Abstract
The percentage of peripheral CD56+CD16+ NK cells in the early follicular phase on days 2–3 of the menstrual cycle in repeated implantation failure (RIF) patients was used to evaluate the impact of intravenous immunoglobulin (IVIG) on ART cycles. A total 283 patients with RIF consisting of at least 3 ART failures and at least 2 high quality embryo transfers were recruited. A logistic regression analysis for the peripheral immunological profile was completed to predict implantation success and compare the implantation and pregnancy rates between groups with ≤10.6 and >10.6% of CD56+CD16+ NK cells in the early follicular phase. The logistic regression and receiving operating curve analyses showed that patients with ≤ 10.6% of peripheral CD56+CD16+ NK cells in the early follicular phase showed a lower pregnancy rate within the RIF group without IVIG. Patients with peripheral CD56+CD16+ NK cells ≤ 10.6% and without IVIG treatment showed significantly lower implantation and pregnancy rates (12.3 and 30.3%, respectively) when compared with the CD56+CD16+ NK cells >10.6% group (24.9 and 48.0%, respectively, p < 0.05). Furthermore, the patients with CD56+CD16+ NK cells ≤ 10.6% given IVIG starting before ET had significantly higher implantation, pregnancy, and live birth rates (27.5, 57.4, and 45.6%, respectively) when compared with the non-IVIG group (12.3, 30.3, and 22.7%, respectively, p < 0.05). Our results showed that a low percentage of peripheral CD56+CD16+ NK cells (≤10.6%) in the early follicular phase is a potential indicator of reduced pregnancy and implantation success rates in RIF patients, and IVIG treatment will likely benefit this patient subgroup.
Highlights
With advances in assisted reproduction techniques (ART), high quality embryos can be imbedded into the uterus for pregnancy
When a single variable in the peripheral monocyte profile was used in the analysis model, both CD19 and CD56+CD16+ natural killer (NK) cell percentages demonstrated a significant correlation with ART pregnancy outcome (Table 2)
We found that a decreased percentage of peripheral CD56+CD16+ NK cells in the early follicle phase was significantly associated with low pregnancy rates using a logistic regression analysis
Summary
With advances in assisted reproduction techniques (ART), high quality embryos can be imbedded into the uterus for pregnancy. A substantial number of women suffer from the repeated implantation failure (RIF) of several embryos, regardless of quality [1]. Defective crosstalk between the embryo and endometrium in unexplained RIF patients was attributed to circulating peripheral blood mononuclear cells (PBMC) and immunological responses, with the exception of inherent genetic, anatomical, chromosomal, or endocrine abnormalities [2]. Increasing evidence indicates that immune cell or immunologic factors play an important role in the failure of both natural and ART-induced pregnancies [3,4,5]. Monocyte/macrophage lineage cell markers increase in the decidua/myometrium during pregnancy and may control trophoblast cell invasion into the myometrium while preventing a rejection of the semi-allogenic conceptus to provide an important barrier against invading pathogens [5, 6]
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