Excerpt
Aspects of the immunological relationship between mother and conceptus still remain a mystery, although the recent advances in molecular biology have enlightened some of the parameters that participate in feto-maternal cross-talk during implantation. The atypical expression of major histocompatibility complex (MHC), the specific roles of some hormones and cytokines, as well as the temporal and spatial distributions of uterine natural killer (uNK) cells, represent substantive parameters of feto-maternal immunotolerance during implantation [
1]. Although human maternal and fetal immunology is difficult to investigate, aberrant immune responses and an imbalanced cytokine network may be related to infertility, implantation failures after IVF, and recurrent pregnancy losses [
2]. Patients with recurrent implantation failure (RIF) should be tested for inherited and acquired thrombophilias. Each patient should be individually assessed and counseled regarding management with low-molecular-weight heparin (LMWH). Empirical treatment with LMWH, aspirin, or corticosteroids is not effective for women with RIF who have negative thrombophilic tests [
3]. If thrombophilic tests are normal, patients should be tested for immunological causes. The findings of a recent study suggest that increases in the percentage of CD56(dim) cells and NK cytotoxicity in peripheral blood may be important contributing factors for both RSA and IVF failure [
4]. Human leukocyte antigen (HLA)-DQA1*0505 sharing or the maternal killer immunoglobulin-like receptor (KIR) repertoire is associated with recurrent spontaneous abortion (RSA) or repeated implantation failure (RIF) [
5] and if abnormal, the patient might then benefit from intravenous immunoglobulin (IVIg) therapy [
3]. IVIg has been successful in the treatment of recurrent miscarriage and recurrent implantation failure among women with elevated anti-phospholipid antibodies (APA) and/or NK cell activity [
6]. When the pregnancy outcomes of women with a history of reproductive failure and elevated NK cell cytotoxicity treated with intralipid were compared with women treated with IVIg, no differences were seen [
6]. Side-by-side comparison showed that synthetic pre-implantation factor (sPIF) is equally effective to inhibit NK cell toxicity at a lower dose than intravenous gamma immunoglobulin or intralipid treatment currently used [
7]. sPIF is not yet available commercially, but intralipid infusions are available globally. Intralipid (IL) is a synthetic product composed of 10 % soybean oil, 1,2 % egg yolk phospholipids, 2.25 % glycerin, and water. When indicated, IL is infused 7–10 days prior to embryo transfer (ET), and one more time again after a positive pregnancy in women whose NKa is due to an autoimmune causes (antiphospholipid antibodies and/or antithyroid antibodies) [
8]. In cases of alloimmune implantation dysfunction (DQa and/HLA matching between the embryo recipient and the male partner), the same applies, but in this situation, the infusion is repeated at 2–4 week intervals until the 24th week of pregnancy [
8]. IL costs about 10 times less than IVIg, is not a blood product, and is without significant side effects [
8]. …
