Shapiro Maren, Romanski Phillip, Thomas Ann, Lanes Andrea, Yanushpolsky Elena
Obstetrics & Gynecology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Center for Reproductive Health, University of California, 499 Illinois Street, 6th floor, San Francisco, CA, 94158, USA.
Fertil Res Pract. 2021 May 28;7(1):12. doi: 10.1186/s40738-021-00104-8.
A number of studies have looked at dual triggers with hCG and GnRH agonist (GnRHa) in varying doses, but the question remains: what is the optimal dose of hCG to minimize ovarian hyperstimulation syndrome (OHSS) and still offer adequate pregnancy rates? The purpose of this study was to compare pregnancy and OHSS rates following dual trigger for oocyte maturation with GnRHa and a low-dose hCG versus hCG alone. A secondary objective was the assess pregnancy outcomes in subsequent frozen cycles for the same population.
A total of 963 women < 41 years old, with a BMI 18-40 kg/m and an AMH > 2 ng/mL who underwent fresh autologous in vitro fertilization (IVF) with GnRH antagonist protocol at a University-based fertility center were included in this retrospective cohort study. Those who received a low dose dual trigger with hCG (1000u) and GnRHa (2 mg) were compared to those who received hCG alone (10,000u hCG/250-500 μg Ovidrel). Differences in implantation rates, pregnancy, live birth, and OHSS were investigated.
The dual trigger group was younger (mean 33.6 vs 34.1 years), had a higher AMH (6.3 vs 4.9 ng/mL,) more oocytes retrieved (18.1 vs 14.9) and a higher fertilized oocyte rate (80% vs 77%) compared with the hCG only group. Yet, the dual trigger group had a lower probability of clinical pregnancy (gestational sac, 43.4% vs 52.8%) and live birth (33.4% vs 45.8%), all of which were statistically significant. There were 3 cases of OHSS, all in the hCG-only trigger group. In subsequent frozen cycles, pregnancy rates were comparable between the two groups.
The dual trigger group had a better prognosis based on age and AMH levels and had better stimulation outcomes, but significantly worse pregnancy outcomes, suggesting the low dose hCG (1000u) in the dual trigger may not have provided adequate luteal support, compared to an hCG-only trigger (10,000u hCG/250-500 μg Ovidrel). Interestingly, the pregnancy rates were comparable in subsequent frozen cycles, further supporting the hypothesis that the issue lies in inadequate luteal phase support, rather than embryo quality. Based on these findings, our program has changed the protocol to 1500u of hCG in a dual trigger.
多项研究探讨了不同剂量的人绒毛膜促性腺激素（hCG）与促性腺激素释放激素激动剂（GnRHa）联合触发，但问题依然存在：为将卵巢过度刺激综合征（OHSS）降至最低并仍能提供足够的妊娠率，hCG的最佳剂量是多少？本研究的目的是比较GnRHa与低剂量hCG联合触发卵母细胞成熟与单独使用hCG后的妊娠率和OHSS发生率。次要目的是评估同一人群后续冷冻周期的妊娠结局。
本回顾性队列研究纳入了963名年龄小于41岁、体重指数（BMI）为18至40kg/m²且抗缪勒管激素（AMH）>2ng/mL的女性，她们在一家大学附属的生殖中心接受了采用GnR拮抗剂方案的新鲜自体体外受精（IVF）。将接受hCG（1000单位）和GnRHa（2毫克）低剂量联合触发的患者与接受单独hCG（10000单位hCG/250 - 500μg艾泽）的患者进行比较。研究了着床率、妊娠、活产和OHSS的差异。
与仅使用hCG组相比，联合触发组患者更年轻（平均33.6岁对34.1岁），AMH更高（6.3对4.9ng/mL），回收的卵母细胞更多（18.1对14.9），受精卵率更高（80%对77%）。然而，联合触发组临床妊娠（妊娠囊）的概率较低（43.4%对52.8%），活产概率较低（33.4%对45.8%），所有这些差异均具有统计学意义。有3例OHSS，均在仅使用hCG触发组。在后续冷冻周期中，两组的妊娠率相当。
基于年龄和AMH水平，联合触发组预后较好，刺激效果更佳，但妊娠结局明显更差，这表明与仅使用hCG触发（10000单位hCG/250 - 500μg艾泽）相比，联合触发中低剂量hCG（1000单位）可能未提供足够的黄体支持。有趣的是，后续冷冻周期的妊娠率相当，进一步支持了问题在于黄体期支持不足而非胚胎质量的假设。基于这些发现，我们的方案已将联合触发中hCG的剂量改为1500单位。
