7 Sep 2012
INTRODUCTION: Patients judged to have diminished ovarian reserve (DOR) or premature ovarian failure (POF) due to age or unknown factors, were placed on 25mgs micronized oral dehydroepiandrosterone (DHEA) T.I.D. Initial treatment was 1 to 2 months of cycle monitoring followed by an aromatase inhibitor (AI) for 2-3 months, and if pregnancy did not occur, patients underwent COH+IUI. IVF was recommended when all other protocols failed.
METHODS: All patients of 42yrs 11 months of age (N=146) and younger are included in this study. Patients older than 43 years were excluded. We subdivided these women into: group 1: women <35 yrs (N=21); group 2: aged 35-39 yrs (N=70) and group 3: 40-43 yrs (N=55).
All IVF cycles were pretreated with an endometrial biopsy for possible improvement in implantation rates¹-². All cycles were treated with recombinant FSH dose of 300-450 IU/day with either antagonist at lead follicle1.4cm or microdose lupron flare. ICSI was done for all patients, overall male factor was present in 32.9% of cases: 19% for group 1, 35.7% for group 2 and 34.5% for group 3.
RESULTS: Group 1: Four out of 21 cycles (19%) cancelled due to very poor response. Of the 17 completed cycles the pregnancy rate per cycle started (PR/CS) was 33.3%, and pregnancy rate per embryo transfer (PR/ET) was 41%. Clinical loss rate was 14.3% and the take home baby rate per embryo transfer (THBR/ET) was 35.3%.
Group 2: In this group of 70, 14 cycles were cancelled (20%) one did not have an embryo transfer (1.43%), PR/CS was 40%, PR/ET was 51%, Clinical loss rate was 25%, and THBR/ET was 36.4%.
Group 3: From 55 cycles, 7 cycles cancelled (12.7%), PR/CS was 30.9%, PR/ET was 37%, Clinical loss rate of 11.8% and THBR/ET was 26.1%.
CONCLUSION: Over 33% of IVF centers worldwide are now using exogenous androgens to improve the PRs, however, only one true RCT has been published to date (showing a 5 fold increase in the PR >40 years of age in women treated with DHEA versus non androgen treated patients)³ . There is a genuine improvement in oocyte quality³, embryo quality, implantation rates, and a reduce pregnancy loss rate⁴-¹⁰. From our point of view it would be unethical to deprive women of any age with a diagnosis of DOR/POF of this form of inexpensive treatment with minimal side effects (1-2%, as yet non published data from our own center). It would be difficult to get IRB approval for an RCT now and even more difficult to get patients to agree to a 6 to 8 month delay in treatment if randomized to the placebo group. How do androgens work in these patients? We know from Casson’s early work¹¹ that the beneficial effects of exogenous androgens probably works through changes in IGFBP and IGF-1 and may be intrinsically related to mitochondrial function and the more efficient functioning of the chromosomal spindle in the presence of elevated intrafollicular androgen levels. This may explain the reduction in incidence of aneuploidy and miscarriage rates in all age groups with a diagnosis of DOR/POF, treated with oral DHEA.
From our own small numbers in the different age groups, in women with the most unfavorable prognosis (DOR/POF), our THBR compares very well with the PR/cycle of IVF/ICSI as reported in other published data¹²-¹³.
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