An Exploratory Study of Matrix Metalloproteinase Protein Changes in Unexplained Infertility

Background: Matrix metalloproteinases (MMPs) have been found to be associated with reproductive complications, including female infertility. This study was conducted to explore the link between MMPs in non-obese women with unexplained infertility (UI) in comparison to women with male factor infertility (MFI) as controls. Methods: This pilot exploratory study was carried out on 25 women, 11 with UI and 14 with MFI, undergoing IVF. Blood was drawn on day 21 of the luteal phase. Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement was undertaken for 12 matrix metalloproteinase proteins. Welch's t-test and a permutation test were used to compare group means, and Pearson's correlations to examine relationships with matrix metalloproteinases. Results: No significant differences were seen for baseline demographics and hormonal parameters between the groups, and parameters of the response following IVF did not differ. In the UI group, MMP-3 levels were lower (p = 0.045), while MMP-1 and MMP-17 levels were higher (p = 0.007 and p = 0.010, respectively) compared to the MFI group. In MFI alone, MMP-1 positively correlated with vitamin D₃ (p < 0.05). Conclusions: This exploratory study suggests altered circulating MMP-1, MMP-3, and MMP-17 profiles in women with unexplained infertility. These findings require confirmation in larger cohorts and in studies examining endometrial tissue expression and MMP functional activity.