Within their first year of using oral contraceptive pills, at least 50 to 60 percent of women report irregular pill taking. Based on this high rate of missed oral contraceptive pills, it seems that contraceptive reliability may be compromised. The finding that follicular development begins initially during the pill-free interval of seven days has led to the idea that missing the first pills of the cycle (thus extending the pill-free interval) would be critical in terms of escape ovulation. Possibly this concern would increase if the woman were using a triphasic combination. Elomaa and associates conducted a study to test the hypothesis that omitting the first three pills of the oral contraceptive pill cycle leads to escape ovulation.

The 99 study subjects were randomly assigned to receive one of the following treatments: 75 μg of monophasic gestodene and 30 μg of ethinyl estradiol, a triphasic gestodene–ethinyl estradiol combination or 150 μg monophasic desogestrel and 20 μg of ethinyl estradiol. Noncompliance was simulated by extending the pill-free period from seven days (study period 1) to 10 days (study period 2). After the 21-day cycle was completed, follicular size was measured by ultrasonography, and hormonal levels were analyzed.

During or after the standard seven-day pill-free interval, the leading follicle grew up to or beyond 13 mm in 9 percent, 6 percent and 27 percent of the subjects in the monophasic gestodene, triphasic gestodene and monophasic desogestrel groups, respectively. During or after the extended pill-free interval, follicular growth of 13 mm or more occurred in 41 percent, 47 percent and 70 percent of patients in each respective group. In study period 1, statistically significant differences were noted between the monophasic gestodene and monophasic desogestrel groups, and between the triphasic gestodene and mono-phasic desogestrel groups. In study period 2, the monophasic desogestrel group differed significantly from the monophasic gestodene group.

Normal ovulation was not observed in any of the patients after either a seven- or a 10-day pill-free period. The diameter of the largest follicle on the third day of treatment was 12 mm. Two days later it was 15 mm, and it grew to 21 mm by treatment day 7. This finding provides strong evidence against normal ovulation but is consistent with a luteinized unruptured follicle. Serum progesterone levels did not indicate normal ovulation. The level of follicle stimulating hormone reached a maximal concentration in most women during the first pill-free period, indicating complete pituitary recovery. Increases in estradiol levels were experienced by all patients, although variability was marked. Results indicated that no normal ovulation occurred in this study of 98 standard oral contraceptive pill cycles and 98 cycles covering the pill-free extended period of 10 days.

The authors conclude that extending the pill-free interval to 10 days does not alone compromise the efficacy of combination oral contraceptive pills. This seems to be true whether monophasic or triphasic oral contraceptive pills are used. However, ovarian recovery as evidenced by estradiol concentrations and follicular growth is significantly more rapid in women using an oral contraceptive pill with only 20 μg of ethinyl estradiol.

The practical consequences of this study, in terms of patient counseling, come from the low risk of ovulation after a patient forgets the first three pills of the new cycle. If no additional pills are missed, ovulation is unlikely to occur. If the woman cannot remember the intake of the pills, she should be advised to use an additional barrier method of contraception for one week.