| Objective: To investigate the effect of follicular phase long-acting Gn RH agonist long protocol on in vitro fertilization(IVF)/ intracytoplasmic sperm injection(ICSI)outcomes of the patients with endometriosis(EMS),poor ovarian responder(POR)and recurrent implantation failure(RIF),and explore its mechanism of improving endometrial receptivity.Methods: 1.The clinical data of 383 cycles with EMS,730 cycles with RIF and 451 cycles with POR who underwent IVF/ICSI in the reproductive center of Yu Huang Ding hospital were retrospectively analyzed from July 2015 to June 2020.The patients were classified by the ovarian stimulation protocols.The outcome parameters of IVF were compared in each group by Kruskal-Wallis test,chi-square test and logistic regression analysis.2.In addition,we evaluated the morphology and coverage of pinopode and expression of HOXA10,Integrinβ3 and LIF in endometrium during implantation window between three groups(follicular phase long-acting Gn RH agonist long protocol,short-acting Gn RH agonist long protocol and Gn RH antagonist protocol)by scanning electron microscope,q RT-PCR and western blotting.Results: 1.These EMS patients who received follicular phase long-acting Gn RH agonist protocol had a significantly higher clinical pregnancy rates(76.53%,61.39% and54.39%,P=0.038 and 0.009)and implantation rates(54.10%,42.63% and 40.19%,P=0.041 and 0.039)compared with short-acting Gn RH agonist long protocol and Gn RH antagonist protocol.In terms of live birth rate,there was no significant difference between follicular phase long-acting Gn RH agonist protocol and short-acting Gn RH agonist long protocol(66.33% and 53.47%,P=0.081),but it was significantly higher than Gn RH antagonist protocol(66.33% and 47.37%,P=0.037).In addition,they also had significantly higher duration of stimulation and total dose of gonadotrophin(Gn)than other groups(P < 0.001).However,serum levels of luteinizing hormone(LH)and estradiol(E2)on Gn initiation day and human chorionic gonadotropin(HCG)day were significantly lower among women who received long-acting Gn RH agonist(P<0.001).Patients with RIF had similar clinical outcomes,the duration of stimulation and total dose of Gn were significantly increased in the long-acting follicular phase regimen group(P<0.001),but serum levels of LH and E2 on h CG day were significantly lower(P<0.001).These RIF patients who received follicular phase long-acting Gn RH agonist protocol had significantly higher implantation rates(40.60%,30.00% and 30.42%,P=0.049 and 0.031)and live birth rates(51.11%,36.81%,and 33.79%,P=0.050 and 0.001)compared with short-acting Gn RHa long protocol and Gn RH antagonist protocol,but there was no significant difference in the three groups of clinical pregnancy rate(55.55%,39.56% and 43.39%,P=0.064 and 0.085).For patients with POR who received follicular phase long-acting Gn RH agonist protocol,the duration of stimulation,total dose of Gn,endometrial thickness and the number of oocytes retrieved and mature oocytes were significantly higher than other groups(P < 0.05).These patients alse had significantly higher cumulative clinical pregnancy rates(50.88%,32.0% and 31.88%,P<0.001 and P = 0.001)compared with mild ovarian stimulation protocol and Gn RH antagonist protocol.In addition,they also had higher implantation rates and clinical pregnancy rates per fresh embryo transfer cycle than mild ovarian stimulation protocol group(54.44% and 35.29%,P=0.026;45.27% and22.41%,P=0.002),but these differences were not statistically significant in live birth rate(47.78%,32.35% and 36.62%,P=0.197 and 0.146).2.In addition,we found that follicular phase long-acting Gn RH agonist protocol could improve the development of pinopode and the expression of HOXA10(P < 0.05).However,there was no significant difference in the expression of integrin β3 and LIF m RNA among the three groups.Conclusions: Follicular phase long-acting Gn RH agonist protocol could improve IVF outcomes of patients with EMS,RIF and POR by improving the endometrial receptivity. |
