Effect of missed combined hormonal contraceptives on contraceptive effectiveness: a systematic review

Combined hormonal contraceptives (CHCs) are popular methods of reversible contraception in the United States, but adherence remains an issue as reflected in their lower rates of typical use effectiveness. The objective of this systematic review was to evaluate evidence on the effect of missed CHCs on pregnancy rates as well as surrogate measures of contraceptive effectiveness (e.g., ovulation, follicular development, changes in hormone levels, cervical mucus quality).

We searched the PubMed database for peer-reviewed articles published in any language from database inception through April 2012. We included studies that examined measures of contraceptive effectiveness during cycles with extended hormone-free intervals or nonadherence (e.g., omission of pills, delayed patch replacement) on days not adjacent to the hormone-free interval. We used standard abstract forms and grading systems to summarize and assess the quality of the evidence.

The search strategy identified 1387 articles, of which 26 met our study selection criteria. There is wide variability in the amount of follicular development and risk of ovulation among women who extended the pill-free interval to 8-14 days; in general, the risk of ovulation was low, and among women who did ovulate, cycles were usually abnormal (i.e., low progesterone levels, small follicles and/or poor cervical mucus) (Level I, good, indirect to Level II-3, fair, indirect). Studies of women who missed one to four consecutive pills or 1-3 consecutive days of delay before patch replacement at times other than adjacent to the hormone-free interval reported little follicular activity and low risk of ovulation (Level I, fair, indirect to Level II-3, poor, indirect). Studies comparing 30 mcg versus 20 mcg mc ethinyl estradiol pills showed more follicular activity when 20 mcg ethinyl estradiol pills were missed (Level I, good, indirect).

Most of the studies in this evidence base relied on surrogate measures of pregnancy risk and ranged in quality. For studies providing indirect evidence on the effects of missed CHCs, it is unclear how differences in surrogate measures correspond to pregnancy risk. Fewer studies examined the transdermal patch and vaginal ring than combined oral contraceptives.