A randomized clinical trial to determine optimal infertility treatment in older couples: the Forty and Over Treatment Trial (FORT-T)

Abstract

Objective: To determine the optimal infertility therapy for women at the end of their reproductive potential.

Design: Randomized clinical trial.

Setting: Academic medical centers and private infertility center in a state with mandated insurance coverage.

Patient(s): Couples with ≥ 6 months of unexplained infertility; female partner aged 38-42 years.

Intervention(s): Randomized to treatment with two cycles of clomiphene citrate (CC) and intrauterine insemination (IUI), follicle stimulating hormone (FSH)/IUI, or immediate IVF, followed by IVF if not pregnant.

Main outcome measure(s): Proportion with a clinically recognized pregnancy, number of treatment cycles, and time to conception after two treatment cycles and at the end of treatment.

Result(s): We randomized 154 couples to receive CC/IUI (N = 51), FSH/IUI (N = 52), or immediate IVF (N = 51); 140 (90.9%) couples initiated treatment. The cumulative clinical pregnancy rates per couple after the first two cycles of CC/IUI, FSH/IUI, or immediate IVF were 21.6%, 17.3%, and 49.0%, respectively. After all treatments, 110 (71.4%) of 154 couples had conceived a clinically recognized pregnancy, and 46.1% had delivered at least one live-born baby; 84.2% of all live-born infants resulting from treatment were achieved via IVF. There were 36% fewer treatment cycles in the IVF arm compared with either COH/IUI arm, and the couples conceived a pregnancy leading to a live birth after fewer treatment cycles.

Conclusion(s): A randomized controlled trial in older women with unexplained infertility to compare treatment initiated with two cycles of controlled ovarian hyperstimulation/IUI versus immediate IVF demonstrated superior pregnancy rates with fewer treatment cycles in the immediate IVF group.

Clinical trial registration number: NCT00246506.

Keywords: Advanced reproductive age; FORT-T Trial; clomiphene citrate; controlled ovarian hyperstimulation; follicle-stimulating hormone; intrauterine insemination (IUI); in vitro fertilization; unexplained infertility.

Figure 1. Screening, Randomization, and Enrollment of Study Couples

When we considered only the first 2 cycles of treatment, the results were identical except for two couples in the IVF arm who discontinued treatment after the first IVF cycle. ^a 25 couples chose to discontinue treatment after a median of 4.0 cycles (interquartile range, 3 to 5 cycles) over a median duration of 12.2 months (interquartile range, 8.8 to 17.4 months). ^b The median duration of follow-up for these couples whom we were unable to contact was 18.3 months (interquartile range, 12.0 to 21.4 months) and was 17.5 months (interquartile range 12.3 to 21.9 months) among couples who completed follow-up.