Intravenous immunoglobulin and idiopathic secondary recurrent miscarriage: a multicentered randomized placebo-controlled trial.

Abstract

BACKGROUND:

Idiopathic secondary recurrent miscarriage may be associated with an abnormal maternal immune response to subsequent pregnancies. Intravenous immunoglobulin (IVIG) has been studied in randomized controlled trials (RCTs) with conflicting results. Therefore, a definitive trial was proposed.

METHODS:

We conducted an investigator-initiated, multicentered, randomized, double-blinded, placebo-controlled trial comparing IVIG with saline in women with idiopathic secondary recurrent miscarriage, defined as a history of at least one prior ongoing pregnancy followed by three or more consecutive unexplained miscarriages. Subjects received either IVIG 500 mg/kg or the equivalent volume of normal saline. Preconception infusions were administered 14-21 days from the projected next menstrual period. With documentation of pregnancy, the subject received the same infusion every 4 weeks until 18-20 weeks of gestation. The primary outcome was an ongoing pregnancy of at least 20 weeks of gestation.

RESULTS:

A total of 82 patients enrolled, of whom 47 had an index pregnancy. All ongoing pregnancies resulted in live births. Therefore, the live birth rates were 70% (16/23) in the IVIG group and 63% (15/24) in the control group (P = 0.760); odds ratio (OR) 1.37 [95% confidence interval (CI) 0.41-4.61]. Including only clinical pregnancies (embryo with cardiac activity at 6 weeks of gestation), the live birth rates were equivalent, 94% (16/17) and (15/16), respectively (P > 0.999); OR 1.07 (95% CI 0.06-18.62). Meta-analysis of randomized controlled trials (RCTs) evaluating IVIG for idiopathic secondary recurrent miscarriage revealed live birth rates of 70% (31/44) in the IVIG group and 62% (28/45) in the control group (P = 0.503); common OR 1.44 (95% CI 0.59-3.48).

CONCLUSIONS:

This is the largest RCT to date in which IVIG was evaluated in women with idiopathic secondary recurrent miscarriage; no treatment benefit was found. The meta-analysis, which combined our study results with two prior RCTs, also showed no significant effect of treatment with IVIG.

• Authors: Mary D Stephenson, William H Kutteh, Susan Purkiss, Cliff Librach, Patricia Schultz, Edwina Houlihan, Chuanhong Liao
• Journal: Human reproduction (Oxford, England) (Hum Reprod) Vol. 25 Issue 9 Pg. 2203-9 (Sep 2010) ISSN: 1460-2350 [Electronic] England
• PMID: 20634190 (Publication Type: Journal Article, Meta-Analysis, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Immunoglobulins, Intravenous

Topics

• Abortion, Habitual (immunology, prevention & control)
• Adult
• Double-Blind Method
• Early Termination of Clinical Trials
• Female
• Humans
• Immunoglobulins, Intravenous (therapeutic use)
• Pregnancy
• Pregnancy Outcome
• Pregnancy Rate