OBJECTIVE

IVIG is an established treatment in several autoimmune and inflammatory diseases and has been tested in several RCTs in recurrent miscarriage (RM) patients. Although clinically different disorders, RIF has been suggested to share many characteristics with early RM. Immunological parameters that seem associated with both RIF and RM are increased numbers of peripheral blood natural killer cells. There were several reviews of IVIG efficacy in RM patients with high NK cell, but there were few studies in RIF patients.

DESIGN

This retrospective study included 295 cases third IVF cycles between January 2011 and October 2015.

MATERIALS AND METHODS

In 295 cases with previous two IVF-ET failure cycles, 81 women had blood tests for NK cell assay and were treated with intravenous immunoglobulin (IVIG) 400mg/kg on ET day and repeated if pregnancy test was positive (IVIG group). We divided IVIG group into two groups with high NK cell (≥12%) group and normal NK cell (<12%) group.

RESULTS

Total pregnancy rate of third IVF cycle was 29.8% (88/295). In 81 cases, patients had blood tests for NK cell assay and were treated with intravenous immunoglobulin (IVIG group). Among IVIG group, patients with high NK cell (≥12%) were 58.0% (47/81) and normal NK cell (<12%) were 42.0% (34/81). Pregnancy rate was significantly higher in high NK cell group than in normal NK cell group [55.3% (26/47) vs. 26.5% (9/34), p=0.018]. And pregnancy rate was significantly higher in IVIG group with high NK cell than in no IVIG treatment patients [55.3% (26/47) vs. 24.8% (53/214), p=0.015]. But pregnancy rate showed no significant difference between normal NK cell IVIG group and no IVIG treatment patients [26.5% (9/34) vs. 24.8% (53/214), p=0.926]. IVIG treated patients with high NK cell showed improved IVF outcome than patients without IVIG treatment. But IVIG treatment with normal NK cell did not affect IVF outcome.

CONCLUSIONS

IVIG treatment enhances pregnancy rate in RIF patients with high NK cell, but do not affect IVF outcome in patients with normal NK cell. Our results showed that more than half of RIF patients had increased NK cell level. In these patients, IVIG treatment was resulted in increasing more than twice pregnancy rate. Therefore if clinicians encounter repeated IVF failure, we recommend proper evaluation and treatment about RIF causes including NK cell.