Effects of Dehydroepiandrosterone on the Response of Ovarian Stimulation During In Vitro Fertilization Cycle in Infertile Women With Diminished Ovarian Reserve : Before and After Clinical Trials

Introduction Ovarian reserve or residual ovarian reserve can be used to predict the success of using assisted reproductive technology. In fact, a patient is believed to have a diminished ovarian reserve (DOR) when she has ovarian counts lower than what is expected for her age (1). DOR is one of the major obstacles for a successful assisted pregnancy. In addition, DOR is reported in 5-18% of in vitro fertilization (IVF) cycles and the pregnancy rate in these patients, who undergo various fertility protocols, is as low as 2%-4% (2,3). Dehydroepiandrosterone (DHEA), in an androgenic steroid, is produced by the zona reticularis cells of the adrenal cortex and the ovarian theca cells. DHEA is an important pre-hormone in the production of intrafollicular steroids by the ovaries and its positive effects on ovulation stimulation were first described in 2009 (4). However, the mechanism of actions regarding DHEA consumption remains theoretical. DHEA affects early follicular maturation by modified androgen receptor (AR) transcription, enhances follicle-stimulating hormone (FSH) receptor expression, regulates FSH action in granulosa cells (GCs), and increases the antral follicular counts (AFC) and the expression of AR pre ovulatory GCs (5-10). Taking DHEA oral supplements causes an increase in serum levels of insulin-like growth factor I, which increases the maturity and quality of oocytes. (8). Various Abstract Objectives: The use of dehydroepiandrosterone (DHEA) before initiating in vitro fertilization (IVF) cycles to increase the ovarian reserve is considered as one of the best therapies in women with diminished ovarian reserve (DOR). Therefore, the present study aimed to compare the effect of DHEA on women (below and above 35 years old) with DOR and to find if this therapy is useful at an earlier age. Materials and Methods: This clinical trial study was conducted on 35 infertile women with DOR who referred to Imam Khomeini hospital in Sari, Iran, during 2017. The intervention lasted for 6 weeks and DHEA tablets were used before the start of the intra-cytoplasmic sperm injection-embryo transfer (ICSI-ET) cycle. Antral follicular counts (AFCs) and the serum levels of anti-Mullerian hormone (AMH) were estimated before and after the intervention, followed by performing the ICSI. Finally, the changes in AMH levels and AFC, the number and quality of ovum and embryos and pregnancy, along with the rates of implantation and abortion were measured as well. Results: The mean AMH levels (P = 0.02) and AFC (P < 0.001) after DHEA consumption varied significantly from those before administering the DHEA, and the increase in the AFC was more significant in the age group under 35 years (P = 0.03). In addition, these changes were more significant in body mass of less than 25 kg/m2 (P = 0.04). Conclusions: In general, the supplementation of DHEA in women with insufficient ovarian capacity probably improves IVF prognosis and other parameters including AFC and AMH, especially in women under 35 years old. Further, based on different evidence, the probability of pregnancy occurrence in women is lower with increased body mass index (BMI).