Contraception: Etonogestrel implant

INTRODUCTION — The etonogestrel implant is a single-rod progestin contraceptive placed subdermally in the inner upper arm for long-acting reversible contraception in women. It is marketed in the United States as Nexplanon. It is a bioequivalent of its predecessor, Implanon, so the studies of Implanon cited here also apply to Nexplanon.

This topic will review the etonogestrel contraceptive implant. Information on contraceptive counseling and other progestin-only contraceptive topics can be found separately:

●(See "Contraception: Counseling and selection".)

●(See "Intrauterine contraception: Background and device types", section on 'Levonorgestrel IUD'.)

●(See "Depot medroxyprogesterone acetate (DMPA): Formulations, patient selection and drug administration".)

●(See "Contraception: Progestin-only pills (POPs)".)

In this topic, when discussing study results, we will use the terms "woman/en" or "patient(s)" as they are used in the studies presented. However, we encourage the reader to consider the specific counseling and treatment needs of transgender and gender diverse individuals.

DESCRIPTION AND STRUCTURE — The implant consists of a 40 mm by 2 mm semirigid plastic (ethylene vinyl acetate) rod containing 68 mg of the progestin etonogestrel (the 3-keto derivative of desogestrel) (figure 1). Etonogestrel is slowly released (figure 2), initially at 60 to 70 mcg/day, decreasing to 35 to 45 mcg/day at the end of the first year, to 30 to 40 mcg/day at the end of the second year, and then to 25 to 30 mcg/day at the end of the third year and beyond [1]. Data from a prospective study indicate the mean etonogestrel serum concentration is maintained at a level to provide contraception at least through the fifth year of implant use [2]. The threshold serum etonogestrel level required to suppress ovulation is 90 pg/mL [3]. While etonogestrel levels may be affected by individual characteristics and genetic variants, this information does not change clinical care [4].

The Nexplanon rod is radio-opaque, so magnetic resonance imaging is not needed for locating an impalpable implant as it was for Implanon, its predecessor. The applicator (insertion trocar) guides subdermal insertion and makes inadvertent failure to insert the implant unlikely because the cap will not open if the implant is not in the needle; a finger pressure-activated lever ensures that the trocar completely discharges the contraceptive implant under the skin if the trocar is fully advanced (figure 3).

PATIENT SELECTION

Candidates — Most women are candidates for etonogestrel implant contraception; there are few medical disorders where the risk of the method exceeds the benefit (eg, current breast cancer, active liver disease). The United States Centers for Disease Control and Prevention Medical Eligibility Criteria for Contraceptive Use and the World Health Organization Medical Eligibility Criteria for Contraceptive Use list medical eligibility criteria for nonbarrier contraceptives [5].

Women at high risk of unintended pregnancy, including adolescents and patients undergoing induced abortion, are excellent candidates for the etonogestrel implant because these people are at increased risk of discontinuing other methods. In a secondary analysis including over 6100 sexually active patients aged 14 years and older, patients younger than 20 years preferred long-acting contraceptives (etonogestrel implant and intrauterine devices [IUDs]) and were highly likely to continue using the etonogestrel implant 12 months after insertion [6]. The etonogestrel implant is also successfully used by women undergoing an induced abortion [7].

Contraindications — Standard contraindications to use of hormonal contraceptives include [8]:

●Known or suspected pregnancy

●Current or past history of thrombosis or thromboembolic disorders

●Hepatic tumor or active liver disease

●Undiagnosed abnormal genital bleeding

●Known or suspected breast cancer, history of breast cancer, or other progestin-sensitive cancer

●Allergic reaction to any component of the method

The inclusion of thromboembolic disease as a contraindication is mainly based on combined hormonal products that include both estrogen and a progestin. However, progestin-only contraceptives may be a reasonable option for some patients with past or active thromboembolic disease. (See 'Risk of thromboembolic event' below.)

Implant versus other progestin contraceptives — Other progestin-only contraceptives include the levonorgestrel (LNG)-releasing IUDs, depot medroxyprogesterone acetate injections, and progestin-only oral pills. The advantages of progestin-only contraceptives as a class are that they contain no estrogen, are reversible, and do not require surgery. Disadvantages of the class include unscheduled or break-through bleeding, which are common with implants but less so with intrauterine progestins. Both the etonogestrel implant and the LNG-releasing IUDs provide long-acting and extremely effective contraception while the injections and pills are highly effective if regularly resupplied and used according to prescribing guidance (figure 4). The implant and IUDs are not visible, although the rod and IUD strings can be palpated; depot medroxyprogesterone acetate injection is the most private option but can cause amenorrhea.

