INCIDENCE OF MALE FACTOR INFERTILITY
About 15% of all married couples experience reproductive difficulty. The male factor is at least partly responsible in about 50% of infertile couples.
Spontaneous conception rates during evaluation may be as high as 25% in those that have not received any treatment at all. There are many pre-testicular, testicular and post-testicular causes of male factor infertility. Some are treatable causes, whereas others may be potentially treatable; but many remain untreatable.
A cornerstone in male factor infertility evaluation is the semen analysis.
- Semen is regarded as abnormal if any of the following is present:
- Volume is less than 1.5 ml or greater than 5 ml.
- Sperm concentration is less than 20 x 106 per ml.
- Total sperm number is fewer than 50 million.
- Sperm motility is less than 50%.
- Forward progression and quality are graded below 2 (1-4).
- Sperm morphology reveals less than 30% of oval forms.
During the evaluation, appropriate timing of intercourse with the aid of ovulation kits (which are readily available from your drug store) can be helpful. In addition to the use of the ovulation kit, the understanding of the ovulatory cycle (including sexual habits and frequency of intercourse) can be discussed.
Work-related stresses and marital difficulties can result in decreased libido and decreased coital frequency. Optimal timing of intercourse is approximately 48 hours prior to the time of the ovulatory peak.
Lubricants and jellies as well as saliva may cause deterioration of sperm motility. Regular sauna or hot tub use may also impair sperm production by elevating scrotal and testicular temperature. Similarly, cigarette smoking, marijuana and alcohol may reduce the number of normal sperm, density and motility. Infections such as the mumps virus or sexually transmitted organisms such as Chlamydia may be implicated in infertility. In general, though, asymptomatic genital infections are not an important cause of male infertility.
Various occupational and environmental factors as well as therapeutic agents have been implicated in infertility.
It is also important to remember that spermatogenesis takes about 74 days from initiation to development of mature spermatozoa, and therefore evaluation of treatment and its effect on the ejaculate takes at least 3 months.
1. Empiric therapy.
About 40% of infertile males fall into this category of unexplained infertility.
A. Clomiphene citrate.
This is a synthetic nonsteroidal anti-estrogen which increases FSH and LH through blocking feedback inhibition on the pituitary. Clomiphene may be given 12.5 to 50 mg per day and may be given continuously or on a 25-day cycle with a 5-day rest period each month.
Controversy still exists as to whether this medication is helpful or not. It is certainly not helpful in those with elevated baseline serum FSH levels, severely diminished sperm counts or those with no sperm. In addition, a small percentage of men will actually experience a decline in sperm density and motility while taking this medication.
B. Androgen therapy.
In general, several large prospective randomized placebo-controlled studies have not shown any significant beneficial effect from the use of oral testosterone-type medications.
C. Testosterone rebound therapy.
This form of treatment may also result in the opposite effect with persistently decreased sperm numbers. However, this treatment may have a place in those with very low sperm counts (less than .1 million per cc) and consists of administering I.M. testosterone 250 mg every 1-2 weeks until no sperm is identified in the ejaculate. This may take about 5 months. At this time, the testosterone administration is stopped while awaiting the testosterone rebound and sperm production, which can take about 3-6 months from the time the testosterone injections are stopped.
FSH treatment in oligospermic men who have had previous IVF fertilization failure may result in an improvement of sperm function without obvious change in numbers.
E. Prostaglandin inhibitors.
Prostaglandin inhibitors, such as Indomethacin, may increase sperm density and motility in sub-fertile men with elevated seminal levels of prostaglandins.
Certain antioxidants such as glutathione, when administered to oligospermic sub-fertile males, may improve sperm motility and morphology.
The validity of the use of various vitamins such as C and E and the Chinese herbal medicine (TJ-7) have been touted for many years in the treatment of sub-fertility in men, but their usefulness has not been established. Others have suggested dietary supplements using carnitine, as in Proxeed. However, these vitamins and supplements are inexpensive and relatively innocuous.
2. Treatment of Infection.
Treatment of symptomatic infections is appropriate. The treatment of asymptomatic infections found on routine semen culture is controversial.
3. Immunologic Infertility and Sperm Antibodies.
In general, the use of steroid therapy to reduce the production of sperm antibodies is not helpful or useful.
4. Treatment of Retrograde Ejaculation.
This problem can be found in those who have had retroperitoneal lymph node dissection, diabetic neuropathy, spinal cord injury, or previous bladder neck surgery. Certain medications may also compromise antegrade ejaculation.
If retrograde ejaculation persists, patients are given oral bicarbonate to alkalinize bladder urine to allow sperm ejaculated into the bladder to survive. The sperm retrieved with a catheter and bladder washout after ejaculation may then be artificially inseminated.
