1. Clinical Trial : Analysis & Interpretation of Results Fixed dose combination therapy of antioxidants in treatment of idiopathic oligoasthenoteratozoospermia: results of a randomized, double blind, placebo-controlled clinical trial

2. The Investigator group Dr. P.M. Gopinath (Principle Investigator ) Dr. Sonia Malik Dr. Ajit Saxena Dr. Bharti Kalra Dr. Kapil Kochhar

3. Background Many studies have shown that Co Q 10, L- Carnitine, Zinc and lycopene are effective in management of male subfertility individually. No studies had done on novel combination of FDC Oxidative stress is major contributing factor for increase incidence of male subfertility

4. Study hypotheses Treatment with FDC will improve sperm count, sperm motility and morphology Role of micronutrient (nutraceutical) for management of male subfertility. Treatment with FDC will improve male subfertility

5. Design Placebo-controlled, double-blind randomized, prospective, multicentre study, treatment trial Duration: 1 year No of patients: 200 Study drugs: 2 FDC BID 1 FDC BID 2 Placebo BID

6. Endpoints Primary Efficacy Analysis: Improvement in sperm count, motility, & morphology Secondary Efficacy Analysis: Pregnancy Rate

7. Design 140 patients randomized into 3 groups Group 1: 2 FDC BID Group 2: 1 FDC + 1 FDC BID Group 3: 2 Placebo BID Group 1 Vs. Group 3 Group 2 Vs. Group 3 Separate effect in each group from baseline

8. Baseline characteristics

9. Improvement in Sperm count (Million/mL) in each arm from baseline

10. Improvement in Sperm Count from Baseline

11. Improvement in Motile Sperm (%)in each arm from baseline

12. Improvement in Motile Sperms from Baseline

13. Improvement in Sperm with rapid progression: WHO A (%)

14. Change in Sperm with WHO Grade A motility

15. Improvement in Sperm with Normal Morphology

16. Reduction of Sperm with Abnormal Morphology

17. No. of Pregnancy during or after treatment A total of 15 spontaneous pregnancies observed during the study (6 pregnancies in 2 FDC BID and 7 pregnancies in 1 FDC BID and 2 pregnancies in Placebo) Three times more pregnancies seen with antioxidant FDC treatment over the placebo

18. First Indian nutracuetical with evidence

19. First Indian nutracuetical shows improvement in morphology of Sperm

20. Recent Advances: L Carnitine for Male Infertility Daily 2000 mg of L Carnitine required for Medical management of male subfertility Sigman and coworkers compared the effects of L-carnitine, ie, 2000 mg/day L-carnitine and 1000 mg/day L-acetylcarnitine for 24 weeks, with placebo statistically or clinically significant differences were found between the two groups

21. Lycopene Improve acids arachidonic acid/docosahexaenoic acid ratio Lycopene improves the distorted ratio between AA/DHA in the seminal plasma of infertile males Three months of treatment with lycopene led to a significant improvement in the AA/DHA ratio in seminal plasma of males Facilitated the spontaneous as well as IVF conception Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2013 Feb 25.

24. This RCT Accepted in COGI 2013 Our research on Paternia accepted in COGI 2013

25. Astaxanthin Health claim rejection by EFSA for Male subfertility Not effective in Spermatogenesis

28. Conclusion Very few medical fields have changed as dramatically over the past decade as reproductive medicine, particularly in terms of the diagnostic and treatment strategies for male infertility. These advances include oxidative stress and male subfertility. The nutraceutical theory remain the safest and most cost- effective ways of treating infertile men, and, perhaps more importantly for the couples involved, many of these techniques enable couples to conceive naturally.