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Male factor infertility

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Male factor infertility

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Male factor infertility

  1. 1. Male infertility Aboubakr Elnashar Benha University, Egypt ABOUBAKR ELNASHAR
  2. 2. ABOUBAKR ELNASHAR CONTENTS 1.CAUSES 2.EVALUATION 3.TREATMENT
  3. 3. CAUSES Pretesticular: Hypothalamic pituitary disease (Secondary hypogonadism): 1-2% Testicular: Primary hypogonadism: 10-15% Post-testicular defects disorders of sperm transport: 10 to 20 % Idiopathic: Seminiferous tubule dysfunction: 60-80% including microdeletions of the Y chromosome ABOUBAKR ELNASHAR
  4. 4. EVALUATION ●History ●Examination ●Investigation 1. Conventional Semen analyses 2. Specialized Semen analysis 3. Endocrine testing 4. Genetic tests ABOUBAKR ELNASHAR
  5. 5. I. STANDARD SEMEN ANALYSIS IV. GENETIC TESTS 1. Karyotyping 2. Y chromosome microdeletions 3. Cystic fibrosis conductance regulator (CFTR) gene mutation II. SPECIALIZED SEMEN ANALYSIS 1. Sperm autoantibodies 2. Semen Fructose 3. Semen culture 4. Sperm function tests CASA SDF III. ENDOCRINE TESTS 1. T 2. LH and FSH 3. Prolactin ABOUBAKR ELNASHAR
  6. 6. I. STANDARD SEMEN ANALYSIS A. Macroscopic 1. Delayed liquefaction 2. Increased viscosity 3. Semen volume 4. pH B. Microscopy 1. Agglutination 2. Concentration 3. Motility 4. Morphology 5. Round cells 6. Leukocytes ABOUBAKR ELNASHAR
  7. 7. Semen analysis: WHO, 2010 : : Lower reference limitParameter 1.5 mlVolume 7.2pH 15 million/mlConcentration 39 million/ejaculateTotal sperm number 40% or PR: 32% Total motility: (PR+NP) 58% live spermatozoaVitality 4% (strict criteria).Normal forms ABOUBAKR ELNASHAR
  8. 8. ABOUBAKR ELNASHAR
  9. 9. Other threshold values Peroxidase-positive leukocytes (106 per ml): <1.0 Mixed Antiglobulin Reaction (MAR) test (motile spermatozoa with bound particles, %): <50 Immunobead test (motile spermatozoa with bound beads, %) <50 Seminal fructose (ųmol/ejaculate): ≥13 Seminal neutral glucosidase (mU/ejaculate): ≥20 Seminal zinc (ųmol/ejaculate): ≥2.4 ABOUBAKR ELNASHAR
  10. 10. Collection: After 2-7 d of sexual abstinence at the doctor's office Masturbation If this is not possible: condoms without chemical additives delivered to the laboratory within 1 h At least 2 samples collected 1-2 w apart & not more than 3 months apart. {marked variation of sperm production within one individual} Any systemic disease during sperm generation time (72 days for spermatogenesis & 14 days for transport through the epididymis & vas): ±negative impact. ABOUBAKR ELNASHAR
  11. 11. ABOUBAKR ELNASHAR
  12. 12. Prediction of fertility The likelihood of infertility increased with decreases in any of the 3 parameters: M, NM, C Normal morphology had the greatest discriminatory power. ABOUBAKR ELNASHAR
  13. 13. II. SPECIALIZED SEMEN ANALYSIS Not routinely performed used to determine the cause of male infertility 1. Sperm autoantibodies 2. Semen biochemistry (semen fructose) 3. Semen culture 4. Sperm cervical mucus interaction tests 5. Sperm function tests Computer aided sperm analysis (CASA) Sperm chromatin/DNA assays Acrosome reaction Zona free hamster oocyte penetration test Human zona pellucida binding test Sperm reactive oxygen species generation ABOUBAKR ELNASHAR
  14. 14. 1. Sperm autoantibodies 4 to 8%of subfertile men. Agglutination: Stick of motile spermatozoa to each other. ≥10%: suggestive but not conclusive of immunological infertility. should be confirmed by Mixed antiglobulin reaction (MAR) Immunobead test both of which detect sperm surface antibodies. ABOUBAKR ELNASHAR
