male%20infertility
MALE INFERTILITY

Infertility is the inability to conceive despite regular unprotected sexual intercourse for one year.

Male infertility as the sole cause accounts for 20% & 30-40% as a contributory factor to infertility in couples.

Causes include: hypothalamic pituitary disease, primary testicular disease, disorders of sperm transport, genetic disorders, idiopathic infertility, infections, immune system disorders, iatrogenic causes, and chronic illness.

Principles of Therapy

  • Treatment involves psychotherapy, medical management, surgical treatment, & different assisted reproductive techniques
  • Goals of treatment include restoration of sexual function & fertility, & to obtain & maintain virility
  • Treatment of male infertility should be started as soon as diagnosis has been established, especially if the female partner is >35 years old
  • Patients should be informed of the possible risks & benefits that can be acquired from various treatments prior to initiation
  • Pharmacologic management of male infertility may be applicable for patients diagnosed w/ hypogonadotropic hypogonadism, & sexual dysfunction
  • There are still no proven medical treatment for infertility caused by Y chromosome microdeletions, Sertoli cell only syndrome, & Germ cell arrest at primary spermatocyte or earlier stage
  • Testosterone replacement is not recommended as androgen replacement therapy for men w/ hypogonadism who are seeking treatment for infertility
    • Gonadotropins (hCG, hMG) & GnRH should be used instead


Pharmacotherapy

Antibiotics
  • Eg Doxycycline, Erythromycin, Norfloxacin, Trimethoprim
  • May be used for men positive for leukocytes in their semen w/ identified infection
  • Infection eradication aims to reduce the causative organisms contained in the semen & prostatic secretions, control inflammation, & improve sperm parameters for fertility purposes
Antidepressants
  • Eg Clomipramine, Desipramine, Fluoxetine, Imipramine, Paroxetine, Sertraline
  • Treatment option for patients w/ premature ejaculation
  • Effectively delays ejaculation, w/ effects seen a few days to 2 weeks after start of daily treatment
Antihistamines
  • Eg Brompheniramine, Ephedrine
  • May be used in men w/ retrograde ejaculation or delayed ejaculation
Dapoxetine
  • Potent selective serotonin re-uptake inhibitors (SSRI) that has been especially designed as an on-demand oral treatment for premature ejaculation
  • Studies have shown that Dapoxetine significantly improved time to ejaculation
  • Clinical trials have shown that if taken 1-2 hours before intercourse it was effective from the first dose on IELT & increased ejaculatory control, decreased distress, & increased satisfaction
Dopamine Agonists
  • Eg Bromocriptine, Cabergoline
  • Used for patients w/ hypogonadotropic hypogonadism secondary to hyperprolactinemia caused by pituitary adenomas 
  • Mechanism of action: ergot alkaloid that binds to & stimulates dopamine receptors on lactotroph cells to inhibit prolactin secretion
  • May also cause shrinkage of adenomas & restoration of gonadal function
Please refer to Hyperprolactinemia Disease Management Charts for more information
Glucocorticoids
  • Eg Prednisone
  • Used for patients w/ sperm autoimmunity
Gonadotropins
Human Chorionic Gonadotropin (hCG)
  • Used to treat prepubertal cryptorchidism to induce testicular descent
  • Descended testis after treatment w/ hCG may reascend later in life
  • Used to stimulate spermatogenesis in men w/ hypogonadotropic hypogonadism when given w/ menotropins
    • Also considered as a treatment option for unexplained infertility
Human Menopausal Gonadotropin (hMG), Human FSH (hFSH), Recombinant Human FSH (rhFSH)
  • hMG contains a combination of FSH & LH derived from human postmenopausal urine
  • Used in combination w/ hCG for spermatogenesis stimulation
  • Effectively stimulates sperm production in men w/ hypogonadotropic hypogonadism
Gonadotropin-Releasing Hormone (GnRH)
  • Eg Gonadorelin
  • Also known as follicle-stimulating hormone-releasing hormone (FSH-RH), luteinizing hormone-releasing hormone (LH-RH), gonadoliberin, luliberlin
  • Pulsatile GnRH is used as an alternative option to hCG for men w/ hypogonadotropic hypogonadism due to hypothalamic disease
  • Used to replace GnRH in the system, thereby initiating stimulation of the pituitary gland to produce LH & FSH; LH & FSH production in turn stimulates testosterone production for spermatogenesis
Local Anesthetics
  • Eg Lidocaine, Prilocaine
  • Several studies have shown that topical desensitizing agents help in delaying ejaculation by reducing the sensitivity of the glans penis
  • Reduced vaginal sensation due to residual topical anesthetics limits the use of this treatment option
Phosphodiesterase-5 Inhibitors (PO)
  • Eg Sildenafil, Tadalafil, Udenafil, Vardenafil
  • Oral phosphodiesterase-5 (PDE5) inhibitors should be offered as a 1st-line therapy for erectile dysfunction
  • Have proven efficacy & safety in both non-selected populations of men w/ erectile dysfunction & in specific subgroups of patients (eg men w/ DM & those who have had a prostatectomy)
  • Contraindicated in patients taking nitrates
  • Sexual stimulation is still required
  • Works peripherally; inhibits phosphodiesterase type 5, which is found in the penile tissue
    • Increases smooth muscle relaxation in the corpora cavernosa & enhances penile rigidity
Tramadol
  • On-demand oral doses of Tramadol was comparable to Dapoxetine in delaying ejaculation in patients w/ premature ejaculation
  • Delays ejaculation by stimulation of the m-opioid receptors & serotonin production in the CNS
Empirical Treatments
Androgens
  • Eg low-dose Testosterone, Mesterolone
  • Have been used w/ the assumption that these may cause “rebound” spermatogenesis stimulation & epididymal sperm maturation
Clomiphene citrate, Raloxifene, Tamoxifene
  • Have been used for the management of unexplained/idiopathic infertility
  • Further studies are needed to prove the efficacy of Clomiphene citrate & Tamoxifene in the management of infertility in male patients
  • Mechanism of action: blocks the negative feedback of estrogens in the hypothalamic-pituitary axis, thereby increasing the secretion of FSH, LH & testosterone
  • Studies have shown significant increases in sperm concentration & motility & increased conception rates in couples given Clomiphene citrate therapy

