Fertility Clinic Tokyo, 2-11-16 Ebisu-Nishi Shibuya-ku, Tokyo 150-0021, Japan.
Reprod Biol Endocrinol. 2013 May 11;11:37. doi: 10.1186/1477-7827-11-37.
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.
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.
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).
A 2-week course of antibiotics and corticosteroids effectively improves the uterine environment underlying RIF by reducing MMP activity.
最近，辅助生殖技术中复发性植入失败（RIF）的概念已经扩大。慢性子宫炎症是植入失败的已知原因，与宫腔冲洗中基质金属蛋白酶（MMP）活性升高有关。据报道，RIF 患者的 MMP 活性高于生育能力正常的女性。在本回顾性研究中，我们评估了治疗 RIF 患者宫腔内 MMP 活性过高的疗效。
在纳入研究的 597 名患者中，360 名患者进行了 MMP 测量，237 名患者未进行（对照组）。所有患者都未能怀孕，尽管至少进行了两次优质胚胎移植。通过酶学（MMP 测试）检测宫腔冲洗液中的明胶酶 MMP-2 和 MMP-9 活性。根据酶谱上条带的强度（代表 MMP 活性的程度），所有样本均分为两组（阳性或阴性）。对初次试验阳性的患者进行 2 周的喹诺酮类抗生素和皮质类固醇治疗，然后进行第二次 MMP 试验。治疗后第二次 MMP 试验的阴性结果以及随后的妊娠和流产率用于评估治疗效果。数据采用 Mann-Whitney U 检验和卡方检验进行分析。
在进行 MMP 测试的患者中，有 15.6%的患者结果阳性（MMP 活性高）。治疗后，89.3%的患者第二次 MMP 测试结果为阴性。这些患者的妊娠率（42.0%）明显高于对照组（26.6%），流产率（28.5%比 36.5%）也较低。
2 周的抗生素和皮质类固醇治疗可通过降低 MMP 活性有效改善 RIF 的子宫环境。
