Treatment of recurrent IVF failure and human leukocyte antigen similarity by intravenous immunoglobulin

Abstract

This study sought to assess the efficacy of intravenous immunoglobulin (IVIg) in improving pregnancy rates and outcome, in a select group of patients with repeated IVF failure and human leukocyte antigen (HLA) similarity. Couples suffering from recurrent IVF failure, defined as at least seven attempts at embryo transfer with no successful implantations, who were found to share at least three HLA loci, and a negative cross-match test, were included in the study. The treatment consisted of two 30 g IVIg doses: one before oocyte retrieval, and a second as soon as a fetal pulse was identified on ultrasound. Ten couples comprised the study group. In total, these couples had undergone 98 IVF cycles with no successful pregnancies prior to initiation of the study. Following a total of 18 IVIg courses, seven women conceived, two women twice. Up to date, five women have delivered at least one live fetus, at 27 weeks or later. One woman is currently in the early third trimester of a twin pregnancy, and one woman had a late abortion at 19 weeks. The results suggest that couples with recurrent IVF failure and HLA similarity, may benefit from IVIg treatment.

Assessment and treatment of repeated implantation failure (RIF)

“…On the other hand, high dose IVIg administration carries less risk and was found to benefit patients with RIF who share HLA alleles with their partner [34]. Though the number of shared alleles justifying administration of IVIg treatment has not been determined, we have successfully treated patients with as few as one shared allele.…”

“…The HLA compatibility system evidently plays a role in this recognition. Couples who share common HLA alleles may experience recurrent pregnancy loss [20], or as suggested by Elram et al [34], may suffer from RIF. The exact molecular mechanism to explain why shared HLA alleles among couples are associated with recurrent pregnancy loss or RIF is still obscure.…”

“…Though the number of shared alleles justifying administration of IVIg treatment has not been determined, we have successfully treated patients with as few as one shared allele. Treatment consists of 30 g of IVIg before embryo transfer (ET) and a second similar dose when a fetal heart rate is noticed [34].…”

“…The benefit of such treatment is still questionable, and the data are conflicting [4,24]. Elram et al [34] were the first to suggest that patients with RIF and HLA allele sharing can benefit from IVIg treatment. Nevertheless, due to the high costs of both HLA testing and IVIg treatment, we suggest that the assessment of the immune system contribution to RIF be carried out last, and only after all other causes are investigated, treated or ruled out.…”

“…However, in the extreme situation, it may interfere with implantation, since dissimilarity of HLA is crucial also at the very beginning of the implantation process, during which the immune system plays an important role. If such a similarity is found, high dose IV immunoglobulin (IVIg) should be offered before embryo transfer as suggested by Elram et al [34], followed by an additional dose as soon as a heart beat is visualized, at about 6 weeks of gestation. Preliminary results using intralipid infusion to support implantation are rather encouraging.…”