Antegrade ejaculation may be established after a period of days with one of several medications, including Phenylpropanolamine 75 mg twice daily for two weeks, Ephedrine 50 mg four times a day for two weeks, Sudafed 60 mg four times daily for 6 weeks or Tofranil 25 mg three times a day for two weeks.
Electro-ejaculation may be necessary in those who have had ejaculatory problems resulting from the conditions listed above, including transverse myelitis, multiple sclerosis and such. The ejaculation is stimulated through a rectal probe which delivers an electric current. In many patients, an ejaculate can be produced but the sperm motility rarely exceeds 10-20%, and additional treatments may be necessary.
Varicocelectomy or ligation of the varicosed gonadal veins, usually on the left side only and far less commonly on both sides, appears to have a beneficial effect on sperm density. Patients who have oligospermia, decreased motility and an increase in tapered forms may see a better improvement in their semen parameters after varicocele ligation.
This procedure may have more effect in increasing sperm numbers from 10 million per ml but is not likely to improve those who have counts of 40 million per ml or higher. The operation improves semen quality in approximately 66% of men and doubles the chance of conception. The benefits of interrupting these internal spermatic veins are in controlling venous reflux to the testicle and its apparent but not proven deleterious effects.
The operation is usually performed under a general anesthetic in an outpatient setting and is usually done through an inguinal, retroperitoneal or laparoscopic approach.
Patients with recurrent varicoceles after previous surgery with residual abnormal semen parameters may benefit from a percutaneous or radiologic technique to obliterate the spermatic veins using coils, balloons or sclerosing agents.
Many men who have had a vasectomy and subsequently remarry may seek to become fertile again through a vasectomy reversal. In general, the best results are achieved in those where the vasectomy was performed less than 10 years prior to the vas reversal. The technical success as measured with sperm in the ejaculate is on the order of 90+%, and the pregnancy rate is on the order of 40%.
This procedure is usually performed using the operating microscope in an outpatient setting. Most insurance companies, however, will not pay for this procedure. (See Vasectomy Reversal section.)
Obstruction of the epididymal tubule may necessitate microsurgery to allow a direct microtubular anastomosis between the epididymal tubule and the vas. This anastomosis should be placed as low on the epididymis as possible, as spermatozoa gain maturation and an increased capacity for motility as they move from the head to the tail of the epididymis.
Transurethral Resection (TUR) of the Ejaculatory Duct
Transurethral resection, by resecting the distal ducts in the floor of the prostatic urethra lateral to the verumontanum, can be done endoscopically. Candidates for this procedure are men with azoospermia, normal sized testes, normal testicular biopsy, and transrectal ultrasonography (or vasography) showing dilated ejaculatory ducts suggesting obstruction.
Microsurgically aspirated sperm from the epididymis usually combined with in vitro fertilization has been done using open and percutaneous techniques.
Assisted Reproductive Techniques
A. Semen Processing.
The goal of the processing is to gain a sample of concentrated, highly motile sperm in a small volume. Processing methods vary from dilution and centrifugation followed by re-suspension to more elaborate methods of sperm processing, including swim-up procedures, centrifugation through Percoll density gradients, and sperm migration through columns of various compounds, gels or glass beads. In addition, compounds such as Pentoxifylline may enhance sperm motility and improve fertilization.
B. Intrauterine Insemination (IUI).
IUI for male factor infertility is still controversial but may be very effective in bypassing the cervix and bringing about conception.
C. In Vitro Fertilization (IVF).
In IVF, women are stimulated hormonally to induce multiple follicles that are monitored by ultrasound. HCG is then used to cause oocyte maturation, and then these eggs are retrieved transabdominally or transvaginally. Concurrently, semen is collected from the male partner and processed. The processed semen and eggs are then placed in inseminating dishes and then transferred into the uterine cavity 24-48 hours later.
D. Gamete Intrafallopian Tube Transfer (GIFT).
In this technique, fertilization is allowed to occur in vitro by retrieving eggs laparoscopically, mixing the eggs with sperm, and then injecting the egg-sperm mixture into the fallopian tube. Ectopic pregnancy rates in IVF and GIFT procedures are similar at about 5%. Alternative techniques involve the in vitro fertilization of human eggs followed by transfer of the early stage human embryo into the fallopian tube.
This encompasses several techniques designed to overcome the sub-fertile male’s spermatozoa’s inability to breach the zona pellucida of the egg.
A. Intracytoplasmic Sperm Injection (ICSI). A micropipette is used under a microscope to inject sperm deep into the egg cytoplasm.
B. Alternative methods of micromanipulation have had low success rates.