Smart Shortcuts Only Experts Know About Male Infertility


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Smart Shortcuts Only Experts Know About Male Infertility

  1. 1. Smart Shortcuts Only ExpertsKnow About Male InfertilitySandro Esteves, M.D., Ph.D.Director, ANDROFERTAndrology & Human Reproduction ClinicCampinas, BRAZILEvening Symposium , June 2013Kingdom of Saudi Arabia
  2. 2. Esteves, 2Sperm Chromatin Integrity is a newdiagnostic test that go far beyond routinesemen analysis. Learn how to use it.Obesity is a risk factor for male infertility:learn how to use aromatase inhibitors toincrease sperm production.Azoospermia is not a synonymous ofsterility. Biological fatherhood is possibleeven in the worst scenarios.
  3. 3. Esteves, 3Smart ShortcutsOnly ExpertsKnow AboutMale InfertilitySandro Esteves, 2013Review this Lecture at:
  4. 4. Esteves, 4• Normal sperm chromatin essential forpaternal genetic transmissionBackground• Unexplained infertility• Recurrent pregnancy loss• Poor outcomes in IUI and IVFSperm DNAFragmentation• Quantification of sperm DNA strandbreaksPrinciple• Semen, spermatozoaSpecimen• Nuclear dyes (Acridine orange, SCSA)• Direct assessment (TUNEL, COMET)• Nuclear matrix assays (SCD)TechniquesEsteves SC & Agarwal A. Novel concepts in male infertility.Int Braz J Urol 2011; 37:5-15.
  5. 5. Esteves, 5Sperm with intact DNA have “halos”:Represent dispersed chromatinwithout breaksSperm with fragmented DNA have no“halos”:Represent DNA strand breaksSperm ChromatinDispersion (SCD) TestEsteves et al. Arch Gynecol Obstet. 2012; 286: 217-29.Halosperm®Semen/SpermatozoaQuantitative Test:Normal: <20% cells with fragmented DNA
  6. 6. Cochrane Review 2011Outcome NstudiesNparticipantsEffect size(OR; 95% CI)Live birth 3 214 4.85 [1.92, 12.24]Pregnancy rate 15 964 4.18 [2.65, 6.59]DNA fragmentation 1 64 -13.80 [-17.50, -10.10]Miscarriage, spermcount, sperm motility6-16 242-700 No effectImprove the outcomes of live birth and pregnancy rate forsubfertile couples undergoing ART cyclesShowell MG et al. Antioxidants for male subfertility.Cochrane Database Syst Rev 2011 Jan 19;(1):CD007411.Esteves, 6
  7. 7. 19%1.5%Normal ElevatedLive Birth Rates withIntrauterine InseminationOR = 0.07[95% CI: 0.01-0.48]Bungum et al. HumReprod 2007; 22: 74–9Esteves, 726%42%IVF ICSIPregnancy by Method in Casesof Elevated Sperm DNAFragmentation
  8. 8. Robinson L et al. Hum Reprod. 2012; 27(10): 2908-17Population: Meta-analysis of 16 cohort studies(2,969 couples), 14 prospective.Techniques for DNA Assessment:Acridine orange-based assays, TUNEL and COMET.Findings:Significant increase in miscarriage rates in patientsundergoing IVF/ICSI with high sperm DNA damagecompared with those with low DNA damage.Risk ratio (RR) = 2.16 (1.54, 3.03), P < 0.00001).Esteves, 8
  9. 9. Esteves, 9• Hyaruronic Acid Binding• Polarization Microscopy• MSOME• Electroforetic Sperm Isolation• Magnetic-activated Cell Sorting• Microarray Technology• ProteomicsSpermSelectionTechniquesNormalcy of SpermChromatin ContentCurrent non-invasivetechniquescannot directlyassess spermDNA integrityDyes are used to reach thenucleus, using fixedspecimens
  10. 10. Sperm % TUNEL + % CPR %IREjaculated (N=18) 23.6 ± 5.1 6 2Testicular (N=18) 4.8 ± 3.6 44 21P value < 0.001 <0.05 <0.01Greco E et al. Hum Reprod 2005;20:226–30*Absolute differences between two specimens ranging from -3.3% to -56.3%.Moskovtsev et al. Fertil Steril 2010; 93(4): 1142–6.Testicular Spermatozoa have three-fold lowerDNA damage (13.3%) when compared withEjaculated Spermatozoa (39.7%)*
  11. 11. Sperm Chromatin Integrity is akey biomarker of spermfunction.SCD is a new and easy-to-usediagnostic test to assesssperm chromatin integrity.Test results have prognosticvalue in for assistedconception and aid inclinical management.Sperm Chromatin Integrity is a newdiagnostic test that go far beyond routinesemen analysis. Learn how to use it.
