Update On Clinical Andrology
Volume 1 Issue 1 Winter 1993

A Newsletter addressing contemporary issues in male fertility and male sexual function

Editor:
BRUCE R. GILBERT,M.D.,PH.D.
Associate Professor of Urology - Cornell University Medical College
Associate Professor of Urology - SUNY at Stony Brook
Diplomate American Board of Urology
Diplomate American Board of Bioanalysis
Fellow American College of Surgeons
email: bruce.gilbert@verizon.net

INSIDE THIS ISSUE
Fertility in the Azoospermic Patient
Imaging
The No-Scalpel Vasectomy
Pharmacologic Erections
Late Breaking News:
A majority of men with Peyronie's disease were found to have "venous leak"
Imaging of the seminal vesicles and ejaculatory ducts yields diagnoses
Fertility in the Azoospermic Patient
Microsurgical sperm retrieval and microinsemination techniques change the way we define sterility

Azoospermia (the absence of sperm in a normal ejaculate) with normal testicular production of sperm (demonstrated by testicular biopsy) is present in up to 5% of men with primary subfertility. If we include men with known obstruction of the reproductive tract not amenable to surgical reconstruction then we might be dealing with as many as 15% of all men with either primary or secondary subfertility. This later group includes men who have suffered trauma or persistent infection of the genital tract not responsive to antibiotics, or men who have had failed attempted reconstruction as well as men with a congenital (present since birth) absence of the vas deferens (the tube that carries sperm from the testis to the penis) .

In the postpubertal male, sperm mature along the seminiferous tubules over a 70 to 80 day period. Sperm then enter the rete testis and efferent ductules prior to undergoing further maturation in the epididymis (Figure 1). It is in the epididymis that sperm motility usually begins. However, in men with congenital absence of the vas deferens, or obstruction of the vas deferens or epididymis, motile sperm are found in the rete testis and efferent ductules. It is at this point that sperm can be retrieved for use in IVF.

Epididymal retrieval of sperm is usually done for men after thorough evaluation by a Urologist with expertise in male factor subfertility. This would include a detailed history and physical examination and oftentimes a transrectal ultrasound of the prostate together with at least two semen analyses (each with a post ejaculate urine) performed by an andrologic laboratory. If hormonal studies (testosterone, FSH,LH,prolactin, estradiol) are not grossly abnormal, a bilateral testis biopsy is done to document sperm production by the testis prior to scheduling epididymal sperm retrieval together with oocyte retrieval for IVF.

Up until 1989 only anecdotal cases had been reported in which pregnancy resulted with the use of epididymal sperm. Since 1989 several groups have successfully retrieved sperm from the epididymis of azoospermic men for use in IVF.

The following represents our results at The New York Hospital-Cornell Medical Center. It should be emphasized that these results required a coordinated effort between the urologic microsurgeon, the reproductive endocrinologist and the embryologist. It is primarily the embryologist whose expertise in sperm processing and egg micromanipulation makes this possible.

This series involved 24 couples who underwent microsurgical retrieval of sperm from the epididymis in conjunction with IVF. Seventeen men had un-reconstructible vasal obstruction due to congenital absence of the vas deferens while seven had multiple failed vasoepididymostomy procedures. Sperm were retrieved in 26 cycles on 24 patients. An adequate number oocytes were retrieved in 23 cycles. Sperm quantity was acceptable in all cases but sperm quality was poor with a median sperm motility of 10% and mean normal sperm morphology of 6% by strict criteria. 41 of the 285 oocytes retrieved (14%) had monospermic fertilization. 7% with standard fertilization, 4% with partial zona dissection (PZD) and 3% by subzonal insertion (SZI).

57% of the 23 cycles (13/23) had fertilization and embryo transfer with 46% of these (6/13) achieving an ongoing pregnancy. Two pregnancies are still ongoing, one miscarried with 6 healthy children delivered (triplet, twin and singleton). The bottom line......6 of the 24 couples (25%), in which the man was azoospermic, achieved a pregnancy.

Costs for the procedure include the routine costs for IVF as well as an additional fee for microinsemination. These usually total $8,000 to $10,000.... Urologic fees are dependent upon whether a unilateral or bilateral procedure is performed. These range between $4,000 and $6,000. Urologic fees are oftentimes well reimbursed by many insurance companies.

Subfertility is, as we now know, a couples' dilemma. One third of the time there is primarily a female factor, one third of the time there is primarily a male factor and one third of the time there are combined factors. With increased sophistication of IVF technology and our knowledge of sperm development we continue to improve our ability to effectively treat male factor problems. Microinsemination requires as few as three viable sperm per oocyte. Thus severe alterations in sperm quantity or quality will not necessarily prevent couples from having a biologic child. This underscores the need for a thorough evaluation of both partners prior to embarking on therapy .
Imaging
Transrectal and scrotal ultrasonography become state-of-the-art in evaluation of the subfertile male

Ultrasonography is rapidly becoming the "genitourinary stethoscope." In male factor subfertility the ability to evaluate the paratesticular structures, the region of the ejaculatory ducts and retroperitoneum has made possible the diagnosis of various pathologies previously only able to be diagnosed by invasive procedures. For example, the presence of utricular or ejaculatory duct cysts and/or seminal vesicle obstruction can be readily visualized by transrectal ultrasound (Figure 3). This would allow transurethral resection to be performed without the need for a formal vasotomy and vasogram. In addition, the identification of epididymal obstruction, documentation of varicoceles both before and after repair, evaluation of testicular parenchyma in the presence of a hydrocele and accurate measurement of testicular size aid greatly in our understanding of the pathology which, in turn, allows a more precise therapeutic intervention.

