Insulin-like growth factor-1 and soluble FMS-like tyrosine kinase-1 prospectively predict cancelled IVF cycles

Abstract

Purpose: To identify biomarkers that prospectively predict IVF cycle cancellation.

Methods: In this prospective study, sera were obtained prior to any intervention, from women about to undergo an IVF cycle. The sera were assayed by ELISA for levels of insulin-like growth factor (IGF)-1, IGF-2, IGF binding protein (BP)-1, and soluble fms-like tyrosine kinase (sFLT-1). The cancellation or progression of the IVF cycle was subsequently obtained by chart review. Associations between serum components and outcome were analyzed by the Mann-Whitney test. Receiver operator curves were constructed to evaluate the strength of the correlations between biomarkers and cycle cancellation, as assessed from the area under the curve (AUC).

Results: A total of 205 women were included. Twenty-seven (13.2%) cycle cancellations due to poor response were recorded. Women with a cancelled cycle had reduced anti-Mullerian hormone (AMH) values (p < 0.001) and antral follicle count (p = 0.003). There were no significant differences between the two groups with regard to age and BMI. Median concentrations of IGF-1 and sFLT-1 were elevated in sera from women whose IVF cycles were cancelled as compared to those with ongoing cycles (p = 0.015 and p < 0.001, respectively); AUC for IGF-1 and sFLT-1 were 0.67 and 0.75, respectively. Concentrations of sFLT-1 remained significantly higher in patients with cancelled cycles even after controlling for AMH levels. There were no differences in IGF-2 and IGFBP-1 levels between the two groups.

Conclusions: Measurement of circulating IGF-1 and sFLT-1 levels prior to initiation of an IVF cycle has the potential to identify women whose cycles have an increased likelihood to be subsequently cancelled.

Keywords: Cycle cancellation; IGF-1; sFLT-1.

Fig. 1

Serum IGF-1 at baseline (day 2 of IVF cycle, before administration of medications) and cancellation or progression of IVF cycle

Fig. 2

Serum sFLT-1 at baseline (day 2 of IVF cycle, before administration of medications) and cancellation or progression of IVF cycle

Fig. 3

Serum sFLT-1 at baseline (day 2 of IVF cycle, before administration of medications) and different levels of AMH. Low AMH was ≤1 ng/ml, normal AMH was 1–4 ng/ml and high AMH was >4 ng/ml

Fig. 4

Serum sFLT-1 at baseline, for women with AMH < 1, (day 2 of IVF cycle, before administration of medications) and cancellation or progression of IVF cycle

Fig. 5

Serum sFLT-1 at baseline, for women with AMH ≥ 1, (day 2 of IVF cycle, before administration of medications) and cancellation or progression of IVF cycle

Fig. 6

Receiver operator curve (ROC) for IGF-1 to predict cycle cancellation. Area under the curve was 0.672 (p = 0.017)

Fig. 7

Receiver operator curve (ROC) for sFLT-1 to predict cycle cancellation. Area under the curve was 0.758 (p = 0.015)

Fig. 8

Receiver operator curve (ROC) for low AMH to predict cycle cancellation. Area under the curve was 0.831 (p < 0.001)

Fig. 9

Receiver operator curve (ROC) for AFC to predict cycle cancellation. Area under the curve was 0.750 (p = 0.003)

Fig. 10

Receiver operator curve (ROC) for the combination of sFLT-1 and AFC to predict cycle cancellation. Area under the curve was 0.743 (p = 0.006)

Fig. 11

Receiver operator curve (ROC) for the combination of sFLT-1 and AMH to predict cycle cancellation. The combination of sFLT-1 and AMH had an area under the curve (AUC) of 0.923 (p < 0.001).