Effect on pregnancy rates of the delay in the administration of levonorgestrel for emergency contraception: a combined analysis of four WHO trials

Background: Levonorgestrel is an effective method for emergency contraception (EC) and is used worldwide. Consistent with its mechanism of action in delaying ovulation, the earlier it is administered within 72 h of an unprotected act of intercourse, the more effective it is. There is uncertainty, however, about its effectiveness after 72 h. This analysis explores the effect of 24-h intervals of delay in levonorgestrel administration on pregnancy rates when used until 120 h of an unprotected act of intercourse.

Study design: Data were analyzed from 6794 women participating in four World Health Organization randomized trials and receiving 1.5 mg of levonorgestrel for EC in a single dose or split into two doses 12 h apart, within 48, 72 or 120 h of an act of unprotected intercourse. The pregnancy rates among women in successive days after an unprotected act of intercourse and odds ratios of pregnancy were calculated using logistic regression with the first day as the reference.

Results: For the four trials combined, odds ratios for pregnancy in the second, third and fourth day with respect to the first day were not significantly different from 1 at the 5% level of significance. On the fifth day, the odds ratio of pregnancy compared to the first day was almost 6.

Conclusions: Levonorgestrel for EC should be administered as soon as possible after unprotected intercourse. Delaying levonorgestrel administration until the fifth day after unprotected intercourse increases the risk of pregnancy over five times compared with administration within 24 h. It is uncertain whether levonorgestrel administration on the fifth day still offers some protection against unwanted pregnancy.