补肾宁心方治疗亚临床POI不孕症的疗效及其对血清ET-1水平的影响

Effects of Bushen Ningxin Decoction in the treatment of infertility with subclinical POI and its influence on serum ET-1 level

目的:观察补肾宁心方治疗亚临床早发性卵巢功能不全(POI)不孕症的临床疗效及其对患者血清内皮素-1(ET-1)水平的影响。方法:纳入96例心肾不交证亚临床POI不孕症患者,随机分为对照组和治疗组,每组各48例。对照组患者给予雌二醇片/雌二醇地屈孕酮片口服,治疗组患者在对照组治疗基础上加用补肾宁心方口服,两组患者均连续预治疗3个周期。预治疗后,所有患者均给予来曲唑、尿促性素(HMG)促排卵助孕治疗,观察周期为1个月经周期。预治疗前后,比较两组患者的改良Kupperman评分、血清雌二醇(E2)、卵泡刺激素(FSH)、抗米勒管激素(AMH)及ET-1水平,B型超声检测患者的双侧卵巢基础窦卵泡数(AFC)和卵巢血流指标[阻力指数(RI)、搏动指数(PI)、舒张末期流速(EDV)、收缩期峰值流速(PSV)],并计算PSV/EDV(S/D)值。助孕治疗中,比较两组患者的排卵率、妊娠率,以及HMG用量、人绒毛膜促性腺激素(HCG)注射日子宫内膜厚度。结果:治疗过程中,治疗组7例患者剔除或脱落,对照组7例患者剔除或脱落,最终治疗组41例、对照组41例纳入统计分析。(1)改良Kupperman评分:治疗后,两组患者的改良Kupperman评分较治疗前均显著降低(P<0.05),且治疗组患者的评分低于对照组(P<0.05)。(2)血清性激素及ET-1水平:治疗后,两组患者的E2、AMH水平均明显升高(P<0.05),FSH、ET-1水平明显降低(P<0.05),且治疗组患者的E2、AMH水平高于对照组(P<0.05),FSH、ET-1水平低于对照组(P<0.05)。(3)AFC及卵巢血流指标:治疗后,治疗组患者的AFC及卵巢EDV较治疗前均明显升高(P<0.05),卵巢RI、PI及S/D值较治疗前均明显降低(P<0.05);对照组患者的AFC及卵巢EDV较治疗前亦明显升高(P<0.05),卵巢RI较治疗前亦明显降低(P<0.05);且治疗组患者的AFC及卵巢EDV高于对照组(P<0.05),卵巢RI及S/D值低于对照组(P<0.05)。(4)排卵率、妊娠率:治疗组患者的排卵率为53.66%、妊娠率为26.83%,对照组患者的排卵率为31.71%、妊娠率为9.76%,治疗组患者的排卵率、妊娠率均高于对照组(P<0.05)。(5)HMG用量及HCG注射日子宫内膜厚度:助孕周期中,治疗组患者的HMG用量较对照组明显减少(P<0.05),HCG注射日治疗组患者的子宫内膜厚度较对照组明显增厚(P<0.05)。结论:心肾不交证亚临床POI不孕症患者,在激素补充治疗的同时联合补肾宁心方口服,可更有效地缓解临床症状,促进卵巢功能恢复,使助孕疗效更佳。

Objective: To observe the clinical efficacy of Bushen Ningxin Decoction in the treatment of infertility with subclinical premature ovarian insufficiency(POI) and its influence on the level of serum endothelin-1(ET-1). Methods: Ninety-six infertile patients of subclinical POI with syndrome of disharmony between heart and kidney were included and randomly divided into the control group and treatment group, 48 cases in each group. The patients in the control group were orally treated with complex packing of estradiol tablets/estradiol and dydrogesterone tablets, and the patients in the treatment group were orally treated with Bushen Ningxin Decoction based on the treatment for the control group. The patients in both groups were continuously pretreated for 3 courses. After pretreatment, all patients were treated with letrozole and Menotrophin(HMG) to stimulate ovulation and assist pregnancy, and the observation period was one menstrual cycle. Before and after pretreatment, the improved Kupperman score and the serum levels of estradiol(E2), follicle-stimulating hormone(FSH), anti-Müllerian hormone(AMH) and ET-1 were compared between the two groups. The basal antral follicle counting(AFC) of bilateral ovary and the ovarian blood flow indexes, including resistance index(RI), pulsatility index(PI), end diastolic velocity(EDV) and peak systolic velocity(PSV), were detected by B-type ultrasound, and the PSV/EDV(S/D) ratio was calculated. In the treatment of assisting pregnancy, the rates of ovulation and pregnancy, the HMG dosage and the endometrial thickness on the day of human chorionic gonadotropin(HCG) injection were compared between the two groups. Results: During the treatment, 7 patients in the treatment group and 7 patients in the control group were excluded or shed, finally 41 patients in the treatment group and 41 patients in the control group were included for statistical analysis.(1)The improved Kupperman score: After treatment, the improved Kupperman score in both groups was significantly decreased compared with that before treatment(P<0.05), and the score in the treatment group was lower than that in the control group(P<0.05).(2)Serum levels of sex hormones and ET-1: After treatment, the levels of E2 and AMH in both groups were significantly increased(P<0.05), and the levels of FSH and ET-1 were significantly decreased(P<0.05). The levels of E2 and AMH in the treatment group were higher than those in the control group(P<0.05), and the levels of FSH and ET-1 in the treatment group were lower than those in the control group(P<0.05).(3)AFC and ovarian blood flow indexes: After treatment, the AFC and ovarian EDV in the treatment group were significantly increased compared with those before treatment(P<0.05), and the ovarian RI, PI and S/D ratio were significantly decreased compared with those before treatment(P<0.05);the AFC and ovarian EDV in the control group were also significantly increased compared with those before treatment(P<0.05), and the ovarian RI was significantly decreased compared with that before treatment(P<0.05). The AFC and ovarian EDV in the treatment group were higher than those in the control group(P<0.05), and the ovarian RI and S/D ratio in the treatment group were lower than those in the control group(P<0.05).(4)Rates of ovulation and pregnancy: The rates of ovulation and pregnancy in the treatment group were 53.66% and 26.83% respectively. The rates of ovulation and pregnancy in the control group were 31.71% and 9.76%, respectively. The ovulation rate and pregnancy rate in the treatment group were higher than those in the control group(P<0.05).(5)HMG dosage and endometrial thickness on the day of HCG injection: In the treatment course of assisting pregnancy, the HMG dosage of the treatment group was significantly lower than that of the control group(P<0.05), and the endometrial thickness on the day of HCG injection in the treatment group was significantly thicker than that in the control group(P<0.05). Conclusion: Hormone supplementation therapy combined with Bushen Ningxin Decoction oral administration can more effectively alleviate the clinical symptoms of the infertile patients of subclinical POI with syndrome of disharmony between heart and kidney, promote the recovery of ovarian function, and make the effect of assisting pregnancy better.