GnRH-a长方案、短方案和GnRH-ant方案治疗卵巢低反应的疗效评估

Evaluation of the Efficacy of GnRH-a Long Protocol, Short Protocol, and GnRH-ant Protocol in the Treatment of Ovarian Hyporesponsiveness

摘要: 目的：对比3种促排卵方案对卵巢低反应(POR)的治疗效果。方法：回顾性选取本院生殖中心接诊的行体外受精–胚胎移植(IVF-ET)的POR共300个周期，根据促排卵方案的不同分为3组：促性腺激素释放激素激动剂(GnRH-a)长方案108个周期(长方案组)、GnRH-a短方案82个周期(短方案组)、促性腺激素释放激素拮抗剂(GnRH-ant)方案110个周期(拮抗剂组)。记录3组促性腺激素药物(Gn)总量、GN天数、总获卵数及临床妊娠结局等。根据根据获卵数不同对3组患者进行分层，对比各亚组的卵泡输出率(FORT)差异。结果：3组Gn总量、Gn天数、总获卵数、2PN数、hCG日LH及P水平比较，差异均有统计学意义(P < 0.05)，hCG日E₂、内膜厚度、MII数及优质胚胎数比较，差异均无统计学意义(P > 0.05)。长方案组Gn总量、hCG日P最高，总获卵数最多，Gn天数最长，2PN数最少，hCG日LH最低；拮抗剂组Gn总量最少、Gn天数最短，2PN数最多；短方案组总获卵数最少。3组正常受精率、临床妊娠率、周期取消率、早产流产率、异位妊娠率比较，差异均无统计学意义(P > 0.05)。长方案组OHSS发生率显著高于另外两组(P < 0.05)，短方案组与拮抗剂组OHSS发生率比较差异无统计学意义(P > 0.05)。获卵数 ≤ 4个时，3组年龄、AMH、AFC及FORT比较，差异均无统计学意义(P > 0.05)；获卵数 > 4个时，3组FORT比较差异有统计学意义(P < 0.05)，长方案组FORT显著高于另外两组(P < 0.05)，短方案组与拮抗剂组FORT比较差异无统计学意义(P > 0.05)。FORT截断值为62.30%时，对IVF-ET临床妊娠有较高的预测价值(AUC = 0.811)，灵敏度、特异度分别为85.27%和70.11%，95%CI为0.748~0.889。结论：3种促排卵方案治疗POR的助孕结局相似，但短方案的获卵数偏少，长方案的Gn用量大、费用高，拮抗剂方案促排时间短、Gn用量少，在时间–经济成本方面更具优势。但对于获卵数 > 4个次优反应患者，长方案的卵泡同步性发育更具优势。

Abstract: Objective: To compare the therapeutic effects of three ovulation promotion regimens on ovarian low response (POR). Methods: A total of 300 cycles of POR undergoing in vitro fertilization embryo transfer (IVF-ET) received from our reproductive center were retrospectively selected and divided into three groups according to different ovulation promotion protocols: 108 cycles of gonadotro-pin-releasing hormone agonist (GnRH-a) long protocol (long protocol group), 82 cycles of GnRH-a short protocol (short protocol group), and 110 cycles of gonadotropin-releasing hormone antagonist (GnRH-ant) (antagonist group). The total amount of gonadotropin drugs (Gn), the number of days of GN, the total number of oocytes retrieved, and clinical pregnancy outcomes were recorded in the three groups. Three groups of patients were stratified according to the number of oocytes retrieved, and the differences in follicle output rate (FORT) among each subgroup were compared. Results: There were statistically significant differences in the total amount of Gn, the number of days of Gn, the total number of oocytes retrieved, the number of 2PN, the level of LH and P on the day of hCG among the three groups (P < 0.05), but there was no statistically significant difference in the num-ber of E₂, intimal thickness, MII, and high-quality embryos on the day of hCG among the three groups (P > 0.05). The total amount of Gn and daily P of hCG in the long protocol group were the highest, the total number of eggs captured was the highest, the number of Gn days was the longest, the number of 2PN was the lowest, and the daily LH of hCG was the lowest; The total amount of Gn in the antagonist group was the lowest, the number of Gn days was the shortest, and the number of 2PN was the highest; the total number of eggs captured in the short- acting group was the lowest. There was no significant difference in the normal fertilization rate, clinical pregnancy rate, cycle cancellation rate, premature abortion rate, and ectopic pregnancy rate among the three groups (P > 0.05). The incidence of OHSS in the long-acting group was significantly higher than that in the other two groups (P < 0.05), while there was no statistically significant difference in the incidence of OHSS between the short-acting group and the antagonist group (P > 0.05). When the number of eggs re-trieved was ≤4, there was no statistically significant difference in age, AMH, AFC, and FORT among the three groups (P > 0.05). When the number of eggs retrieved was greater than 4, there was a sta-tistically significant difference in FORT among the three groups (P < 0.05), while the long protocol effect group had a significantly higher FORT than the other two groups (P < 0.05). There was no sta-tistically significant difference in FORT between the short protocol effect group and the antagonist group (P > 0.05). When the cutoff value of FORT was 62.30%, it had a high predictive value for IVF-ET clinical pregnancy (AUC = 0.811), with sensitivity and specificity of 85.27% and 70.11%, re-spectively, and 95%CI was 0.748 to 0.889. Conclusion: The outcomes of the three ovulation pro-moting regimens in the treatment of POR are similar, but the number of oocytes obtained in the lu-teal phase is relatively small, while the amount of Gn used in the follicular phase is large and the cost is high. The antagonist regimen has a shorter ovulation promoting time and less Gn used, which is more advantageous in terms of time economic cost. However, for patients with suboptimal re-sponses with more than 4 oocytes retrieved, synchronous follicular development with a long follic-ular phase scheme has a more advantageous advantage.