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DHEA in Oocyte Yield and Quality




              BAIJU P A
           NCARE IVF CENTRE
     PARAPPANANGADI, MALAPPURAM   Page 1
Dr               Ba
     Ne            iju
       ek
            o




                Page 2
Page 3
DHEA - Hype or Hope…???


        Follicular Dynamics

  Androgen in Follicular Dynamics

          What is DHEA?

   Role of DHEA in Failing Ovaries

        Side effects of DHEA

         Literature Search

          Other Adjuvants
                                     Page 4
8 million
                    300-400 cycles in reproductive age
                       1000 follicles recruited/cycle


                        4,00,000
                                              25,000


        4 million
                                                       1000




                                                Page 5
Page 6
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AMH as a predictive marker in ART:
Lamarca et al: HR Update; Vol 16, No: 2, Pages 113-130; 2010
                                                      Page 8
Biological Plausibility of
Androgens in Folliculogenesis


                            Page 9
Page 10
Page 11
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Greatest Challenge in ART…!!!
           9-25%


                            Page 13
Current trends of marriage and
                              pregnancy




                                          Poor
                                        Responders




Maria et al. Ann. N.Y. Acad. Sci. 2008; 1127: 27–30, Gianaroli et al. Hum Reprod.
  2010;25: 2374–2386, Schoolcraft et al. Fertil Steril. 2011 Sep; 96(3):638-40.
                                                                   Page 14
Page 15
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Mild therapeutically well tolerated male hormone
       (85% in Adrenals & 15% in Ovaries)
                                                   Page 17
Page 18
Wild Yam Extract


                   Page 19
•   Alzheimer’s Disease
                            •   Cervical Cancer
                            •   Infertility
•   Adrenal Insufficiency   •   Sexual Dysfunction
•   SLE                     •   Chronic Fatigue
•   Depression                  Syndrome
•   Obesity                 •   HIV/AIDS
                            •   RA
                            •   Psoriasis
                            •   Schizophrenia




                                             Page 20
•Recruitment of Dormant Follicles from Pool
           •Reduction of Apoptosis
       •Direct Effect on Granulosa Cells
     •Improved Mitochondrial Function



                                          Page 21
New Concept in Oocyte Aging
(Barad & Gliecher – Submitted for Publication 2012)




     Recruitment of more “young “ –
    chromosomally competent oocytes
    by altering internal follicular milieu




              Quality of oocytes
              Quantity of oocytes
              Quality of embryos
          Decreased Miscarriage Rates
                Improved LBR

                                             Page 22
Age                           DHEA



                                          IGF-1


Low Androgen
   Levels
                    Reduction of Apoptosis
Poor Meiotic    Activation of GC & TC Function
Competence     Improved Mitocondrial Function
                  Improved Steroidal Milieu
                Recruitment of young oocytes



Poor Quality
 Ooocytes
                       Normal oocyte
                        maturation
                                       Page 23
Page 24
Most common side
               effects…!!!




More energized…         Improved sexual drive…

                                    Page 25
Page 26
Since first-trimester placenta produces DHEA , maternal DHEA exposure at
moderate dosages in very early pregnancy should not constitute significant risk

(Loganath, A., Peh, K.L., Wong, P.C., 2002. Evidence for the biosynthesis of DHEA
from cholesterol by first trimester human placental tissue: source of androgens.
                         Horm. Metab. Res. 34, 116–120.)
                                                                      Page 27
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1. Is there a scientifically explainable
   basis?
2. Does it harm?
3. Do we have robust evidence in           Questions
   other alternatives?                       to be
4. Does it cause financial burden?
5. What are deleterious effects of 3-      asked???
   4 months delay in Rx ?




                                               Page 36
Page 37
Other Adjuvants




                  Page 38
Page 39
Pre-Ovulatory
                                                                    Over-ripeness
                                                                      Ovopathy
                                                                   (PrOO Concept)

MTHFR gene polymorphisms resulting in suboptimal oocyte maturation: a discussion of folate status,
               neural tube defects, schizophrenia, and vasculopathy ,Piet H et al;
                        Jr of Experimental & Clinical Assisted Reproduction
                                             2008, 5:5                             Page 40
Page 41
Page 42
•Delayed child bearing is the most important
     precipitating factor which increases the
           number of poor responders

•Physiological rise in itnra-ovarian testosterone
 can be achieved with DHEA supplementation

•Improved Ovarian Response to treatment can
 be expected with 3-4 months of DHEA in DOR

