Background: Mild in-vitro fertilisation (IVF) treatment might lessen both patients' discomfort and multiple births, with their associated risks. We aimed to test the hypothesis that mild IVF treatment can achieve the same chance of a pregnancy resulting in term livebirth within 1 year compared with standard treatment, and can also reduce patients' discomfort, multiple pregnancies, and costs. Methods: We did a randomised, non-inferiority effectiveness trial. 404 patients were randomly assigned to undergo either mild treatment (mild ovarian stimulation with gonadotropin-releasing hormone [GnRH] antagonist co-treatment combined with single embryo transfer) or a standard treatment (stimulation with a GnRH agonist long-protocol and transfer of two embryos). Primary endpoints were proportion of cumulative pregnancies leading to term livebirth within 1 year after randomisation (with a non-inferiority threshold of -12·5%), total costs per couple up to 6 weeks after expected date of delivery, and overall discomfort for patients. Analysis was by intention to treat. This trial is registered as an International Standard Randomised Clinical Trial, number ISRCTN35766970. Findings: The proportions of cumulative pregnancies that resulted in term livebirth after 1 year were 43·4% with mild treatment and 44·7% with standard treatment (absolute number of patients=86 for both groups). The lower limit of the one-sided 95% CI was -9·8%. The proportion of couples with multiple pregnancy outcomes was 0·5% with mild IVF treatment versus 13·1% (p<0·0001) with standard treatment, and mean total costs were €8333 and €10745, respectively (difference €2412, 95% CI 703-4131). There were no significant differences between the groups in the anxiety, depression, physical discomfort, or sleep quality of the mother. Interpretation: Over 1 year of treatment, cumulative rates of term livebirths and patients' discomfort are much the same for mild ovarian stimulation with single embryos transferred and for standard stimulation with two embryos transferred. However, a mild IVF treatment protocol can substantially reduce multiple pregnancy rates and overall costs.,
The Lancet
Erasmus MC: University Medical Center Rotterdam

Heijnen, E. M., Eijkemans, R., de Klerk, C., Polinder, S., Beckers, N., Klinkert, E., … Fauser, B. (2007). A mild treatment strategy for in-vitro fertilisation: a randomised non-inferiority trial. The Lancet, 369(9563), 743–749. doi:10.1016/S0140-6736(07)60360-2