22 Sep 2011
Introduction:Since Casson et al first published a small number of patients ( 7) who seemed to benefit in their fertility quest using Dehydroepiandrosterone (DHEA) , many other authors from at least 5 countries have published more extensive information since 2005. Drs Gleicher and Barad from the C.H.R in New Yorkwere the leaders in this aspect of a “new “ innovative treatment. We have had some of our own data and some in combination with Gleicher et al published at ASRM 2008 and 2009, CFAS 2009, RB and E 2009 and I.F.G.I Florence 2010. As we have been using DHEA in many patients with diminished ovarian reserve (DOR ) since Feb, 2006 we have accumulated a large number of patients and treatment cycles and modalities and herein share our most recent findings with you.
Materials and Methods:From February 2006 to April 2010 we started 347 patients whom we put on DHEA and were available for follow up and analysis. Our definition for DOR or poor ovarian responders is in keeping with current day accepted criteria of day 3 increased F.S.H ., decreased A.M.H., decreased A.F.C. and previous poor response to ovarian stimulation or prolonged days of gonadotrophin stimulation and high doses used. Our standard office policy in such cases is to give detailed information both from published data and from sites like WWW.DHEA.COM and have the patient sign an informed consent before starting DHEA. Any side effects are documented and DHEA is discontinued if these are significant. All pregnancies were followed to delivery to document any major or minor congenital defects.
If this patient fitted the definition of D.O.R, then she would start on 25 mgs micronized DHEA t.i.d. and after one or two months would start on an aromatase inhibitor either as 2.5 mgs daily for days 3-7 of the cycle or the step up Letrozole protocol. If pregnancy failed to occur with properly timed intercourse by 3 cycles then we progressed to COH-IUI in most cases. If pregnancy did not occur with in 3 cycles of this regimen, IVF with ICSI was advised .
Results:66 PTS LESS THAN 35 YR WERE TREATED IN THE MANNER DESCRIBED AND RESULTED IN THE FOLLOWING CUMULATIVE PREGNANCY RATES
A: 7 OF 12 (58.3%) GOT PREGNANT ON DHEA ALONE
B: 4 OF 5 (80%) GOT PREGNANT ON LETROZOLE + DHEA
C: 6 OF 8 (75%) GOT PREGNANT ON C.O.H. -I.U.I. + DHEA
D: 14 OF 41 (34.1%) GOT PREGNANT WITH I.V.F./ I.C.S.I. + DHEA. TAKE HOME BABY RATE FOR THIS GROUP WAS 64.3%
142 PATIENTS WERE AGED 35 TO 39 INCLUSIVE.
A: 14 OF 34 (41.1%) GOT PREGNANT ON DHEA ALONE.
B: 9 OF 16 (56.2%) GOT PREGNANT ON LETROZOLE + DHEA (2 WITH ADDITION OF I.U.I.)
C: 22 OF 28 (78.5%) GOT PREGNANT ON C.O.H.- I.U.I. + DHEA
D: 35 OF 64 PTS (54.7%) GOT PREGNANT WITH I.V.F./I.C.S.I. + DHEA. TAKE HOME BABY RATE FOR THIS GROUP WAS 70.6%
139 PATIENTS WERE OVER 40 YRS (AVERAGE AGE 41.4)
A: 8 OF 39 (20.5 %) PATIENTS GOT PREGNANT ON DHEA ALONE.
B: 12 OF 18 (66.6 %) GOT PREGNANT ON LETROZOLE + DHEA AND TIMED INTERCOURSE (1 HAD T.D.I.)
C: 14 OF 24 (58.3%) GOT PREGNANT ON C.O.H.- I.U.I. + DHEA (2/24 PATIENTS HAD TIMED INTERCOURSE, FROM WHICH NONE GOT PREGNANT)
D: 19 OF 58 (32.8%) GOT PREGNANT WITH I.V.F./I.C.S.I., TAKE HOME BABY RATE OF 57.9%
N.B. ALL PREGNANCIES ARE STATED AS POSITIVE WITH A DOUBLING OF THE H.C.G. FROM 14 DAYS POST I.U.I. OR EMBRYO TRANSFER OR ULTRASOUND VERIFIED OVULATION.
Conclusion:How DHEA may increase the quantity and more importantly the quality of class 1 to 5 primordial follicles and allow them to go through proper folliculogenesis is unknown but may be mediated through the activation of IGF-1 by an increase in intra-ovarian and intra-follicular testosterone levels. Modification to mitochondrial function via alterations in the LASY system or changes to Caps 3 and 9, altering the polarity of the inner mitochondrial membrane, altering the production of ATP in the mitochondria, influences calcium homeostasis and various other proposed mitochondrial changes may be involved.
These beneficial effects seem to improve the function of the chromosomal spindle leading to a significant reduction in aneuploidy which would account for the reduced pregnancy loss rate we have reported before (ASRM San Francisco). This reduction in aneuploidy has been shown in first polar body biopsy of IVF created eggs in women >40 Y.O. if on DHEA compared to age matched women NOT on DHEA (Dr. N. Gleicher, personal communication 2010). We have documented a pregnancy loss rate in most women on DHEA up to age 38 of 15 to 16 % and at age 42+, a 25% loss versus the expected 50%+ from the literature.
From our analysis of the 310 patients in our ongoing study it seems reasonable to proceed with DHEA using the above progression of treatment modalities, as an effective and affordable alternative to IVF.