COUNSELING POINTS

Mechanism of contraception — Progestins, including etonogestrel, cause changes in cervical mucus and tubal motility that are unfavorable to sperm migration, thus inhibiting fertilization. At high doses, progestins also inhibit gonadotropin secretion, thereby inhibiting follicular maturation and ovulation. This dual effect allows contraceptive efficacy to be maintained even though ovulation is not consistently inhibited in implant users toward the end of the third year of use. Although progestins suppress endometrial activity, which makes the endometrium unreceptive to implantation, this is less important since the major mechanisms of contraceptive action prevent fertilization. Should pregnancy occur while using the etonogestrel implant, the location may be either intrauterine or extrauterine [9].

Efficacy and duration of use — The etonogestrel implant is one of the most effective contraceptives available, with lower failure rates than permanent contraceptive operations, but without the risks of invasive surgery (figure 4). An analysis of 11 clinical trials including 942 women enrolled for two to four years reported that the etonogestrel implant was well-tolerated and effective [10]. No pregnancies occurred while women were using this method of contraception; six pregnancies were reported during the first 14 days after implant removal. The manufacturer cites a Pearl Index of 0.38 pregnancies per 100 woman-years of use, which is similar to that of other long-acting methods of contraception [8].

The etonogestrel implant is approved for three years of use, but observational and trial data indicate that it is at least as effective as the copper intrauterine device (IUD) and the levonorgestrel (LNG) implants for up to five years of use [2,11,12]. For patients who wish to use the implant beyond three years, the author offers a total of five years of use (ie, two years beyond the three years mandated in the package insert).

In a study comparing the etonogestrel implant with the five-year two-rod LNG implant and the copper IUD, no pregnancies occurred in women using the etonogestrel implant (204 women) or the LNG implant (330 women) for a total of five years [11]. While the side effects between the implant groups were similar, women with the etonogestrel implant reported higher rates of subjective heavy menstrual bleeding, although the overall frequency was low (12 versus 9 percent for etonogestrel versus LNG implants). Some offer patients extended use through four or five years (the author uses five years) and discuss the differences between the initial approval data and subsequent studies.

Side effects

Local — In the clinical trial for Nexplanon approval, implant site reactions were reported by nearly 9 percent of women [8]. These reactions included erythema (3 percent), hematoma (3 percent), bruising (2 percent), pain (1 percent), and swelling (0.7 percent). In postmarketing studies, local reactions related to either insertion or removal also included irritation, itching, and fibrosis at the implant site (for removal).

Systemic

●Change in bleeding pattern – Women using the etonogestrel implant may have longer or shorter duration or menstrual bleeding, or no bleeding at all (amenorrhea). The most common side effect of the etonogestrel implant is unscheduled, or irregular, uterine bleeding, reported by approximately 11 percent of users in the initial safety trial, which may or may not decrease with continued use [8]. In the analysis of 11 clinical trials described above [10], unscheduled bleeding was the primary reason for discontinuation, with a rate of 14.8 percent in the United States and Europe, but only 3.7 percent in Southeast Asia, Chile, and Russia. United States users were more likely to discontinue because of prolonged or heavy bleeding than women from other countries (7.0 versus 4.3 percent). 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 time periods had fewer than three bleeding/spotting episodes; one fifth had no bleeding/spotting (amenorrhea); 17 percent had a bleeding episode that lasted more than 14 days, and 6 percent had more than five bleeding/spotting episodes. The number of unscheduled bleeding days was highest in the first three 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.

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 approximately 90 percent of women who discontinued the implant but in only 22 percent of those who continued its use.

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, including short-term use of nonsteroidal anti-inflammatory drugs, combined oral contraceptive pills [13], or supplemental estrogen. Management of unacceptable bleeding patterns is discussed separately. (See "Evaluation and management of unscheduled bleeding in individuals using hormonal contraception", section on 'Progestin-releasing implants'.)

●Bone – The etonogestrel implant does not impact endogenous estradiol levels and thus does not induce significant bone loss, despite creation of a relatively hypoestrogenic state (ie, higher progestogen levels compared with native estradiol levels). In contrast, depot medroxyprogesterone acetate (DMPA), another progestin-only contraceptive that reduces estrogen levels, can decrease bone mineral density. (See "Depot medroxyprogesterone acetate (DMPA): Efficacy, side effects, metabolic impact, and benefits", section on 'Reduction in bone mineral density'.)

●Insulin and lipid metabolism – In a prospective cohort study of healthy women who received etonogestrel implants, reduced levels of insulin, homeostatic model assessment of insulin resistance scores, quantitative insulin sensitivity check index, total cholesterol, high-density lipoprotein, and low-density lipoprotein were reported for the 21 women followed for three years [14]. Although the reductions were statistically significant, the clinical significance of these changes is not known. However, this study is consistent with a prior literature review that concluded that the etonogestrel implant did not appear to have clinically significant effects on lipid metabolism or liver function despite small changes in laboratory values [15].

●Other – The most common adverse events besides unscheduled bleeding that were deemed possibly, probably, or definitely related to the etonogestrel implant included headache (16 percent), weight gain (12 percent), acne (12 percent), breast tenderness (10 percent), emotional lability (6 percent) and abdominal pain (5 percent) [10]. In a study that followed women receiving the etonogestrel implant, LNG implant, and copper IUD, mean weight gain at 36 months of use was 3 kg for both types of implants and 1 kg for the copper IUD [16].

