MEDICAL & SURGICAL TREATMENT OF MALE INFERTILITY by Dr Peter H C Lim Senior Consultant & Head Division of Urology Toa Payoh Hospital SINGAPORE 1129. TESTICULAR BIOPSY: _________________ The indications are azoospermia or severe oligospermia. In the azoospermic, the intention is to differentiate obstruction versus maturation arrest or the occasional patient with "normal FSH germ cell aplasia". The oligospermic patient with at least one normal size testis & normal gonadotropins should have biopsy to exclude incomplete obstruction. In the testis with partial obstruction of the epididymis or vas deferens, the number of spermatids per round tubule can be counted & correlated with the patient's known sperm count. VASOGRAPHY: __________ This is required to delineate excurrent ductal obstruction. It should be reserved for the time of the surgical correction of the obstruction. This can be achieved using contrast medium & Xrays (50:50 mixture of Renografin-60 & saline) or Methylene Blue injection in which case a blue colored urine signifies patency of the vas. No attempt must be made to fill the epididymis with contrast. Careful inspection of the epididymis using optical magnification & tubule fluid sampling is the best method to identify obstruction at the epididymis. VARICOCELE LIGATION: ___________________ Approximately one third to half of men with varicoceles may have some impairment of their fertility. Semen abnormalities in men with varicoceles may demonstrate an increase in abnormal forms, lower motility & sperm concentration & the classic "Stress pattern" is not always found. Not all men with varicoceles require ligation, even if they are requesting fertility evaluation. Careful scrutiny of the Patient, evaluation of multiple semen analyses & a thorough gynecologic evaluation of the patient's partner is mandatory prior to the decision to ligate. Surgical correction entails careful isolation & ligation of the larger spermatic veins as well as their smaller tributaries via a retroperitoneal, inguinal or subinguinal approach. It is important to preserve the testicular artery & lymphatics. Where the radiologic expertise is available, percutaneous ballon embolisation or the use of coils, hot contrast & various sclerosing agents delivered the same way are giving results similar to formal surgery. Results of varicocele ligation generally show distinct improvement of semen parameters in approx. 50-70% of men with most papers reporting 30-45 % pregnany rates. VASOVASOSTOMY: _____________ Various techniques have been described to establish continuity of the vas deferens. Stented & Non-stented, Macrosurgical & Microsurgical methods of approximating the vas have been proposed with success rates ranging from 30- 100%. In the past 10-15 yrs it has become apparent that microsurgical vasovasostomy, whether 1 or 2 layeredappears to hold a higher success rate than other methods described. In all methods however, technical success is directly related to a)accurate approximation of mucosal edges of the vas lumen, b)preservation of the perivasal adventitia & associated blood supply & c)lack of tension at the site of anastomosis. VASOEPIDIDYMOSTOMY: __________________ The various surgical techniques are based either on Martin's fistula formation or Silber's tubule to tubule microsurgical anastomosis. Silber's method or a modification thereof is the currently accepted mode with the best results because of the direct vaso-epididymal anastomosis end to end or end to side. TUR OR INCISION OF EJACULATORY DUCTS: ____________________________________ Obstruction of the ejaculatory ducts can be due to inflammatory, iatrogenic or congenital causes. Patients have a small semen volume with an acid pH. Semen fructose will be low or absent. He will have normal size testes & a "full feeling" epididymis & vas deferens. An incision carefully performed into the floor of the prostate cures. SPERM ASPIRATION & IVF: ______________________ Although this can be done for patients with bilateral congenital absence of the vas, only a 2% pregnancy rate has been reported due to the sperm being of poorer quality. New research which allows for fewer sperms(& the better ones obtained by separation techniques) may permit easier sperm penetration into eggs whose outer shells have been modified. ARTIFICIAL SPERMATOCELES: ________________________ This technique has the potential of multiple aspirations thus permitting more sperms to be obtained. I am using the Robertson(British) type in S'pore. Wagenknecht producced a silicone prosthesis like the British type used successfully in bulls. Kelami & Jimenaz-Cruz both developed their type of spermatocele & the latter reported a pregnancy in 1980. We are currently investigating the appropriate milieu to place within the spermatocele which will allow sperm to retain their viability without causing early capacitation which lessens their effective functional lifespan. Review of the world experience showed 7 pregnancies in 91 patients with 130 spermatoceles. Conception by insemination only occurred when motility