“Missed pill” conception: fact or fiction?

SIR,-The report of Dr B G Molloy and others (18 May, p 1474) is interesting since it provides direct ultrasonographic evidence for follicular development during the seven day "pill free" period in women taking combined oral contraceptives. In one woman folliculogenesis was also evident on the seventh day of the subsequent pill cycle. We have for some time been using measurements of urinary oestrone-3-glucuronide concentrations to assess the antiovulatory effects of oral contraceptives. In women with normal (presumably) ovulatory menstrual cycles oestrone-3glucuronide concentrations of 10-60 nmol/l are seen during the follicular phase, and concentrations increase to 40-220 nmol/l towards mid-cycle; in women taking combined oral contraceptives concentrations are usually less than 30 nmol/l.' In a series of 24 cycles from 14 subjects, however, we observed two cycles during which oestrone-3glucuronide concentrations of 35-155 nmol/l occurred throughout the pill cycle. One woman was in her first cycle of pill use (Trinordiol) and the other had been taking the pill (Ovranette) for several months. These endocrine data therefore complement the ultrasonographic findings of Dr Molloy and others in suggesting that occasionally important follicular development can occur during use of combined oral contraceptives. We have also measured pregnanediol-3a-glucuronide in these women as a measure of luteal activity, but our observations do not suggest that either of these women had actually ovulated. We do not know whether either of these women did in fact miss taking a pill during the early part of the cycle; we would agree, however, that due to the potential for follicular development such an omission could present a possible risk of conception. M A SHAw Department of Pharmacology, University of Leeds, Leeds LS2 9JT D J BACK M C L'E ORME S FM GRIMMER