Intravenous immune globulin: another disappointing treatment for recurrent pregnancy loss.

Abstract

Recurrent pregnancy loss (RPL) occurs in about 1% of couples attempting pregnancy. The majority of cases are unexplained and there are no treatments proven to improve outcomes in idiopathic cases. This is extremely frustrating for patients and clinicians and has led to the widespread use of therapies with uncertain efficacy. High quality data are difficult to obtain because many couples (and their physicians) are unwilling to consider randomisation to placebo arms of clinical trials. In turn, this perpetuates the use of unproven interventions. Many cases of RPL are thought to be due to abnormal inflammation in gestational tissues. Indeed, there is considerable evidence for this in animal models (Sharma. Int J Dev Biol 2014;58:219). However, clear pathophysiologic pathways in humans are lacking. Nonetheless, suppression of inflammation is a biologically plausible treatment for RPL. In this issue of BJOG, Christiansen and coworkers report the results of a randomised controlled trial of intravenous immune globulin (IVIG) and placebo in women with secondary (prior birth reaching 28 weeks’ gestation) RPL (Christiansen BJOG; 2014;122:501–9). Participants received about 0.4 mg/kg of IVIG starting with a positive pregnancy test, with repeat doses on a serial basis until 15 weeks’ gestation in ongoing pregnancies. There was no difference in live births in women treated with IVIG or placebo. The study had numerous strengths including women with at least four losses, enrollment early in gestation and only after normally rising quantitative human chorionic gonadotropins, the use of albumin as a placebo, and a relatively large number of patients. It is noteworthy that maternal side effects including skin rash and headaches were increased in women receiving IVIG. In addition, rare but serious complications of IVIG such as anaphylaxis and haemolytic anaemia may occur. Also, IVIG is quite expensive and cumbersome to receive. Accordingly, IVIG cannot be recommended for the treatment of idiopathic RPL. An interesting secondary outcome was a 10-day increase in average gestational length in pregnancies treated with IVIG. Although this finding may have been due to chance, it is possible that immunosuppression decreases the risk of preterm birth. Low dose aspirin (with anti-inflammatory properties) also has been associated with a decrease in preterm birth (Duley et al. Cochrane Database Syst Rev 2007;18:CD004659) and this observation deserves further study. Results of recent trials for the treatment of women with RPL have been disappointing. For example, low dose aspirin and heparins do not reduce the risk of pregnancy loss (Kaandorp et al. N Engl J Med 2010;362:1586). On the other hand, studies such as the one by Christiansen and colleagues are encouraging. They demonstrate that it is possible to conduct high-quality, ethical trials in women with RPL. Only through similar studies will it be possible to identify novel causes of and effective treatments for RPL. Bob Silver has no conflicts to declare.