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IS THERE A ROLE OF MEDICAL TREATMENT IN MALE INFERTILITY?

IS THERE A ROLE OF MEDICAL TREATMENT IN MALE INFERTILITY?. PROF. DR. BÜLENT SEMERCI EGE UNIVERSITY SCHOOL OF MEDICINE DEPARTMENT OF UROLOGY. MEDICAL TREATMENT IN MALE INFERTILITY. 1- Specific Therapy 2- Empiric Therapy. MEDICAL TREATMENT IN MALE INFERTILITY. 1- Specific Therapy

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IS THERE A ROLE OF MEDICAL TREATMENT IN MALE INFERTILITY?

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  1. IS THERE A ROLE OF MEDICAL TREATMENT IN MALE INFERTILITY? PROF. DR. BÜLENT SEMERCI EGE UNIVERSITY SCHOOL OF MEDICINE DEPARTMENT OF UROLOGY

  2. MEDICAL TREATMENT IN MALE INFERTILITY • 1- Specific Therapy • 2- Empiric Therapy

  3. MEDICAL TREATMENT IN MALE INFERTILITY 1- Specific Therapy A- Endocrine Disorders B- Leucospermia C- Immunological Infertılıty D- Gonadotoxins E- Ejaculatory Dysfunction

  4. A- Endocrine Disorders • Hypogonadotropic Hypogonadism • Accounts for less than 1% of all cases of male infertility • Gonadotropin replacement is the rational treatment and is the only clearly accepted and effective management of associated infertility • Endocrinol Metab Clin North Am. 2007 Jun;36(2):313-31.

  5. A- Endocrine Disorders • Normal malefertility: • Adequatelevels of intratesticulartestosterone • Adequatelevels of follicle-stimulatinghormone (FSH) • FSH has beenshowntoinitiateandmaintainspermatogenesis

  6. A- Endocrine Disorders • Gonadotropin Replacement • FSH administration in men with hypogonadotropic hypogonadism increases sperm count, motility, morphology and testicular volume • J Androl. 2003 Jul-Aug;24(4):604-11.

  7. A- Endocrine Disorders • Gonadotropin replacement treatment • hCG • LH analog • hMG • mimics LH and FSH • Purified FSH • Pulsatile GnRH • Normal Physiology • Kallman Syndrome • İnfrequent, a portable minipump, an inconvenient, costly practice

  8. A- Endocrine Disorders • Gonadotropin Replacement • Initial management: hCG • IM or SC 3000-6000 IU/week, • until adequate serum testosterone levels detected • If sperm undetected after 6 months concomitant treatment • hMG (75-150 IU 2-3 times/week) • FSH (50-150 IU 3 times/week) • Contraception. 2005 Oct;72(4):314-8. • Up to 1-2 years

  9. A- Endocrine Disorders • Predictivefactors of gonodotropinreplacementresponse: • Largertesticularvolume • Priorgonadotropintherapy • Postpubertalstatus • Absence of bilateralmaldescendedtestes

  10. A- Endocrine Disorders • Gonadotropin Replacement • hCG/hMG: effective in anabolic steroid-induced azoospermia • Fertil Steril. 2003 Jun;79 Suppl 3:1659-61.

  11. A- Endocrine Disorders • Gonadotropin Replacement • 24 men with isolated hypogonadotropic hypogonadism • 92% became fertile • 40 pregnancies • 71% sperm concentrations below 20 million/mL • Fertil Steril. 1988 Aug;50(2):343-7

  12. A- Endocrine Disorders • Gonadotropin Replacement • Gonadotropins have proven highly effective in inducing fertility • Eur J Endocrinol. 1998 Sep;139(3):298-303. • Int J Androl. 1994 Oct;17(5):241-7 • Int J Androl. 1992 Aug;15(4):320-9

  13. A- Endocrine Disorders • Androgens • Exogenous testosterone therapy is detrimental for sperm production and has a contraceptive effect • Fertil Steril 1996;65(4):821-9 • Meta-analyses: testosterone and mesterolone • no effect on sperm production • no increase in pregnancy rates