  15. 15. 2. Semen biochemistry Rarely useful in clinical practice. Fructose marker of seminal vesicle function. Low or non-detectable: congenital absence of the vas deferens and seminal vesicles or ejaculatory duct obstruction ABOUBAKR ELNASHAR
  16. 16. 3. Semen culture Indicated: semen samples contain inflammatory cells Results: usually not diagnostic. Precautions during sample collection to prevent skin contamination. The yield of semen culture may be improved by performing a prostatic massage before sample collection. ABOUBAKR ELNASHAR
  17. 17. 5. Sperm function tests Routine: Impractical and costly Selective when the standard semen analysis is normal or near normal ABOUBAKR ELNASHAR
  18. 18. Computer-aided sperm analysis: CASA Assess: 1. sperm concentration 2. morphology. 3. Motility: Quantitative measurement = sperm kinematics sperm velocity (curvilinear, straight line, average path) Amplitude of lateral displacement other derived functions. ABOUBAKR ELNASHAR
  19. 19. Useful in: identifying men with unexplained infertility predicting in vivo and in vitro fertilizing capacity, toxicology studies. Accuracy depend upon: technology analytic conditions, and technical training of the operators. ABOUBAKR ELNASHAR
  20. 20. ABOUBAKR ELNASHAR
  21. 21. Normal= 10 Fragmented= 4 DFI= 4X100/10+4 =28.5% normal normal normal normal normal normal normal normal normal fragmented fragmented fragmented fragmented normal ≥30: male infertility 15-30: RM. ≤15: Excellent to Good fertility potential ABOUBAKR ELNASHAR
  22. 22. ABOUBAKR ELNASHAR There is insufficient evidence to recommend the routine use of SDF testing in evaluation and treatment of infertile couple {level C} ????????? For diagnostic test 1. Results must be reproducible 2. Applicable to a given patient 3. Change management of patient
  23. 23. III. ENDOCRINE TESTS 1. Serum testosterone (T) 2. Serum LH and FSH 3. Prolactin ABOUBAKR ELNASHAR
  24. 24. 1. Serum testosterone (T) Morning T In men with borderline values: Repeat FT ABOUBAKR ELNASHAR
  25. 25. 2. Serum LH and FSH Indication: T is low Interpretation: high FSH and LH: primary hypogonadism low or normal: secondary hypogonadism. low LH + low sperm counts +well-androgenized: exogenous anabolic or androgenic steroid abuse. ABOUBAKR ELNASHAR
  26. 26. 3. Prolactin Indication:  low T normal to low LH 4. Inhibin low serum inhibin concentrations may be an even more sensitive test of primary testicular dysfunction than high serum FSH concentrations, provided the assay is specific for inhibin B ABOUBAKR ELNASHAR
  27. 27. ABOUBAKR ELNASHAR
  28. 28. IV. GENETIC TESTS 1. Karyotyping 2. Y chromosome microdeletions 3. Cystic fibrosis conductance regulator (CFTR) gene mutation ABOUBAKR ELNASHAR
  29. 29. ICSI: Men with severe oligozoospermia and azoospermia father children Genetic risks: 1. Cystic fibrosis conductance regulator (CFTR) gene mutation 2. Somatic and sex chromosome abnormalities 3. Microdeletions of the Y chromosome ABOUBAKR ELNASHAR
  30. 30. ABOUBAKR ELNASHAR
  31. 31. OBSTRUCTIVE AZOOSPERMIA Azospermia + Normal testicular volumes + Normal FSH, and LH and T 1. Bilateral congenital absence of the vas:  physical examination  low fructose level in the semen. 2. Ejaculatory duct obstruction Transrectal US: dilated seminal vesicles. Patients with obstructive azoospermia: urologist specialized in infertility for further evaluation and tt. ABOUBAKR ELNASHAR
  32. 32. ABOUBAKR ELNASHAR
  33. 33. Abnormal semen ICSI Palpable varicocele: Varicoceletomy low FSH &T: Hormonal TT. Infection: TT ? Mild Moderate, Severe or Azoospermia Low Resources 3 trial IUI H. Resources ABOUBAKR ELNASHAR
