Abstract
BackgroundRecently, the concept of recurrent implantation failure (RIF) in assisted reproductive technology has been enlarged. Chronic uterine inflammation is a known cause of implantation failure and is associated with high matrix metalloproteinase (MMP) activity in uterine cavity flushing. MMP activity of women with RIF has been reported to be higher than that of fertile women. In the present retrospective study we evaluated the efficacy of treatment for high MMP activity in the uterine cavity of patients with RIF.MethodsOf the 597 patients recruited to the study, 360 patients underwent MMP measurements and 237 patients did not (control group). All patients had failed to become pregnant, despite at least two transfers of good-quality embryos. Gelatinase MMP-2 and MMP-9 activity in uterine flushing fluid was detected by enzymology (MMP test). All samples were classified into two groups (positive or negative) based on the intensity of the bands on the enzyme zymogram, which represents the degree of MMP activity. Patients who tested positive on the initial test were treated for 2 weeks with a quinolone antibiotic and a corticosteroid, and subsequently underwent a second MMP test. Negative results on the second MMP tests after treatment and subsequent rates of pregnancy and miscarriage were used to evaluate the efficacy of treatment. Data were analyzed by the Mann–Whitney U-test and the chi-square test.ResultsOf the patients who underwent the MMP test, 15.6% had positive results (high MMP activity). After treatment, 89.3% of patients had negative results on the second MMP test. These patients had a significantly better pregnancy rate (42.0%) than the control group (26.6%), as well as a lower miscarriage rate (28.5% vs 36.5%, respectively).ConclusionsA 2-week course of antibiotics and corticosteroids effectively improves the uterine environment underlying RIF by reducing MMP activity.
Highlights
The concept of recurrent implantation failure (RIF) in assisted reproductive technology has been enlarged
We focused on matrix metalloproteinases (MMPs) as candidate biomarkers of chronic and mild uterine inflammation
Since mean total MMP score of RIF patients was Results The 597 RIF patients in the present study were divided into two groups depending on whether they agreed to undergo an MMP test after receiving a comprehensive explanation of the procedure
Summary
The concept of recurrent implantation failure (RIF) in assisted reproductive technology has been enlarged. The number of macrophages and T cells, which mainly secrete inflammatory cytokines, is increased in the endometria of women with an implanted intrauterine device (IUD) [3], and the contraceptive activity of the IUD is brought about by the maintenance of this environment, which is unfavorable for implantation As another example, implantation rates following IVF-ET are lower in patients with hydrosalpinx compared with rates in those with unexplained or male sterility because of the leakage of hydrosalpinx fluid (HF), which contains leukocytes and inflammatory cytokines such as interleukin (IL)-8, IL-12, IL-α, and tumor necrosis factor (TNF)-α, contributes to the deterioration of the intrauterine environment, leading to implantation failure [4,5,6]. Chronic and mild uterine inflammation induces inflammatory cells and alters the expression and subtle balance of various molecules, without any overt clinical symptoms, contributing to implantation failure
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