  14. B- Leucospermia • Antibiotics • The incidence of genital tract infections among men with infetility varies 10%-20% • Organization WH. WHO labaratory manual for the exmination of human semen and semen-cervical mucus interaction. Cambridge (UK): Cambridge University Press; 1992. • Often asymptomatic and difficult to diagnose

  15. B- Leucospermia • Antibiotics • When leukocytospermia, defined as greater than one million WBC/mL, is present in an asymptomatic infertile male on semen analysis, an evaluation for a genital tract infection is recommended • Hum Reprod 10. (7): 1736-1739.1995

  16. B- Leucospermia • Antibiotics • In asymptomatic infertile men with leukocytospermia or in cases of truly unexplained infertility, semen cultures can be considered and appropriate antibiotic treatment instituted depending on the organism isolated

  17. C- Immunological Infertılıty • Corticosteroids • Treatment of antisperm antibodies • İnconsistent and incomplete meta-analysis of four of six randomized, available controlled studies revealed no significant enhancement of fertility • Hum Reprod. 1999 Sep;14 Suppl 1:1-23.

  18. C- Immunological Infertılıty • Corticosteroids • Using before ICSI is a choice for patients with high antisperm antibody titers • Statistical significance is lacking • Hum Reprod Update. 2001 Sep-Oct;7(5):450-6. • Int J Fertil Womens Med. 1998 May-Jun;43(3):165-70

  19. D- Gonadotoxins • Often depend on the job • Prevention from exposure to industrial and agricultural gonadotoxin (lead, manganese etc.,)

  20. E- Ejaculatory Dysfunction • Failure of emission • Retrograde ejaculation

  21. E- Ejaculatory Dysfunction • Causes • Spinal-cord injury • DM • Retroperitoneal surgery • Multiple sclerosis • Bladder neck and prostate surgery

  22. E- Ejaculatory Dysfunction • Medical Therapy: • α- sympathomimetic medications • Ephedrine • Pseudoephedrine • İmipramine • Phenylpropanolamine • If these agents contraindicated or unsuccesful • Vibratory simulation • Electroejaculation (90% of patients producing a semen specimen • J Urol 163. (6): 1717-1720.2000 • Int J Androl 25. (6): 324-332.2002

  23. MEDICAL TREATMENT IN MALE INFERTILITY • Empiric Therapy • A- Antiestrogens • B- Aromatase inhibitors • C- Gonadotropins • D- Alternative therapy

  24. A- Antiestrogens • Clomiphene citrate, a synthetic antiestrogen, is the most commonly used drug in the treatment of idiopathic oligospermia. • Binding estrogen receptors • Inhibition of estrogen at the hypothalamic and pituitary levels • Increasing GnRH, LH, and FSH secretion and stimulating testosterone production and spermatogenesis • Peripheral conversion of testosterone

  25. A- Antiestrogens • Clomiphene citrate: • The first study yielded poor results in 1966 • Within the past 40 years studies have demonstrated conflicting results in sperm counts, morphology, motility and pregnancy rates

  26. A- Antiestrogens • In a meta-analysis of 10 controlled studies involving 738 men • Positive hormonal effect • No improvement in pregnancy rate • Vandekerckhove P., et al:  Clomiphene or tamoxifen for idiopathic oligo/asthenospermia.  Cochrane Database Syst Rev . (2): 2000;CD000151

  27. A- Antiestrogens • More advantageous in men who have mild oligospermia and low serum gonadotropins or increased estrogen • Less likely to be efficacious in men who have elevated baseline gonadotropins and in men who have remarkably abnormal semen analyses or testicular biopsies

  28. A- Antiestrogens • With the advancement of assisted reproduction techniques the goal may be to augment spermatogenesis so that in vitro fertilization • 42 patients who had nonobstructive azoospermia • After 3 to 9 months of therapy with dose titration to achieve testosterone levels of 600-800 ng/dl • 64.3% of patients demonstrated semen analyses containing sperm • J Androl 26. (6): 787-791.2005;[discussion: 792–3]

  29. A- Antiestrogens • Self-limited, common side effects • weight gain • blurred vision • hypertension • gastrointestinal disturbances • insomnia

