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 pregnancy outcome in couples with repeated unexplained in vitro fertilization (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 failure who were preparing for another fresh IVF cycle or replacement of cryopreserved embryos.

Intervention(s): Eligible women underwent a standard IVF stimulation using a long luteal phase GnRH analog protocol. Cryopreserved embryos were replaced after endometrial preparation with oral micronized estradiol and subsequent vaginal progesterone. The women were randomly selected to receive IVIG (500 mg/kg) or an equivalent volume of normal saline. The first infusion was 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 confirmed 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 cycles, 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, stringently defined by known determinants of IVF outcome.