3种不同剂量来曲唑分别联合枸橼酸氯米芬对PCOS不孕患者性激素和内膜的影响

Effects of three different dosage of letrozole combined with clomiphene citrate on the sex hormones and intima of infertile women with PCOS

目的探讨3种剂量来曲唑分别联合枸橼酸氯米芬对多囊卵巢综合征(polycystic ovary syndrome,PCOS)不孕患者性激素和内膜的影响。方法选取2015年1月至2017年12月成都市送子鸟不孕不育医院诊治的129例PCOS不孕患者作为研究对象。按照随机数表法将其平均分为A组、B组和C组,每组43例患者,选择同期月经正常的40例育龄妇女为参照组。A、B和C组患者在月经周期均给予来曲唑联合枸橼酸氯米芬治疗,其中A组患者来曲唑剂量为2.5mg/d,B组患者来曲唑剂量为5mg/d,C组患者来曲唑剂量为7.5mg/d,三组患者最大卵泡直径不小于20mm时通过人绒毛膜促性腺激素(hCG)进行诱发排卵。比较四组成员hCG期间相关激素和血清性激素结合球蛋白(SHBG)水平、子宫内膜厚度及分型、排卵和妊娠情况。结果 A组、B组和C组患者的卵泡刺激素(FSH)、黄体生成素(LH)、雌二醇(E2)和SHBG水平均明显低于参照组成员,睾酮(T)水平均明显高于参照组成员(均P<0.05);A组和B组患者的FSH、LH、E2和SHBG水平均明显低于C组患者,T水平均明显高于C组患者,其差异均具有统计学意义(均P<0.05);A组患者的FSH、LH、E2和SHBG水平均明显低于B组患者,T水平均明显高于B组患者,其差异均具有统计学意义(均P<0.05)。在优势卵泡发育至10mm^12mm、14mm^16mm和18mm^20mm时间节点时:A组、B组和C组患者的雌激素水平和子宫内膜厚度均明显低于参照组成员(均P<0.05);C组患者的雌激素水平和子宫内膜厚度均明显低于A组和B组患者,其差异均具有统计学意义(均P<0.05);B组患者的雌激素水平和子宫内膜厚度均明显低于A组患者,其差异军具有统计学意义(均P<0.05)。四组成员hCG日均未见C型子宫内膜,且四组成员A型、B型占比比较,其差异均无统计学意义(均P>0.05)。四组成员排卵率相比,其无差异均无统计学意义(均P>0.05);A组、B组和C组患者的妊娠率均明显低于参照组成员,且A组和B组患者的妊娠率低于C组患者,A组患者的妊娠率低于B组患者,其差异均具有统计学意义(均P<0.05)。结论来曲唑联合枸橼酸氯米芬可以促进PCOS不孕患者性激素和SHBG的分泌,对雌激素和子宫内膜有一定的抑制作用,但达到胚胎着床的要求,能够提高患者的妊娠率,以7.5mg/d来曲唑剂量的作用效果最为明显。

Objective To investigate the effects of 3 dosage of letrozole combined with clomiphene citrate on sex hormones and intima of infertile women with polycystic ovary syndrome(PCOS). Methods 129 PCOS infertility patients treated in Chengdu Songziniao Infertility Hospital from January 2015 to December 2017 were selected as study subjects and divided into group A, group B, and group C according to the random number table method, with 43 cases in each group. 40 women with normal menstruation age were selected during the same period as the reference group. Patients in group A, B and C were given letrozole combined with clomiphene citrate during the menstrual cycle. The dosage of letrozole was 2.5 mg/d in group A, the 5 mg/d in group B and 7.5 mg/d in group C. The ovulation was induced by human chorionic gonadotropin(hCG) when the maximal follicle diameter was not less than 20 mm in the three groups. The levels of hormones and serum sex hormone-binding globulin(SHBG) during hCG, the endometrial thickness and type, the ovulation and the pregnancy were compared between the four groups. Results The levels of follicle-stimulating hormone(FSH), luteinizing hormone(LH), estradiol(E2), and SHBG in group A, B, and C were significantly lower than those in the reference group, and the levels of testosterone(T) were significantly higher than that in the reference group(all P<0.05). The levels of FSH, LH, E2, and SHBG in group A and B were significantly lower than those in group C, and the levels of T were significantly higher than that in group C(all P<0.05). The levels of FSH, LH, E2 and SHBG in group A were significantly lower than those in group B, and the level of T was significantly higher than that in group B(all P<0.05). When the dominant follicles developed to 10~12 mm, 14~16 mm, and 18~20 mm, the levels of estrogen and endometrial thickness in group A, B, and C were significantly lower than those in the reference group(all P<0.05). The level of estrogen and endometrial thickness in group C were significantly lower than those in group A and B(all P<0.05). The level of estrogen and endometrial thickness in group B were significantly lower than those in group A(all P<0.05). No C-type endometrium was found in the four groups on the day of hCG, and there was no significant difference in the proportions of type A or type B among the four groups(all P>0.05). There was no significant difference in the ovulation rate among the four groups(all P>0.05). The pregnancy rates in group A, B, and C were significantly lower than that in the reference group. The pregnancy rate in group A and B were lower than taht in group C, and the rate was was lower in group A than in group B(all P<0.05). Conclusions Letrozole combined with clomiphene citrate can promote the secretion of sex hormones and SHBG in infertile patients with PCOS. It has a certain inhibitory effect on estrogen and endometrium which can still meet the requirements of embryo implantation and it can improve the pregnancy rate of patients. The effect of letrozole at a dosage of 7.5 mg/d was most pronounced.