本研究旨在观察补肾祛胆方治疗多囊卵巢综合征(PCOS)所致不孕症的疗效和安全性,并运用代谢组学方法探讨其作用机制。选取肾虚血瘀型PCOS所致不孕患者94例,分为治疗组和对照组(n=47)。测量基础体温(BBT),B超用于监测卵泡,卵巢体积,子宫内膜,排卵,和怀孕。血清性激素水平包括卵泡刺激素(FSH),黄体生成素(LH),催乳素(PRL),雌二醇(E_2),孕激素(P),睾酮(T),游离睾酮(FT),雄烯二酮(A2),抑制素B(INHB),并测定抗苗勒管激素(AMH)。凝血功能,中医症状评分,血常规和尿常规,确定肝肾功能和其他安全指标。采用代谢组学方法对26例患者(每组13例)的血清代谢产物进行比较分析。结果显示,治疗组总有效率和妊娠率均高于对照组(P<0.001),提示补肾祛微方调节性激素和卵巢功能。具体来说,它降低了LH的水平,T,FT,A2和INHB(P&lt;0.05或P&lt;0.01)和LH/FSH比率(P&lt;0.05),P水平升高(P<0.05),促进排卵,内皮厚度增加,降低中医症状积分,不引起不良反应。利用代谢组学方法共筛选出24种差异代谢物,PCOS引起的肾虚血瘀不孕症患者性激素和差异代谢产物之间存在相关性。总之,补肾祛微方可能通过脂质和氨基酸代谢调节激素水平。
This study aims to observe the efficacy and safety of Bushen Culuan Formula in the treatment of infertility caused by polycystic ovary syndrome(PCOS) and to explore the mechanism using metabolomics. Ninety-four patients with infertility caused by PCOS with the syndrome of kidney deficiency and blood stasis were selected and assigned into treatment and control groups(n=47). The basal body temperature(BBT) was measured, and B-ultrasonography was employed to monitor follicles, ovarian volume, endometrium, ovulation, and pregnancy. The serum levels of sex hormones including follicle-stimulating hormone(FSH), luteinizing hormone(LH), prolactin(PRL), estradiol(E_2), progestin(P), testosterone(T), free testosterone(FT), androstenedione(A2), inhibin B(INHB), and anti-Müllerian hormone(AMH) were measured. The coagulation function, traditional Chinese medicine(TCM) symptom scores, blood and urine routine, liver and kidney functions and other safety indicators were determined. Metabolomics was employed to comparatively analyze the serum metabolites of 26 patients(13 patients in each group) in the clinical study. The results showed that the total response rate and pregnancy rate of the treatment group were higher than those of the control group(P<0.001), suggesting that Bushen Culuan Formula regulated the sex hormones and ovarian function. Specifically, it reduced the levels of LH, T, FT, A2, and INHB(P<0.05 or P<0.01) and the LH/FSH ratio(P<0.05), elevated the level of P(P<0.05), promoted ovulation, increased endothelial thickness, and lowered TCM symptom scores without causing adverse reactions. A total of 24 differential metabolites were screened by metabolomics, and there were correlations between sex hormones and differential metabolites in the PCOS-induced infertility patients with kidney deficiency and blood stasis. In conclusion, Bushen Culuan Formula may regulate hormone levels through lipid and amino acid metabolism.