Abstract: P-398

Association Between Endometrial and Peripheral Blood Immune Profiles and Reproductive Outcome in Patients with Recurrent Pregnancy Loss, Repeated Implantation Failure and Infertility.

Presenter: Maria Salazar Garcia


Abstract


OBJECTIVE:This study is aimed to investigate if endometrial gene expression is associated with peripheral blood immune profile and reproductive outcome in women with recurrent pregnancy loss, repeated implantation failure and infertility.
DESIGN: Prospective cohort study view more

OBJECTIVE:This study is aimed to investigate if endometrial gene expression is associated with peripheral blood immune profile and reproductive outcome in women with recurrent pregnancy loss, repeated implantation failure and infertility.
DESIGN: Prospective cohort study
MATERIALS AND METHODS: Women were divided into 4 groups according to their reproductive history and included: controls (n=10, fertile women with at least one full term pregnancy), infertile (n=61, failure to achieve a successful pregnancy after 12 months or more of appropriate, timed unprotected intercourse or therapeutic donor insemination), RPL (n= 83, ≥ 2 spontaneous abortions) and RIF (n=64, ≥ 3 unsuccessful IVF/FET cycles). Endometrial biopsy was performed in mid-luteal cycle to determine their endometrial immune profile (EIP). The collected endometrial tissue was investigated for routine pathology evaluation and endometrial dating, and molecular analysis. mRNA was extracted from the endometrial tissue and converted into cDNA. IL-18, IL-15, fibroblast growth factor-inducible 14 (Fn14) and TNF weak inducer of apoptosis (TWEAK) were analyzed by quantitative RT-PCR. In addition, peripheral blood immunophenotype, NK cytotoxicity, and intracellular cytokine expression were analyzed by flow cytometry. 98 women attempted pregnancy within 6 months either by natural cycles (n= 45, 45.9%), IUI (n=7, 7.1%), IVF (n=7,7.1%) or FET (n=39, 39.8%) with personalized immunotherapy according to their profile. Differences between the groups were estimated using T-test and one-way ANOVA for continuous variables and Chi-square for categorical variables. Statistical significance was set at 0.05.
RESULTS: A total of 61 (62.2%) patients became pregnant. 1 patient lost follow up, 36 (59%) have ongoing pregnancies and 24 (39%) miscarried. EIP was significantly different between the groups (P=0.007). 90% of controls had a normal EIP when compared to 42.6% in the Infertility group, 45.8% in the RPL group and 51.6% in the RIF group. The low activation EIP was only presented in 10% of the RIF group while 31.3% and 23% from RPL and Infertility groups presented low immune activation. After the treatment, patients with low and over endometrial immune activation had similar pregnancy rates than the women with no dysregulation (P=0.727). Women who became pregnant had significantly lower peripheral blood NK cytotoxicity at the E:T ratio of 50:1 (23.8%±7.1 vs 27.2%±6.8, P =0.027), and 25:1 (18.6%±5.4 vs 21.0%±6.0, P =0.043) when compared with those of patients who failed to achieve pregnancy. The type of conception cycle (natural, IUI or IVF/FET) was not associated with pregnancy rate (P=0.387).
CONCLUSIONS: Dysregulated endometrial immune profile is associated with infertility, RPL and RIF. Lower peripheral blood NK cytotoxicity levels are associated with successful conception cycles. The pregnancy rate after the personalized immune treatment of endometrial immune profile is similar to that of women with normal endometrial immune profile. Further studies are needed to evaluate the use of EIP and peripheral blood immune profiles as predictors of reproductive outcome.

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