at 1-877-467-5266. Merck is required to coordinate and provide instructors and materials for training, as well as to monitor clinician reporting of adverse events. This reporting system has not revealed any unexpected problems with insertion or removal of Implanon or Nexplanon.

Required Equipment for Etonogestrel Implant Insertion

• A 25-gauge needle (1.5 in. in length) attached to a 2–5 mL syringe.

• 1 % Chloroprocaine or lidocaine without epinephrine.

• Antiseptic solution (e.g., povidone-iodine, chlorhexidine gluconate, isopropyl alcohol).

• An adhesive strip for closure of the puncture site.

• Elastic pressure bandage (e.g., “Kerlix”).

• Surgical gloves (need not be sterile).

• Sterile drape.

• Sterile, preloaded Nexplanon applicator.

Positioning the Patient

The patient is placed in a supine position with the full length of her arm exposed. The manufacturer suggests positioning the upper inner arm by bending the elbow to 90° and rotating the arm out. Some providers find the procedure is easier when the arm is extended, allowing full exposure of the insertion site at the crease between the biceps and triceps muscles. Adequate support under the arm should be provided to ensure comfort with, e.g., a thick book. An insertion site approximately four fingerbreadths superior and lateral to the medial epicondyle of the humerus is identified. The site should be at least 6 cm and no more than 10 cm from the medial epicondyle (Fig. 9.2). The optimum site depends upon an individual woman’s anatomy, such as the length of the upper arm (avoid placing the end of the implant too near the axilla) and the area where the crease between the biceps and triceps muscles is clearest.

Fig. 9.2

The insertion site should be at least 6 cm and no more than 10 cm from the medial epicondyle

To minimize the risk of infection, strict aseptic technique should be maintained throughout the procedure, e.g., do not touch the trocar containing the implant. A sterile drape is placed under the arm, and the insertion site on the arm is cleaned with an antiseptic such as povidone-iodine.

Some clinicians mark the skin to help guide insertion. One mark is made where the rod will be inserted and a second mark is made a few centimeters proximal to the first mark to serve as a direction guide during insertion. However, insertion directly through the marked skin should be avoided as it can result in “tattooing.” Use of skin marks is at the clinician’s discretion.

Anesthesia

Local anesthesia for the incision is obtained by raising a wheal of 1 % chloroprocaine or lidocaine using a 1½ in. 25-gauge needle and injecting 1–3 mL under the skin along the track of the implant insertion needle. A burning sensation is common during injection of the local anesthetic. This effect can be eliminated for most patients by adding 1 meq of sodium bicarbonate to each 10 mL of anesthetic (however, this buffering shortens shelf life to 24 h) [51]. Local anesthesia should be allowed a few minutes to take effect and the insertion site should be tested before beginning the procedure to ensure that the patient is comfortable.

Insert Implant

The operator should be seated and should view the insertion site from the side, not from above the device. Most women feel no more than a pressure sensation during the insertion procedure. The sharp, beveled trocar easily penetrates the skin, making a separate scalpel incision unnecessary. Grasp the applicator above the needle cap on its textured surface between thumb and forefinger. Remove the clear plastic needle cover. Place the needle against the insertion site holding the applicator at an angle 30° to the skin (Fig. 9.3a–c). While applying countertraction to the skin around the insertion site, puncture the skin with the needle tip. Lower the applicator so that it is parallel to the skin and advance the needle in the subdermal connective tissue while lifting the skin with the tip of the needle. Advance the needle to its full length. If the needle is not fully advanced under the skin, the implant will not be correctly inserted. Unlock the slider with downward finger pressure on the lever, then move the slider fully backward (distally) and withdraw the needle.

Fig. 9.3

(a–c) Grasp the applicator above the needle cap on its textured surface between thumb and forefinger. Remove the clear plastic needle cover. Place the needle against the insertion site holding the applicator at an angle 30° to the skin. Reproduced with permission of Merck Sharp & Dohme B.V., a subsidiary of Merck & Co., Inc., Whitehouse Station, NJ, USA. All rights reserved

Verify Placement

Immediately after insertion, palpate the skin to verify correct placement of the rod; both ends should be palpable. Ask the patient to feel her implant, then place an adhesive closure on the insertion puncture and wrap the site with a pressure bandage to minimize bruising. If you cannot feel the implant, check the applicator to make sure the implant is no longer in the applicator. The applicator obturator is purple, while the implant is white. If there is doubt about the presence of the implant, use sonography or an X-ray to determine its presence. Magnetic resonance imaging (MRI) is not required.

