Abstract Study question Male infertility due to idiopathic oligoasthenoteratozoospermia- Does combining Letrozole as antiestrogenic with Coenzyme Q10 as antioxidant give better pregnancy rate ? Summary answer Combination of Co enzyme Q10 with Letrozole can significantly improve semen parameters and outcome of clinical pregnancy rate in idiopathic oligoasthenoteratozoospermic patients. What is known already Elevated levels of reactive oxygen species(ROS) are a major cause of idiopathic male factor infertility which results in sperm membrane lipid peroxidation, DNA damage and apoptosis leading to decrease sperm viability and motility. Antioxidant like Coenzyme Q10 have been used empiricallyin the treatment of oligoasthenozoospermia based on its ability to reverse oxidative stress and sperm dysfunction. Aromatase inhibitor like Letrozolehave been used in idiopathic male infertility by reducing estrogenic effect on spermatogenesis and reducing feedback inhibition of hypothalamopituatarygonadal axis. Thus a therapeutic strategy would need to use supplements to increase sperm energy metabilism, minimise free radical damage. Study design, size, duration Study design: prospective comperative clinical study Primary purpose: treatmenr Size: 60 infertile male attending OPD of SHRISTI HEALTHCARE diagnosed as idiopathic oligoasthenoteratozoospermia Duration: from March2018 to February 2020 Primary outcome: improvement in sperm count, motility and morphology after treatment Secondary outcome: clinical pregnancy rate and live birth rate. Participants/materials, setting, methods Exclusion criteria: Smoker, drug and alcohol abuse, medical treatment with gonadotropin and steroids, varicocele.60 patients were randomisedinto 3 groups. Gr A(N = 20) received Letrozole 2.5mg/day + Co enzyme Q10 300mg/day for 3 months, Gr B(N = 20) received Letrozole 2.5mg/day for 3 months, and Gr C(N = 20) received Coenzyme Q10 300mg/day for 3 months. History taking, general examination, semen analysis, sr.FSH,LH, Testesteron, E2 and scrotal duplex were done for all patients. Main results and the role of chance After treatment, Gr A as compared to Gr B and C showed significant imprivement in all 3 parameters of semen eg sperm count( 3.15±3.38 - 20.9±2.11, p < 0.001), sperm motility( 5.25±3.25 - 42.85±3.30, p < 0.001), sperm morphology( 2.26±7.81 - 25.89±7.05, p < 0.001). Improvement in sperm count and morphology was seen in Gr B(Letrozole gr) but not in sperm motility whereas Gr C ( Co enzyme Q10 gr)showed significant improvement in sperm motility and morphology but not in sperm count. 10 pregnancies occured during follow up period of 1 yr. Clinical pregnancy rate was 30%in Gr A(6/20), 5% in Gr B(1/20), AND 15% in Gr C( 3/20). Live birth rate was 83% in Gr A(5/6), 33.3% inGr C(1/3) whereas sponteneous abortion occured in Gr B pregnancy. Limitations, reasons for caution Limitation of my study was the small sample sizewhich could have some bias in outcome. I did not evaluate DNA fragmentation and level of ROS. Latest evidences report that evaluating ROS can be a diagnostic tool in predictingthe best responder to supplementation. Wider implications of the findings: Majority of studies had investigated the effect of antioxidant and aromatase inhibitor on semen parameter but few concluded their effect on live birth rate. Assisted reproductive techniques are expensive and not universally available, so any pharmacological agent with satisfactory effectiveness should be considered as 1st line treatment of oligoasthenoteratozoospermia. Trial registration number Not applicable