低剂量重组人促卵泡刺激素(rFSH)递增方案诱导排卵的多中心前瞻性研究

目的:探讨在低剂量重组人促卵泡刺激素(rFSH)递增方案诱导排卵中临床结局的预测因子。方法:总结全国22家生殖中心对WHO II型无排卵为主要不孕原因的患者使用低剂量rFSH递增方案共433个诱导排卵周期中418个符合疗效分析的周期的临床妊娠率、单卵泡发生率、周期取消率、卵巢过度刺激综合征(OHSS)发生率;比较37.5 IU和75.0 IU不同rFSH启动剂量的临床、实验室结局,分析单卵泡发育、卵巢诱导成功、周期取消与年龄、体质量指数(BMI)、卵巢储备等预测因子间的关系。结果:①所有对象临床妊娠率为17.94%,单卵泡发育率为57.66%,OHSS发生率为2.31%,多胎妊娠率为0.23%,周期取消率为12.68%;②果纳芬(rFSH)平均治疗天数为12.7±5.6 d,平均总使用剂量为813.8±480.4 IU,平均阈剂量为73.0±29.7 IU;其中75.12%的患者总使用剂量1 000 IU,73.68%的人群刺激天数在5~15 d之间;③启动剂量为37.5 IU者较启动剂量为75 IU者的卵巢诱导时间明显增加(14.1±5.6 d vs 10.9±4.9 d,P=0.000),果纳芬总使用剂量明显减少(767.0±495.0 IU vs879.1±542.7 IU,P=0.000),单卵泡发育率明显增加(62.30%vs 51.15%,P=0.027),周期取消率明显升高(17.62%vs 5.75%,P=0.000);OHSS发生率无明显差异(2.87%vs 1.72%,P=0.532),临床妊娠率和生化妊娠率亦无统计学差异(P0.05);④不同阈剂量下临床妊娠率和生化妊娠率均无统计学差异(P0.05);体质量≥70 kg时阈剂量明显增加;⑤周期取消的预测因素与年龄呈负相关(r=-0.169,OR=0.845,95%CI=0.744~0.960,P=0.010),与既往诱导排卵周期数呈正相关(r=-0.240,OR=1.271,95%CI=1.093~1.478,P=0.002)。结论:低剂量递增方案诱导排卵可以取得较高的单卵泡发育率和临床妊娠率,且降低并发症发生率。不同启动剂量与刺激天数和总使用剂量相关,但对临床结局无明显影响;周期取消可能与年龄和既往诱导排卵周期有关。

Factors Related to Successful Ovulation Induction with Low-dose Recombinant FSH Treatment

Objective： To investigate the predictive factors for clinical outcome in low-dose step-up recombinant follicle stimulating hormone （rFSH） protocol for ovulation induction. Methods： A total of 433 infertile parities, majority of them with WHO group II anovulatory infertility from 22 ART centers in China, underwent a low-dose step-up rFSH protocol for ovulation induction. The clinical pregnancy rate, mono-follicular development rate, cycle cancellation rate and OHSS rate were assessed in 418 cycles fitted with efficacy population. A comparison of difference in duration of ovulation induction, total gonadotrophin dose, mono-follicular develop- ment rate, achieve follicular development rate, clinical pregnancy rate and cycle cancellation rate between 37.5 IU and 75 IU starting dose was performed. Age, body mass index （BMI） and ovarian reserve considered as predictive factor were analyzed to investigate the correlation with mono-follicular development, achieve follicular development, and cycle cancellation. Results： 1） Of overall subjects, clinical pregnancy rate was 17.94%, mono-follicular development rate was 57.66%, OHSS rate was 2.31%, multiple pregnancy rate was 0.23% and cycle cancellation rate was 12.68%; 2） Mean duration of Gonal-f administration was 12.7 ±5.6 d, mean total dose of Gonal-f （rFSH） was 813.8 ±480.4 IU, mean threshold dose was 73.0 ± 29.7 IU. Total dose of Gonal-f wasless than 1 000 IU in 75.12% of subjects and duration of stimulation was between 5-15 d in 73.68% of subjects. 3） Duration of ovulation induction was significantly longer in the 37.5 IU starting dose group than in the 75 IU group （14.1 ±5.6 d vs 10.9 ± 4.9 d, P=0.000）. Total dose of Gonal-f was significantly decreased in 37.5 IU group compared with the 75 IU group （767.0 ± 495.0 IU vs 879.1 ±542.7 IU, P=0.000）. A significantly increase in the mono-follicular development rate was observed in the 37.5 IU group than in the 75 IU group （62.30% vs 51.15%, P=0.027）. There was no statistically significant difference in terms of clinical pregnancy rate and biochemical pregnancy rate （P〉0.05）, but cycle cancellation rate was significantly higher in 37.5 IU group than in the 75 IU group （17.62% vs 5.75%, P=0.000）. OHSS rate was not significantly different between 37.5 IU group and 75 IU group （2.87% vs 1.72%, P=0.532）. 4） There were no statistically significant differences in terms of clinical pregnancy rate and biochemical pregnancy rate according to different threshold doses （P〉0.05）. A significant increase in the threshold dose was observed when body weight was more than 70 kg. 5） Age was negatively correlated with cycle cancellation （r=-0.169, OR=0.845, 95%CI=0.744-0.960, P=0.010） and the number of ovulation induction treatment cycles was a positive predictive factor for cycle cancellation （r=-0.240, 0R=1.271, 95%CI=1.093-1.478, P=0.002）. Conclusion： A low-dose step-up rFSH protocol may result in not only high mono-follicular development rate and clinical pregnancy rate but also a significant decrease in the incidence of OHSS. Different starting doses may lead to different duration of ovulation induction and total gonadotrophin without affecting clinical outcomes. The influence of cycle cancellation seems to be age and the number of ovulation induction treatment cycles.