Treatment of repeated unexplained in vitro fertilization failure with intravenous immunoglobulin: a randomized, placebo-controlled Canadian trial

Objective: To evaluate the effect of intravenous immunoglobulin (IVIG) on p regnancy outcome in couples with repeated unexplained in vitro fertilizatio n (IVF) failure. Design: Prospective, randomized, double blind, placebo-controlled clinical trial. Setting: A university-based and a free-standing IVF program. Patient(s): Fifty-one couples with a history of repeated unexplained IVF fa ilure who were preparing for another fresh IVF cycle or replacement of cryo preserved embryos. Intervention(s): Eligible women underwent a standard IVF stimulation using a long luteal phase GnRH analog protocol. Cryopreserved embryos were replac ed after endometrial preparation with oral micronized estradiol and subsequ ent vaginal progesterone. The women were randomly selected to receive IVIG (500 mg/kg) or an equivalent volume of normal saline. The first infusion wa s given on the day of embryo transfer or during the preceding 72 hours. The second infusion was given 4 weeks later if a clinical pregnancy was confir med by ultrasound. Main Outcome Measure(s): Live-birth rates. Result(s): Overall, the live-birth rates were 4/26 (15%) for the IVIG group and 3/25 (12%) for the placebo group (P=0.52). There were 39 fresh IVF cyc les, which yielded a clinical pregnancy rate of 28%, with live-birth rates of 4/21 (19%) for the IVIG group and 3/18 (17%) for the placebo group (P=0. 59). Conclusion(s): In this randomized clinical trial, IVIG did not improve the live-birth rate in couples with repeated unexplained IVF failure, stringent ly defined by known determinants of IVF outcome. (Fertil Steril(R) 2000;74: 1108-13. (C) 2000 by American Society for Reproductive Medicine).