General Patient Information
About 33 to 35 percent of infertility cases are the result of a "male factor," a disease or condition in the male partner. An equal number of cases stem from the female partner or a combined male-female problem. The traditional recommendation has been that if a couple has been trying to conceive for a year or more without success, they should consider seeking the help of an infertility specialist. More couples are seeking help earlier as the maternal age of conception has increased. Even when an isolated male or female problem is identified, it is critical that both the male and the female partner be fully evaluated as part of a comprehensive infertility workup.
Common causes of male infertility
Varicocele is the most common cause of oligospermia (Low sperm density )and refers to the dilated, tortuous veins of the pampiniform plexus in the spermatic cord. Varicoceles occur on the left in 80% of patients and bilaterally in 18%. The diagnosis is best made after the patient has been standing upright in a warm room for several minutes. Varicoceles have been reported in about 15% of the fertile male population and in 40% of infertile males. The pathophysiology of infertility in association with varicocele is unclear. Testicular arterial blood flow and temperature elevation with decreased Leydig cell function have been demonstrated and may affect the contralateral testis as well. Surgical correction (varicocelectomy) results in semen analysis improvement in 40-70% of patients. Pregnancy occurs in approximately 40% of couples within one year of treatment. Open surgical techniques using subinguinal, inguinal, or retroperitoneal incisions are employed with roughly s! imilar success. It is important to preserve the testicular artery and lymphatics. Laparoscopy confers no benefit when compared to the subinguinal microsurgical approach.
Azoospermia is defined as the absence of sperm in the ejaculate. If may be a "production" problem as in primary testicular failure, or an "obstruction" problem as in ejaculatory duct obstruction. If the problem arises from the failure of the testicles to make sperm, the semen volume is relatively unaffected. Clinical clues to this diagnosis include small testes. In most instances, testosterone production remains normal because the leydig cells (cells that make testosterone in the testis) are unaffected. If serum FSH (follicular stimulating hormone, a brain hormone produced by the pituitary gland) is elevated, the problem is within the seminiferous tubules of the testis and the pituitary is responding appropriately with a compensatory increase in its output of FSH. This condition is referred to as hypergonadotropic hypogonadism, the end result of multiple conditions that limit sperm production.
Less commonly, the FSH may be undetectable, indicating that a hypothalamic or pituitary anomaly is present in which there is an absence of testicular stimulation. This condition is called hypogonadotropic hypogonadism.
Infertility may be secondary to various genetic causes. Some of the genetic causes of infertility are listed below:
- Klinefelter's syndrome occurs in 1:500 live births. The karyotype reveals an extra X chromosome (47, XXY). Testes are small and firm. Gynecomastia may be present. Hormonal evaluation reveals elevated LH and FSH while T may be low.
- XX male syndrome is seen in 1:10,000 males and is the result of translocation of the sex-determining gene from the Y chromosome to either an autosome or one of the X chromosomes. Occasionally, there is an abnormality in one of the other genes that is involved in the testis-determination cascade. These patients are phenotypically male with absent spermatogenesis. They are missing the "spermatogenesis" genes located on the long arm of Y that are required for optimal spermatogenesis.
- DAZ gene cluster deletions are being found in approximately 13% of azoospermic men and in a lesser, but undefined, number of males with oligospermia. Testing is not yet clinically available on a routine basis. Other spermatogenesis genes are actively being searched for and will likely help explain the remainder of the azoospermic population for which there is presently no recognizable etiology.
- Bilateral mumps or viral orchitis, radiation, chemotherapy, and other toxic/inflammatory insults may temporarily or even permanently suppress spermatogenesis. A proper history will elicit these causes.
- Kallmann's syndrome is the consequence of failure of GnRH neurons to migrate from the olfactory area to the hypothalamus during fetal brain development. The problem has been linked to a genetic defect and falls under the category of hypogonadotrophic hypogonadism. Clinical findings include anosmia (inability to smell), infertility and deficient virilization.
Steroid abuse is an increasingly prominent cause of male factor infertility. Anabolic, androgenic steroid abuse suppresses pituitary LH release, leading to decreased intratesticular T production. The end result is severe oligospermia or azoospermia. Though the effects are thought to be reversible, long-term pituitary suppression has been reported. Extremely low, even undetectable FSH and LH levels in a well-virilized patient are the keys to diagnosis. Sperm development can also be affected by smoking cigarettes or marijuana or cocaine abuse. Extreme stress has also been known to cause male erectile dysfunction, and low sperm count.
Excessive Heat Exposure
Sperm production can be hindered by jacuzzis, saunas, and other things that raise the temperature of the testes. Optimal testicular temperature is 94Â°F. The scrotum, a sac that holds the testes, has the ability to move closer to the body, or farther away from the body, in order to regulate testicular temperature.
Genitourinary infections can cause scar tissue in the epididymis or seminal vesicles, which block the flow of sperm and/or semen. They can also stimulate a man's immune system to develop antibodies that mistakenly treat sperm cells as foreign bodies, and impede their ability to penetrate cervical mucous or the egg. Immunologic infertility may be suspected if there is considerable sperm clumping, or agglutination; poor or absent motility with relatively normal sperm density; an abnormal postcoital test result, an unexpected poor result in the hamster egg penetration test; or a history predisposing to the development of antisperm antibodies, e.g., vasectomy. The male's semen should be tested for antibodies against sperm using the techniques described above. Sexually transmitted diseases, and viral infections can also damage the testicles or block sperm progression through the reproductive tract.
