POP: Delayed intake, missing one pill not a major reason for contraceptive failure

Delayed intake of a progestogen-only pill (POP) or missing one pill does not necessarily reduce its theoretical contraceptive protection, with little effect on cervical mucus and ovulation, as shown in a study.

“While some women had theoretical reduced contraceptive protection at some time during the study period, this finding was related to incorrect pill use in only one participant in the delayed pill cycle and two in the missed pill cycle,” according to the investigators.

They pointed out that the apparent lack of effect of the delayed/missed pill intervention on cervical mucus was quite reassuring.

A total of 52 healthy women (mean age 28.3 years, mean body mass index [BMI] 24.0 kg/m²) with regular ovulatory cycles were enrolled in the study. They completed a baseline 28-day cycle with correct once-a-day norgestrel 0.075 mg POP pill use. This was followed by two intervention cycles in which, around mid-cycle, one pill was taken 6 hours late or missed completely, respectively.

The investigators performed ovarian ultrasonography, measured estradiol and progesterone levels, and evaluated cervical mucus every 3–4 days (daily around the time of the incorrect use). They calculated the theoretical contraceptive protection score based on ovarian activity status, cervical mucus, and their temporal relationship.

Of the women, 46 provided complete data for each intervention cycle. Ovulation occurred in 14 women (30 percent) during each of the two intervention cycles, with four during the delayed pill cycle and two during the missed pill cycle, having an abnormal luteal phase. [Contraception 2022;doi:10.1016/j.contraception.2022.09.002]

Meanwhile, seven women in the delayed pill cycle and six in the missed pill cycle were found to have elevated cervical mucus scores temporally associated with the intervention. Despite this, only two women, one in each intervention cycle, had cervical mucus scores in the range considered optimal for conceiving.

“This study demonstrates that … [t]his POP may have a greater margin for error than previously thought, and our study almost certainly overestimates the theoretical risk of pregnancy,” the investigators said.

Nevertheless, they acknowledged that their study may have important limitations, including the possible underestimation of maximum theoretical contraceptive protection scores given that cervical mucus was assessed only every 3–4 days and may have underestimated maximum scores. The study also failed to test delaying pill intake for different time intervals or missing more than one pill, limited recruitment to women with BMI <32 kg/m², and relied on pharmacodynamic surrogates of cervical mucus and ovulation to estimate contraceptive effects.

The current study is the only one to examine the effect of deliberate nonadherence to a POP, in contrast to the wealth of evidence for the combined oral contraceptive pill, the investigators noted.

“We do not think one study is enough for us to recommend changing the current Selected Practice Recommendations regarding the ‘three-hour window’,” they added. [MMWR Recomm Rep 2016;65:1-66]

A dose is considered missed if the time that has elapsed since it should have been taken is more than 3 hours. In such situations, the US Selected Practice Recommendations for Contraceptive Use recommends to do the following: 1) take one pill as soon as possible; 2) continue to take pills daily, one each day, at the same time each day; 3) use back-up contraception (eg, condoms) or avoid sexual intercourse until pills have been taken correctly, on time, for two consecutive days; and 4) consider emergency contraception in case of unprotected sexual intercourse. [MMWR Recomm Rep 2016;65:1-66]