By Rebecca H. Allen, MD, MPH, Editor

Associate Professor, Department of Obstetrics and Gynecology, Warren Alpert Medical School of Brown University, Women and Infants Hospital, Providence, RI

SYNOPSIS: In this national retrospective cohort study of postpartum women, use of the etonogestrel contraceptive implant immediately postpartum was not associated with an increased rate of readmission for venous thromboembolism within 30 days of delivery.

SOURCE: Floyd JL, Beasley AD, Swaim LS, et al. Association of immediate postpartum etonogestrel implant insertion and venous thromboembolism. Obstet Gynecol 2020;135:1275-1280.

The current labeling of the etonogestrel implant (Nexplanon) suggests delaying insertion until 21 days postpartum because of the risk of venous thromboembolism (VTE). This study was conducted to ascertain the rate of readmission for VTE during the first 30 days after delivery in women with and without the etonogestrel implant. The investigators used data from the 2016 Healthcare Cost and Utilization Project Nationwide Readmissions Database, which included 36 million hospital discharges. Using ICD-10 codes, delivery hospitalizations were identified, as well as admissions containing a diagnosis code for both delivery and subdermal contraceptive insertion. Women with a history of VTE or who were taking anticoagulation medications were identified and excluded. Further data were collected, including age, insurance, mode of delivery, medical conditions, and tobacco use. The primary outcome was the rate of readmission for deep vein thrombosis and pulmonary embolism in women readmitted up to 30 days postpartum with and without immediate postpartum etonogestrel implant insertion.

Analysis of the 3.38 million deliveries noted that only 8,639 (0.0025%) of these women underwent postpartum contraceptive implant insertion immediately after delivery. Women who received the implant were younger (25 vs. 29 years of age), more likely to have public health insurance (82% vs. 43%), more likely to be smokers (15% vs. 6%), and more likely to have hypertension (22% vs. 12%). There were no differences in terms of rates of diabetes, thrombophilia, systemic lupus erythematosus, or cesarean delivery. A total of seven VTE cases occurred in the implant group compared to 1,192 in the non-implant group. There was no difference in the rate of VTE among those who received an implant and those who did not (0.85/1,000 deliveries vs. 0.35/1,000 deliveries; odds ratio [OR], 2.41; 95% confidence interval [CI], 0.58-9.89). The difference remained unchanged when adjusting for age, smoking history, peripartum infection, and occurrence of postpartum hemorrhage (OR, 1.81; 95% CI, 0.44-7.45).

COMMENTARY

The U.S. Medical Eligibility Criteria for Contraceptive Use (USMEC) from the Centers for Disease Control and Prevention rates the etonogestrel implant as category 1 (no restrictions on use) in non-breastfeeding women and category 2 (benefits outweigh the risks) in breastfeeding women, for women less than 21 days postpartum.¹ This is in contrast to the current labeling for the etonogestrel implant as mentioned earlier. The authors of this study did not find any increased risk of VTE with etonogestrel implant insertion immediately postpartum, which supports the USMEC recommendations. The study does have limitations in that it only followed patients up to 30 days postpartum and there may be cases of VTE that occurred beyond that. The rate of postpartum VTE has been found to persist until 12 weeks, albeit dropping from nine per 10,000 deliveries in the first week postpartum to 0.1-0.2 per 10,000 deliveries in the 12th week.² Further, the study only examined inpatient readmission for VTE. There could have been subjects treated as outpatients, thus underestimating the risk of VTE. Additionally, database studies are limited by the accuracy of the discharge codes entered.

Further limitations include the number of VTE events found in the study despite using a national database. Although the rates were consistent with other data, there still were only seven events in the etonogestrel implant arm, making the confidence intervals quite wide and, thus, less precise.² A post hoc power analysis indicated that the study only had 61% power to detect a difference between the two groups. Moreover, the study did not account for other contraceptive methods that women in the non-implant group might have been using in the immediate postpartum period, such as depot medroxyprogesterone acetate (DMPA), the progestin-only pill, or the levonorgestrel intrauterine device (IUD). Of these other progestin-only methods, only DMPA has been associated with a slightly increased risk of VTE in the general population in previous studies.³ In a recent study examining DMPA use in the immediate postpartum period (within seven days of delivery), investigators found the risk of VTE to be slightly elevated compared to the control group (0.42/10,000 women-days vs. 0.15/10,000 women-days; adjusted OR 1.94; 95% CI, 1.38-2.72).⁴ Nevertheless, the authors concluded that, although the OR was elevated, the absolute risk was very low, and the USMEC ratings stating the method was safe to use less than 21 days postpartum were appropriate. Providing contraception in the immediate postpartum period is an important option for patients for several reasons. It is convenient, patients have health insurance coverage at that time, and they may not be able to follow up postpartum in the office. Overall, progestin-only methods are considered safe immediately postpartum. This study found nothing to contradict the ratings of the USMEC, and the drug labeling of the etonogestrel implant likely is more conservative than necessary. In our practice, we continue to offer our patients immediate postpartum IUD and implant insertion, DMPA administration, and progestin-only pill prescriptions.

REFERENCES

1. Curtis KM, Tepper NK, Jatlaoui TC, et al. U.S. Medical Eligibility Criteria for Contraceptive Use, 2016. MMWR Recomm Rep 2016;65:1-103.
2. Tepper NK, Boulet SL, Whiteman MK, et al. Postpartum venous thromboembolism: Incidence and risk factors. Obstet Gynecol 2014;123:987-996.
3. Tepper NK, Whiteman MK, Marchbanks PA, et al. Progestin-only contraception and thromboembolism: A systematic review. Contraception 2016;94:678-700.
4. Tepper NK, Jeng G, Curtis KM, et al. Venous thromboembolism among women initiating depot medroxyprogesterone acetate immediately postpartum. Obstet Gynecol 2019;133:533-540.