Post-insertion Care and Follow-Up

Complete the Patient Chart Label for the patient's medical record and the User Card, which must be given to the patient. The woman may remove the pressure bandage in 24 h and the small bandage in 3 days. Most women do not experience pain after insertion, but if it occurs, aspirin, acetaminophen, or nonsteroidal anti-inflammatory agents usually provide relief. The patient may be discharged immediately after the procedure. A routine follow-up visit is not necessary [48]. She should call the provider if she develops pain, discharge, or swelling at the insertion site, fever, or other concerns. She should also contact her provider if she has a change in her health status that could affect safe and effective use of this method, or when she wants to switch contraception methods, remove the implant to attempt pregnancy, or replace the implant when efficacy wanes.

Complications of Insertion

Complications are rare, reported in 0.3–1 % of insertions and 0.2–1.7 % of removals [52, 53]. Potential complications include infection, hematoma formation, local irritation or rash, expulsion, and allergic reactions. The implant may migrate a short distance (<2 cm) over time [54]. The incidence of complications is minimized by clinician training and experience, and the use of strict aseptic technique. Nerve injury can result in impaired sensibility, severe localized pain, or the formation of painful neuroma. There are two case reports of neurologic symptoms during etonogestrel implant insertion in the literature: nerve injury to branches of the medial antebrachial cutaneous nerve during placement [55] and neuropathy due to contact of the implant with the medial antebrachial cutaneous nerve [56].

Removal

The rod can be removed at any time, but should be removed when efficacy begins to decline (3 years after insertion according to the package insert; 5 years according to WHO studies). The hormonal effects end promptly after removal; circulating levels of etonogestrel are undetectable in 1 week. Return of ovulation occurs in 94 % of women within 3–6 weeks after method discontinuation [32, 33]. If the implant is not removed at 3 years, contraceptive effects persist for at least an additional 2 years [37].

Implant removal is an office procedure requiring only local anesthesia. Equipment is the same as that listed above for insertion, except the Nexplanon applicator is replaced by sterile mosquito forceps (curved and straight) and a #11 scalpel. For removing deeply inserted implants, modified (<2 mm diameter ring) vasectomy forceps can be useful. Removal takes about 4 min [39] for Implanon and 2 min for Nexplanon [57]. Fibrous tissue surrounding Nexplanon is rare (4 %) but when present they often increase the removal time [39, 57]. We recommend viewing an instructional video (one may be found via the UpToDate article “Etonogestrel contraceptive implant”) [58], and practicing removal on a model arm before attempting the procedure on a patient. A removal kit containing a model arm and a manual and compact disc illustrating basic technique is available at no charge from Merck (by calling 877-467-5266). The patient should read and sign an informed consent, which is filed in her medical record. We suggest that the patient also be given a copy.

Procedure

Position the patient and prepare the implant site as described above for rod insertion. We prefer to have the patient extend her arm for the insertion procedure but bend her arm for implant removal.

Palpate the distal tip of the rod (the end closest to the elbow). If it is not palpable, then removal should be postponed until the rod can be localized with sonography, or X-ray imaging [see below under imaging techniques]. Push down on the proximal end of the rod (the end closest to the axilla) and inject no more than 0.5 mL of buffered lidocaine with epinephrine into the dermis immediately under the elevated distal tip of the rod, raising a wheal about 5 mm in diameter. Too much anesthetic, especially if it is injected on top of the rod, makes it difficult to palpate the tip of the rod. Massage this area to disperse the anesthetic.

Use your fingers to again apply pressure on the proximal (axillary) end of the rod so that the distal (elbow) end pushes up against the skin. As the rod is pushed against the skin, the blade of a #11 scalpel is positioned so that the point is immediately available to incise the sheath without releasing pressure on the rod. It is best to keep the scalpel in one hand with thumb and index finger while manipulating the rod with the rest of the fingers of both hands. Pushing the rod against the incision with finger pressure is critical for success with this “Pop Out” technique because, if pressure is released, the rod will slip back into its sheath in the subdermal tissue.

Make a 2–3 mm longitudinal incision through the skin over the end of the rod. Deepen the incision until either the rod pops into view or you feel a rubbery sensation against the point of the scalpel blade; the rubbery material is the rod encased in its fibrous sheath. If present, nick the fibrous sheath covering the end of the rod with the tip of the scalpel blade. It may take several nicks in different directions to fully open the sheath.

The end of the rod will come into view as the sheath is opened. Continue to exert finger pressure on the proximal (axillary) end of the rod to push the distal (elbow) end through the incision until it can be grasped with mosquito forceps or fingers and pulled out. Confirm that all 40 mm of the rod have been removed. Close the incision with an adhesive strip (e.g., butterfly bandage) and cover with a pressure bandage to minimize bruising.

