title: Successful implantation after reducing matrix metalloproteinase activity in the uterine cavity.
abstract: BACKGROUND
  Recently, 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.
  
  
  METHODS
  Of 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.
  
  
  RESULTS
  Of 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).
  
  
  CONCLUSIONS
  A 2-week course of antibiotics and corticosteroids effectively improves the uterine environment underlying RIF by reducing MMP activity.
authors.affiliation: Fertility Clinic Tokyo, 2-11-16 Ebisu-Nishi Shibuya-ku, Tokyo 150-0021, Japan. toshiohamatani@z3.keio.jp
authors.forename: Noriko
authors.initials: N
authors.lastname: Yoshii
authors.forename: Toshio
authors.initials: T
authors.lastname: Hamatani
authors.forename: Noboru
authors.initials: N
authors.lastname: Inagaki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hosaka
authors.forename: Osamu
authors.initials: O
authors.lastname: Inoue
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Yamada
authors.forename: Rei
authors.initials: R
authors.lastname: Machiya
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Yoshimura
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Odawara
mesh_terms: D000022:Abortion, Spontaneous; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D016009:Chi-Square Distribution; D010064:Embryo Implantation; D004716:Endometritis / Q000201:enzymology / Q000517:prevention & control; D005260:Female; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D017063:Outcome Assessment, Health Care / Q000706:statistics & numerical data; D011247:Pregnancy; D018873:Pregnancy Rate; D015363:Quinolones / Q000008:administration & dosage; D027724:Reproductive Techniques, Assisted / Q000706:statistics & numerical data; D012189:Retrospective Studies; D013997:Time Factors; D014599:Uterus / Q000187:drug effects / Q000201:enzymology*
chemical_list: D000305:Adrenal Cortex Hormones; D000900:Anti-Bacterial Agents; D015363:Quinolones; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9