Successful implantation after reducing matrix metalloproteinase activity in the uterine cavity

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.

Endometrial microbes and microbiome: Recent insights on the inflammatory and immune “players” of the human endometrium

“…However, as above reported, the laboratory dependence and the possible contamination from vaginal and endocervical content may limit the utility of the endometrial cultures. Moreover, the impact of CE on reproductive capacity is controversial: its prevalence ranges from 0.8% to 19% in the general population, and from 30% to 45% in infertile patients, mainly with recurrent implantation failure and recurrent pregnancy loss . Mechanisms underlying the CE‐associated poor obstetric outcomes are not clearly understood.…”

The evolution of embryo implantation

“…Indeed MMP9 is involved in successful cytotrophoblast invasion and specifically dissolves collagen type IV, a major component of the endometrial basal membrane (Librach et al ., 1991). Further evidence for the important role of MMP2 and MMP9 in successful implantation has been found in the clinic (Yoshii et al ., 2013). That study examined the role of these genes in recurrent implantation failure (RIF).…”

“…Three hundred and sixty patients underwent MMP measurements, and those patients that had high MMP2 and MMP9 levels (as measured by gelatin enzyme zymography) were subsequently treated with antibiotics and steroids. This treatment reduced the MMP levels in the vast majority of patients, and the patients who underwent such treatment had significantly better pregnancy rate as well as a significantly lower miscarriage rate than was observed in control patients (Yoshii et al ., 2013). The molecular evolution of MMP2 and MMP9 has not been investigated, but we would expect that adaptive evolutionary changes could be associated with the emergence and increased depth of implantation in specific species.…”

Difference of Cyclooxygenase-2 (COX2) Expression in Endometrium Between Patients with Polycystic Ovary Syndrome (PCOS) and Fertile Women

“…During the start of the menstrual cycle estrogen levels increase to increase endometrial cell proliferation. At the time of ovulation, progesterone levels released by follicles that experience luteinization lead to cell differentiation so that the endometrium is mature and optimal for embryo implantation (Yoshii et al, 2013).…”