Difficult Removals

If the rod will not move toward the incision with finger pressure, it can be grasped with a hemostat or modified vasectomy forceps (filed down to a 2 mm diameter grasping ring). Note that the incision will usually have to be lengthened in order to admit the clamp (Fig. 9.4). It may be necessary to inject more local anesthetic, and to dissect around the rod with a straight mosquito clamp. The disadvantage of instrument removal is that it can be more painful, cause more bleeding, require a larger incision, and increase the risk of breaking the rod. If a rod is damaged, further attempts to grasp it with clamps may result in deeper fractures. To decrease this risk, the rod should be grasped by its end whenever possible and with as little traction as possible for exposure and removal. Use of 4 × 4 sponges to gently dissect through the fibrous tissue is a gentle and often successful maneuver.

Fig. 9.4

Rod removal. From [66], used with permission

If it is not possible to grasp and push up on the end of a deeply implanted rod to open the fibrous sheath, use a scalpel to cut longitudinally, not across, the sheath covering the rod. Rarely, removal of a cut or broken rod will require an additional incision at the proximal end of the rod so that the remaining piece can be extracted. When the rod must be grasped around its diameter, rather than at the end, the vasectomy forceps are particularly useful.

Imaging Techniques

Deeply placed rods that cannot be palpated under the skin, should be localized with imaging studies (Implanon can be identified with high resolution sonography or magnetic resonance imaging [MRI]; Nexplanon can be identified with high resolution sonography, plain X-ray, computed tomography, or MRI). Such “lost” rods should be located with a high frequency (10–15 MHz), linear ultrasound transducer prior to attempting the removal [59–61]. Use a transverse orientation to identify an acoustic shadow (the rod itself is more difficult to see), measure the depth, and draw a line representing the rod location on the surface of the skin. A thin wire (e.g., an opened paper clip) held under the transducer may be used to help mark the skin surface in relation to the impalpable rod. If the rod is very deep (>1.5–2 cm), sonography should be used during the removal procedure because movement of the patient’s arm may change the location of skin marks in relation to the underlying implant.

Patients with “very” (>2 cm) deep (as determined sonographically) implants should be referred to an experienced gynecologist, e.g., at one of the 30 “Family Planning Fellowship” training sites at major medical schools around the country (www.familyplanningfellowship.org). The contraceptive specialist can then work with interventional radiologists to remove the implant under direct imaging and controlled conditions. A case series of implant removal with a hook-wire marker method used in breast tumor surgery has been proposed [62].

Removal of contraceptive implants is never an emergency; there is no evidence that their presence adversely affects pregnancies or other conditions. Therefore, we suggest waiting until removal can be performed by a surgeon with expertise in removal of difficult contraceptive implants. Consultation with an orthopedic or plastic surgeon without specific expertise managing this problem is rarely required and not advised.

Reinsertion

If the patient wants to continue to use implant contraception, a new rod can be inserted immediately through the same incision that was used to remove the old rod. Alternatively, the new implant can be placed in the other arm.

Jadelle

Each Jadelle rod contains 75 mg of levonorgestrel for a total of 150 mg, 66 mg less than that in the six Norplant capsules. The thin, flexible Jadelle rods are wrapped in silastic tubing (the same material used by Norplant), 43 mm in length and 2.5 mm in diameter, thus slightly longer and thicker than Norplant [63]. Whereas the levonorgestrel in Norplant is packed into the capsules in crystal form, the core of the Jadelle rod is a mixture of levonorgestrel and an elastic polymer (dimethylsiloxane/methylvinylsiloxane). Long-term clinical trials indicate that the performance and side effects are similar to Norplant, but removal is faster [64, 66].

Because the release rates with the two levonorgestrel systems are comparable (Table 9.4), it is reasonable to conclude that clinical studies with Norplant and Jadelle should yield similar results. While Norplant has been more extensively studied, clinicians can assume that the findings apply as well to Jadelle, except that Norplant was shown to be effective for 7 years and Jadelle for 5.

Table 9.4 Release rate of levonorgestrel in two contraceptive implants

Summary

Implants offer women a highly effective, long-term and easy to use method of contraception. They may be used in most women, including women with contraindications to estrogen, adolescents, women with chronic illnesses, and breastfeeding women. Implantable contraception is safe and cost-effective immediately postabortion and postpartum. Providers interested in placing and removing implants should undergo appropriate training, but all providers counseling women about contraception should offer implantable contraception as a first-line method.