Fertility and combined oral contraceptives – unintended pregnancies and planned pregnancies following oral contraceptive use – results from the INAS-SCORE study

Abstract

Objectives: To estimate the real-use contraceptive effectiveness of the combined oral contraceptive containing dienogest and estradiol valerate (DNG/EV) and whether DNG/EV compared to other combined oral contraceptives (oCOC) has a negative effect on return to fertility.

Methods: Transatlantic, prospective, non-interventional cohort study conducted in the USA and seven European countries with two main exposure groups and one exposure subgroup: new users of DNG/EV and other COC (oCOC), particularly levonorgestrel-containing COCs (LNG). In a planned secondary analysis, pregnancy outcomes were investigated including contraceptive effectiveness and pregnancy following contraceptive cessation. The influence of age, parity and OC-type were assessed.

Results: 50,203 COC users were followed for 105,761 woman-years (WY). There were 677 unintended pregnancies reported: 451 in the USA and 226 in Europe. The contraceptive failure rate in Europe was 0.5 events/100 WY (95% CI: 0.4–0.5) and in the USA 1.9 events/100 WY (95% CI: 1.7–2.1). Differences in compliance (1.3 pregnancies/100 WY) accounted for 90% of the geographical difference seen between Europe and the USA. DNG/EV showed lower contraceptive failure rates compared to the comparators; 0.9% DNG/EV, 2.1% oCOC and 2.8% LNG after 4 years. Overall, 1167 (2.3%) of women stopped contraceptive use with the intention of becoming pregnant with 89% conceiving within 2 years. No significant differences were seen between groups after adjusting for age.

Conclusion/Discussion: DNG/EV is associated with similar contraceptive effectiveness in typical-use settings when compared to oCOC and LNG. There was no difference observed between cohorts in fertility following OC use.

Chinese abstract

目标：评估含地诺孕酮和戊酸雌二醇（DNG/EV）的复方口服避孕药在实际使用中的避孕有效性, 以及与其他复方口服避孕药（oCOC）相比, DNG/EV是否对生育能力的恢复产生负面影响。

方法：在美国和七个欧洲国家进行跨大西洋的, 前瞻性非干预性队列研究, 有两个主要暴露组和一个暴露亚组：DNG/EV和其他COC（oCOC）的新用户, 特别是含左炔诺孕酮的COC。在计划中的二次分析里, 对避孕有效性和停止避孕后的妊娠情况进行调查评估。年龄, 产次和OC类型的影响被列入评估中。

结果：50,203名COC用户被随访了105,761妇女年（WY）。据报告有677例病例意外怀孕：451例在美国, 226例在欧洲。欧洲的避孕失败率为0.5事件/100WY（95％CI：0.4-0.5）, 在美国为1.9事件/100WY（95％CI：1.7-2.1）。符合性差异（1.3次妊娠/100 WY）占欧洲和美国之间的地理差异的90％。与对比组相比, DNG/EV的避孕失败率较低;使用4年后, 三者的避孕失败率分别为：DNG/EV 0.9％, oCOC 2.1％和LNG 2.8％。总体而言, 1167例（2.3％）妇女停止使用避孕药具后, 在两年内怀孕的占89％。在调整年龄的差异后, 各组之间没有显著性差异。

结论/讨论：与oCOC和LNG相比, DNG/EV在正确使用环境中有类似的避孕有效性。在使用OC后, 各组生育力的差异无显著性意义。

Keywords:

• Prospective cohort study
• active surveillance
• dienogest
• estradiol valerate
• Pearl Index
• contraceptive effectiveness

Acknowledgements

The authors would like to express their appreciation to the members of the independent Safety Monitoring and Advisory Council for their constructive criticism and unfailingly fair scientific discussion. The authors would also like to highlight the contributions of numerous colleagues who were responsible for the field work in the individual countries, management of the study database and validation of patient-reported adverse events. The results of this publication would not be possible without their unseen and tireless work.

Disclosure statement

The study was funded by a manufacturer of hormonal contraceptives. The study was supervised by an independent Safety Monitoring and Advisory Council with full authority over the study (including study protocol, protocol amendments, data analyses and stopping the study). The funder had no access to the source data and did not participate in designing the study, analysing the data, preparing or reviewing this publication.

Funding

This study was funded by an unconditional grant from Bayer AG, Germany.