Risk of thromboembolic event — Large epidemiologic studies have not identified an increased risk of stroke, myocardial infarction, or venous thromboembolism (VTE) in users of progestin-only oral contraceptives [17-19], and none of these events occurred in the trials on which approval was based [10]. For this reason, the United States Centers for Disease Control and Prevention have indicated progestin-only contraceptives represent a reasonable contraceptive choice for women with risk factors for, or a past history of, venous thromboembolic disease [5,20]. Subsequently published data support this conclusion [21].

●Evidence supporting low absolute risk – 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 [21]. For thrombotic stroke, there were three events among users (incidence 12/100,000 person-years, relative risk [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). A database study comparing VTE rates in postpartum patients who did and did not receive etonogestrel implants reported similar 30-day VTE readmission rates for the two groups [22].

●Contrast with product package labeling – The above recommendation differs from etonogestrel implant package labeling, which lists current or past thrombosis as a contraindication to use [23]. Etonogestrel is the synthetic 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 VTE 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 [24].

Noncontraceptive benefits — In addition to being extremely effective, long-acting, and private, the etonogestrel implant generally lightens menstrual bleeding (although women can have irregular bleeding). The etonogestrel implant has been used to treat endometriosis-related pain, although data are limited [25,26].

Risk of STI acquisition — The etonogestrel implant does not protect the patient from acquisition of sexually transmitted infections (STIs), nor does it make STI infection more likely. Users of the long-acting injectable contraceptive DMPA may be at increased risk of human immunodeficiency virus acquisition and transmission compared with noncontraceptive users. There is no evidence that other contraceptive progestins, including the etonogestrel implant, have similar effects. In contrast to DMPA, progestins such as etonogestrel are more closely related to testosterone rather than progesterone and are administered at relatively lower doses.

All women at risk for STI acquisition are counseled regarding concomitant condom use. (See "External (formerly male) condoms", section on 'Protection from STIs'.)

Patient acceptability — Accumulating evidence supports the safety, efficacy, and acceptability of this contraceptive method [27,28]. In women using contraception, use of the contraceptive implant increased from 0.3 to 0.8 percent between the time periods 2006 to 2010 and 2011 to 2013 [29]. For comparison, of women using contraception in the 2013 to 2015 National Survey of Family Growth, 16 percent used combined oral contraceptives and 7 percent used IUDs [30].

Because both intrauterine and subdermal contraception are highly effective with long durations of action (5 to 12, or possibly more, years [31]), studies of acceptability often consider them together as long-acting reversible contraception (LARC) despite marked differences in side effects such as timing and volume of bleeding. For example, a prospective, partially randomized patient preference trial of long-acting methods among women who initially preferred pills or injectables (short-acting methods) found that, at two years, acceptability of implants and IUDs and continuation rates were greater and unintended pregnancy rates lower compared with those who received the pills and injectables they initially preferred over LARC methods [32]. A study of interpregnancy interval (IPI) among 112,000 postpartum women in California reported a fourfold increase in probability of an IPI greater than 18 months among women who received either implants or IUDs at a postpartum visit [33]. These investigators also reported that IPI shorter than 18 months was associated with an increased risk of premature birth and that use of LARC postpartum was by far the most effective intervention to decrease premature births in California. Thus, implants and IUDs appear to be effective in reducing not only unintended pregnancies but also premature births.

Since 2013 [29], use of long-acting reversible contraception (LARC) has further accelerated, with about equal rates of increase for implants and IUDs. For example, from 2013 to 2019 the rate of postpartum implant placement in US hospitals rose from about 5 in 10,000 deliveries to 65 [34]. The increase in US postpartum LARC use is due, in part, to changes in insurers' hospital and postpartum care reimbursement policies to include LARC [35]. In regions with concern for restricted access to contraceptives, patients should be counseled about the option for postpartum LARC as they may be unable to access the methods at a future time. (See 'Preinsertion planning' below.)

PREINSERTION PLANNING

●Clinician training – Clinicians who wish to provide Nexplanon insertion must complete three hours of training in patient selection, counseling, insertion, and removal. A voluntary monitoring program documented that participants in the training program experienced few complications with insertion or removal [36]. Clinicians who received Nexplanon training prior to October 2018 are required to complete a second training module available online. Information on initial or repeat training can be found through the manufacturer's website (www.nexplanontraining.com). Trained clinicians can be found through Planned Parenthood's health center finder program.

Those already trained for Implanon can take an online course to qualify for use of Nexplanon (www.nexplanon-usa.com). When all registered Implanon providers completed online Nexplanon training, Implanon was taken off the market.