 •Robust evidences in terms of increasing LBR
     with DHEA treatment is still lacking

•“ABSENCE OF EVIDENCE IS NOT EVIDENCE OF
               ABSENCE”

•Role of CoQ10 & Folic acid in improving oocyte
         quality has to explored further

                                             Page 43
Page 44

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Baiju dhea 15.11.12

  • 1. DHEA in Oocyte Yield and Quality BAIJU P A NCARE IVF CENTRE PARAPPANANGADI, MALAPPURAM Page 1
  • 2. Dr Ba Ne iju ek o Page 2
  • 4. DHEA - Hype or Hope…??? Follicular Dynamics Androgen in Follicular Dynamics What is DHEA? Role of DHEA in Failing Ovaries Side effects of DHEA Literature Search Other Adjuvants Page 4
  • 5. 8 million 300-400 cycles in reproductive age 1000 follicles recruited/cycle 4,00,000 25,000 4 million 1000 Page 5
  • 8. AMH as a predictive marker in ART: Lamarca et al: HR Update; Vol 16, No: 2, Pages 113-130; 2010 Page 8
  • 9. Biological Plausibility of Androgens in Folliculogenesis Page 9
  • 13. Greatest Challenge in ART…!!! 9-25% Page 13
  • 14. Current trends of marriage and pregnancy Poor Responders Maria et al. Ann. N.Y. Acad. Sci. 2008; 1127: 27–30, Gianaroli et al. Hum Reprod. 2010;25: 2374–2386, Schoolcraft et al. Fertil Steril. 2011 Sep; 96(3):638-40. Page 14
  • 17. Mild therapeutically well tolerated male hormone (85% in Adrenals & 15% in Ovaries) Page 17
  • 19. Wild Yam Extract Page 19
  • 20. Alzheimer’s Disease • Cervical Cancer • Infertility • Adrenal Insufficiency • Sexual Dysfunction • SLE • Chronic Fatigue • Depression Syndrome • Obesity • HIV/AIDS • RA • Psoriasis • Schizophrenia Page 20
  • 21. •Recruitment of Dormant Follicles from Pool •Reduction of Apoptosis •Direct Effect on Granulosa Cells •Improved Mitochondrial Function Page 21
  • 22. New Concept in Oocyte Aging (Barad & Gliecher – Submitted for Publication 2012) Recruitment of more “young “ – chromosomally competent oocytes by altering internal follicular milieu Quality of oocytes Quantity of oocytes Quality of embryos Decreased Miscarriage Rates Improved LBR Page 22
  • 23. Age DHEA IGF-1 Low Androgen Levels Reduction of Apoptosis Poor Meiotic Activation of GC & TC Function Competence Improved Mitocondrial Function Improved Steroidal Milieu Recruitment of young oocytes Poor Quality Ooocytes Normal oocyte maturation Page 23
  • 25. Most common side effects…!!! More energized… Improved sexual drive… Page 25
  • 27. Since first-trimester placenta produces DHEA , maternal DHEA exposure at moderate dosages in very early pregnancy should not constitute significant risk (Loganath, A., Peh, K.L., Wong, P.C., 2002. Evidence for the biosynthesis of DHEA from cholesterol by first trimester human placental tissue: source of androgens. Horm. Metab. Res. 34, 116–120.) Page 27
  • 36. 1. Is there a scientifically explainable basis? 2. Does it harm? 3. Do we have robust evidence in Questions other alternatives? to be 4. Does it cause financial burden? 5. What are deleterious effects of 3- asked??? 4 months delay in Rx ? Page 36
  • 38. Other Adjuvants Page 38
  • 40. Pre-Ovulatory Over-ripeness Ovopathy (PrOO Concept) MTHFR gene polymorphisms resulting in suboptimal oocyte maturation: a discussion of folate status, neural tube defects, schizophrenia, and vasculopathy ,Piet H et al; Jr of Experimental & Clinical Assisted Reproduction 2008, 5:5 Page 40
  • 43. •Delayed child bearing is the most important precipitating factor which increases the number of poor responders •Physiological rise in itnra-ovarian testosterone can be achieved with DHEA supplementation •Improved Ovarian Response to treatment can be expected with 3-4 months of DHEA in DOR •Robust evidences in terms of increasing LBR with DHEA treatment is still lacking •“ABSENCE OF EVIDENCE IS NOT EVIDENCE OF ABSENCE” •Role of CoQ10 & Folic acid in improving oocyte quality has to explored further Page 43