1. Department of Biological Science, National Sun Yat-sen University, Kaohsiung, Taiwan;
2. Department of Obstetrics and Gynecology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan;
3. Department of Obstetrics and Gynecology, National Yang-Ming University School of Medicine, Taipei, Taiwan;
4. Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan;
5. Department of Obstetrics and Gynecology, National Yang-Ming University Hospital, Ilan, Taiwan;
6. Immunology Center, Taipei Veterans General Hospital, Taipei, Taiwan;
7. Department of Medical Research, China Medical University Hospital, Taichung, Taiwan;
8. Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung, Taiwan;
9. Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Taiwan;
10. Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan ;
11. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan;
12. Department of Pharmacy and Master Program, College of Pharmacy and Health Care, Tajen University, Pingtung County, Taiwan.
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.
Keywords: apoptosis, cumulus cells, dehydroepiandrosterone, mitochondria, poor ovarian responders.