Intravenous immunoglobulin and idiopathic secondary recurrent miscarriage: a multicentered randomized placebo-controlled trial.
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.
Stephenson
Mary D
MD
University of Chicago Recurrent Pregnancy Loss Program, Department of Obstetrics and Gynecology, University of Chicago, 5841 S. Maryland Avenue (MC 2050), Chicago, IL 60637, USA. mstephen@babies.bsd.uchicago.edu
Kutteh
William H
WH
Purkiss
Susan
S
Librach
Cliff
C
Schultz
Patricia
P
Houlihan
Edwina
E
Liao
Chuanhong
C
D000026:Abortion, Habitual / Q000276:immunology / Q000517:prevention & control*; D000328:Adult; D004311:Double-Blind Method; D057239:Early Termination of Clinical Trials; D005260:Female; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D011247:Pregnancy; D011256:Pregnancy Outcome; D018873:Pregnancy Rate
D016756:Immunoglobulins, Intravenous