P-643 Long-term pregnancy outcomes in women with normogonadotropic anovulation and clomiphene failure: follow-up study of the M-ovin trial

Abstract

Abstract Study question What are the long-term outcomes after gonadotrophins versus clomiphene citrate (CC) with or without intrauterine insemination (IUI) in women with normogonadotropic anovulation and clomiphene failure? Summary answer The long-term cumulative chance for delivering at least one live birth is 78% for continuing CC and 84% for switching to gonadotrophins. What is known already CC has long been used as first line treatment for ovulation induction in women with normogonadotropic anovulation, but the best treatment for CC failure was unknown. Between 2009 and 2015, 666 women with normogonadotropic anovulation and CC failure were randomised to gonadotrophins or continued treatment with CC for another six cycles, with or without IUI. Switching to gonadotrophins increased the chance of live birth by 11% over continued treatment with CC after six failed ovulatory cycles, at a cost of €15 258 per additional live birth, while the addition of IUI did not increase live birth rates. Study design, size, duration We asked women that had been included in the M-ovin trial 6 to 13 years ago for consent to participate in this follow-up study. In the M-ovin trial, 666 women that failed to conceive over 6 ovulatory cycles had been allocated to switching to gonadotrophins versus continuing treatment with CC. Participants/materials, setting, methods The participating women were asked to complete a web-based questionnaire. The primary outcome of this study was cumulative live birth. Secondary outcomes included fertility treatments, clinical pregnancies, multiple pregnancies, miscarriage, stillbirth, ectopic pregnancy, neonatal outcomes and pregnancy complications. Main results and the role of chance We managed to contact 570 women of the 666 (85.6%) and retrieved follow-up data for 347 women of whom 176 had been originally allocated to gonadotrophins and 171 to CC. After a median follow-up time of 8 years (range 6-13), 148 women had a live birth (84.1%) in the gonadotrophin group and 133 women had a live birth (77.8%) in the CC group (RR 1.40 95% CI 0.90 – 2.17). A second live birth occurred in 80 of 176 women (45.5%) in the gonadotrophin group and in 77 of 171 women in the CC group (45.0%) (RR 1.01, 95% CI 0.83 – 1.22). A third live birth occurred in 7 of 176 women (4.0%) in the gonadotrophin group and in 11 of 171 women (6.4%) in the CC group. The use of fertility treatments in the follow-up period was comparable between both groups. The number of twin pregnancies were also comparable. Limitations, reasons for caution In 10.7% of the women, most having a follow-up period above 10 years, contact details had been lost. Therefore, not all eligible women could be approached to participate in this study. It should be realised that preliminary results are presented. Wider implications of the findings In women with normogonadotropic anovulation and CC failure, continuous treatment with CC for another six cycles is an effective alternative in view of the long-term live birth rates, without the extra costs of gonadotrophins. Trial registration number This follow-up study was registered in the OSF Register, https://osf.io/pf24m. The original M-ovin trial was registered in the Netherlands Trial Register, number NTR1449.