The aim of the study was to investigate the effects of dehydroepiandrosterone (DHEA) supplementation on IVF (In vitro fertilization) outcomes and the gene expression of cumulus cells (CCs) in patients with poor ovarian response (POR). This was a prospective self-controlled study, including ten patients with POR. All women received DHEA supplementation (30 mg, t.i.d.) for around 3 months before starting the a new IVF cycle. Biochemical, ultrasound parameters and treatment outcomes were determined before and after DHEA therapy. Moreover, CCs were isolated to examine the gene expression level of nine genes, including Hyaluronan synthase (HAS2), Versican (VCAN), Thrombospondin 1 (THBS1), Runt-related transcription factor 2 (RUNX2), Chromobox homolog 3 (CBX3), Tripartite motif-containing 28 (TRIM28), B-cell lymphoma 2 (BCL2), BCL2-associated X protein (BAX), Ankyrin repeat domain 57 (ANKRD57), Syndecan 4 (SDC4), Activated leukocyte cell adhesion molecule (ALCAM), Gremlin 1 (GREM1), Prostaglandin-endoperoxide synthase 1 (PTGS1), Prostaglandin-endoperoxide synthase 2 (PTGS2), Sprouty homolog 4 (SPRY4), Coagulation factor II receptor-like 1 (F2RL1), Ribosomal protein S6 kinase, polypeptide 2 (RPS6KA2), solute carrier family 38, member 2 (SLC38A2), YTH domain familyï¼member 2 (YTHDF2), Cytochrome oxidase 17 (COX17), E3 ubiquitin protein ligase (UBR3), Krueppel-like factor 4 (KLF4), prostaglandin E receptor 2 (PTGER2), exostoses 1 (EXT1) by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). It showed significant changes in day 3 follicle-stimulating hormone (FSH), estradiol, antral follicle count (AFC) and Anti-Müllerian Hormone (AMH) (p < 0.0001, < 0.0001, < 0.05 and < 0.001, respectively), as well as number of oocytes retrieved, fertilized oocytes, day 3 embryos, transferred embryos (p < 0.0001, < 0.0001, < 0.05 and < 0.001, respectively) after DHEA therapy. In addition, the gene expression levels of extracellular matrix (ECM), including HAS2, VCAN, THBS1, showed significant increase after DHEA treatment. Although the gene expression levels of BCL2 and BAX, which are apoptotic genes, showed decrease; however, BCL2/BAX ratio elevated significantly, suggested that DHEA may play a role in anti-apoptosis. The study demonstrated that DHEA shows benefit for artificial reproductive outcomes and upregulates the gene expression of CCs in POR patients. Advisors/Committee Members: Chen Chun-Lin (chair), Wen Zhi-Hong (chair), Cheng Jiin-Tsuey (committee member), Chang Shiuh-Young (chair), Wang Peng-Hui (chair).