●Examination and testing – For healthy women, no physical examination or laboratory tests are indicated before insertion of an etonogestrel implant [37]. Although some medical conditions represent contraindications to hormone use, 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 implant can be inserted at any time as long as the clinician is reasonably certain that the patient is not pregnant. 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 inferred if the patient meets any of the criteria in the table (table 1). A pregnancy test at least two weeks after the last episode of sex is needed only when there is doubt. 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.

INSERTION PROCEDURE — A clinician who has been trained in the technique can insert the implant in less than two minutes [38].

Equipment — The following equipment should be available for etonogestrel implant insertion:

●A 25-gauge needle (1.5 inches in length) attached to a 2 to 5 mL syringe

●1 percent chloroprocaine or lidocaine without epinephrine

●Antiseptic solution (eg, povidone iodine, chlorhexidine gluconate, isopropyl alcohol)

●An adhesive strip for closure of the puncture site

●Elastic pressure bandage (eg, "Kerlex")

●Surgical gloves (need not be sterile if a "no touch" technique will be used)

●Sterile drape

●Sterile, preloaded Nexplanon applicator

Position the patient — Two options for positioning the patient's arm have been described:

●Arm straight – The patient lies supine with the full length of the arm exposed and supported by the table. Some clinicians prefer the arm to be straight in order to improve access to the skin over the triceps muscle and avoid the sulcus between the biceps and triceps [sulcus is shown in the image with arm bent (figure 5)].

●Arm bent at elbow – The manufacturer suggests positioning the upper inner aspect of the patient's nondominant arm by bending the patient's elbow 90 degrees and rotating the arm upward and outward so that the patient's hand is opposite the head (figure 5). The planned insertion site is noted or marked over the triceps muscle (ie, the implant should not be inserted into the sulcus to avoid injuring the neurovascular bundle within the groove). (See 'Identify planned insertion site' below.)

Identify planned insertion site — The clinician measures "8 to 10 cm (3 to 4 inches) from the medial epicondyle of the humerus and 3 to 5 cm (1.25 to 2 inches) posterior to (below) the sulcus (groove) between the biceps and triceps muscles" (ie, overlying the triceps muscle and not the sulcus itself) [8]. Insertions that are more than 3 to 5 cm below the sulcus are acceptable if needed to avoid insertion into the sulcus itself.

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 may result in "tattooing", although this has not been reported as a significant problem. We do not find skin marks helpful.

The optimum site depends upon individual anatomic features, 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. Once the insertion site has been identified, we place a sterile drape under the arm and clean the insertion site with an antiseptic solution.

Administer anesthesia — Inject 1 to 2 mL of 1 percent chloroprocaine or lidocaine into the dermis to raise a wheal along the planned track of the rod insertion needle. Inject the local anesthetic just under the skin with a 25-gauge, 1.5-inch needle on a 2 to 5 mL syringe.

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 hours).

Insert — The operator should be seated and should view the insertion site from the side, not from above the device. A seated clinician can more easily make a subdermal insertion that avoids the sulcus. As noted above (see 'Position the patient' above), the planned insertion site should be 8 to 10 cm (3 to 4 inches) above the medial epicondyle of the nondominant arm and overlying the triceps muscle (ie, not overlying the sulcus between the biceps and triceps muscles) [8]. The implant is inserted subdermally (ie, just under the skin). Care is taken to avoid insertion into the sulcus between the biceps and triceps muscles that contains a large neurovascular bundle.

The sharp, beveled trocar easily penetrates the skin; a separate incision is not necessary. The clinician grasps the applicator above the needle cap on its textured surface between thumb and forefinger and removes the clear plastic needle cover. Next, the clinician places the needle against the insertion site holding the applicator at an angle 30 degrees to the skin (figure 6 and movie 1). While applying counter traction to the skin around the insertion site, the clinician punctures the skin with the needle tip. The clinician then lowers the applicator so that it is parallel to the skin and advances the needle in the subdermal connective tissue while lifting the skin with the tip of the needle without forcing the tip into the skin above. If this occurs, withdraw the needle a few millimeters and redirect it under the skin. The needle must be advanced to its full length. If the needle is not fully advanced under the skin, the implant will not be correctly inserted. Lastly, the slider is unlocked with downward finger pressure on the lever, and then, the clinician moves the slider fully backward (distally) and removes the applicator.

Most patients feel no more than a pressure sensation during the insertion procedure.

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 the implant, then place an adhesive closure (eg, "Steri strip") on the insertion puncture and wrap the site with a pressure bandage. Check the applicator to make sure the implant is no longer in the cannula. The applicator obturator is purple, while the implant is white. If there is doubt about the presence of the implant, use sonography or a radiograph to determine its presence. Magnetic resonance imaging (MRI) is not required because Nexplanon is radio-opaque.

Complications — Complications are rare, reported in 0.3 to 1 percent of insertions and 0.2 to 1.7 percent of removals [39,40]. Potential complications include infection, hematoma formation, local irritation or rash, expulsion, and allergic reactions [8]. The implant may migrate a short distance (less than 2 cm) over time [41]. The incidence of complications is minimized by clinician training and experience, and the use of strict aseptic technique.

