Association of tissue inhibitor of metalloproteinase-3 (TIMP-3) serum level and its genetic polymorphism with pregnancy outcome of patients undergoing in vitro fertilization and embryo transfer.

Objectives: Tissue inhibitors of metalloproteinase-3 (TIMP-3) and matrix metalloproteinases (MMPs) play a major role in embryo implantation and placentation. This study aimed to investigate the relationship between TIMP-3 serum level and TIMP-3 genetic polymorphism with pregnancy outcome in patients undergoing in vitro fertilization and embryo transfer (IVF-ET).

Material and methods: This project included 100 infertile women who became pregnant after IVF (IVF+) and 100 infertile women who failed to conceive after IVF (IVF-). Genotyping was performed using Restriction Fragments Length Polymorphism Polymerase Chain Reaction (PCR-RFLP), and the serum level was measured by Enzyme-Linked Immunosorbent Assay (ELISA).

Results: The frequencies of TT, TC, and CC in the IVF+ group were 41%, 37% and 22%, respectively, while in the IVF- group were 18%, 43% and 39%, respectively. The C and T allele frequencies were 40.5% and 59.5% in the IVF+ group and 60.5% and 39.5% in IVF- group, respectively. The C allele conferred a 2.25-fold increased risk of IVF failure (OR 2.25; 95% CI 1.5-3.35; p = 0.0001). Also, there was a significant increase in TIMP-3 serum levels in the IVF- group (193.29 ± 29.50 ng/mL), which was higher than the IVF+ group (166.74 ± 17.60 ng/mL; p = 0.00002), was demonstrated. It was shown that the TT genotype is associated with decreased TIMP-3 serum levels in IVF- group (CC, CT, and TT, values were 143.19 ± 88.49 ng/mL, 117.55 ± 15.73 ng/mL, 61.17 ± 44.36 ng/mL, respectively).

Conclusions: It is concluded that there is a relationship between TIMP-3 gene polymorphism and its serum concentration with IVF-ET outcome. We also suggest that the TT genotype might be involved in IVF-ET outcome.