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Semelhante a Subclinical Infections and Male Infertility
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Subclinical Infections and Male Infertility
- 1. Sandro C. Esteves, MD., PhD. Director, ANDROFERT Andrology& Human Reproduction Clinic Campinas, BRAZIL Subclinical Infections and Male Infertility ISO 9001:2008 Reproductive Andrology Surgery Workshop II Reproductive Medicine Unit -JahraHospital -Kuwait 2014
- 2. Subclinical Male Genital Tract Infection (MAGI) ANDROFERT androfert.com.br ANDROLOGY AND HUMAN REPRODUCTION CLINIC -REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 2 2014 December ANDROFERT Urethritis, prostatitis
- 3. Macrophage Neutrophils ROS production by leukocytes is 100x higher than defective sperm ANDROFERT androfert.com.br ANDROLOGY AND HUMAN REPRODUCTION CLINIC -REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 3 2014 December ANDROFERT
- 4. Chemical species with unpaired electron capable to oxidize lipids, proteins and nucleic acids: Superoxide anion (•O-2) Hydroxyl radical (•OH); Hydrogen peroxide(H2O2) Peroxylradical (ROO•); Hypochlorite ion (OCl-) Generated from sperm aerobic metabolism and leukocytes Reactive Oxygen Species (ROS) Sperm and Seminal Plasma Antioxidants: Enzymatic(SOD, catalase, GPX): inactivate ROS by conversion into other substances Non-enzymatic(ascorbic acid, alpha-tocopherol, carnitine, etc): neutralize ROS ANDROFERT androfert.com.br ANDROLOGY AND HUMAN REPRODUCTION CLINIC -REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 4 2014 December ANDROFERT
- 5. Yanushpolskyet al 1996, Saleh& Agarwal2002, Aziz et al 2004 ANDROFERT androfert.com.br ANDROLOGY AND HUMAN REPRODUCTION CLINIC -REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 5 2014 APRIL ANDROFERT 25% 34% 39% % DNA Damage (SCSA)
- 6. Anti-bacterial properties (Zinc) Semen Culture Unreliable ANDROFERT androfert.com.br ANDROLOGY AND HUMAN REPRODUCTION CLINIC -REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 6 2014 December ANDROFERT
- 7. Leukocytospermia>1.0 x 106leukocytesper mLofsemenmarker of reproductive tract inflammation Spontaneous resolution in 50% of cases Braniganet al 1995, Erelet al 1997, Lackneret al 2008 ANDROFERT androfert.com.br ANDROLOGY AND HUMAN REPRODUCTION CLINIC -REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 7 2014 December ANDROFERT granulocyte macrophage lymphocyte
- 8. ANDROFERT androfert.com.br ANDROLOGY AND HUMAN REPRODUCTION CLINIC -REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 8 2014 December ANDROFERT Round cells Neubauerchamber 15 minutes Peroxidase Positive Peroxidase Negative 20 μlsemen + 20μl PBS + 40 μlbenzidine+ H2O2solution
- 9. •Yanushpolskyet al, 1995; Erelet al., 1997 •Braniganet al., 1995 Antibiotics •Lackneret al., 2006 •Gamberaet al., 2007 Cicloxigenase-2 Inhibitors •Oliva& Mutigner, 2006 Antihistamines •Tremellenet al., 2007 •Piombiniet al., 2008 Antioxidants Treatment of Subclinical MAGI and Associated Inflammatory Changes ANDROFERT androfert.com.br ANDROLOGY AND HUMAN REPRODUCTION CLINIC -REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 9 2014 December ANDROFERT
- 10. Subclinical MAGI Azitromycin1.0g single dose (couple) + frequent ejaculation (every 2-3 days) + Antioxidants 42% leukocytospermiaresolution (N=278; Androfert) ANDROFERT androfert.com.br ANDROLOGY AND HUMAN REPRODUCTION CLINIC -REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 10 2014 December ANDROFERT Neisseria gonorrheae Chlamydia pneumoniae Chlamydia trachomatis Mycoplasma pneumoniae Ureaplasmaurealyticum
- 11. Max Min 75th % 25th % Median -10 10 30 50 70 90 110 LEUCO_PR LEUCO_PO MOT_PRE MOT_POS MORF_PRE MORF_POS VIT_PRE VIT_POS P=0.001 P=0.04 P=0.50 P=0.58 Azitromycin 1.0g single dose (couple) + frequent ejaculation (every 2-3 days) ANDROFERT androfert.com.br ANDROLOGY AND HUMAN REPRODUCTION C LINIC - REFERRAL C ENTER FOR MALE REPRODUCTION S ESTEVES, 11 2014 December ANDROFERT
- 12. MAGI -Clinical Management Ascorbic acid (Vit. C) -tocopherol(Vit. E) Glutathione N-acetyl-cysteine Carnitine, Coenzyme Q10 Lycopene. Picnogenol Pentoxifylline. Selenium Shao-Fu-Zhu-Yu-Tang Astaxanthin Lepidiummeyenii -linolenicacid and lignans Folic acid, Zinc Combine OA Antibiotics First line therapy Varicocele Genital Infection Smoking Medication Drug abuse Systemic diseases Pollution Radiation Focus on identifying source of increased ROS ANDROFERT androfert.com.br ANDROLOGY AND HUMAN REPRODUCTION CLINIC -REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 12 2014 December ANDROFERT