More serious complications include:

●Injuries to branches of the medial antebrachial cutaneous nerve (Implanon insertion) and ulnar nerve (removal) have been reported [42,43]. Nerve injury can result in impaired sensibility, severe localized pain, or the formation of painful neuroma. Such injuries should be suspected in patients who present with neuropathic pain, dry erythematous skin (due to loss of autonomic nerve supply), and, with severe injuries, pain that is elicited in the territory of the nerve by gently tapping over the site of suspected injury (Tinel's sign) [43].

●Migration of the implant has also been reported. Several case reports have documented implant migration into the pulmonary arterial system and removal with percutaneous interventional techniques [44-47]. If the implant is no longer palpable, the patient should undergo imaging to identify its location. If imaging of the upper arm does not identify the implant, then chest imaging should follow. Nexplanon can be identified with high-resolution sonography, plain radiograph, computed tomography, or MRI. Correct subdermal insertion that avoids placement near the neurovascular bundle in the sulcus between the biceps and triceps is intended to make this rare complication even less likely.

POSTINSERTION 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. We also document in our record which arm was used for implant insertion as well as the patient's palpation of the implant in that arm. This information is useful for other health care providers who may be called upon to remove the implant.

Most patients do not experience pain after insertion, but if it occurs, aspirin, acetaminophen, or nonsteroidal anti-inflammatory agents should provide relief.

Patients may be discharged immediately after the procedure. A routine follow-up visit is not necessary [37]. Patients should call their provider if they develop pain, discharge, or swelling at the insertion site; fever; or other concerns. Patients should also contact the provider if they have a change in health status, or if they want to switch contraception methods, remove the implant to attempt pregnancy, or replace the implant (three to five years after insertion).

Back-up contraception — Abstinence or back-up contraception is suggested for the first 7 days after insertion if the implant is inserted >5 days since the beginning of the patient's last menstrual period [37]. This is a conservative approach because changes in cervical mucus occur rapidly: within 36 hours of insertion. Options for back-up contraception include continued use of the woman's previous method of contraception or use of condoms (external or internal). For women who are postpartum, not exclusively breastfeeding, and have not resumed menses, back-up contraception is suggested for those who are ≥21 days postpartum. For women who are postpartum, exclusively breastfeeding, and have not resumed menses, back-up contraception is suggested for those who are >6 months postpartum. For women who are postabortion, back-up contraception is suggested if the implant is not placed on the day of the abortion. In the author's practice, abortion patients who desire implant insertion generally prefer placement while in the recovery room.

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 seven 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 seven days before removing the IUD and switching to the implant. Back-up contraception is suggested if the implant is inserted >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 (if she has had vaginal intercourse within the prior five days) and use back-up contraception if the implant is inserted >5 days since the beginning of the patient's last menstrual period.

Symptoms requiring evaluation — We ask patients to notify us if they have any change in their health status such as new medical diagnosis or initiation of new medications. In addition, we advise women who experience new onset of the following symptoms to be evaluated immediately [48]:

●Persistent lower leg pain

●Severe chest pain or heaviness

●Sudden shortness of breath, sharp chest pain, or coughing blood

●Symptoms of a severe allergic reaction, such as swollen face, tongue or pharynx; trouble swallowing; or hives and trouble breathing

●Sudden severe headache that is not consistent with usual headaches

●Weakness or numbness in an arm or leg, or difficulty speaking

●Sudden partial or complete blindness

●Yellowing skin or whites of eyes, especially with fever; tiredness; loss of appetite; dark-colored urine; or light-colored bowel movements

●Severe pain, swelling, or tenderness in the lower abdomen

●New breast lump or mass

●Problems sleeping, lack of energy, tiredness, or change in mood

●Heavy menstrual bleeding

●Concern that the implant may have broken or bent

REMOVAL AND RETURN OF OVULATION — The rod can be removed at any time but should be removed at the end of three to five years (three years per package insert, five years per data). (See 'Efficacy and duration of use' above.)

The hormonal effects end promptly after removal; circulating levels of etonogestrel are undetectable in one week, and more than 90 percent of women ovulate within three to four weeks of removal (figure 7). If the implant is not removed, contraceptive effects persist, possibly for several years.

Implant removal is an office procedure requiring only local anesthesia. Equipment is the same as that listed above for insertion (see 'Preinsertion planning' above), except the Nexplanon applicator is replaced by sterile mosquito forceps (curved and straight) and a #11 scalpel (figure 8). For removing deeply inserted implants, a modified (<2 mm diameter) vasectomy forceps can be useful for grasping a deeply placed implant away from its end (figure 9). Removal of a properly placed implant takes approximately four minutes [38].

We recommend viewing an instructional video and then 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 from the manufacturer.

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 (see 'Position the patient' above). We prefer to have the patient extend her arm for the insertion procedure but bend her arm for implant removal (figure 10).

