DHEA supplementation improves endometrial HOXA-10 mRNA expression in poor responders

Abstract

Objective:The study was planned to investigate whether DHEA supplementation had an impact on endometrial receptivity in women who were poor responders (POR).Material and Methods:Twenty-eight POR women who were undergoing hysteroscopy and five fertile control subjects were included. The POR women were equally subdivided into two separate groups as patients who were currently using DHEA and those who were not. Endometrial samples of the subjects were obtained during hysteroscopy at the late follicular phase. Expression levels of endometrial HOXA-10, HOXA-11, and LIF mRNA were measured with the using real-time polymerase chain reaction. Spontaneous clinical pregnancy rates were also noted.Results:Compared with POR women who were not given DHEA, upregulated endometrial HOXA-10 (7.33-fold) and HOXA-11 (2.39-fold) mRNA expression were detected in POR women on DHEA. The increase in HOXA-10 mRNA was significant (p<0.03). The fold increase in HOXA-11 mRNA was found as 2.39, which indicated a positive upregulation. However, this fold increment was insignificant (p<0.45). An insignificant increase in spontaneous clinical pregnancy rates in POR women on DHEA (53.3%) was observed compared with POR women who were not given DHEA (43.8%).Conclusion:Oral DHEA supplementation in POR upregulates endometrial HOXA-10 mRNA expression, which is known to positively modulate endometrial receptivity.

New Insights into the Process of Placentation and the Role of Oxidative Uterine Microenvironment

“…In line with these results are the recent findings of Banerjee and coworkers reporting that low H 2 O 2 levels increase EVT invasion, while high levels induce apoptosis [191, 194]. Interestingly, an age-related decrease in adrenal synthesis of dehydroepiandrosterone (DHEA) is believed to grant increased antioxidant capacity to decidualized cells and improve endometrial receptivity [198–200].…”

Dehydroepiandrosterone (DHEA) role in enhancement and maintenance of implantation (DREAM): randomised double-blind placebo-controlled trial—study protocol

“…9 It is well known that both homeobox genes (HOXA-10 and HOXA-11) and leukaemiainhibitory factor play a key role in the decidualization and implantation process [10][11][12] and recent evidence shows upregulation of HOXA-10, HOXA-11 and leukaemiainhibitory factor with DHEA supplementation. 6 DHEA supplementation also increased vascular endothelial growth factor-mediated angiogenesis which may enhance decidualization. [13][14][15] With the increasing age, there is a decline in the synthesis of androgens from adrenal glands and ovary leading to a progressive fall in the level of androgens including local endometrial androgen and their metabolites.…”

“…Open access (IGFBP-1) 3 and upregulation of progesterone, 4 glucocorticoid, mineralocorticoid and androgen 5 receptors in the endometrium. 6 The androgen precursor, dehydroepiandrosterone (DHEA) has been studied and researched extensively for improving the various outcome measures of ovarian stimulation in women with advanced age or poor ovarian response. Though several meta-analyses 7 8 showed beneficial effects of DHEA in women with diminished ovarian reserve, its potential role in enhancing decidualization is not explored well.…”

“…The use of DHEA has not been associated with any major side effects. It is commonly used in patients with a Open access decreased ovarian reserve and a recent study by Çelik et al 6 have shown its beneficial effect in implantation. We will be using DHEA in those who have low serum testosterone only for a limited period of 14 days, hence we expect fewer side effects.…”

“… 1 It is a complex process with the expression of various genes including HOXA10, HOXA11, FOXO1, 2 WNT4, insulin-like growth factor binding protein 1 (IGFBP-1) 3 and upregulation of progesterone, 4 glucocorticoid, mineralocorticoid and androgen 5 receptors in the endometrium. 6 …”