Positive Autoantibodies Are Associated With Adverse In Vitro Fertilization-Embryo Transfer Outcomes

Background:Autoantibodies refer to antibodies against own tissues,organs,cells and cell components,anti-Ro/SSA and/or anti-La/SSB（anti-SSA/SSB）antibodies and anticardiolipin（a CL）and/or anti-β2-glycoprotein-I antibodies（anti-β2-glycoprotein-I,aβ2GPI）are common autoantibodies,and these antibodies have been reported to be closely related to adverse pregnancy outcomes,and immune-inflammatory disorders may be the underlying immunopathological mechanism.However,the effects of antiSSA/SSB antibodies and a CL and/or aβ2GPI antibodies on in-vitro fertilization（IVF）outcomes have not been systematically studied.Methods: The study included 55 anti-SSA/SSB antibodies-positive infertile women and61 autoantibodies-negative control women,and 44 a CL and/or aβ2GPI antibodiespositive infertile women and 88 autoantibodies-negative control women,In order to exclude the influence of different ovulation induction protocols on the results,we further divided the study group and controls into the gonadotropin-releasing hormone（Gn RH）agonist protocol group,Gn RH antagonist protocol group and progestin-primed ovarian stimulation（PPOS）protocol group for data statistics and analysis.We analyzed baseline and clinical characteristics,oocytes quality（number of oocytes,M II oocytes rate and fertilization rate）,embryo quality（number of embryos,perfect and available embryo rate,blastocyst formation rate）,implantation capacity（clinical pregnancy rate,implantation rate,miscarriage rate and take-home baby rate）,as well as related immune indicators such as T helper（Th）,regulatory T cells（Treg）,and cytokines between anti-SSA/SSB antibodies-positive women and a CL and/or aβ2GPI antibodies-positive and controls,respectively.Results: 1.Baseline and clinical characteristics,including age,body mass index（BMI）,basal sex hormone levels,thyroid-related hormones,fasting blood glucose and fasting insulin between anti-SSA/SSB antibodies-positive women and a CL and/or aβ2GPI antibodies-positive women and controls were not statistically different.2.Compared with controls,anti-SSA/SSB antibodies-positive women had decreased proportions of peripheral blood Th and natural killer（NK）cells.3.Compared with controls,anti-SSA/SSB antibodies-positive women had increased peripheral blood Th17 cells and decreased Treg cells,a CL and/or aβ2GPI antibodiespositive women had increased peripheral blood Th1 and Th17 cells,and decreased Th2 and Treg cells.4.Compared with controls,anti-SSA/SSB antibodies-positive women had significantly higher levels of serum tumor necrosis factor（TNF）-ɑ and interleukin（IL）-17 A,a CL and/or aβ2GPI antibodies-positive women had significantly higher levels of serum IL-2,TNF-ɑ,Interferon（IFN）-γ,and IL-17 A,and a significantly lower level of IL-4.5.Compared with controls,anti-SSA/SSB antibodies-positive women and a CL and/or aβ2GPI antibodies-positive women had lower perfect and available embryo rates,M II oocytes rate and blastocyst formation rate.6.Compared with controls,anti-SSA/SSB antibodies-positive women and a CL and/or aβ2GPI antibodies-positive women had lower clinical pregnancy rate,implantation rate,and take-home baby rate,and higher miscarriage rate.7.Compared with before treatment,a CL and/or aβ2GPI antibodies-positive women receiving low dose aspirin,hydroxychloroquine sulfate and low molecular weight heparin had higher perfect and available embryo rates,M II oocytes rate,blastocyst formation rate,clinical pregnancy rate,implantation rate and take-home baby rate.8.Compared with controls,anti-SSA/SSB antibodies-positive women had significantly lower neonatal birth weight,while week of delivery,mode of delivery,preterm birth rate and Apgar score at 5 min were not statistically different.Conclusion: Anti-SSA/SSB antibodies and a CL and/or aβ2GPI antibodies are associated with adverse embryonic and clinical IVF outcomes.Screening for these autoantibodies and proper counselling and treatment for couples undergoing IVF-ET should be considered.Underlying immunopathology associated with autoantibodies and reproduction should be explored further.