  34. 34. METHODS OF THERAPY 1. Limited available treatment 2. Specific treatment 3. Treatment of uncertain efficacy 4. Empirical treatment 5. Art ABOUBAKR ELNASHAR
  35. 35. I. LIMITED AVAILABLE TREATMENT Causes of irreversible infertility for which no medical therapy is available. e.g. Severe damage of seminiferous tubules ABOUBAKR ELNASHAR
  36. 36. ABOUBAKR ELNASHAR
  37. 37. II. SPECIFIC TREATMENT Only for hypogonadotropic hypogonadism. 1. Hyperprolactinemia Medication: medication should be discontinued, lactotroph adenoma: dopamine agonist: cabergoline or bromocriptine. ABOUBAKR ELNASHAR
  38. 38. 2. Other causes Hypothalamic or pituitary diseases: gonadotropins only men who have hypogonadotropic hypogonadism due to hypothalamic disease can be treated with GnRH. ABOUBAKR ELNASHAR
  39. 39. III. TREATMENT OF UNCERTAIN EFFICACY ABOUBAKR ELNASHAR
  40. 40. lnfectios Leukospermia, No symptoms Culture is negative: 10-day course of Erythromycin or Trimethoprim-sulfamethoxazole or Quinolone. ABOUBAKR ELNASHAR
  41. 41. Varicocele: (AUA&ASRM, 2004 & AFU, 2006) Imaging examinations: not indicated to characterize the varicocele. TT when all of the following conditions are present: 1. Varicocele: Palpable 2. Semen: Abnormal (at least one abnormality) 3. Couple's infertility: Documented 4. Female infertility problem: Curable ABOUBAKR ELNASHAR
  42. 42. 5. Obstructive azoospermia Diagnosis: Azoospermia or severe oligospermia + normal size testis normal FSH normal testicular histology. ABOUBAKR ELNASHAR
  43. 43. Obstruction of the epididymis microsurgical end-to-end anastomosis of the epididymal duct to epididymal duct or to vas. ABOUBAKR ELNASHAR
  44. 44. Ejaculatory duct obstruction Transurethral resection of the ejaculatory ducts ICSI can be combined to use sperm from men who have obstructive azoospermia to fertilize ova of their partners and achieve pregnancy. ABOUBAKR ELNASHAR
  45. 45. Obstruction due to vasectomy surgical reanastomosis appears to be preferable to ICSI. Congenital bilateral absence of the vas deferens ICSI ABOUBAKR ELNASHAR
  46. 46. IV. EMPIRICAL THERAPY Examples: CC Aromatase inhibitors and Other hormones, vitamins, and kallikrein ABOUBAKR ELNASHAR
  47. 47. ABOUBAKR ELNASHAR
  48. 48. V. ASSISTED REPRODUCTIVE TECHNIQUES Indications of IUI: Mild male factor infertility  up to 6 cycles of IUI (NICE, 2004; ESHRE Capri Workshop, 2009)  No IUI, Advise them to try to conceive for a total of 2y (including up to 1y before their fertility investigations) before IVF will be considered. Exceptions: Social, Cultural, Religious (NICE, 2013) ABOUBAKR ELNASHAR
  49. 49. Male subfertility:  Oligospermia, Asthenozoospermia, Teratozospermia (OAT syndrome).  Severe male infertility: not candidate for IUI Count<5million/ml Normal morphology <2.5% or Motility <10  ICSI is more cost effective than IUI when the mean total motile sperm count is <10 million (Van Voorhis et al,2001) ABOUBAKR ELNASHAR
  50. 50. Indications of ICSI (NICE, 2004; 2014) 1.Severe deficits in semen quality 2.Obstructive azoospermia 3.Non-obstructive azoospermia 5. Mild deficits in semen quality (high resource) 4. Previous IVF cycle with failed or very poor fertilizationa) ABOUBAKR ELNASHAR
  51. 51. Abnormal semen ICSI Palpable varicocele: Varicoceletomy low FSH &T: Hormonal TT. Infection: TT ? Mild Moderate, Severe or Azoospermia Low Resources 3 trial IUI H. Resources ABOUBAKR ELNASHAR
  52. 52. ABOUBAKR ELNASHAR You can get this lecture from: 1.My scientific page on Face book: Aboubakr Elnashar Lectures. https://www.facebook.com/groups/2277 44884091351/ 2.Slide share web site 3.elnashar53@hotmail.com 4.My clinic: Elthwara St. Mansura

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