  30. B- Aromatase inhibitors • Aromatase inhibitors have been used to block the conversion of androgens to estrogen and therefore increase testosterone with the hopes of improving male infertility. • Steroidal (eg, testolactone) • Nonsteroidal (eg, anastrazole) • Highly potent and less likely to cause interruption of the adrenal axis beyond aromatase inhibition • Lowering serum estradiol and increasing testosterone/estradiol ratio • Only in men with Klinefelter syndrome was anastrozole not significantly effective • J Urol 167. (2 Pt 1): 624-629.2002

  31. B- Aromatase inhibitors • Semen parameters and testosterone/estradiol ratios improved in a study of 63 hypergonadotropic hypogonadic infertile men • J Urol 165. (3): 837-841.2001 • Controlled studies looking at pregnancy rates using aromatase inhibitors are lacking • Patients who have hepatic disease, and liver function tests should be monitored

  32. C- Gonadotropins • Treatment of idiopathic infertility • Randomized controlled trials have observed no significant effect of hCG, hMG, or rhFSH on pregnancy rates or seminal parameters • Hum Reprod 13. (3): 596-603.1998 • Clin Endocrinol Metab 65. (6): 1081-1087.1987

  33. C- Gonadotropins • FSH may be beneficial subsets of patients, such as those who have normal plasma levels of FSH and inhibin B and a testicular tubular appearance of hypospermatogenesis without maturation disturbances • FSH 100 IU on alternate days increased stimulation of spermatogenesis • Significant increases in testicular volume and sperm parameters were detected with doses of 150 IU • Fertil Steril 80. (6): 1398-1403.2003

  34. C- Gonadotropins • FSH may be useful in infertile men who have certain defects in sperm structure, such as those who have apoptotic or immature sperm, because treatment seems to improve the quality of sperm micro-organelles • Increase in spontaneous pregnancies • Hum Reprod 12. (9): 1955-1968.1997 • Fertil Steril 73. (1): 24-30.2000

  35. C- Gonadotropins • Several controlled studies have found better quality embryos and implantation rates after pretreatment of infertile men undergoing in vitro fertilization (IVF)/intra-cytoplasmic sperm injection (ICSI) • Fertil Steril 80. (6): 1398-1403.2003 • Fertil Steril 72. (4): 670-673.1999

  36. C- Gonadotropins • The role of FSH in treating idiopathic oligospermia • In patients who have hypospermatogenesis • Patients attempting IVF/ICSI

  37. D- Alternative therapy • 30% of men presenting for infertility evaluation use alternative therapies • tocopherol (vitamin E) • ascorbic acid (vitamin C) • acetylcysteine • glutathione • pentoxifiline • Urology 63. (1): 141-143.2004

  38. D- Alternative therapy • Tocopherol improved sperm function (sperm–zona pellucida binding capacity) and IVF rates • Fertil Steril 64. (4): 825-831.1995 • Fertil Steril 66. (3): 430-434.1996

  39. D- Alternative therapy • Acetylcysteine and retinol (vitamin A) together with tocopherol and essential fatty acids: • increased sperm count, • decreased ROS, • augmented acrosome reaction • Prostaglandins Leukot Essent Fatty Acids 63. (3): 159-165.2000

  40. D- Alternative therapy • Folic acid and zinc supplements : • Increase sperm concentration • No effect in seminal and hormonal parameters • Int J Androl 29. (2): 339-345.2006 • Fertil Steril 77. (3): 491-498.2002

  41. D- Alternative therapy • L-carnitine: • a vital component of sperm metabolism and maturation • improvement sperm concentration and motility • Reprod Biomed Online 8. (4): 376-384.2004

  42. D- Alternative therapy • Pentoxifiline • Phosphodiesterase inhibitor • Augmenting the fertilizing potential of asthenozoospermic sperm samples, presumably by improving sperm movement • Commonly used doses: 400mg / 3 times a day

  43. D- Alternative therapy • Results are encouraging • Side effects are minimal • Recommended as adjunctive therapy

  44. RECOMMENDATIONS • Medicaltreatment of maleinfertility can only be advised in cases of hypogonadotrophichypogonadism • Medicaltreatment of maleinfertility can be valuable in conjuctionwithadvancedassistedtechniques • Drugsareusuallyineffective in thetreatment of idiopathicmaleinfertility

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