Palpate the distal tip of the rod (the end closest to the elbow). If the implant is not palpable, then removal should be postponed until the rod can be localized with sonography or radiograph imaging. (See 'Difficult removals' below.)

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 approximately 5 mm in diameter. Too much anesthetic makes it difficult to locate 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. If pressure is released, the rod will slip back into the fibrous sheath in the subdermal tissue.

Make a 2 to 3 mm longitudinal incision through the skin over the end of the rod. Deepen the incision until you feel a rubbery sensation against the point of the scalpel blade; this is the rod encased in a fibrous sheath. 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 (eg, Steri strip or butterfly bandage) and cover with a pressure bandage to minimize bruising.

Difficult removals — Common causes of difficult removals include rods that are immobile, damaged, and deeply placed or not palpable.

●Immobile rod – If the rod will not move toward the incision with finger pressure, it can be grasped with a hemostat or modified vasectomy forceps (with the grasping ring modified to <2 mm diameter) (figure 9), but the incision will usually have to be lengthened in order to admit the clamp. 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.

●Damaged or broken rod – Once a rod is cut with a scalpel or clamp, it can break with further attempts to grasp it. To decrease this risk, the rod should be grasped by its end whenever possible and with as little traction as needed for exposure and removal.

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 removed. When the rod must be grasped around its diameter, rather than at the end, the vasectomy forceps are particularly useful.

●Deep placement – Rods that are placed too deeply and cannot be palpated under the skin can be seen 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 radiograph, computed tomography, or MRI). Such "lost" rods should be located prior to removal with a high-frequency (10 to 15 megahertz), short focus, linear ultrasound transducer like the ones used to locate vessels and nerves. [49-52]. In addition, one study reported successful identification of nonpalpable etonogestrel rods using near-infrared light to locate the implant in five patients [53].

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 (eg, 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 to 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 [54]. Using continuous ultrasound guidance, one center reported 100 percent success rate for removal of deep contraceptive implants with minimal complication (bruising) [52].

Patients with "very" (>2 cm) deep (as determined sonographically) implants should be referred to an experienced gynecologist (eg, at one of the Fellowship in Complex Family Planning training sites at major medical schools around the country). The contraceptive specialist can then work with interventional radiologists to remove the implant under direct imaging and controlled conditions. Removal of contraceptive implants is never an emergency; there is no evidence that their presence adversely affects pregnancies or other conditions. We suggest waiting for removal by a surgeon with expertise in difficult contraceptive implants. Consultation with a plastic, orthopedic, or neurosurgeon is rarely required but can be important if neighboring structures are threatened by implant location. A list of "Centers of Experience" in removing deeply placed and nonpalpable implants is available from the manufacturer if referral for removal is necessary. The Society of Family Planning also maintains a list for referrals.

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, or it can be placed in the other arm.

DRUG INTERACTIONS — Contraceptive efficacy may be decreased in women taking medications that affect the metabolism of etonogestrel.

●Antiretroviral drugs – Antiretroviral therapy is compatible with etonogestrel implant use [5,37,55]. While efavirenz (EFV), fosamprenavir (FPV), and ritonavir-boosted therapies may impact etonogestrel levels, the benefits of the implant are generally thought to outweigh the risks and the implant can be prescribed for and/or continued in persons taking these drugs [5,55]. However, individuals considering the etonogestrel implant should be informed of reduced serum etonogestrel levels, and documented unintended pregnancies, in those using EFV in conjunction with the implant [56-62]. The overall incidence of unintended pregnancy appears to be low and does not preclude use of the implant by patients taking EFV, but those who strongly desire to avoid pregnancy may prefer a different contraceptive method. For those who are using condoms to reduce risk of sexually transmitted infections, the condoms will provide additional contraceptive benefit.

Supporting data include:

•Lower serum etonogestrel levels – In a study of 74 postpartum individuals receiving one of three antiretroviral regimens who initiated the etonogestrel implant, those using EFV had significantly lower median etonogestrel serum concentrations than those using ritonavir-boosted atazanavir or ritonavir-boosted lopinavir therapies (median serum concentrations of etonogestrel with EFV: 125 pg/mL [n = 26], ritonavir-boosted atazanavir: 604 pg/mL [n = 22], and ritonavir-boosted lopinavir: 428 pg/mL [n = 26]) [58]. Forty-two percent of women using EFV had etonogestrel serum concentrations below the minimum needed to suppress ovulation while none of the individuals taking the ritonavir-boosted regimens had subthreshold serum concentrations (minimum required etonogestrel serum concentration = 90 pg/mL [8]). As serum levels were measured six to seven weeks after insertion, it is not known how many individuals would develop subthreshold serum concentrations over the five-year lifespan of the implant. In addition, bleeding pattern effects were not assessed.

•Contraceptive failure – Case reports of unintended pregnancy in users of EFV and the etonogestrel implant have been published [56,62]. One report described contraceptive failure in two women infected with HIV who were using the etonogestrel implant and taking antiretroviral therapy (efavirenz-zidovudine-lamivudine in one woman and efavirenz-emtricitabine-tenofovir in the other) [56]. The pregnancies occurred at 23 and 27 months of implant use and the patients' body mass indices were 27 and 24 kg/m², respectively. 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.

