DEHYDROEPIANDROSTERONE (DHEA) SUPPLEMENTATION AND PREGNANCY OUTCOME: EFFECT ON PREGNANCY RATE AND SPEED OF CONCEPTION. H. Brill, D. H. Barad, N. Gleicher. Center For Human Reproduction – NYC, New York City, NY.
OBJECTIVE: We, and other authors, previously reported on the beneficial effects of dehydroepiandrosterone (DHEA) supplementation on ovarian function in women with diminished ovarian reserve. Whether these beneficial effects, however, also translate into improved pregnancy rates has never before been investigated in controlled fashion. The objective of this study was, therefore, to investigate whether DHEA affects pregnancy rates.
DESIGN: Historical Case-Control study.
MATERIALS AND METHODS: DHEA treatment was initiated in June 2004. 88 consecutive women with a history of diminished ovarian reserve, evidenced by inadequately poor response to ovulation induction, who, in spite of prior recommendations to pursue egg donation, had decided to continue with IVF cycles, represented the DHEA study group. Historical controls were 101 consecutive women, treated at the same center before we began study of DHEA supplementation. The controls had maximal baseline day 2/3FSH levels above the 95% CI of the mean for their respective ages. After a brief work-up, control patients were treated with vitro fertilization (IVF), using ovulation induction with a microdose agonist /gonadotropin protocol (maximal gonadotropin stimulation 450-600 IU). Study group patients received DHEA supplementation at a dosage of 25 mg TID for an average period of 3.7 0.3 months, followed by IVF. During DHEA supplementation patients were encouraged to be sexually active and offered ovulation support with clomiphene citrate/low dose gonadotropin (maximally 225 IU daily) and/or intrauterine inseminations. At time of this analysis, amongst DHEA patients, 62 had reached IVF, 9 had undergone at least one ovarian stimulation cycle prior to reaching IVF, and 17 had not reached any intervention. Patient characteristics and intermediate-time outcomes were statistically compared between DHEA and control patients, using logistic regression adjusted for age, day three FSH and racial/ethnic status to compare odds of clinical pregnancy rates, and a Cox proportional hazards analysis was calculated for the occurrence of clinical pregnancy from time of initial presentation. Comparisons are presented as means 1 standard error.
RESULTS: Mean ages were (41.5 0.4 vs. 40.2 0.4 years) for both groups. The overall treatment period was marginally longer in DHEA patients (8.1 0.7 vs. 7.8 1.0 months). DHEA treated patients revealed a trend towards higher day 3 FSH (15.9 1.2 vs. 13.5 1.1 mIU/ml) and significantly higher baseline estradiol (86.2 6.6 vs. 51.10 6.6 pg/ml; p0.05) as well as lower oocyte numbers ( 3.7 .35 vs. 5.8 4.2; p 0.05) and embryos transferred ( 2.12 0.16 vs. 2.7 0.19; n.s.). The DHEA group, nevertheless, demonstrated a significantly increased cumulative pregnancy rate (27 % vs. 11 %; p 0.005). After adjustment of the model for age, race and day 2/3 FSH, the odds of clinical pregnancy in association with DHEA supplementation were OR3.36; 95% CI 1.5-7.78; p 0.005). DHEA treated patients also demonstrated a lower IVF cancellation rate (10% vs. 26. %; p 0.05), and a trend towards a lower miscarriage rate (24% vs. 44%).
CONCLUSION: These data offer further evidence that DHEA supplementation in women with diminished ovarian reserve, independent of age, leads to increased, and more rapid, conception rates.
