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Cycle day 2 insulin-like growth factor-1 serum levels as a prognostic tool to predict controlled ovarian hyperstimulation outcomes in poor responders
Fertility and Sterility ( IF 6.7 ) Pub Date : 2020-06-01 , DOI: 10.1016/j.fertnstert.2020.02.111
Limor Man 1 , Jovana Lekovich 1 , Chelsea Canon 2 , Zev Rosenwaks 3 , Daylon James 3
Affiliation  

OBJECTIVE To study whether patients exhibiting poor ovarian response have abnormal levels of serum insulin-like growth factor (IGF)-1 on cycle day 2 when compared with age-matched normal and high responders. DESIGN Retrospective cohort. SETTING University-based practice. PATIENT(S) All women between the ages of 21 and 42 years who underwent in vitro fertilization treatment cycle without estrogen pretreatment at our institution between 2013 and 2015. INTERVENTION(S) Patients were separated into three groups: poor responders (≤4 oocytes retrieved/cycle cancellation), normal responders (8-12 oocytes), and high responders (≥18 oocytes). Subanalysis focused on the next cycle for poor responders adjacent to the nonpretreated index cycle, in which estrogen pretreatment was implemented. MAIN OUTCOME MEASURE(S) Serum cycle day 2: IGF-1, insulin-like growth factor-binding protein (IGFBP)-3 levels, and IGF-1:IGFBP3 ratio, number of eggs retrieved, number of two pronuclei embryos, cumulative pregnancy rate, and live birth. RESULT(S) A total of 184 patients met the inclusion criteria. The poor responder group exhibited a more than twofold increase in the cycle day IGF-1 serum levels when compared with normal responders and a threefold increase when compared with the high responders. Cycle day 2 IGF-1 level >72 ng/mL in poor responders had 70% sensitivity and 78% specificity for a negative controlled ovarian hyperstimulation cycle outcome with an area under the curve of 0.83. Luteal estrogen pretreatment in the poor responder group was associated with a significant reduction in IGF-1 levels. Significantly, more retrieved and mature oocytes, as well as two pronuclei embryos, were achieved in the pretreated poor responder group when compared with the yield from their adjacent nonpretreated index cycles. Furthermore, cumulative rates were higher for intrauterine pregnancies, and lower for negative pregnancy outcome. CONCLUSION(S) Patients who respond poorly to controlled ovarian stimulation, despite normal cycle day 2 follicle-stimulating hormone levels, have significantly higher serum cycle day 2 IGF-1 levels when compared with age-matched normal and high responders. Cycle day 2 IGF-1 level >72 ng/mL in poor responders was predictive of a negative cycle outcome. Luteal estrogen pretreatment in the poor responder group was associated with a significant reduction in IGF-1 levels, improved response to stimulation, and higher cumulative rates for intrauterine pregnancies, and lower for negative pregnancy outcome.

中文翻译:

周期第 2 天胰岛素样生长因子 1 血清水平作为预测不良反应者受控卵巢过度刺激结果的预后工具

目的 研究与年龄匹配的正常和高反应者相比,卵巢反应差的患者在周期第 2 天的血清胰岛素样生长因子 (IGF)-1 水平是否异常。设计回顾性队列。设置 基于大学的实践。患者(S) 2013 年至 2015 年期间在我们机构接受体外受精治疗周期且未接受雌激素预处理的所有 21 至 42 岁女性。 干预(S) 患者分为三组:反应差(≤4 个卵母细胞) /周期取消)、正常反应者(8-12 个卵母细胞)和高反应者(≥18 个卵母细胞)。亚组分析侧重于与未预处理指标周期相邻的低反应者的下一个周期,在该周期中实施了雌激素预处理。主要结果测量(S)血清周期第 2 天:IGF-1,胰岛素样生长因子结合蛋白 (IGFBP)-3 水平、IGF-1:IGFBP3 比率、取卵数、两个原核胚胎数、累积妊娠率和活产。结果 共有 184 名患者符合纳入标准。与正常反应者相比,低反应者组的周期日 IGF-1 血清水平增加了两倍以上,与高反应者相比增加了三倍。周期第 2 天 IGF-1 水平 >72 ng/mL 的不良反应者对负控卵巢过度刺激周期结果具有 70% 的敏感性和 78% 的特异性,曲线下面积为 0.83。不良反应组的黄体雌激素预处理与 IGF-1 水平显着降低有关。值得注意的是,更多取回和成熟的卵母细胞,以及两个原核胚胎,与相邻的非预处理指数周期的产量相比,预处理的不良反应者组实现了这一目标。此外,宫内妊娠的累积率较高,而阴性妊娠结果的累积率较低。结论(S)与年龄匹配的正常和高反应者相比,尽管周期第 2 天促卵泡激素水平正常,但对控制性卵巢刺激反应不佳的患者在周期第 2 天的血清 IGF-1 水平显着更高。不良反应者的周期第 2 天 IGF-1 水平 >72 ng/mL 是负周期结果的预测。不良反应组的黄体雌激素预处理与 IGF-1 水平显着降低、对刺激的反应改善、宫内妊娠累积率较高以及阴性妊娠结果较低相关。
更新日期:2020-06-01
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