Krashin Jamie W, Rivera-Montalvo Maritza, Leeman Lawrence, Trujillo Victoria Y, Petersen Timothy R, Sanchez Dominique, Bender Emily, Carroll Smita, Bulleit Erin, Alcantara Jasmin, Turok David K, Black Patricia, Espey Eve
Department of Obstetrics & Gynecology, University of New Mexico, Albuquerque, NM.
Department of Obstetrics & Gynecology, University of New Mexico, Albuquerque, NM; Women's Group of North Florida, Gainesville, FL.
Am J Obstet Gynecol. 2025 Mar 20. doi: 10.1016/j.ajog.2025.03.019.
Breastfeeding and access to contraception are important to patient and public health. The etonogestrel contraceptive implant is a popular and highly effective long-acting progestin contraceptive with few medical contraindications. Despite theoretical concern about early exogenous progestin exposure inhibiting lactogenesis, previous studies showed reassuring lactogenesis and long-term breastfeeding with immediate placement. However, no studies compare placement within 24 hours postpartum to delayed placement at a postpartum visit.
We studied the association between etonogestrel contraceptive implant placement within 24 hours vs at least 2 weeks postpartum and breastfeeding continuation at 8 weeks postpartum.
We conducted a noninferiority randomized controlled trial of postpartum participants who planned to breastfeed and use the etonogestrel implant at 2 university hospitals in the Mountain West. Participants were at least 13 years old, fluent in English or Spanish, had term deliveries, and lacked contraindications to implant use. They were randomized 1:1 to implant placement within 24 hours or at least 2 weeks postpartum. We collected baseline participant characteristics from chart review and questionnaires. Participants reported breastfeeding status and implant use via electronic questionnaires at 2, 4, 8, 12, and 24 weeks postpartum. The study was powered to assess a 15% noninferiority margin between groups of the primary outcome, any breastfeeding at 8 weeks in the per protocol population.
We enrolled 150 participants (n=78 immediate, n=72 delayed). After removing participants who declined implant placement, withdrew, or were ineligible (n=8) or lacked primary outcome data (n=16), the modified intention-to-treat analysis included 126 participants (n=69 immediate, n=57 delayed). The per protocol analysis included 115 participants (n=62 immediate, n=53 delayed) after excluding additional participants who received the implant outside of the placement timing windows (n=11). Participants were similar in age, race, and ethnicity, as well as previous breastfeeding experience, delivery mode, and epidural use; the delayed group reported prior implant use less frequently (29% vs 43%). In the per protocol analysis, 77.4% (48/62) of participants in the immediate group and 81.1% (43/53) in the delayed group reported any breastfeeding at 8 weeks; the lower limit of the one-sided 95% confidence interval around this -3.7% difference was -16%, exceeding our predefined noninferiority margin. The difference between groups in the modified intention-to-treat group was smaller (-0.6%) and within the noninferiority margin (-12.8% lower limit of the 1-sided 95% confidence interval): 78.3% (54/69) immediate and 78.9% (45/57) delayed. Implant continuation at 24 weeks trended toward favoring immediate placement (96%, 52/54) compared to in those assigned to delayed placement, (85%, 39/46, P=.08). Exclusive or any breastfeeding and implant continuation through 24 weeks were similar between groups.
The results demonstrated no clinically important differences in breastfeeding and implant continuation outcomes though our primary outcome exceeded our predefined noninferiority margin. These reassuring data add to the evidence base for supporting etonogestrel implant initiation for breastfeeding people whenever they desire it postpartum.
母乳喂养和获得避孕措施对患者及公众健康都很重要。依托孕烯避孕植入剂是一种广受欢迎且高效的长效孕激素避孕药，几乎没有医学禁忌证。尽管理论上担心早期外源性孕激素暴露会抑制泌乳，但先前的研究表明，立即植入时泌乳和长期母乳喂养情况令人安心。然而，尚无研究比较产后24小时内植入与产后随访时延迟植入的情况。
我们研究了产后24小时内与至少产后2周植入依托孕烯避孕植入剂与产后8周母乳喂养持续情况之间的关联。
我们在西部山区的2所大学医院对计划母乳喂养并使用依托孕烯植入剂的产后参与者进行了一项非劣效性随机对照试验。参与者年龄至少13岁，英语或西班牙语流利，足月分娩，且无植入剂使用禁忌证。他们按1:1随机分为产后24小时内植入或至少产后2周植入。我们通过病历审查和问卷收集了参与者的基线特征。参与者在产后2、4、8、12和24周通过电子问卷报告母乳喂养状况和植入剂使用情况。该研究旨在评估主要结局（即符合方案人群中8周时的任何母乳喂养情况）在两组之间15%的非劣效性界值。
我们招募了150名参与者（即时植入组78名，延迟植入组72名）。在剔除拒绝植入、退出或不符合条件的参与者（8名）或缺乏主要结局数据的参与者（16名）后，改良意向性分析纳入了126名参与者（即时植入组69名，延迟植入组57名）。在排除了在植入时间窗口之外接受植入的额外参与者（11名）后，符合方案分析纳入了115名参与者（即时植入组62名，延迟植入组53名）。参与者在年龄、种族和民族以及既往母乳喂养经历、分娩方式和硬膜外麻醉使用方面相似；延迟植入组报告先前使用过植入剂的频率较低（29%对43%）。在符合方案分析中，即时植入组77.4%（48/62）的参与者和延迟植入组81.1%（43/53）的参与者在8周时报告有任何母乳喂养；围绕这一-3.7%差异的单侧95%置信区间下限为-16%，超过了我们预先定义的非劣效性界值。改良意向性分析组中两组之间的差异较小（-0.6%）且在非劣效性界值内（单侧95%置信区间下限为-12.8%）：即时植入组为78.3%（54/69），延迟植入组为78.9%（45/57）。与延迟植入组相比，24周时植入剂的持续使用情况倾向于支持即时植入（96%，52/54），而延迟植入组为（85%，39/46，P=0.08）。两组之间纯母乳喂养或任何母乳喂养以及24周时植入剂的持续使用情况相似。
结果表明，尽管我们的主要结局超过了预先定义的非劣效性界值，但在母乳喂养和植入剂持续使用结局方面没有临床重要差异。这些令人安心的数据为支持产后有意愿的母乳喂养者随时开始使用依托孕烯植入剂增加了证据基础。