of the sperm was greater than 20%. MEDICAL TREATMENT FOR MALE INFERTILITY TREATMENT FOR IDIOPATHIC INFERTILITY: ____________________________________ Male infertility has multiple causes & similarly has varying treatments. Approximately 25% of infertile male patients are classified as having idiopathic infertility. In these patients, no physical or biochemical abnormalities can be identified. The infertility is attributed to either an abnormal semen analysis or an abnormal result of the zona free hamster ova penetration assay which cannot be explained by other medical causes. Although many regimens are available, none constitute clearly effective therapy & can be divided into distinct groups. Pharmacologic treatment hopes to improve semen quality. Post-ejaculate sperm processing attempts to improve the fertility potential of inadequate semen samples. Lastly, IVF & GIFT , which may be combined with semen processing, may allow for conception with subnormal semen samples. Pregnancy rates for simple IUI for male factor infertility range from 7%-55% with a mean of 22%. The results of IVF for male factor infertility are significantly lower than that of the general IVF population. However, once fertilisation has been obtained, the results are nearly similar ie. 28% implantation with 20% term pregnancies. Since Prof C Chen will discuss the Reproductive Assisting Techniques & the newer Programs, the rest of my presentation on medical treatment will be on Pharmacologic Treatment. Antiestrogen Therapy: These block sex hormones from inhibiting FSH & LH in the brain. It results in increased release of LH & FSH, which in turn stimulates testosterone production. The rationale is that the increased testosterone improves spermatogenesis. Clomiphene citrate improves sperm density in 4-89% and improved motility in 0-70% of patients. Pregnancy rates are reported as 30% or less. Tamoxifen is another antiestrogen which may improve sperm concentration but there is usually no change in motility. HCG and HMG: HCG is given empirically to patients with defects in sperm count or motility to correct a presumed intratesticular deficiency of testosterone. Improved semen analysis occurs in 34-90% of patients with pregnancy rates of 0-41%. Some patients actually experience a depression of sperm count due to increased estrogen production by the testes. HMG has approx. equal LH & FSH activity but its use has produced increased sperm counts in about 50% of cases with conception rates between 0-17% only. Whether one adds FSH to HCG regimes or give HCG & HMG together as combination therapy does not appear to improve these results any better. GnRH: GnRH is secreted by the brain in a pulsatile fashion approximately every 90 min. A computerised pump is used to deliver this. It is expensive & results so far may not justify its great cost. Testosterone Rebound: After 10 or more weeks of therapy, loss of sperm production may be demonstrated. Upon cessation of treatment, sperm concentration usually returns to pretreatment levels over a 3-4 month period and improved sperm counts in 20-70% of patients with pregnancy rates of 9-43%. Kallikrein: This can improve sperm motility in 50% cases with increases in sperm concentration in a minority. Agents of doubtful use: Phosphodiesterase Inhibitors eg. pentoxifylline, Aminoacids eg. Arginine, vitamins eg.Vit C , or Vit E, minerals eg Zinc. Antiprostaglandins: With 75mg/day of indomethacin or ketoprofen a significant increase in sperm count & motility with a 35% pregnancy rate was noted. This is relatively nontoxic form of therapy to counter the inhibitory effect of prostaglandins on spermatogenesis & sperm motility. SPECIFIC MEDICAL THERAPY: ________________________ Endocrine Disorders: Hypogonadotrophic hypogonadism will respond to gonadotropin replacement therapy eg. HCG/HMG or GnRH administration. Bromocriptin will counter the deleterious effect of raised prolactin levels. Congenital adrenal hyperplasia will respond to exogenous steroid replacement. Thyroid disorders eg. hypo or hyperthyroidism should be treated with thyroxine in the former or propranolol in the latter. Ejaculatory Disorders: Retrograde ejaculation can be treated with pseudoehedrine, imipramine or instructions to ejaculate with a full bladder. A bladder wash procedure with recovery with catheterisation may be necessary in intractable cases. Failure of emission eg in the paraplegic, is besy treated by Electroejaculation & we are currently doing this for our S'pore Paraplegics. Infection: Antibiotic therapy eg. Tetracyclines, Doxycycline should be reserved for men with positive cultures or documented pyospermia as sperm motility & viability are adversely affected by genital tract infection. Immunologic Disorders: Treatment for confirmed presence of antisperm antibodies with methylprednisolone gives pregnancy rates of 6-56%. Because of the potential risks with steroid therapy, artificial insemination with sperm washing, protease digestion of bound sperm antibodies IVF have been offered as alternative methods albeit less effective.