Non-Pharmacological Therapy

 Supplements

  • Eg antioxidants, vitamin & mineral supplements (Eg Carnitine, Cinnoxicam, Coenzyme Q10, Kallikrein,Pentoxifylline, Selenium, Vitamin E, Vitamin C, Zinc)
  • Oxidative stress may be contributory to the semen quality during spermatogenesis, for w/c several studies have cited that antioxidant intake may help in infertility
  • May improve pregnancy rates & live births in subfertile males
  • Further studies are needed to prove the efficacy of different supplements for male infertility

Psychotherapy & Behavioral Therapy

  • May help men w/ sexual dysfunction especially those w/ delayed ejaculation & anorgasmia
  • Goals of psychotherapy in men & couples suffering from sexual dysfunction are:
    • Help men develop sexual skills that will enable them to delay ejaculation or achieve an orgasm while broadening their sexual scripts, increasing sexual self-confidence & diminishing performance anxiety
    • Focus on resolving psychological & interpersonal issues that may have precipitated, maintained or be the consequence of the symptom for the man, partner or couple
  • Psychotherapy offers men, women & couples benefit, including the development of sexual skills, address ejaculation dysfunction improving relationship concerns & sexual self-confidence

Assisted Reproductive Techniques

  • Techniques used to initiate pregnancy in couples w/ the male partner diagnosed w/ moderate-severe oligospermia & azoospermia
  • May be used for patients w/ azoospermia in semen analysis but positive for sperm extracted from the seminiferous tubules
  • Should be considered for couples w/ persistent infertility despite radical treatments
Intracytoplasmic Sperm Injection (ICSI)
  • Involves direct injection of a single sperm into the cytoplasm of an oocyte
  • Treatment option for male infertility secondary to sperm autoimmunity, very severe oligospermia, asthenospermia, teratospermia, & non-obstructive azoospermia
  • Indications: <2 million motile sperm/ejaculate, <5% normal sperm morphology, <5% sperm w progressive motility, positive sperm autoantibodies
Intrauterine Insemination (IUI)
  • Involves direct placement of washed sperm into the upper uterine cavity prior to ovulation
  • May be considered for couples unable to conceive due to retrograde ejaculation or mild male infertility
  • May also be considered in couples w/ cervical mucus-antisperm antibodies
In Vitro Fertilization (IVF)
  • May be considered for couples unable to conceive due to retrograde ejaculation or moderate oligospermia
  • Amniocentesis or pre-implantation genetic diagnosis may be considered if previously diagnosed w/ autosomal abnormality
Sperm Retrieval Techniques
  • Sperm is obtained from men w/ obstructive azoospermia & is used to fertilize the partner’s ova during assisted reproduction
Aspiration Techniques
  • Eg Microsurgical Epididymal Sperm Aspiration (MESA), Percutaneous Epididymal Sperm Aspiration (PESA), Testicular Sperm Aspiration (TESA)
  • May be considered for men w/ CBAVD
Post-Orgasmic Urine
  • Used to retrieve sperm in men w/ retrograde ejaculation for possible use in ART on the day of ovulation
  • May be considered if w/ spinal cord injury & after treatment failure
Testicular Sperm Extraction (TESE)
  • Technique of choice for patients w/ non-obstructive azoospermia as part of ICSI during testicular biopsy, w/ the obtained spermatozoa cryopreserved
  • Procedure used to effectively retrieve sperm from the testis or epididymis
  • May be considered for men w/ CBAVD & Klinefelter syndrome
  • The only procedure that allows sperm retrieval in patients w/ intratesticular obstruction
Vibrostimulation & Electroejaculation
  • Vibrostimulation is the 1st-line therapy for men w/ anejaculation due to spinal cord injury but w/ intact lumbosacral spinal cord segment
    • May also be used in delayed ejaculation & retrograde ejaculation
  • Electroejaculation is used if vibrostimulation fails to retrieve sperm
Other Procedures
  • Artificial insemination w/ donor sperm may be considered by couples w/ male-factor infertility who have failed w/ other assisted reproductive techniques
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