The Application of Dehydroepiandrosterone on Improving Mitochondrial Function and Reducing Apoptosis of Cumulus Cells in Poor Ovarian Responders

Abstract

Poor ovarian responders (PORs) pose a great challenge for in vitro fertilization (IVF). Previous studies have suggested that dehydroepiandrosterone (DHEA) may improve IVF outcomes in PORs. The current study attempted to investigate the clinical benefits of DHEA in PORs and the possible mechanisms of DHEA on cumulus cells (CCs). This was a prospective study performed at one tertiary center from January 2015 to March 2016. A total of 131 women who underwent IVF treatment participated, including 59 normal ovarian responders (NORs) and 72 PORs. PORs were assigned to receive DHEA supplementation or not before the IVF cycle. For all patients, CCs were obtained after oocyte retrieval. In the CCs, mRNA expression of apoptosis-related genes and mitochondrial transcription factor A (TFAM) gene, terminal deoxynucleotidyl transferase dUTP nick end labeling assay, mitochondrial dehydrogenase activity and mitochondrial mass were measured. The results indicated that PORs with DHEA supplementation produces a great number of top-quality embryos at day 3 and increased the number of transferred embryos and fertilization rate compared with those without DHEA supplementation. Additionally, supplementation with DHEA in PORs decreased DNA damage and apoptosis in CCs while enhancing the mitochondrial mass, mitochondrial dehydrogenase activity and TFAM expression in CCs. In conclusion, our results showed that the benefits of DHEA supplementation on IVF outcomes in PORs were significant, and the effects may be partially mediated by improving mitochondrial function and reducing apoptosis in CCs.

Androgens and ovarian function: translation from basic discovery research to clinical impact

“…On the other hand, a loss of androgen actions, as in ARKO models, leads to elevated levels of follicular atresia, evident by the presence of pyknotic granulosa cells and degenerate oocytes (Hu et al 2004, Shiina et al 2006, Walters et al 2007. Clinical evidence supporting this mechanism come from the findings from one study that compared to normal ovarian responders, POR patients supplemented with DHEA were reported to produce a greater number of top-quality embryos on day 3 and increased fertilization rates, and their cumulus cells displayed reduced DNA damage and expression of apoptosis-related genes (Lin et al 2017). Similarly in another study, cumulus cells collected before and after DHEA treatment in women with POR displayed an increase in the ratio of BCL2 (anti-apoptotic) to BAX (pro-apoptotic) (Tsui et al 2014).…”

Dehydroepiandrosterone (DHEA) supplementation improves in vitro fertilization outcomes of poor ovarian responders, especially in women with low serum concentration of DHEA-S: a retrospective cohort study

“…However, direct action of DHEA on the target organs has been proposed [ 42 , 43 ] but is still inconclusive. Regarding the molecular mechanism, our previous studies revealed that DHEA supplementation could improve mitochondrial function and reduce apoptosis in the cumulus cells [ 44 ] and human granulosa cell line [ 45 ].…”

Effects of Dehydroepiandrosterone (DHEA) Supplementation to Improve Ovarian Response and IVF Outcomes on Women with Poor Ovarian Response

“…However, it is important to observe that some studies have shown that DHEA supplementation for IVF in women with decreased ovarian reserve did not increase the clinical rate of pregnancy. It is therefore noted that the mechanism of action of this steroid hormone remains obscure and that there are several controversies about it [28][29][30][31][33][34][35].…”