Medical Management of Male Infertility

Article No. 9

Medical Management of Male Infertility

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INTRODUCTION

Infertility is regarded as ‘Male Factor’ when an alteration in sperm concentration and/or motility and/or morphology is present in at least one sample of two sperm analyses, which comply with the World Health Organization (WHO) 2011 guidelines. It is partly responsible for infertility in 50% of these couples.Therefore identifying the pathology and treating it may allow couple to improve their fertility potential and conceive naturally.

Factors affecting choice of therapy

• Age of couple & duration of infertility
• Severity of OATS
• Past illness(mumps-related orchitis)
• Reversible, correctable gonadotoxic factors like exposure to hot environmental conditions (furnacesetc)
• Antioxidants trial already given
• Socioeconomic status
• Psychosocial pressure

Aims of medical therapy

• To improve count, motility and morphology of sperms.
• Increase rates of spontaneous conception.
• Lower rates of miscarriages due to DNA abnormalities in sperm.

Specific Medical therapy

Non specific or Emperical therapy

1.Hormonal agents

2.Antioxidants

Inspite of doing IVF/ ICSI, there is high incidence of implantation failure and early pregnancy loss. If the DNA of sperm is damaged, it will result in a poor pregnancy outcome. Between 30% to 80% of idiopathic male subfertility cases are considered to be due to effects of oxidative stress on sperm.

Spermatozoa are vulnerable to ROS because their plasma membrane and cytoplasm contain large amounts of polyunsaturated fatty acids.

Eg. Glutathione 250mg/day, Lycopene 4-8g/d, Vit E 400-800mg/d, Vit C.

3.Spermvitalisers

Energises the sperms (improves motility) and increases fertilization. May assist in sperm maturation and some have antioxidant properties.

Eg . L & Acetyl carnitine 1g thrice a day

Coenzyme Q10 100-300mg/d

Carnitines are used by spermatozoa for mitochondrial membrane stabilisation and energise the sperm.

4. Nutritional supplements

May be of some benefit in nutritionally depletedpatients.

Eg. Multivitamins with zinc,selenium, folic acid and B12.

Conclusion

 

 

Further reading:

1. 1. Chronic scrotal fungal dermatitis –
      • Can cause thickening of scrotal skin &­ local temperature.
      • Treatment – Topical antifungal and steroids.
   2. Genital tract infections – Leucocytospermia (WBC count in semen > 1 x 106 / ml). Prevalence 10-20%.
      • Semen culture
      • Common organisms – Streptococcus fecalis, E coli, Chlamydia trachomatis, Ureaplasmaurealyticum.
      • Because of the difficulty of culturing, Doxycycline 200mg/day is given for 15days on empirical basis
      • Antibiotics maybe added later as per culture reports,eg. – Fluoroquinolones 0.5 – 1g / day, Cotrimoxazole or Erythromycin 1.5-2 g/day for 2-3 weeks.
      • Culture negative patients – Anti inflammatory therapy and frequent ejaculations
      • Refractory leucocytospermia – Sperm washing and IUI.
   3. Immunological infertility –
      • Oral steroids - To suppress antibody production, but efficacy not confirmed by double blind randomised trial.
      • Pregnancy rates are 0 to 44%, with maximum pregnancy seen after treatment for more than 3 months.
      • Treatment - Tab predinisolone 5mg, thrice a day for 10days with tapering of dose.
   4. Chronic epididymo-orchitis
      • Clinical evidence of chronic filarial epididymo-orchitis like enlarged adherent epididymis, thickened cord etc.
      • Treatment – Diethylcarbamazine (DEC) 100mg thrice a day for 20 days + Doxycycline 100mg twice a day for 10 days, followed by low dose steroids.
   • Androgens - Administered at a dose that will not influence the pituitary gonadal axis, may have direct stimulatory effect (in low doses) on spermatogenesis or influence sperm transport and maturation, with no effect on sperm motility. Helpful in hypogonadotropic hypogonadism.
     • Eg. Mesterolone 25 thrice a day.
     • Testosterone undecanoate80 – 160mg / day
   • Antiestrogen - Inhibit the negative feedback effect of estrogen by blocking estrogen receptors in hypothalamus and thus ­ gonadotrophins.  ­ FSH & LH stimulate sertolileydig cells and improve spermatogenesis.
     • Aromatase inhibitors increase FSH. In older men with so-called late-onset hypogonadism, aromatase inhibitors may emerge as an attractive alternative for traditional testosterone supplementation to improve testosterone levels.
     • Who will benefit? -Idiopathic male infertility
     • Who will not be benefited? -High Baseline FISH, Severe OATS,Azoospermia
     • Eg. Clomiphene citrate 25 mg / day
     • Tamoxifen citrate 10-20mg/ day
   • Aromatase inhibitors – Inhibit peripheral conversion of testosterone to estrogen and enhance spermatogenesis.
     • Normal testosterone (T)/ Esterogen (E2) is 1: 16
     • Low  T/E ratio indicates high Aromatase activity
     • Useful in a subpopulation of patients with low T/E2 ratio(eg. obese men)
     • EgLetrozole 2.5mg daily orally
   • Gonadotrophins – Helpful in men with idiopathic infertility (subclinical endocrinopathy) with normal hormonal levels.
     • Eg HCG 1500 IU or HMG 37.5 – 75 IU thrice a week
     • InjrFSH 300 IU daily followed by 3-6 cycles of IUI followed by ICSI.
   • Give a very clear road map of therapy
   • Individualised treatment, with timeline and endpoints established beforehand
   • Treatment should be of atleast 3 months, followed by repeat semen analysis.
   • Give realistic expectations.
   • Do not waste time and money over medical therapy if circumstances call for assisted reproductive therapy.
   1. Willem de Ronde et al. Aromatase inhibitors in men: effects and therapeutic optionsReprodBiolEndocrinol. 2011; 9: 93. doi: 10.1186/1477-7827-9-93 .
   2. Patel DP et al . Hormone-Based Treatments in Subfertile Males. CurrUrol Rep. 2016 Aug;17(8):56. doi: 10.1007/s11934-016-0612-4.
   3. Owen RC et al .Testosterone supplementation in men: a practical guide for the gynecologist and obstetrician.CurrOpinObstet Gynecol. 2015 Aug;27(4):258-64. doi: 10.1097/GCO.0000000000000192.
   4. Ho CC Treatment of the Hypogonadal Infertile Male-A Review. Sex Med Rev.2013 May;1(1):42-49. doi: 10.1002/smrj.4.