  12. 12. Obesity is a risk factor for male infertility:how to use aromatase inhibitors to increasesperm productionEsteves, 12
  13. 13. Jensen et al. Fertil Steril 2004; 82: 863; Hammoud et al. Fertil Steril 2008; 90: 2222; Kriegel etal. RBM Online 2009; 19: 660; Martini et al. Fertil Steril 2010; 94: 1739.Esteves, 13
  14. 14. Esteves, 14
  15. 15. Aromatase Inhibitors forInfertile Obese MenSerum Levels of TotalTestosterone and EstradiolT/E2 RatioNormal > 10Zumoff et al. Reversal of the hypogonadotropic hypogonadism of obese men byadministration of the aromatase inhibitor testolactone. Metabolism 2003; 52: 1126. Raman& Schlegel Aromatase inhibitors for male infertility. J Urol 2002; 167: 624.T/E2 <10Aromatase HyperactivityAnastrozole 1 mgq1d 60 daysEsteves, 15
  16. 16. Raman JD, Schlegel PN. Aromatase inhibitors for male infertility. J Urol. 2002;167:624- ratio Ejaculate volume(mL)Sperm Count(million/mL)Anastrazole for oligozoospermic men(1mg q1d for 3-6 months)Pre-treatment Post-treatmentAromatase Inhibitors forObesity-related Male InfertilityEsteves, 16
  17. 17. hCG PreparationsLH activity(IU/ampuleor vial)Ampoule/vial fillingmethod% ProteincontaminationSource Technology Route ofadministrationUrinary hCG 1,000-10,000Filled-by-bioassay<5% Urine ChemicalextractionIMRecombinanthCG250µg Filled-by-mass (FbM)Negligible TransfectedCHO cellsRecombinantDNASCEsteves SC, Papanikolaou V; Fertil Steril 2011; Vol 96:S230SC self-injectionw/pre-filledsyringe, qw
  18. 18. Aromatase Inhibitors forObesity-related Male Infertility1. Peripheral androgen aromatizationis enhanced in men with elevatedBMI. Obese men show increasedplasma estradiol and lowtestosterone levels.2. Lowering estradiol levels, by administration of AI,increases LH and FSH levels by pituitary modulation,and increase testosterone levels.3. Aromatase inhibitors stimulate sperm production;effects upon fertility are still to be determined.
  19. 19. • Normal sperm production• Mechanical blockage• Vasectomy, Post-infectious, CongenitalObstructive• Sperm production deficientor absent• Cryptorchidism, Radiation,Chemotherapy, Trauma,Genetic, Orchitis,Varicocele, Gonadotoxins,UnexplainedNon-obstructiveComplete absence of sperm in the ejaculate1-3% male population; ~10-15%% male infertilityAzoospermia is not a synonymous ofsterility. Biological fatherhood is possibleeven in the worst scenarios.Esteves, 19
  20. 20. • Sperm productionreduced or absent• Geographic locationunpredictableSpermRetrievalfor ARTUntreatableconditionTESA• 15%-50%SRRConventionalTESE• 20%-63%SRRMicro-TESE• 40%-67%SRRFriedler et al. 1997; Ezeh et al. 1998; Schlegel 1999; Amer et al. 2000; Okada et al. 2002; Okubuet al. 2002; Tsujimura et al. 2002; Ramon et al. 2003; Verza Jr. & Esteves 2011.
  21. 21. SC, Int Braz J Urol 2013
  22. 22. Azoospermia is not a synonymous ofsterility. Biological fatherhood is possibleeven in the worst scenarios.1. Testicular failure (non-obstructive azoospermia) is themost severe form of maleinfertility and cannot be treated.2. Sperm retrieval and ICSI only option for achievingbiological fatherhood.3. Micro-TESE, a microsurgical-guided biopsy,increases SR success and preserve testicularfunction.