Dehydroepiandrosterone (DHEA) supplementation results in supraphysiologic DHEA-S serum levels and progesterone assay interference that may impact clinical management in IVF

Abstract

Purpose Dehydroepiandrosterone (DHEA) is often prescribed for poor responders in IVF in an effort to improve response to ovarian stimulation. The effect of DHEA supplementation and resultant supraphysiologic DHEA-S serum levels on sex steroid assays has not been evaluated in this population. This study seeks to determine the relationship between DHEA supplementation and progesterone measurements to characterize the degree of interference with particular immunoassays. Methods Characterization was accomplished in two phases. First, DHEA-S standard control reagents with no progesterone present were assayed for both DHEA-S and progesterone levels. Second, serum pools from 60 unique IVF patients' serum were used to create six pooled serum samples: three from patients on DHEA supplementation and three from patients not on DHEA supplementation. The three pools were composed of patients whose serum fell into low, medium, and high progesterone ranges. Baseline DHEA-S and progesterone were measured, and the mean level of DHEA-S in the mid-range progesterone pool was used as the mid-point for addition of DHEA-S standard to the serum pools from patients without DHEA supplementation. Progesterone from these pools was then measured on three commercially available immunoassay systems. Results The first experiment revealed a linear increase in progesterone when analyzing the DHEA-S standard ranging from 0.5 ng/mL in the blank control (no DHEA-S) to up to 2.0 ng/ mL in the high control (DHEA-S >700 μg/mL), indicating that the DHEA-S cross-reacts with the progesterone assays. In the second experiment, patients' serum DHEA-S and progesterone were measured from pooled serum samples of those taking DHEA and those not taking DHEA. Adding DHEA-S to the pooled serum of those not taking DHEA resulted in a linear increase in progesterone levels on two of three commercially available immunoassays (p < 0.05). Conclusions DHEA-S can interfere with standard progesterone immunoassays used in clinical ART programs, and thus serum progesterone levels in IVF patients on DHEA supplementation may not reflect truly bioactive progesterone.

Does DHEA supplementation in IVF patients result in supraphysiological DHEA-S serum concentrations?

“…In conclusion, we believe that the DHEA-S concentrations reported by Franasiak et al [1] should be in μg/dL instead of μg/mL. When the corrected units are used, serum DHEA-S concentrations in IVF patients not on DHEA supplements will be 131-142 μg/dL (1.3-1.4 μg/mL), while those receiving DHEA will be 284-392 μg/dL (2.8-3.9 μg/mL).…”

“…The units reported in Fig. 2 of the authors' article is μg/dL while the remainder of the text and figure/table legends use μg/mL [1]. The authors also claim in their conference abstract [3] that the concentration of the Siemens ADVIA Centaur DHEA-S controls range from 0 to >1500 μg/mL.…”

“…Dear Editor, We read with interest the paper by Franasiak et al entitled BDehydroepiandrosterone (DHEA) supplementation results in supraphysiologic DHEA-S serum concentrations and progesterone assay interference that may impact clinical management in IVF^ [1]. This paper provided evidence that DHEA supplementation could lead to increased circulating DHEA-S concentrations and clinically significant false elevations in progesterone results.…”

“…In addition, a review of commercially available DHEA-S assays reveals that the analytical and reportable range for DHEA-S is 0-1500 μg/ dL (0-15 μg/mL) ( Table 1). We also replicated part of the experiment performed by the authors [1] using our Siemens ADVIA Centaur assay. We measured an aliquot of our high and low DHEA-S calibrator on the progesterone assay to determine degree of cross reactivity.…”

Accuracy of Two Progesterone Immunoassays for Monitoring In Vitro Fertilization

“…At follow-up weeks later, clinicians learned that the patient had been tak-ing a supplement during the time of the unexpected results, despite previously denying use. In response to the clinicians, we performed an interference study using reference values of progesterone obtained on the LC-MS/MS and determined that a component in the supplements [dehydroepiandrosterone] contributed to the unexpected progesterone values obtained on the Centaur IA system (data not shown), as previously reported (10). Ultimately, the Architect IA analyzer was selected as the primary instrument for progesterone measurement because of its greater accuracy and specificity, and its comparable turnaround time, reagent cost, and specimen requirements to the Centaur IA system.…”