| Objective:Our objective is to study whether the endometrial receptivity will be ameliorated by oral metformin in experimental endometriosis-mice,and then,to investigate the effect of metformin on pregnancy outcome of patients after laparoscopic conservative surgery for infertility related with minimal-mild endometriosis,so as to provide research basis for the possibility of metformin in the treatment of endometriosis-related infertility.Materials and Methods:The experimental endometriosis-mice was induced by operation of autologous transplantation,and the formation of ectopic lesions was confirmed by histochemistry.Metformin was given by intragastric administration to experimental endometriosis-mice.The pseudopregnant mice were induced by mating with sterilized male mice those were underwent vasectomy,and the expression levels of markers related with endometrial receptivity of the pseudopregnant mice were detected by q RT-PCR and WB,while the cellular localization by immunohistochemistry.A RCT was conducted to compare the clinical pregnancy rate and the final pregnancy outcome during the following one year after given oral metformin or blank control(100 cases in each group)two months in women who performed laparoscopic conservative surgery for infertility related with minimal-mild endometriosis.Results:1.The experimental endometriosis-mice were successfully induced by autologous transplantation,and the ectopic lesions were stable within 8 weeks at least,and then an appropriate concentration of metformin was selected to be 300mg/kg/d.2.The expression levels of integrin-αvβ3 and Leukemic inhibitory factor(LIF)in endometrium of pseudopregnant mice at 4~+or 8 weeks after operative conducting endometriosis were significantly lower than those of the control mice after sham operation,while the expression level of insulin-like growth factor binding protein-7(IGFBP-7)was not significantly changed.3.The expression of integrin-β3 and LIF were slightly up-regulated,and IGFBP-7 was significantly up-regulated in the endometrium of experimental endometriosis-mice by given metformin for 4 weeks.4.In the RCT,a total of 200 patients(100 cases in metformin treatment group and 100 cases in blank control group)after laparoscopic conservative surgery for infertility related with minimal-mild endometriosis were included.At present,follow-ups of 169 cases(78 cases in metformin treatment group and 76 cases in blank control group)have been completed,and 20 cases(13 cases in metformin treatment group and 7 cases in blank control group)were withdrawn from the study.5.According to the current follow-up results,the clinical pregnancy rate of the metformin treatment group were lower than those of the blank control group,but the difference has no statistically significance,so as the and live birth rate.Furthermore,it can be found that the increase of cumulative pregnancy rate in the blank control group was rapidly fast in the first 5 months after pregnancy preparation,and began to slow down after 5 months,while the increase in the metformin group was slow in the first 6 months,and began to relatively accelerate after 6 months.Conclusion:The endometrial receptivity of experimental endometriosis-mice induced by autologous transplantation is impaired,however,it can be improved by metformin at the molecular level.but oral metformin may not be benefit to the clinical pregnancy rate and final pregnancy outcome of patients after laparoscopic conservative surgery for infertility related with minimal-mild endometriosis. |
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