Verschuere Hannah, Laenen Annouschka, Debrock Sophie, Tomassetti Carla, Lie Fong Sharon
Leuven University Fertility Center, Department of Gynecology and Obstetrics, University Hospitals Leuven, Leuven, Belgium.
Fertility Clinic Brussels, Clinic St. Jean Brussels, Brussels, Belgium.
Front Endocrinol (Lausanne). 2024 Dec 4;15:1481546. doi: 10.3389/fendo.2024.1481546. eCollection 2024.
Few data is available on the natural course of luteinizing hormone (LH) during ovarian stimulation, but it has been suggested that 'oversuppressed' LH could decrease fertility outcomes. Our aim with this study is to evaluate the changes in LH depending on the used stimulation protocol to better define LH oversuppressioin.
Patients undergoing oocyte retrieval in a tertiary fertility center between 01-01-2015 and 30-09-2020 after stimulation with a short-agonist (SA) or antagonist (A) protocol were included. Data were retrospectively retrieved from 858 electronic patient records, of which 338 SA cycles and 783 A cycles. A continuous profile was set out to evaluate the pooled measurements of the mean LH in time during ovarian stimulation and linear mixed modeling was used to compare the change of LH between 4 time points: the day prior to start of gonadotrophins (T1), stimulation day 5 (T2), stimulation day 6 (T3) and on the day of oocyte maturation trigger (T4). Oversuppression of LH was defined as a decrease of LH > 50% after initiation of GnRH antagonist and LH levels < 1.2 IU/l after GnRH antagonist. A subanalysis was performed for type of gonadotrophin (recFSH vs hp-hMG).
In the SA protocol, an initial LH peak was followed by a slow decrease of LH until triggering. In the A protocol, LH decreased after gonadotrophin initiation with a further rapid decrease after initiation of the antagonist and remained low until trigger. LH levels dropped > 50% in 26.2% of the antagonist cycles and LH levels were < 1.2 IU/l in 45.3% of cycles after initiation of GnRH-antagonist.
The course of LH in the SA protocol differs from the A protocol where low mean LH levels are seen. Oversuppression of LH, or iatrogenic LH deficiency as described in earlier studies, may be a rather pervasive phenomenon during stimulation with an antagonist protocol and warrants further investigation to elucidate the clinical relevance of low LH levels during ovarian stimulation.
关于卵巢刺激过程中促黄体生成素（LH）的自然病程，可用数据较少，但有研究表明，“过度抑制”的LH可能会降低生育结局。本研究的目的是评估根据所用刺激方案，LH的变化情况，以更好地界定LH过度抑制。
纳入2015年1月1日至2020年9月30日期间，在一家三级生殖中心接受短方案激动剂（SA）或拮抗剂（A）刺激后进行卵母细胞取卵的患者。数据从858份电子病历中回顾性获取，其中338个SA周期和783个A周期。绘制连续曲线以评估卵巢刺激期间平均LH的汇总测量值，并使用线性混合模型比较4个时间点之间LH的变化：促性腺激素开始使用前一天（T1）、刺激第5天（T2）、刺激第6天（T3）和卵母细胞成熟触发日（T4）。LH过度抑制定义为GnRH拮抗剂开始使用后LH下降>50%，且GnRH拮抗剂使用后LH水平<1.2 IU/L。对促性腺激素类型（重组FSH与高纯度人绝经期促性腺激素）进行了亚组分析。
在SA方案中，最初出现LH峰值，随后LH缓慢下降直至触发。在A方案中，促性腺激素开始使用后LH下降，拮抗剂开始使用后进一步快速下降，并在触发前一直保持低水平。在26.2%的拮抗剂周期中，LH水平下降>50%，在GnRH拮抗剂开始使用后，45.3%的周期中LH水平<1.2 IU/L。
SA方案中LH的变化过程与A方案不同，A方案中LH平均水平较低。LH过度抑制，或如早期研究所描述的医源性LH缺乏，在拮抗剂方案刺激期间可能是一种相当普遍的现象，需要进一步研究以阐明卵巢刺激期间低LH水平的临床相关性。
