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通过在卵巢刺激开始时测量血清 LH 预测 GnRH 激动剂触发后卵母细胞产量不佳。

Predicting suboptimal oocyte yield following GnRH agonist trigger by measuring serum LH at the start of ovarian stimulation.

机构信息

Centre for Reproductive Medicine, UZ Brussel, Laarbeeklaan, Jette, Belgium.

IVI-RMA, Lisboa, Avenida Infante Dom Henrique, Lisboa, Portugal.

出版信息

Hum Reprod. 2019 Oct 2;34(10):2027-2035. doi: 10.1093/humrep/dez132.

DOI:10.1093/humrep/dez132
PMID:31560740
Abstract

STUDY QUESTION

Are the LH levels at the start of ovarian stimulation predictive of suboptimal oocyte yield from GnRH agonist triggering in GnRH antagonist down-regulated cycles?

SUMMARY ANSWER

LH levels at the start of ovarian stimulation are an independent predictor of suboptimal oocyte yield following a GnRH agonist trigger.

WHAT IS KNOWN ALREADY

A GnRH agonist ovulation trigger may result in an inadequate oocyte yield in a small subset of patients. This failure can range from empty follicle syndrome to the retrieval of much fewer oocytes than expected. Suboptimal response to a GnRH agonist trigger has been defined as the presence of circulating LH levels <15 IU/l 12 h after triggering. It has been shown that patients with immeasurable LH levels on trigger day have an up to 25% risk of suboptimal response.

STUDY DESIGN, SIZE, DURATION: In this retrospective cohort study, all patients (n = 3334) who received GnRH agonist triggering (using Triptoreline 0.2 mg) for final oocyte maturation undergoing a GnRH antagonist cycle in our centre from 2011 to 2017 were included. The primary outcome of the study was oocyte yield, defined as the ratio between the total number of collected oocytes and the number of follicles with a mean diameter >10 mm prior to GnRH agonist trigger.

PARTICIPANTS/MATERIALS, SETTING, METHODS: The endocrine profile of all patients was studied at initiation as well as at the end of ovarian stimulation. In order to evaluate whether LH levels, not only at the end but also at the start, of ovarian stimulation predicted oocyte yield, we performed multivariable regression analysis adjusting for the following confounding factors: female age, body mass index, oral contraceptives before treatment, basal and trigger day estradiol levels, starting FSH levels, use of highly purified human menopausal gonadotrophin and total gonadotropin dose. Suboptimal response to GnRH agonist trigger was defined as <10th percentile of oocyte yield.

MAIN RESULTS AND THE ROLE OF CHANCE

The average age was 31.9 years, and the mean oocyte yield was 89%. The suboptimal response to GnRH agonist trigger cut-off (<10th percentile) was 45%, which was exhibited by 340 patients. Following confounder adjustment, multivariable regression analysis showed that LH levels at the initiation of ovarian stimulation remained an independent predictor of suboptimal response even in the multivariable model (adjusted OR 0.920, 95% CI 0.871-0.971). Patients with immeasurable LH levels at the start of stimulation (<0.1 IU/l) had a 45.2% risk of suboptimal response, while the risk decreased with increasing basal LH levels; baseline circulating LH <0.5 IU/L, <2 IU/L and <5 IU/L were associated with a 39.1%, 25.2% and 13.6% risk, respectively.

LIMITATIONS, REASONS FOR CAUTION: The main limitation of the study is its retrospective design.

WIDER IMPLICATIONS OF THE FINDINGS

This is the largest study of GnRH agonist trigger cycles only, since most of the previous research on the predictive value of basal LH levels was performed in dual trigger cycles. LH values should be measured prior to start of ovarian stimulation. In cases where they are immeasurable, suboptimal response to GnRH agonist trigger can be anticipated, and an individualized approach is warranted.

STUDY FUNDING/COMPETING INTEREST(S): There was no funding and no competing interests.

TRIAL REGISTRATION NUMBER

Not applicable.

摘要

研究问题

在 GnRH 拮抗剂下调周期中,卵巢刺激开始时的 LH 水平是否可预测 GnRH 激动剂扳机后卵母细胞产量不佳?

总结答案

卵巢刺激开始时的 LH 水平是 GnRH 激动剂扳机后卵母细胞产量不佳的独立预测因素。

已知情况

GnRH 激动剂排卵触发可能导致一小部分患者的卵母细胞产量不足。这种失败的范围从空卵泡综合征到比预期少取卵。 GnRH 激动剂扳机的反应不佳定义为触发后 12 小时循环 LH 水平<15IU/l。已经表明,在触发日 LH 水平无法测量的患者中,反应不佳的风险高达 25%。

研究设计、大小和持续时间:在这项回顾性队列研究中,纳入了 2011 年至 2017 年期间在我们中心接受 GnRH 激动剂触发(使用曲普瑞林 0.2mg)以进行最终卵母细胞成熟的所有接受 GnRH 拮抗剂周期的患者(n=3334)。该研究的主要结局是卵母细胞产量,定义为收集的卵母细胞总数与 GnRH 激动剂触发前平均直径>10mm 的卵泡数之比。

参与者/材料、设置、方法:在开始和卵巢刺激结束时研究了所有患者的内分泌情况。为了评估 LH 水平不仅在卵巢刺激结束时而且在开始时是否可以预测卵母细胞产量,我们进行了多变量回归分析,调整了以下混杂因素:女性年龄、体重指数、治疗前口服避孕药、基础和触发日雌二醇水平、起始 FSH 水平、使用高纯人绝经期促性腺激素和总促性腺激素剂量。 GnRH 激动剂扳机的反应不佳定义为<第 10 个百分位数的卵母细胞产量。

主要结果和机会的作用

平均年龄为 31.9 岁,平均卵母细胞产量为 89%。 GnRH 激动剂扳机反应不佳的截断值(<第 10 个百分位数)为 45%,有 340 名患者表现出这种情况。在混杂因素调整后,多变量回归分析表明,即使在多变量模型中,卵巢刺激开始时的 LH 水平仍然是反应不佳的独立预测因素(调整后的 OR 0.920,95%CI 0.871-0.971)。刺激开始时 LH 水平无法测量(<0.1IU/l)的患者反应不佳的风险为 45.2%,而随着基础 LH 水平的升高,风险降低;基线循环 LH<0.5IU/L、<2IU/L 和<5IU/L 分别与 39.1%、25.2%和 13.6%的风险相关。

局限性、谨慎的原因:该研究的主要局限性是其回顾性设计。

研究结果的更广泛意义

这是仅关于 GnRH 激动剂扳机周期的最大研究,因为之前关于基础 LH 水平预测价值的大多数研究都是在双重扳机周期中进行的。LH 值应在开始卵巢刺激前测量。如果无法测量,则可以预期 GnRH 激动剂扳机的反应不佳,需要采取个体化方法。

研究资金/利益冲突:没有资金和利益冲突。

试验注册编号

不适用。

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