SUBCLINICAL INFLAMMATION LINKED TO ELEVATED AMH LEVELS AND DECREASED IVF PREGNANCY RATES

Abstract

OBJECTIVE: To investigate whether elevated levels of high-sensitivity C-reactive protein (hs-CRP), indicative of subclinical inflammation, may contribute to an increased prevalence of infertility. MATERIALS AND METHODS: All in vitro fertilization (IVF) and preimplantation genetic testing for aneuploidies (PGT-A) cycles resulting in embryo biopsies over a 12-month period at a large, multi-center, private practice were included in the analysis. A total of 93 patients were analyzed, stratified into two groups based on pregnancy outcomes: 75 pregnant patients (8 biochemical, 8 spontaneous abortions, and 59 ongoing pregnancies) and 18 non-pregnant patients. A multiparametric analysis was performed using cluster analysis to evaluate the significance of hs-CRP with respect to pregnancy. Statistical analyses included a two-tailed Student's t-test for continuous variables, a Chi-squared test for categorical variables, and Pearson correlation for correlation matrix analysis, with a p-value <0.05 defining statistical significance. GraphPad Prism (GraphPad Software) was utilized for statistical analysis. RESULTS: Hs-CRP levels were compared between pregnant and non-pregnant patients. While not significant (p=0.38), a trend emerged suggesting relatively higher levels of hs-CRP in the non-pregnant patient population. Subsequently, a multiparametric analysis was performed where we compared AMH, date of transfer, age, BMI, TSH, EMS, hs-CRP, TG, TPO, PCOS, and TSH with respect to pregnancy outcomes using cluster matrix analysis. The results demonstrated a significant positive correlation between hs-CRP and AMH in non-pregnant women (p=0.004). As a follow-up, the patient population was stratified based on their AMH levels (<1, 1-2, or >2 mg/mL), and hs-CRP levels were compared. Results highlighted that, in the non-pregnant patient cohort with AMH >2, hs-CRP levels were significantly higher than in patients with AMH <1 (p=0.008) or 1-2 (p=0.010). Between pregnant and non-pregnant patients with AMH >2, hs-CRP levels were significantly higher in the non-pregnant population only (p=0.0004). CONCLUSIONS: There is limited research on the direct association between hs-CRP and AMH levels, particularly in relation to pregnancy failure. However, both hs-CRP and AMH have been separately linked to pregnancy outcomes. Our findings, for the first time, suggest that Subclinical Inflammation due to high CRP could be associated with high AMH levels and could result in IVF treatment failure. Further studies are required to find If therapy targeting subclinical inflammation could help increase the rate of pregnancy in women with high AMH. Additionally, it is crucial to identify factors that could influence the interaction between AMH and HS-CRP with respect to pregnancy outcomes. IMPACT STATEMENT: Our study reveals a potential link between subclinical inflammation, high AMH levels, and IVF treatment failure. Further studies will help to come up with additional specific treatment strategies which may have an additional effect on successful IVF outcomes. SUPPORT: This work was supported in part by the IVFMD, South Florida Institute for Reproductive Medicine.