Successful implantation after reducing matrix metalloproteinase activity in the uterine cavity

Noriko Yoshii, Toshio Hamatani, Noboru Inagaki, Takeshi Hosaka, Osamu Inoue, Mitsutoshi Yamada, Rei Machiya, Yasunori Yoshimura, Yasushi Odawara

Research output: Contribution to journalArticle

16 Citations (Scopus)

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.

Original languageEnglish
Article number37
JournalReproductive Biology and Endocrinology
Volume11
Issue number1
DOIs
Publication statusPublished - 2013 May 11

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Matrix Metalloproteinases
Spontaneous Abortion
Pregnancy Rate
Adrenal Cortex Hormones
Anti-Bacterial Agents
Gelatinases
Control Groups
Assisted Reproductive Techniques
Matrix Metalloproteinase 2
Quinolones
Matrix Metalloproteinase 9
Chi-Square Distribution
Nonparametric Statistics
varespladib methyl
Embryonic Structures
Retrospective Studies
Inflammation

Keywords

  • Endometritis
  • Matrix metalloproteinase (MMP)
  • Recurrent implantation failure (RIF)
  • Uterine flushing
  • Uterine inflammation

ASJC Scopus subject areas

  • Developmental Biology
  • Endocrinology
  • Reproductive Medicine

Cite this

Successful implantation after reducing matrix metalloproteinase activity in the uterine cavity. / Yoshii, Noriko; Hamatani, Toshio; Inagaki, Noboru; Hosaka, Takeshi; Inoue, Osamu; Yamada, Mitsutoshi; Machiya, Rei; Yoshimura, Yasunori; Odawara, Yasushi.

In: Reproductive Biology and Endocrinology, Vol. 11, No. 1, 37, 11.05.2013.

Research output: Contribution to journalArticle

Yoshii, Noriko ; Hamatani, Toshio ; Inagaki, Noboru ; Hosaka, Takeshi ; Inoue, Osamu ; Yamada, Mitsutoshi ; Machiya, Rei ; Yoshimura, Yasunori ; Odawara, Yasushi. / Successful implantation after reducing matrix metalloproteinase activity in the uterine cavity. In: Reproductive Biology and Endocrinology. 2013 ; Vol. 11, No. 1.
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AU - Yoshii, Noriko

AU - Hamatani, Toshio

AU - Inagaki, Noboru

AU - Hosaka, Takeshi

AU - Inoue, Osamu

AU - Yamada, Mitsutoshi

AU - Machiya, Rei

AU - Yoshimura, Yasunori

AU - Odawara, Yasushi

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N2 - 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.

AB - 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.

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KW - Uterine flushing

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