●Antiseizure medications – While enzyme-inducing antiseizure medications (phenytoin, carbamazepine, barbiturates, primidone, topiramate, and oxcarbazepine) appear to lower etonogestrel levels, the benefits of the etonogestrel implant are considered to outweigh the risks by both the World Health Organization and the Centers for Disease Control and Prevention (risk category 2 for both) [5,55]. Alternatively, individuals who require antiseizure medications and desire long-acting reversible contraception can use either the copper or levonorgestrel intrauterine devices without restriction [5,55].

•Carbamazepine – In a pharmacologic study of 10 healthy women using the etonogestrel implant who were treated with carbamazepine up to 300 mg twice daily for three weeks, the serum etonogestrel level dropped below the threshold for ovulatory suppression (<90 pg/mL) after carbamazepine administration [63]. The median concentrations before and after coadministration were 158.1 pg/mL (range 128 to 347) and 50.9 pg/mL (range 39 to 202), but the number of ovarian follicle-like structures and endometrial thickness did not change. The small, three-week study could not assess unintended pregnancy, but it supports prior case reports of women who conceived while using the etonogestrel implant and carbamazepine [64,65].

•Topiramate – Topiramate-induced reduction of etonogestrel levels in contraceptive implant users is clinically important because topiramate is frequently used for treatment of migraine headaches, which typically occur in reproductive-aged females, and topiramate use during pregnancy has been associated with cleft lip and palate [66,67]. In a study that included data for 27 females using the contraceptive implant and receiving six weeks of topiramate, the mean six-week etonogestrel concentration was 105 pg/mL (range 46.2-859 pg/mL) compared with baseline etonogestrel levels of 142 pg/mL (range 76.2-771) [68]. The threshold etonogestrel level for suppressing ovulation is 90 pg/mL, but low-dose, sustained-release, progestin-only methods do not require ovulation suppression to achieve high efficacy.

UNIQUE POPULATIONS

●Adolescents – Up to 75 percent of adolescent pregnancies are unintended [69]. Thus, long-acting reversible contraception (LARC) meets a need for younger patients. In a meta-analysis of 12 studies assessing continuation rates of LARC by individuals <25 years old, the 12-month continuation rate of the etonogestrel implant was 84 percent [70]. Contraceptive needs and counseling of adolescents is discussed in detail separately. (See "Contraception: Issues specific to adolescents".)

●HIV – Although the body of evidence is limited, use of the etonogestrel implant does not appear to increase the risk of HIV acquisition or disease progression [71]. A discussion on the issues surrounding contraceptive selection in women with HIV infection is presented elsewhere. (See "HIV and women", section on 'Choice of contraception'.)

●Obese – The etonogestrel implant is not contraindicated in obese women [5]. Although the effectiveness of the etonogestrel implant has not been adequately studied in women more than 130 percent of their ideal body weight (body mass index greater than 30 kg/m²), data show no decrease in contraceptive efficacy even though etonogestrel concentration is affected by weight (figure 11) [72]. These data are described separately. (See "Contraception: Counseling for females with obesity", section on 'Contraceptive implant'.)

●Postabortion – The etonogestrel implant has no risks specific to abortion and can be inserted any time after any type of abortion (surgical, medication-induced, or spontaneous). (See "Contraception: Postabortion", section on 'Progestin-only implant'.)

●Postpartum and lactating – The etonogestrel implant can be used by both postpartum and lactating women. No delay is required to start the implant as the benefits are believed to outweigh the risks. Immediate placement has been found to more be cost-effective when compared with delayed insertion [73,74]. VTE risk does not appear to be elevated [22]. (See "Contraception: Postpartum counseling and methods", section on 'Counseling regarding venous thromboembolism risk and hormonal contraception in the postpartum period'.)

Use of the implant in postpartum individuals, its safety in lactation, and general risk of thrombosis in postpartum patients is presented elsewhere. (See "Contraception: Postpartum counseling and methods".)

●Perimenopause – The contraceptive implant can be used by eligible women of all ages, including those age >45 years [5]. Women experiencing irregular menstrual bleeding are counseled that while 20 percent of women in a 90-day period will experience amenorrhea, continued unscheduled or irregular bleeding is likely.

●Medical comorbidities – Most women with medical co-morbidities are candidates for etonogestrel contraception. One exception is women with prior or active progestin-sensitive cancer (eg, breast or endometrial cancer). Full lists of medical eligibility criteria for contraception use are available online at United States Medical Eligibility Criteria for Contraceptive Use and World Health Organization Medical Eligibility Criteria for Contraceptive Use.