- 13. Oral Antioxidants How I prescribe Vitamin C 500mg; Vitamin E 400 mg Folic acid 2 mg; Zinc 25 mg Selenium 26 mcg Minimum 2 months Old concept ~80 days New concept ~60 days From initiation of sperm production to ejaculation MisellLM et al. J Urol. 2006 Esteves& Agarwal. Novel concepts in male infertility. IntBrazJ Urol2011 ANDROFERT androfert.com.br ANDROLOGY AND HUMAN REPRODUCTION CLINIC -REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 13 2014 December ANDROFERT
- 14. Outcome No. studies Effect size (OR; 95% CI) Live birth 3 4.85 [1.92, 12.24] Pregnancy rate 15 4.18 [2.65, 6.59] DNA fragmentation 1 -13.80 [-17.50,-10.10] Miscarriage, sperm count, sperm motility 6-16 No effect Oral Antioxidants ShowellMG et al. CochraneDatabase Syst Rev 2011 ANDROFERT androfert.com.br ANDROLOGY AND HUMAN REPRODUCTION CLINIC -REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 14 2014 December ANDROFERT
- 15. MAGI may decreases fertility mainly via oxidative stress effects Antibiotic therapy is suggested, but effect on fertility is still unclear (GR-B) EAU guidelines in male infertility 2014 MAGI Key Messages ANDROFERT androfert.com.br ANDROLOGY AND HUMAN REPRODUCTION CLINIC -REFERRAL CENTER FOR MALE REPRODUCTION S ESTEVES, 15 2014 December ANDROFERT
- 16. Thank you Obrigado شكرا
Notas do Editor
- OS is defined as the imbalance between prooxidative and antioxidative molecules in a biological system which arises as a consequence of excessive production of free radicals and impaired antioxidant defense mechanisms.
- It is common to find leukocytes in the semen. Leukocytospermia is defined as the presence of > 1 million leukocytes per mililiter of semen. Among the leukocytes, neutrophils are the most important category and usually arise from the epididymis and prostate. Neutrophils are also named “granulocytes” as they have granules containing peroxidase enzyme. Leukocytospermia prevalence in subfertile males: 10-20% (Wolff, 1995)
- It is common to find leukocytes in the semen. Leukocytospermia is defined as the presence of > 1 million leukocytes per mililiter of semen. Among the leukocytes, neutrophils are the most important category and usually arise from the epididymis and prostate. Neutrophils are also named “granulocytes” as they have granules containing peroxidase enzyme. Leukocytospermia prevalence in subfertile males: 10-20% (Wolff, 1995)
- Neurophils can be easily detected in the semen based on the capacity of peroxidase to react with hydrogen peroxide. In this test, an aliquot of semen is incubated with hydrogen peroxide and a substrate to facilitate the reaction to occur. The final result is the oxidation of the substrate in the presence of granulocytes and hydrogen peroxidase. Neutrophils granules containing peroxidase show a brown color.
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- Based on several studies, our center has derived an empiric regimen of synthetic vit C and E, folate, zinc and selenium for men demonstrating elevated oxidative stress levels in their semen profile.
- Cochrane review analyzed 34 randomized controlled trials ( RCT) involving 2876 couples. The study evaluated the effect of oral antioxidant supplementation for male partners of couples undergoing assisted reproduction techniques (ART). A recent Cochrane meta-analysis on the use of oral antioxidants in male infertility found that these agents significantly improved pregnancy rates and live births and decreased sperm DNA damage [101]. An associated statistically significant increase in live birth rate [pooled odds ratio (OR) = 4.85; 95% CI 1.92–12.24; P = 0.0008; I (2) = 0%] has been obtained when men taking antioxidants were compared to controls. No studies reported harmful side effects from the antioxidant therapy used. Nevertheless, improvements in semen parameters were not well evident. The evidence suggests that antioxidant supplementation in subfertile males may improve the outcomes of live birth and pregnancy rate for subfertile couples undergoing fertility treatment. However, clinical trials are still necessary to identify the superiority of one antioxidant over the other in different subpopulations of infertile males, as well as other important aspects such as dose and duration of therapy.