Department of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei, Taiwan.
Infertility Center, Chien-Shin Hospital, Kaohsiung, Taiwan.
Front Endocrinol (Lausanne). 2023 Aug 7;14:1216584. doi: 10.3389/fendo.2023.1216584. eCollection 2023.
Risk factors associated with a suboptimal response to Gonadotropin-releasing hormone (GnRH) agonists include a high or low body mass index (BMI), prolonged use of oral contraceptive pills, and low luteinizing hormone (LH) levels on either the start or trigger days of controlled ovarian stimulation (COS). However, this approach may increase the need for a dual trigger and may also result in a higher incidence of ovarian hyperstimulation syndrome (OHSS) in hyper-responders. We aimed to investigate whether the maximum LH level during stimulation can serve as a predictive factor for achieving an optimal oocyte yield using the GnRH agonist trigger alone.
We retrospectively reviewed all antagonist protocols or progestin-primed ovarian stimulation (PPOS) protocols triggered with GnRH agonist only between May 2012 and December 2022. Subjects were divided into three groups, depending on basal LH level and LH maximum level. The freeze-all strategy was implemented in all cycles: Group 1, consistently low LH levels throughout COS; Group 2, low basal LH level with high LH max level during COS; Group 3, consistently high LH levels throughout COS. The primary outcome was the oocyte yield rate. The secondary outcome includes the number of collected oocytes, suboptimal response to GnRH agonist trigger, oocyte maturity rate, fertilized rate, clinical pregnancy rate, ongoing pregnancy rate, and live birth rate. The pregnancy outcomes were calculated for the first FET cycle.
Following confounder adjustment, multivariable regression analysis showed that Group 1 (cycles with consistently low LH levels throughout COS) remains an independent predictor of suboptimal response (OR: 6.99; 95% CI 1.035-47.274). Group 1 (b = -12.72; 95% CI -20.9 to -4.55) and BMI (b = -0.25; 95% CI -0.5 to -0.004) were negatively associated with oocyte yield rate. Patients with low basal LH but high LH max levels had similar clinical outcomes compared to those with high LH max levels through COS.
The maximum LH level during COS may serve as an indicator of LH reserve and could be a more reliable predictor of achieving an optimal oocyte yield when compared to relying solely on the basal LH level. In the case of hyper-responders where trigger agents (agonist-only or dual trigger) are being considered, we propose a novel strategy that incorporates the maximum LH level, rather than just the basal or trigger-day LH level, as a reference for assessing LH reserve. This approach aims to minimize the risk of obtaining suboptimal oocyte yield and improve overall treatment outcomes.
与促性腺激素释放激素(GnRH)激动剂反应不佳相关的风险因素包括高或低体重指数(BMI)、长期使用口服避孕药以及在控制性卵巢刺激(COS)开始或触发日的黄体生成素(LH)水平较低。然而,这种方法可能会增加对双重触发的需求,并且在高反应者中也可能导致更高的卵巢过度刺激综合征(OHSS)发生率。我们旨在研究在 GnRH 激动剂触发单独使用时,刺激期间的最大 LH 水平是否可以作为获得最佳卵母细胞产量的预测因素。
我们回顾性分析了 2012 年 5 月至 2022 年 12 月期间仅使用 GnRH 激动剂触发的拮抗剂方案或孕激素预激卵巢刺激(PPOS)方案。根据基础 LH 水平和 LH 最大水平将受试者分为三组。在所有周期中都采用了全冷冻策略:第 1 组,COS 期间 LH 水平持续较低;第 2 组,COS 期间基础 LH 水平较低,但 LH 最大值较高;第 3 组,COS 期间 LH 水平持续较高。主要结局是卵母细胞产量率。次要结局包括收集的卵母细胞数量、对 GnRH 激动剂触发的反应不佳、卵母细胞成熟率、受精率、临床妊娠率、持续妊娠率和活产率。妊娠结局是计算第一个 FET 周期的。
经过混杂因素调整,多变量回归分析显示,第 1 组(COS 期间 LH 水平持续较低的周期)仍然是 GnRH 激动剂触发反应不佳的独立预测因素(OR:6.99;95%CI 1.035-47.274)。第 1 组(b = -12.72;95%CI -20.9 至 -4.55)和 BMI(b = -0.25;95%CI -0.5 至 -0.004)与卵母细胞产量率呈负相关。基础 LH 水平较低但 LH max 水平较高的患者与 LH max 水平较高的患者相比,其临床结局相似。
COS 期间的最大 LH 水平可能是 LH 储备的指标,并且与仅依赖基础 LH 水平相比,它可能是预测获得最佳卵母细胞产量的更可靠指标。在考虑使用触发剂(仅激动剂或双重触发)的高反应者的情况下,我们提出了一种新策略,该策略将最大 LH 水平(而不仅仅是基础或触发日 LH 水平)纳入评估 LH 储备的参考,以降低获得低质量卵母细胞的风险,并改善整体治疗结局。