LISBON – Dehydroepiandrosterone supplementation was no match for the powerful effects of ovarian aging in women with diminished ovarian reserve in the DITTO trial.
Women who received oral dehydroepiandrosterone (DHEA) for at least 12 weeks prior to ovarian stimulation had a median of four oocytes retrieved, the same number as those given placebo.
Adjunct DHEA was also no better than placebo with regard to clinical pregnancy (28.6% vs. 36.0%; relative risk, 0.79) and live birth (25% vs. 32%; RR, 0.78) rates.
There were three miscarriages in each group, Dr. Kanna Jayaprakasan reported to an overflow crowd at the annual meeting of the European Society of Human Reproduction and Embryology.
The double-blind, randomized pilot trial was designed to test whether DHEA supplementation would improve in vitro fertilization (IVF) outcomes in women predicted to have poor ovarian response and to evaluate the feasibility of conducting a large multicenter DHEA trial.
“Successful recruitment for this pilot trial suggests a large definitive trial is feasible, but the lack of effect on IVF outcome – not even a trend – suggests it is a low priority,” Dr. Jayaprakasan of Royal Derby (England) Hospital and the University of Nottingham (England), said.
An animal study by the same investigators suggested that DHEA, a weak androgenic steroid secreted by the adrenal glands as well as the ovaries, might be a useful therapy to delay the effects of ovarian aging (Hum. Reprod. 2014;29:146-54).
Data from randomized controlled trials (RCTs) supporting its efficacy in humans, however, are limited, he said.
DHEA supplementation was associated with fewer miscarriages and significantly more live births in infertile women with normal ovarian reserve in a recent blinded RCT (Reprod. Biol. Endocrinol. 2015;13:18.).
Results were mixed, however, in a nonblinded RCT involving poor responders (Hum. Reprod. 2010;25:2496-500) in which DHEA 75 mg daily for at least 6 weeks (mean, 13.5 weeks) before ovulation induction had no impact on the number of oocytes retrieved, but more than quadrupled the live birth rate, compared with no pretreatment after two cycles (23% vs. 4%; P = .05).
The DITTO (Dehydroepiandrosterone Intervention to Treat Ovarian Aging) study used the same 75-mg daily dose of DHEA for up to 16 weeks (median, 12 weeks) before egg collection in 60 women, aged 23-43 years, with diminished ovarian reserve (antral follicle count <10 or serum Mullerian hormone level <5 pmol/L).All patients underwent a standard long downregulation protocol using human gonadotropin 300 IU/day. Seven women did not start the trial medication, leaving 28 DHEA patients and 25 patients allocated to matched placebo capsules evaluable for analysis.
DHEA levels were similar at baseline in the DHEA and control groups (9.4 vs. 7.5 ng/mL). Compliance was good, with DHEA levels significantly higher at the prestimulation stage in the study group than in controls (16.3 vs. 11.1 ng/mL; P <.01), Dr. Jayaprakasan said.Meeting attendees questioned whether longer DHEA supplementation might improve IVF outcomes, perhaps by affecting the gonadotropin-responsive follicle pool. While it is difficult to know whether prolonged DHEA would result in an improved outcome, it is less likely, he said.
As for whether the DITTO results nix further DHEA supplementation in poor responders, but leave the door open in normal responders, Dr. Jayaprakasan said, “I think there is no evidence to support its routine use in predicted poor or normal responders currently, and its use should be restricted to randomized controlled studies rather than a blanket approach.” The University of Nottingham supported the research. The authors reported having no relevant financial disclosures.