A systemic review of intravenous immunoglobulin G treatment in women with recurrent implantation failures and recurrent pregnancy losses

Abstract

Over the last few decades, the advancement in reproductive technologies and protocols to improve embryo quality through culture techniques and genetic testing to eliminate chromosomally abnormal embryos resulted in better pregnancy rates and outcomes after fertility treatments. Unfortunately, some patients still struggle with recurrent implantation failures (RIFs) and recurrent pregnancy losses (RPLs). Immune etiologies have been attributed to play an important role in some of those patients. Maintaining a pre‐conceptional anti‐inflammatory environment for implantation and pregnancy continuation yields superior results. Intravenous immunoglobulin G (IVIG) treatment has been reported to enhance reproductive outcome in patients with RIF and RPL with immune dysregulations. In this systemic review, we analyzed outcomes of IVIG trials for RIF and RPL, its mechanism of action, dosing, administration, side‐effects, and evidence for its use in women with RIF and RPL.

Outcomes of Empirical Treatment With Intravenous Immunoglobulin G Combined With Low-Dose Aspirin in Women With Unexplained Recurrent Pregnancy Loss

“… 33 To summarize, most recent meta-analyses suggested that initiation of IVIG before conception, and treatment in women with abnormal immunity such as increased NK cell levels, could have a potentially beneficial effect on the live birth rate, although the evidence is still at level 2. 31 In our study, the live birth rate was high regardless of type of RPL, timing of IVIG, and presence of autoantibodies. However, our study population had more patients with primary RPL, who were treated after conception.…”

“…The subgroup analyses vary from study to study, and due to heterogeneity of study populations, opinions on the efficacy of IVIG in recent meta-analyses are conflicting. 4 6 29 30 31 For example, Wang et al 29 concluded that IVIG may have potential benefits in the live birth rate in URPL, but evidence is insufficient (relative risk [RR], 1.25; 95% confidence interval [CI], 1.00–1.56; P = 0.05). However, subgroup analysis showed that the live birth rate marginally increased in secondary RPL (RR, 1.26; 95% CI, 0.99–1.60; P = 0.06), which is similar to that of the Egerup et al’s study, 32 and significantly increased in patients who received IVIG before conception (RR, 1.67; 95% CI, 1.3–2.14; P < 0.001).…”

“…The live birth rate was 75% up to 12 weeks of pregnancy and 95% up to 30 weeks of pregnancy. However, considering the half-life of IVIG, Saab et al 31 recommended that the interval of IVIG should not exceed 3 to 4 weeks. In our study, a low-dose of IVIG was administered every 2 weeks, leading to a high live birth rate in both the natural pregnancy and ART groups, so this protocol seems to be appropriate for patients with URPL.…”

Human immune globulin treatment controls Zika viremia in pregnant rhesus macaques

“…One potential cause for increased perivillous fibrin in both Ig-treated groups compared to the mock controls is direct injury to the syncytiotrophoblast from nonspecific antibody binding to the syncytiotrophoblast that could be activating complement. Interestingly, human IVIG is used to treat several disorders in pregnancy, and does not seem to lead to direct syncytiotrophoblast injury in those instances, suggesting that the nonspecific injury to the rhesus macaque villi may be a species-specific effect of the administration of human IgG [ 31 , 32 ]. There has been some evidence of increased fetal growth restriction and perhaps pre-term birth in a recently tested HIG product to prevent congenital CMV; therefore it is important to continue to assess safety of these products during pregnancy [ 33 ].…”

Transaminase elevation during the first trimester and early pregnancy loss in patients with recurrent spontaneous abortion: a cross-sectional study

“…Hepatocellular injury caused by high-dose IVIG has been reported 27 . A previous review recommended that patients with recurrent pregnancy loss should have liver function tests before using IVIG 28 . Our results clearly indicate that IVIG using in early pregnancy increased the risk of liver injury.…”