P-504 Pregnancy outcome of intravenous immunoglobulin in women with recurrent pregnancy loss
Authors: Han J , Lee S K , Park J , Park J C , Han A 
Published: June 2023

Abstract

Study question
Does intravenous immunoglobulin(IVIG) increase live births in recurrent miscarriage(RM) women with cellular immune abnormality such as high NK cell level and cytotoxicity and TNF-α/IL-10 ratio?

Summary answer
IVIG treatment increased the live birth rate of RM women with abnormal cellular immunity.

What is known already
Various causes of RM have been identified but even with a detailed evaluation, almost half of the cases have unidentified etiologies. Immune imbalance is one of the proposed potential etiologies of these idiopathic RM. To regulate abnormal cellular immunity, treatment such as IVIG is proposed to improve pregnancy outcomes. However, the use of IVIG in RM is still controversial.
In addition, one of the widely used indicators of immune imbalance in pregnancy is the NK cell level, but there is a disagreement in setting the cut-off value. The percentage varies from 12 to 18%.

Study design, size, duration
RM was defined as women with two or more spontaneous abortions and in total, 987 RM women visited Department of Obstetrics and Gynaecology, Konyang University Hospital(KYUH) from January 2007 to December 2020. Only those with a full evaluation and known treatment outcome were included. A total 204 idiopathic RM and 209 RM women with known aetiology were enrolled.

Participants/materials, setting, methods
We investigated the pregnancy outcome by sorting the patients into seven subgroups depending on abnormal cellular immunity including NK cell level, NK cell cytotoxicity and TNF-α/IL-10 ratio. Then, to verify the cut-off value(16.1%) of NK cell level which we set in our previous study, patients were classified into three groups according to their NK cell level: 1) &lt;12%(low), 2) 12-16%(moderate), 3) &gt;16%(high).

Main results and the role of chance
Among all RM women with at least one abnormal cellular immunity were treated with IVIG and the overall live birth rate (LBR) was 80.2%. The group which did not have IVIG treatment showed an overall LBR of 78.0%. Within the 7 groups with abnormal cellular immunity, the group with both high NK cell toxicity and TNF-α/IL-10 ratio showed the highest LBR, 100% of LBR and the group with both high NK cell level and TNF-α/IL-10 ratio showed the lowest treatment outcome, 71.4%. To verify the adequacy of our cut-off value, after excluding those with high NK cell cytotoxicity and TNF-α/IL-10 ratio, 152 patients were classified into low, moderate, and high level of NK cells. LBR were 81.0%, 72.5%, and 76.9%.

Limitations, reasons for caution
The study was designed retrospectively, resulting in numerous follow-up losses. It is a single-centered study that may not be enough to generalize the diagnosis method and treatments from these findings. Moreover, IVIG is an expensive drug that may lead to certain patient preferences.

Wider implications of the findings
The study may provide evidence in selecting RM patients with immune abnormalities to be treated with IVIG and raise their pregnancy outcomes. We can also apply these results to the reproductive failure group. A detailed evaluation and an evidence-based treatment are important.

Trial registration number
not applicable