Progestogen-only emergency contraception.

Madam We read with great interest the editorial on progestogen-only emergency contraception (POEC).1 The author refers incorrectly to a July 2002 article as the first case report of ectopic pregnancy following failed postcoital POEC. In late 2000 we undertook a post-marketing surveillance study of POEC prescription in France in order to investigate the efficacy and safety of this method in ‘real life’ use. Our results, published in July 2001, covered in excess of 2500 POEC prescriptions and included reports of three cases of ectopic pregnancy following POEC failures.2 We addressed the question of a possible association between POEC use and ectopic pregnancy via a two-fold analysis of the data available at that time. First, as an incidence rate within the context of the study results. Second, as an extrapolated incidence based on the number of spontaneously reported cases of ectopic pregnancies after POEC failures relative to the number of POEC units that we knew had been bought during the same period. We concluded at that time that it was unlikely that the incidence of ectopic pregnancy was increased after POEC failure. A recently published World Health Organization (WHO) multicentre clinical study presented data from an additional 2712 women who had taken levonorgestrel emergency contraception, thus bringing us one step closer to an estimation of incidence in a controlled clinical environment where there is minimal risk of under-reporting.3 In this study, 44 pregnancies were observed (1.6%) of which one was tubal (2.2%); an incidence rate not significantly different from the reported spontaneous incidence of 11–19 per 1000 pregnancies.4 This conclusion is supported by recent data on POEC’s mechanism of action, which seems to be different from that of progestogen-only pills. It appears that POEC acts mainly by ovulation blockade or delay and that postovulatory events play little, if any, role in its efficacy.5 Our own data, based on nearly 4 years of postmarketing surveillance, show that altogether approximately 4.4 million units of our POEC product have been sold, mainly in the European Union. To date, eight ectopic pregnancies have been spontaneously reported after failure of POEC. Assuming that the pregnancy rate following POEC use is 1.6% in clinical trials3 and closer to 3% in real-world use,2 at least 70 000 pregnancies and thus a minimum of 700 spontaneous ectopic pregnancies should have been reported. The fact that we have received spontaneous reports of only eight ectopic pregnancies confirms that severe adverse events are indeed significantly under-reported. Even if as few as 1% of ectopic pregnancies are reported, the current data do not substantiate a conclusion of increased risk associated with POEC use. We agree with the authors that further research is merited to determine whether pregnancies following POEC use are more likely to be ectopic than those occurring in the general population. Nevertheless, it is important to point out that POEC protects against ectopic pregnancy overall by preventing conception. Because POEC is not 100% effective, however, patients and providers should be alert to the symptoms of ectopic pregnancy in the event of a method failure. Our product’s patient information leaflet specifically defines ectopic pregnancy and salpingitis and cautions women who have a history of either one to seek medical advice prior to taking POEC. The summary of product characteristics reminds providers of the importance of performing a pregnancy test in case of suspected failure (menstrual period delayed by more than 5 days or abnormal bleeding at the expected date of the menstrual period). We conclude that the data presented by the authors do not warrant any change in our current recommendations. We shall remain vigilant regarding this issue and will take appropriate measures to communicate any new information as it becomes available.