Anticardiolipin and/or anti-β2-glycoprotein-I antibodies are associated with adverse IVF outcomes

Abstract

Objective: The purpose of the study is to evaluate the effects of anticardiolipin (aCL) and/or anti-β2-glycoprotein-I (aβ2GPI) antibodies, namely antiphospholipid antibodies (aPL), on in vitro fertilization (IVF) outcomes.

Materials and methods: The study group comprised infertile women with aPL undergoing IVF-ET cycles. Controls were infertile women with tubal etiology without aPL. The impact of aPL on reproductive outcomes, such as oocyte quality, embryo quality, and implantation capacity, was compared between the study group and controls. Additionally, peripheral blood T cell subsets, such as T helper (Th)1, Th2, Th17, and T regulatory (Treg) cells and cytokines, were analyzed by the flow cytometry. Differences between the study group and controls were analyzed.

Results: A total of 132 infertile women, including 44 women with aPL, and 88 controls were sequentially recruited for this study. Women with aPL had lower numbers of total and perfect/available embryos and lower rates of MII oocytes, blastocyst formation, perfect and available embryos, implantation, clinical pregnancy, and take-home baby. Additionally, imbalanced Th1/Th2 and Th17/Treg ratios, significantly higher levels of serum IL-2, TNF-α, IFN-γ, and IL-17A, and a significantly lower serum IL-4 were noticed in women with aPL compared to controls.

Conclusion: Women with aPL such as aCL and/or aβ2GPI antibodies were associated with adverse IVF outcomes. Early screening for aPL and appropriate consultation for couples undergoing IVF should be considered. In addition, underlying immunopathology and inflammatory immune mechanisms associated with aPL should be further explored.

Keywords: IVF outcomes; anti-β2-glycoprotein-I; anticardiolipin; antiphospholipid syndrome; pregnancy outcome.

Figure 1

The patient selection scheme for aCL and/or aβ2GPI antibody (aPL) positive women.

Figure 2

Composition and distribution of aCL and/or aβ2GPI antibodies (aPL). The most frequent antibody class was IgG, followed by IgM. The least prevalent antibody class was IgA. Additionally, multiple antibody-positive women accounted for 22.07% of all aPL-positive women.

Figure 3

The comparison of peripheral blood Th1, Th2, Th17, and Treg cells, and Th1/Th2 and Th17/Treg ratios in women with positive (n=10) and negative (n=10) aCL and/or aβ2GPI antibodies (aPL). Women with aPL had significantly higher levels of peripheral blood Th1 and Th17 cells and significantly lower levels of peripheral blood Th2 and Treg cells than controls. Th1/Th2 and Th17/Treg ratios were significantly higher in women with aPL than in controls. (A) The proportion of Th1 and Th2 cells in women with aPL and controls; (B) The proportion of Th17 and Treg cells in women with aPL and controls; (C) Comparison of the proportion of Th1, Th2, and Th1/Th2 ratio between women with aPL and control; (D) Comparison of the proportion of Th17, Treg, and Th17/Treg ratio between women with aPL and controls. **P<0.01, *P<0.05.

Figure 4

Comparison of serum levels including IL-2 (A), IL-4 (B), IL-6 (C), IL-10 (D), TNF-α (E), IFN-g (F), and IL-17A (G) in women with positive (n=25) and negative (n=25) aCL and/or aβ2GPI antibodies (aPL). Women with aPL had significantly higher levels of serum IL-2, TNF-α, IFN-γ, and IL-17A and significantly lower serum IL-4 than controls. However, IL-6 and IL-10 levels were not different. **P<0.01, *P<0.05.

Figure 5

Comparison of the clinical pregnancy rate, implantation rate, miscarriage rate, and take-home baby rate among aCL and/or aβ2GP1 antibody (aPL) positive women without treatment (the aPL group), aPL negative women (the control group), and aPL-positive women with treatment (the aPL treatment group). Regardless of stimulation protocol, the clinical pregnancy rate, implantation rate, and take-home baby rates of the control and aPL treatment groups were higher than those of the aPL group. When comparing the total embryo transfer outcomes of three protocols, the clinical pregnancy rate, implantation rate, and take-home baby rate of the control and the treatment groups were significantly higher than those of the aPL group. However, the miscarriage rates were not different among the three groups. (A) The fresh embryo transfer outcomes of GnRH agonist protocol; (B) The fresh embryo transfer outcomes of GnRH antagonist protocol; (C) The frozen embryo transfer outcomes of PPOS protocol; and (D) The total embryo transfer outcomes of three protocols. **P<0.01, *P<0.05.