Disclosures: Dr. Stephenson disclosed receiving faculty honorarium from EMD Serono Inc. The study was supported by the Canadian Blood Services/Bayer Partnership Fund, the National Institutes of Health, and Talecris BioTherapeutics.
ATLANTA — Intravenous immunoglobulin was not beneficial in the treatment of idiopathic secondary recurrent miscarriage in the largest prospective randomized IVIG trial in this setting.
The live birth rate was 70% for women who received intravenous immunoglobulin and 63% for those given saline in the phase III multicenter trial of 77 women with a history of pregnancy of at least 20 weeks followed by at least three unexplained miscarriages of less than 20 weeks, all with the current partner. The difference was not statistically significant.
Once a pregnancy reached 6 weeks' gestation, the live birth rate was 94% in both groups, said Dr. Mary D. Stephenson, director of the recurrent pregnancy loss program at the University of Chicago.
Mean birth weights were significantly higher in the IVIG group at 3,711 g vs. 3,140 g in the control group (P value less than .010). When preterm infants and twins were excluded, however, birth weights were not statistically different (3,711 g vs. 3,358 g).
The study was designed to enroll 178 women, but was stopped early based on these interim results, said Dr. Stephenson, who called the key finding surprising.
She suggested that the favorable live birth rates in both groups may have been due to close monitoring with ultrasound in the first trimester and supportive care throughout the pregnancy, which have been shown to be advantageous in women with recurrent miscarriage.
“I also think it could be because we're not yet there in being able to select the most appropriate patients that could benefit from such immunotherapy,” she said. “Only 18% of prior miscarriages had been sent for chromosome testing, so that raises the question as to whether there were too many miscarriages that may have had random chromosome errors.”
A recent meta-analysis of eight randomized trials involving 442 women found a significant increase in live births following IVIG use in women with a secondary recurrent miscarriage (odds ratio, 2.71), while women with a primary miscarriage did not have the same benefit (OR, 0.66). The authors recommended further randomized trials, however, as the studies had small sample sizes and lacked homogeneity (BJOG 2007;114:134-42). When data from the current study were combined with data from the four prior secondary miscarriage trials in the meta-analysis, the odds ratio for a live birth was 2.16, favoring IVIG, Dr. Stephenson said.
The current study enrolled 82 women and after 5 withdrawals, randomized 38 women to IVIG (Gamunex or Gamimune) 500 mg/kg and 39 women to an equivalent volume of normal saline infused prior to ovulation for a maximum of six cycles and continued every 4 weeks until 18-20 weeks of pregnancy.
There were 23 pregnancies in the IVIG group and 24 in the control group. There was no difference in mean maternal age (36 vs. 35 years), mean body mass index (26 vs. 25 kg/m