Abstract
The objective of this study was to evaluate predicting factors for supraphysiologic serum estradiol elevation during controlled ovarian stimulation (COS) with administration of letrozole and gonadotropins in patients with estrogen-dependent cancer. Use of aromatase inhibitors is recommended to prevent the potential effects of elevated serum estradiol levels and recurrence of tumor in patients with estrogen-dependent cancers during COS. Although previous studies reported that letrozole have shown an effective lowering of peak estrogen levels, a part of patients shows supraphysiologic levels of estrogen associated with ovarian stimulation despite the administration of letrozole. From January 2009 to December 2019, patients with estrogen-dependent cancer who underwent COS with antagonist protocol using a letrozole (5 mg/ day) to keep estrogen levels low were included in this study. Early monitoring serum estradiol was measured in all patients on the 4-6th day of stimulation. Subjects were classified into two groups according to the serum estradiol level on hCG triggering day, physiologic estradiol group (≤400 pg/mL) and supraphysiologic estradiol group (>400 pg/mL). A total of 96 COS cycles were retrospectively analyzed. Supraphysiologic level of serum estradiol was found in 21.9% of the patients. Mean age, AMH, duration of stimulation, total dose of gonadotropins administered were not different between the two groups. However, early monitoring serum estradiol level was significantly higher in the supraphysiologic estradiol group (67.1±47.9 vs. 115.6±78.1, p = 0.001) and was associated with the occurrence of supraphysiologic elevation of serum estradiol on hCG triggering day. Patients with early monitoring serum estradiol ≥84.5 pg/mL had an odds ratio of 5.376 [95% CI, 1.613–17.913] for supraphysiologic elevation of serum estradiol compared to those with early monitoring serum estradiol below 84.5 pg/mL. In conclusion, early monitoring serum estradiol is an independent predicting factor for supraphysiologic level of serum estradiol on hCG triggering day in the COS cycles using letrozole and gonadotropins.
Highlights
The population of estrogen-dependent cancers which includes breast cancer and endometrial cancer is growing recently and a considerable number of patients are diagnosed at their reproductive age [1]
The study population was divided into two groups according to peak serum E2 level; patients with peak serum E2 level 400 pg/mL were included in physiologic E2 group, whereas those with peak serum E2 level >400 pg/mL were assigned to supra-physiologic E2 group
Monitoring serum E2 levels measured on the early period of stimulation were found to be an independent predictor for supraphysiologic serum E2 elevation, and the present study determined the best cut-off for early monitoring serum E2 to predict the occurrence of supraphysiologic serum E2 elevation
Summary
The population of estrogen-dependent cancers which includes breast cancer and endometrial cancer is growing recently and a considerable number of patients are diagnosed at their reproductive age [1]. Potential options for fertility preservation (FP) in women with cancer includes embryo cryopreservation, oocyte cryopreservation, ovarian tissue cryopreservation and maturation of oocytes in vitro [6]. Among the fertility preservation options, embryo cryopreservation is the most established method which provides 25–35% possibility of pregnancy [7]. As the pregnancy rate and perinatal outcome are improved through the introduction of vitrification, the number of oocyte cryopreservation for the purpose of fertility preservation before chemotherapy is increasing in unmarried women [8]
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