Value of Dehydroepiandrosterone Supplementation in Women with Poor Ovarian Reserve Undergoing Assisted Reproductive Technique (ICSI/IVF): Randomized Controlled Trial

Abstract

SUMMARY O varian failure is a natural consequence of the aging process. Approximately 10% of women deviate from age specific standards and before reaching menopause, suffer from premature ovarian aging (POA), also called occult primary ovarian insufficiency (Barad et al., 2007) POA represents a milder precursor stage to premature ovarian failure (POF). Diminished ovarian reserve (DOR) is defined by elevated age specific baseline follicular stimulating hormone (FSH) levels and/or decreased antimullerian hormone (AMH) levels <1 ng/ml, indicative of DOR at all ages (Singer et al., 2009). The levels of FSH may vary in different women but the fertility potential decreases significantly when levels are >15 mIU/ml (Kara et al., 2013). Those women with FSH ≥15 but <40 mIU/ml with age under 40 years come under the definition of POA. Either in vitro fertilization (IVF) with donor oocytes or adoption is often advised as a last resort to treatment for such women with DOR (Barad et al., 2006). Diminished ovarian reserve (DOR) whether due to physiological ageing of the ovaries (Van Rooij et al., 2005) and premature ovarian ageing (Barad et al., 2007a), represent one of the few unresolved problems of modern infertility care. Preliminary reports and researches have shown supporting and encouraging effects of DHEA in women with diminished ovarian reserve undergoing assisted reproductive technique ICSI/IVF and primary ovarian insufficiency (POI), although data from randomized controlled trials are limited. Subsequent publications from Gleicher and Barad provided support for the use of DHEA in DOR and poor responders (Gleicher and Barad, 2008; Gleicher et al., 2009, 2010a). A meta-analysis conducted by (Sunkara, et al., 2011) showed no significant difference in the number of oocytes retrieved and ongoing pregnancy and live-birthrates with androgen supplementation compared with the control groups. Therefore, the aim of this study was to evaluate the effect of DHEA supplementation on ovarian reserve markers and clinical pregnancy rate in women with poor ovarian reserve who were undergone ICSI/IVF. The study was conducted on 56 patients with poor ovarian reserve. There ages were between 20-40 years old and diagnosed by serum FSH>15 IU/ml, serum AMH<1 ng/ml, and antral follicular count AFC<4 in second or third day of menstrual cycle, attended infertility outpatient clinic in Ain shams university. All patients were subjected to full medical history, past history, surgical history, menstrual and obstetric history, physical examination, laboratory investigation (CBC, UREA, CRETININ, AST, ALT, FSH, LH, E2, PROLACTIN, AMH, T3, T4, TSH), Transvaginal ultrasonography, then follow up were applied for patients in the study to detect statistical changes in ovarian reserve markers which was our primary outcome or statistical change at pregnancy rate which was the secondary and main outcome. In our study we found that there were significant negative correlations between DHEA supplementation and FSH level, as FSH level is was significantly decreased after 12 weeks of DHEA supplementation. In our study we found significant positive correlation not only between DHEA supplementation and serum AMH level, but also between DHEA supplementation and AFC which were significantly increased after 12 weeks of DHE supplementation. In our study we reported negative significant correlation between DHEA supplementation and duration of HMG stimulation as well as numbers of HMG ampoules, as they significantly declined after 12 weeks of DHEA supplementation. So DHEA significantly increase ovarian response to gonadotropins stimulation. Pregnancy rate in ICSI are closely correlated to the number of retrieved oocytes, and less than an optimal number is associated with poor outcome. In our study we noted positive significant correlation between DHEA supplementation and (ovulation rate, numbers of retrieved oocytes, numbers of MII phase oocytes, numbers of fertilized embryos, and rate of good quality embryos), as all of them were increased significantly after 12 weeks of DHEA supplementation.