Infertility is defined as the inability to achieve pregnancy after one year of unprotected intercourse. An estimated 15% of couples meet this criterion and are considered infertile, with approximately 35% due to female factors alone, 30% due to male factors alone, 20% due to a combination of female and male factors, and 15% unexplained. Conditions of the male that affect fertility are still generally underdiagnosed and undertreated.
Causes of infertility in men can be explained by deficiencies in sperm formation, concentration (eg, oligospermia [too few sperm], azoospermia [no sperm in the ejaculate]), or transportation.
Treatment options are based on the underlying etiology and range from optimizing semen production and transportation with medical therapy or surgical procedures to complex assisted reproduction techniques.
A number of patients with hypogonadotropic hypogonadism respond to GnRH therapy or gonadotropin replacement.
HCG is an LH analogue that may be used alone or in combination with HMG for Leydig cell stimulation.
Clomiphene citrate and tamoxifen are antiestrogens that block the negative feedback loop at the pituitary level, allowing a potentially increased release of gonadotropins.
Patients with CAH may respond to therapy with glucocorticoids, while those with isolated testosterone deficiency may respond to testosterone replacement.
Exogenous testosterone decreases intratesticular testosterone production, thus inhibiting Sertoli cell function and spermatogenesis.
Treat patients with hyperprolactinemia with bromocriptine, a dopamine antagonist, or cabergoline.
Antisperm antibodies
Patients with antisperm antibody levels greater than 1:32 may respond to immunosuppression using cyclic steroids for 3-6 months. However, patients need to be aware of the potential side effects of steroids, including avascular necrosis of the hip, weight gain, and iatrogenic Cushing syndrome.
Retrograde ejaculation
Imipramine or alpha-sympathomimetics, such as pseudoephedrine, may help close the bladder neck to assist in antegrade ejaculation. However, these medicines are of limited efficacy, especially in patients with a fixed abnormality such as a bladder neck abnormality occurring after a surgical procedure.
Alternatively, sperm may be recovered from voided or catheterized postejaculatory urine to be used in assisted reproductive techniques. The urine should be alkalinized with a solution of sodium bicarbonate for optimal recovery.
More recently, the injection of collagen to the bladder neck has allowed antegrade ejaculation in a patient who had previously undergone a V-Y plasty of the bladder neck and for whom pseudoephedrine and intrauterine insemination had failed.[16]
Semen processing
Patients with poor semen quality or numbers may benefit from having their semen washed and concentrated in preparation for intrauterine insemination.
Couples with an abnormal postcoital test result due to semen hyperviscosity may benefit from a precoital saline douche or semen processing with chymotrypsin.
Lifestyle
Patients should be encouraged to stop smoking cigarettes and marijuana and to limit environmental exposures to harmful substances and/or conditions.
Stress-relief therapy and consultation of other appropriate psychological and social professionals may be advised.
Infections should be treated with appropriate antimicrobial therapy.
Artificial insemination
Artificial insemination (AI) involves the placement of sperm directly into the cervix (ie, intracervical insemination [ICI]) or the uterus (ie, intrauterine insemination [IUI]). AI is most useful for couples in whom the postcoital test indicated no sperm, those who have very low sperm density or motility, or those who have unexplained infertility.
IUI allows the sperm to be placed past the inhospitable cervical mucus and increases the chance of natural fertilization. This results in a 4% pregnancy rate if used alone and a pregnancy rate of 8-17% if combined with superovulation. Both processes require semen processing.
Patients in whom IUI has failed 3-6 times should consider proceeding to IVF.
Assisted reproduction techniques
Patients with severe oligospermia, azoospermia, unexplained infertility, or known defects that preclude fertilization by other means are candidates for assisted reproduction techniques. Assisted reproduction techniques use donated or retrieved eggs that are fertilized by the male partner's sperm or donor sperm. The fertilized embryos are then replaced within the female reproductive tract. These techniques result in a 15-20% delivery rate per cycle and may eventually be successful in 50% of cases. However, the high cost and technical difficulty of the procedures generally preclude their routine use as first-line therapy.
In vitro fertilization
IVF involves fertilization of the egg outside the body and reimplantation of the fertilized embryo into the woman's uterus. Indications for IVF include previous failures with IUI and known conditions of the male or female precluding the use of less-demanding techniques.
IVF generally requires a minimum of 50,000-500,000 motile sperm. Harvesting eggs initially involves down-regulating the woman's pituitary with a GnRH agonist and then performing controlled ovarian hyperstimulation.
Follicular development is monitored by ultrasonographic examination and by checking serum levels of estrogen and progesterone. When the follicles are appropriately enlarged, a transvaginal follicular aspiration is performed.
A mean of 12 eggs are typically retrieved per cycle, and they are immediately placed in an agar of fallopian-tube medium. After an incubation period of 3-6 hours, the sperm are added to the medium using approximately 100,000 sperm per oocyte. After 48 hours, the embryos have usually reached the 3- to 8-cell stage. Two to 4 embryos are usually implanted in the uterus, while the remaining embryos are frozen for future use. Pregnancy rates are 10-45%.
Overall, IVF is a safe and useful procedure. Risks include multiple pregnancies and hyperstimulation syndrome. Additionally, an increased risk of hypospadias occurs in boys (1.5% vs 0.3%), probably because of the increased maternal progesterone used for egg harvesting.[22]
Finally, the use of this technology has led to many ethical issues, such as the fate of embryos after divorce.
Gamete intrafallopian transfer (GIFT) and zygote intrafallopian transfer (ZIFT)
These procedures allow the placement of semen (GIFT) or a fertilized zygote (ZIFT) directly into the fallopian tube by laparoscopy or laparotomy. Success rates have been estimated to be 25-30% using these techniques. Unfortunately, these procedures require general anesthesia and have associated risks. Fertilization and implantation within the uterus are not guaranteed, and these procedures cannot be performed in patients with fallopian tube obstruction. GIFT and ZIFT are rarely used as a therapeutic option.
Intracytoplasmic sperm injection
ICSI is indicated in patients who have failed more conservative therapies or those with severe abnormalities in which no other treatment would be effective, including patients with sperm extracted directly from the epididymis or testicle.
Oocytes are processed with hyaluronidase to remove the cumulus mass and corona radiata. A micropipette is used to hold the egg while a second micropipette injects the sperm. The oocyte is positioned with the polar body at the 6-o'clock or 12-o'clock position, and the sperm is injected at the 3-o'clock position to minimize the risk of chromosomal damage in the egg.
After incubation for 48 hours, the embryo is implanted in the woman. Van Steirteghem et al (1993) reported a 59% fertilization rate and a 35% pregnancy rate using ICSI in 1409 oocytes.[23]
Fresh or cryopreserved sperm appear to have similar success rates.[24]
The potential complications, ethical issues, and high costs of ICSI need to be considered and individualized.
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