Blockage of sperm transportation or semen (the fluid that includes sperm as well as secretions from the seminal vesicles, prostate, and periurethral glands) will result in obstructive azoospermia. Some types of mechanical obstruction (i.e. that of the epididymis or vas deferens near the testicles) may be amenable to reconstructive microsurgery. A combination of history, physical examination and laboratory results often point to an obstructive pathology and there is no need for a testis biopsy prior to definitive reconstruction. At this initial surgery, the level of obstruction is determined. Obviously, if the patient had a prior vasectomy, that will be the site of blockage. Microsurgical expertise is required to optimize the patient's chances for a successful outcome.
Partial obstruction of the ductal system may occur at the level of the ejaculatory ducts or epididymis. Surgical correction via transurethral resection of ejaculatory ducts or microsurgical reconstruction may lead to a normalization of semen parameters. Partial ejaculatory duct obstruction is suggested by a reduced semen volume and seminal deficiency out of proportion to what would be expected from history, physical examination, and hormonal evaluation. Transrectal sonography is ideal to confirm a suspected diagnosis.
The term oligoasthenoteratospermia refers to generalized abnormalities of sperm density, movement, and morphology or shape. The first step in the treatment of oligoasthenoteratospermia is identification and possible elimination of spermatotoxins. Repeat semen analysis should be performed two to three months after discontinuation of any identified toxic agents. Although clomiphene citrate, human chorionic gonadotropin (hCG), Tamoxifen citrate, oral Kallikrein, Pentoxiphylline, and Folinic acid have been used for medical treatment of oligoasthenoteratospermia, there are few double-blind placebo-controlled studies have been few and empiric therapy without a specific etiology and diagnosis is not likely to be successful.
Possible Treatment Options
Vasectomy reversal is carried out in those men who wish to restore their fertility potential. Postoperative patency rates are excellent but do depend upon the number of years since the vasectomy. The longer the duration, the more likely there has developed a secondary site of obstruction in the epididymis. Although some surgeons will always perform an anastomosis of one end of the vas to the other (vasovasostomy), others will move back to the epididymis if no sperm are found in the testicular end of the vas and create a vasal-epididymal tubule connection (vasoepididymostomy). This is done at a location where the epididymal tubule contains sperm, thus assuring that the anastomosis is proximal to any secondary obstructive site and that there is patency through the epididymal tubule from testis to that point. Pregnancy rates do not equal patency rates, as female factors, poor sperm activity, etc may dampen the chances of conceiving.
Microsurgical reconstruction of congenital or post-inflammatory occlusions almost always involve vasoepididymostomy. Patency and pregnancy rates depend upon the microsurgical experience of the surgeon as well as the level at which the anastomosis occurs. There appears to be little difference between the cauda and corpus of the epididymis vis-a-vis these rates but there is a definate diminishment in both when the anastomosis is to the caput region.
Microsurgical Epididymal Sperm Aspiration (MESA)
When reconstruction is not possible, microsurgical sperm aspiration is carried out. Microsurgical epididymal sperm aspiration (MESA) should also be considered at the time of reconstruction so that if the attempt does not lead to sperm in the ejaculate, at least there is a cryopreserved specimen that can be used as the sperm source for ICSI. Obviously, before extracting and freezing this vasal or epididymal sperm, the couple needs to have made the decision that they would indeed carry out an ICSI cycle with any cryopreserved sperm if that was their only option.
Assisted Reproductive Technologies
- Intrauterine Insemination (IUI) is often the first therapeutic step after all maneuvers to directly improve each partner has not led to pregnancy achievement. At the time of ovulation a semen specimen is processed to remove the seminal fluid and concentrate the sperm fraction, which is then placed, into the uterine cavity via a transcervical catheter. This delivers sperm to the upper reproductive tract, closer to the fallopian tubes where fertilization occurs. It is performed in an office setting without the need for anesthesia. The female partner may be regulated with oral medications to more precisely time ovulation. Parenteral medications may also be added to stimulate multiple follicular development and increase the chances of conception by increasing the number of oocytes released. If the semen parameters support the use of IU, it is traditionally the first adjunctive therapy that the couple uses. Appropriate couples will be successful in 15-20% of cases.
- In-Vitro Fertilization (IVF) involves incubation of harvested oocytes with processed spermatozoa in in-vitro culture. fertilized oocytes (embryos) are then either transferred to the uterine cavity using a transcervical catheter or cryopreserved if of adequate quality. The success of in-vitro fertilization depends on both oocyte and sperm quality. Fertilization rates are generally in the range of 60-70% with term delivery achieved in 15% of couples. IVF is recommended if sperm quality is adequate and the couple have failed a protocol of IUI. If sperm have been shown to lack fertilizing ability, or if they are expected to lack such capacity (sperm harvested from the epididymis,) or if they are too few sperm in the ejaculate to initiate IVF, then intracytoplasmic sperm injection (ICSI) is employed.
- Intracytoplasmic Sperm Injection (ICSI) utilizes delicate micromanipulation equipment to physically place an individual spermatozoa into the cytoplasm of a harvested oocyte. This procedure bypasses all mechanical fertilization barriers. It is particularly useful in situations of severe oligospermia and when the spermatozoa are functionally deficient.