●Physical or intellectual disability – There are no contraindications to etonogestrel implant use specific to women with intellectual or physical disabilities. However, some women may request menstrual suppression for ease of menstrual hygiene. As the amenorrhea rate with the etonogestrel implant is only approximately 20 percent, the 52 mg levonorgestrel-releasing intrauterine devices and combined hormonal contraceptives are preferred for this indication. (See "Hormonal contraception for menstrual suppression".)

RESOURCES FOR PATIENTS AND CLINICIANS

●bedsider.org – A free website developed by the National Campaign to Prevent Teen and Unplanned Pregnancy, a private nonprofit group.

●CHOICE Project – A free website sponsored by the Washington University School of Medicine in St. Louis that provides resources on contraceptive options and training resources for clinicians.

●Center for Young Women's Health – A free website run by Boston Children's Hospital that addresses reproductive health needs of teens and young adults.

●Beyond the Pill – A free website run by the University of California, San Francisco.

●SexandU.ca – An educational site run by the Society of Obstetricians and Gynaecologists of Canada that includes descriptions of various methods and a tool to help with selection of birth control.

●Planned Parenthood – A nonprofit organization dedicated to reproductive health with resources for patients and clinicians.

●Association of Reproductive Health Professionals – A nonprofit organization that provides resources for patients including an interactive tool to compare birth control methods.

●ACOG Contraceptive FAQs – American College of Obstetricians and Gynecologists addresses frequently asked questions (FAQs) about progestin-only contraception (pills and injection)

●ACOG LARC Program – American College of Obstetricians and Gynecologists Long-Acting Reversible Contraception Program.

●United States Medical Eligibility Criteria for Contraceptive Use

●United States Selected Practice Recommendations for Contraceptive Use

●World Health Organization Medical Eligibility Criteria for Contraceptive Use

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Contraception".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topic (see "Patient education: Long-acting methods of birth control (The Basics)")

●Beyond the Basics topic (see "Patient education: Long-acting methods of birth control (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Device information – The etonogestrel implant consists of a 40 mm by 2 mm semi-rigid plastic (ethylene vinyl acetate) rod containing 68 mg of the progestin etonogestrel (the 3-keto derivative of desogestrel) (figure 1). The single rod is placed subdermally in the inner upper arm above the elbow and not in the sulcus between the biceps and triceps. It is approved for three years of use but provides highly effective reversible contraception for up to five years in most individuals. (See 'Description and structure' above and 'Efficacy and duration of use' above.)

●Eligibility – Most pregnancy-capable individuals are candidates for etonogestrel implant contraception; there are few medical disorders where the risk of the method exceeds the benefit (eg, current breast cancer). The United States Centers for Disease Control and Prevention Medical Eligibility Criteria for Contraceptive Use and the World Health Organization Medical Eligibility Criteria for Contraceptive Use list medical eligibility criteria for nonbarrier contraceptives. (See 'Patient selection' above.)

●Efficacy – The etonogestrel implant is among the most effective contraceptives available, with efficacy as good or better than permanent contraception, but without the risks of invasive surgery (figure 4). (See 'Efficacy and duration of use' above.)

●Unscheduled bleeding – Unscheduled bleeding is the most common side effect and reason for discontinuation. (See 'Counseling points' above.)

●Evaluation – For healthy women, no physical examination or laboratory tests are indicated before insertion of an etonogestrel implant, but pregnancy should be excluded (table 1). Only clinicians trained in insertion and removal should attempt either. (See 'Preinsertion planning' above.)

●Insertion procedure – Insertion of the etonogestrel implant is an office procedure performed under local anesthesia. A trained clinician can insert the implant into the subdermal skin overlying the triceps muscle in approximately two minutes. Immediately after insertion, the clinician and patient should palpate the skin to verify correct placement of the rod. Complications related to insertion and removal are uncommon. (See 'Insertion procedure' above.)

●Follow-up care and back-up contraception – The patient may be discharged immediately after the procedure. A routine follow-up visit is not necessary. Abstinence or back-up contraception is suggested for the first seven days after insertion if the implant is inserted >5 days since the beginning of the patient's last menstrual period. Women who have been using intrauterine devices (IUDs) are counseled regarding need for back-up contraception or abstinence prior to IUD removal. (See 'Postinsertion care and follow-up' above.)

●Change in health status or medication – We ask patients to notify us if they have any change in their health status such as new medical diagnosis or initiation of new medications, particularly antiretroviral or antiseizure drugs.

•(See 'Symptoms requiring evaluation' above.)

•(See 'Drug interactions' above.)

●Implant removal – Implant removal is an office procedure requiring only local anesthesia. Ovulation resumes shortly after removal. (See 'Removal and return of ovulation' above.)

•Duration of efficacy – The rod can be removed at any time but is labeled for removal at the end of three years (although efficacy has been demonstrated up to five years, and the author supports this approach for interested patients).

•Immediate insertion of new implant – If the patient wants to continue to use this method of contraception after three years, a new rod can be inserted immediately through the same incision that was used to remove the old rod or in the other arm. (See 'Reinsertion' above.)