Published Research > E.A.J. Ryan, S. Blanco Mejia, M. Maroleanu, M. Moruzanu, E.A. Claessens. Exogenous androgens can improve pregnancy and take home baby rates in women over 40 years of age. Fact or fiction. Meeting of the Canadian Fertility and Andrology Society, Toronto, Canada. September 2011.


22 Sep 2011

ABSTRACT:  Over the past several years , from many parts of the medical world there have been attempts made to improve the prognosis of women with diminished ovarian response , whether due to age or other factors. We hereby present more evidence that exogenous androgens may be pivotal in achieving this goal.

INTRODUCTION: Since Casson et al [1] suggested an improved ovarian response from exogenous use of androgens  in those women classified as poor ovarian responders (POR) or women with diminished ovarian reserve (DOR) or premature ovarian aging (POA/POI), very little follow up documentation was published until 2005. Barad and Gleicher [2] reported in that year an increase in oocyte production with oral DHEA co-treatment. This same group published data in 2006-2010 that showed better oocyte and embryo quality, improved pregnancy rates and reduced pregnancy loss rates in women with POR/DOR/POA/POI.  Publications from Mamas and Mamas [3], and the more recently first published RCT  from Weiser, Shulman et al [4] gives us a deeper insight into this issue. In our own clinic, we decided to do an analysis of all patients over 40 years of age who had failed to get pregnant on either DHEA alone, DHEA with oral Letrozole or DHEA with controlled ovarian stimulation with sperm wash intra uterine insemination (COH / IUI), who then needed IVF treatment.

RESULTS:
Third Group: 15 clinical pregnancies (plus 2 chemicals):
Cycle characteristics resulting in clinical pregnancies. 
Average Day 3 AFC   7.13
Average # eggs retrieved 9.53
Average # eggs fertilized (2 p.n.) 4.9
Average # embryos @ 72 hrs 4.5
Average Estradiol @ HCG, 5944 pMol/L
Average progesterone @ HCG, 7.8 ng/ml
Average endometrial thickness @ HCG, 1.14cms (0.8 -1.4cms)
Average total dose F.S.H. used,  4214 I.U.
17 patients achieved pregnancy / embryo transfer (29%)
 15 patients achieved a clinicalpregnancy (20.8% /cycle started / 25.4 % per embryo transfer)
Clinical preg rate / E.T. if only women under 43 yrs included (15/47 = 31.9% )
Average age 41.2 (range 40 - 47 years)
Male factor co morbidity 5/15 (33.3 %)
Pregnancy loss rate 5/15 33.3% ( clinical preg.loss)
Take home baby rate / embryo transfer 10/59, 16.9% (all ages)
Take home baby rate in women 40-43 yrs age 10/47 (21.3%)/ embryo transfer ( One baby lost at 41wks during labor , not included))
 

CONCLUSION: Much has been written since 2000 on whether exogenous androgens have any benefit in helping women, of whatever age, who have DOR/POR/POA/POI and a high miscarriage rate, in achieving a term pregnancy and reducing their pregnancy loss rates. We have advised approx 600 patients to go on DHEA up to Sept 1st 2010 that we were able  to do a follow up analysis on. Many of these 600 women whom we advised to go on DHEA either failed to follow up for treatment, did not take the DHEA for whatever reason or moved to other clinics. We have 164 pregnancies in this group that we have previously reported on (CFAS Vancouver 2010). This present subgroup of 72 pts are in the worst scenario group, namely L.M.A with a significant percentage of male factor cases, having failed to get pregnant with other forms of  treatments. Our stats, in spite of small numbers, are in keeping with the only RCT published in the world to date (Wiser/Shulman et al) and other publications as Dr Hyman et al from Shaare Zedek Medical Center Jerusalem (ASRM Denver 2010) regarding IVF success rates in women over 40, up to age 42yrs /11 months. We wish to note the very persistent high FSH to LH ratio seen in all our 72 patients, a very simple yet apparently true representation of ovarian reserve/oocyte status in older women as first pointed out by S.J. Muasher from Norfolk VA, back as the mid 1980. Gleicher and Barad have pointed out the fallacy of very low AMH’s levels as being absolutely indicative of an inability to get pregnant, as we have seen in our own practice. What we have learned from our rather small total group of 72 IVF cycles in women over 40 yrs,  is that if the patient  is 43 yrs and older, and has not got pregnant either spontaneously on DHEA, with Aromatase inhibitors with DHEA ( Letrozole), COH / IUI and DHEA , then the likelihood of a successful pregnancy with IVF is very low. In spite of this information we have a 46yr old lady who got pregnant on her 3rd cycle of DHEA with COH / IUI and has since delivered a normal female 7 lbs 11 oz. We do not have information on AMH levels in many of our patients as many did not wish to have this test done due to costs involved. The FSH on day 3 of IVF cycles is likely higher due to the elevated estradiol levels on that same day falsely depressing the FSH levels. This type of information is very useful in counseling patients regarding options and whether going to a DEP program is the best alternative earlier rather than later.   Gleicher’s recent article in Reprod. Biology and endocrinology 2011. 9.23 . is an erudite dissertation  on our still poor understanding of increasing woman’s age and its relationship to diminished egg number and quality. The use of exogenous androgens and the future role of mitochondrial nutrients (i.e Co Enzyme Q 10)  in our treatment of this spectrum of related conditions presents some very exciting options. A health canada approved RCT would be the best scientific option.