改良超长方案改善多囊卵巢综合征(PCOS)不孕患者子宫内膜容受性的研究

Study of modified super-long protocol on endometrial receptivity of patients with PCOS in IVF/ICSI-ET

目的:探讨改良超长方案降调节结合人绝经期促性腺激素(h MG)在多囊卵巢综合征(PCOS)不孕患者行体外受精/卵胞质内单精子注射-胚胎移植术(IVF/ICSI-ET)助孕中的疗效及机理。方法:1将行IVF/ICSI-ET的PCOS患者随机改良超长方案降调后促排卵组(A组,n=86)和标准的长效长方案促排卵组(B组,n=80);观察比较2种促排方案的实验室及临床结局。2分别于取卵后第6日收集A组和B组中因卵巢过度刺激综合征(OHSS)原因取消移植者的子宫内膜组织各5例(分别为C组和D组),用电子显微镜、Real-time PCR和Western blotting、免疫组织化学方法观察内膜组织胞饮突分布以及同源框A10(HOXA10)、溶血磷脂酸受体3(LPAR3)、环氧化酶2(COX2)基因的表达变化。结果:1 Gn用量(IU)、用药时间(d)、h CG注射日E2水平和LH水平、平均获卵数、受精率、优质胚胎率、周期取消率、移植胚胎数、重度OHSS发生率、流产率、异位妊娠率A、B组间均无统计学差异(P>0.05)。A组种植率及移植妊娠率(60.65%和79.49%)均高于B组(44.53%和61.19%,P<0.05)。与B组相比,A组患者h CG注射日P水平及P/E2明显降低,子宫内膜(EM)的厚度、形态、血流情况明显改善(P<0.05)。2 C组子宫内膜上出现大量呈蘑菇状、表面光滑、边界清楚的完全发育胞饮突,D组的胞饮突的数量少于C组,且形态发育不佳,还可见少量退化的胞饮突。在着床期C组子宫内膜LPAR3、COX2、HOXA10的表达水平显著高于D组。结论:对PCOS不孕患者实施IVF/ICSI-ET助孕过程中,采用改良的Gn RH-a超长方案降调节+h MG超促排卵可通过多种机理提高患者的着床率和妊娠率。

Objective： To explore the clinical outcomes and mechanism of modified super-long protocol down-regulation in combination with human menopausal gonadotropin （hMG） in polycystic ovary syndrome （PCOS） infertile women undergoing in vitro fertilization/intracytoplasmic sperm injection and embryo transfer （IVF/ICSI-ET） prospectively. Methods： 1） PCOS patients who underwent IVF/ICSI-ET were divided into two groups： super-long protocol group （n=86） and long protocol group （n=80）. The average number of obtained oocytes, fertilization rate, implantation rate, pregnancy rate, abortion rate, thickness, morphology and pulsed Doppler study of uterine artery of endometrium on the day of hCG administration were compared. Otherwise, the related indexes of two groups such as serum progestogen （P）, estradiol （E2） and luteinizing hormone （LH） level and P/E2 on the day of hCG administration were compared. 2） PCOS patients in our hospital who were cancelled for the high risk of ovarian hyperstimulation syndrome （OHSS） in IVF/ICSI-ET were divided into two groups： super-long protocol group （n=5） and long protocol group （n=5）. The expressions of homeoboxA10 （HOXA10）, lysophosphatidic acid receptor 3 （LPAR3） and cytochrome c oxidase subunit II （COX2） in two groups were detected by immunohistochemistry, Real-time PCR, Western blotting, and pinopodes by electron microscopy of the patients in two groups on the sixth day after oocyte retrival were comparatively studied. Results： 1） The average number of obtained oocytes, good-quality embryo rate, cancellation rate, severe OHSS rate showed no significant differences between the two groups （P〉0.05）. The serum P level and P/E2 on the day of hCG administration in modified super-long down-regulation protocol were decreased. In the group of modified super-long down-regulation protocol, the endometrial thickness, morphology and blood flow detected by Doppler ultrasounds were significantly optimized compared with conventional long protocol. 2） We can detecte a large number of distribution uniform in size, smooth surface, clear boundary, membranous protrusions mushroom, which was fully developed pinopodes in the endometrium of patients in modified long protocol. And in the group of long protocol, the pinopodes distribute focally, the surface was not smooth, much of them was covered with microvilli. Expressions of LPAR3, COX2, HOXA10 in the endometrium were higher in the modified super-long protocol group than those in long protocol group in the period of implantation widow. Conclusion： Modified super-long protocol plus hMG raised the thickness of endometrium, improved the morphology and blood flow, thus improved the implantation rate and the pregnancy rate for PCOS infertile patients in IVF/ICSI-ET. Modified super-long protocol may improve the level of endometrial pinopodes, LPAR3, COX2, HOXA10 expression to improve endometrial receptivity.