Docstoc

MEDICAL TREATMENT OF MALE INFERTILITY

Document Sample
MEDICAL TREATMENT OF MALE INFERTILITY Powered By Docstoc
					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
  A- Endocrine Disorders
  B- Leucospermia
  C- Immunological Infertılıty
  D- Gonadotoxins
  E- Ejaculatory Dysfunction
       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.
       A- Endocrine Disorders
 Normal male fertility:
  – Adequate levels of intratesticular testosterone
  – Adequate levels of follicle-stimulating hormone
    (FSH)
  – FSH has been shown to initiate and maintain
    spermatogenesis
       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.
      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
       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
       A- Endocrine Disorders
 Predictive factors of gonodotropin
  replacement response:
  – Larger testicular volume
  – Prior gonadotropin therapy
  – Postpubertal status
  – Absence of bilateral maldescended testes
       A- Endocrine Disorders
 Gonadotropin Replacement
  – hCG/hMG: effective in anabolic steroid-induced
    azoospermia
       – Fertil Steril. 2003 Jun;79 Suppl 3:1659-61.
      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
       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
       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
            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
             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
            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
    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.
    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
           D- Gonadotoxins
 Often depend on the job
 Prevention from exposure to industrial and
  agricultural gonadotoxin (lead, manganese
  etc.,)
    E- Ejaculatory Dysfunction
 Failure of emission
 Retrograde ejaculation
    E- Ejaculatory Dysfunction
 Causes
  – Spinal-cord injury
  – DM
  – Retroperitoneal surgery
  – Multiple sclerosis
  – Bladder neck and prostate surgery
 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
MEDICAL TREATMENT IN MALE
       INFERTILITY
• Empiric Therapy
  • A- Antiestrogens
  • B- Aromatase inhibitors
  • C- Gonadotropins
  • D- Alternative therapy
          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
            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
           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
          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
          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]
          A- Antiestrogens
– Self-limited, common side effects
   weight gain
   blurred vision
   hypertension
   gastrointestinal disturbances
   insomnia
   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
     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
         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
          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
         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
           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
           C- Gonadotropins
 The role of FSH in treating idiopathic
  oligospermia
  – In patients who have hypospermatogenesis
  – Patients attempting IVF/ICSI
       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
      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
      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
      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
      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
        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
     D- Alternative therapy
– Results are encouraging
– Side effects are minimal
– Recommended as adjunctive therapy
       RECOMMENDATIONS
 Medical treatment of male infertility can only
  be advised in cases of hypogonadotrophic
  hypogonadism
 Medical treatment of male infertility can be
  valuable in conjuction with advanced
  assisted techniques
 Drugs are usually ineffective in the
  treatment of idiopathic male infertility

				
DOCUMENT INFO
Shared By:
Categories:
Stats:
views:162
posted:4/19/2011
language:English
pages:44