Scrotal Ultrasound Examination
Ultrasound scanning of the scrotum has continued to be a mainstay in the evaluation of both acute as well as chronic scrotal lesions. Through the use of high resolution and high frequency (7.5 to 10 MHz) images, both testicular as well as paratesticular structures can be evaluated. In the evaluation of the subfertile male, testicular size can be objectively assessed and followed through therapy. Also the presence (and resolution) of varicoceles can be documented. Other uses of scrotal ultrasonography include; evaluation of scrotal masses (testicular versus extratesticular, cystic versus solid), evaluation of hydrocele, evaluation of the acute scrotum (particularly color flow doppler) and evaluation of the traumatized scrotum.

Indications for scrotal ultrasound in male factor subfertility include:
1) palpable epididymal or testicular mass
2) testicular pain
3) thickened scrotal skin - making clinical exam difficult or imprecise
4) significant titers of antisperm antibody
Scrotal ultrasound is also useful in measuring the size of the testes as well as documenting the resolution of varicoceles post operatively. With the increased incidence of carcinoma-in-situ found in the subfertile male, scrotal ultrasound can also provide documentation of the intratesticular echogenicity. This is particularly important in subfertile men with atrophic testis.

Transrectal Ultrasound Examination (TRUS)
The use of high resolution and high frequency (5-10 MHz) transducers has allowed superb imaging of the prostate, seminal vesicles and ejaculatory ducts. The advantages of TRUS over other imaging modalities ( CT scan, MRI, vasography) include better resolution, rapid evaluation, it's relatively non-invasive nature and lower cost. In evaluating the subfertile male TRUS has become increasingly important as a part of the office evaluation.

Indications for TRUS in evaluating the subfertile male include:
1) Azoospermia
2) Abnormal digital rectal
examination
3) Retrograde ejaculation
4) Suspicion of partial obstruction ( volume 1.5cc, motility 10% or a forward progression 2 (3 to 4 is normal ), less than 20% normal forms, pyospermia or hematospermia).
5) Hematospermia or Pyospermia

In the azoospermic patient, seminal vesicle and ejaculatory duct obstruction can be documented .
In the patient with a low ejaculate volume, partial obstruction of the ejaculatory duct can be diagnosed as well as abnormalities of the seminal vesicles.
Also in patients with pyospermia, the characteristic findings associated with acute and chronic prostatic infections can be assessed.
Figure 3 - 30 yo with a low volume ejaculate. TRUS demonstrated an obstructing utricular cyst.
The No-Scalpel Vasectomy
a simple, in office procedure for male contraception

Vasectomy has become a popular form of contraception. More than 500,000 men in the United States choose vasectomy each year. It is also known to be one of the safest and most effective means of permanent birth control.

Vasectomy is a surgical procedure that interrupts the normal passage of sperm. In this procedure the vas deferens, the tubes that carry sperm from the testicle to the ejaculatory ducts, are severed and the open ends are blocked.

The No-Scalpel Vasectomy is an even safer and less invasive procedure that shortens the time to recovery and reduces the already low complication rate of this procedure. Developed in China in 1974, it differs from conventional vasectomy in how local anesthesia is given and how the two vas deferens are secured. Worldwide, more than 15 million men have successfully had this procedure.

The No-Scalpel Vasectomy uses an innovative technique to anesthetize the scrotum and vas deferens. The vas deferens is gently isolated by the physician and held just beneath the scrotal skin by a specially designed instrument which holds the vas deferens firmly without pinching. Without a scalpel, a single small opening is made through the skin and the vas deferens is delivered through this opening. A small length of vas deferens is removed and the open ends sealed in a conventional fashion. The tiny hole in the scrotal skin heals without sutures.
Pharmacologic Erections
A combination of well known agents taps the benefits of each without their adverse side effects
A penile erection results when the nerves to the erectile tissue of the penis are stimulated to release certain chemical substances called neurotransmitters. These substances initiate both an increase in arterial blood inflow to the erectile tissue and a decrease in blood drainage from the erectile tissue. When the pressure within this erectile tissue is sufficiently increased the penis is then adequately rigid for successful penetration and intercourse.
Although we have yet to isolate the specific neuro-transmitter(s), diligent researchers have demonstrated that a penile erection rigid enough for sexual intercourse may result following the injection of a small amount of a drug or drug combination into the erectile tissue of the penis. The action of these drugs in the erectile tissue mimics those of the natural neurotransmitter(s), hence enabling many impotent patients to resume their normal sexual activity.This treatment for impotence is a rational option for patients who suffer from erectile dysfunction on the basis of physical cause(s). This is especially true in two types of organic impotence: (1) neurologic impotence and (2) mild vasculogenic impotences. Thus this treatment may be used as an alternative or deferral to the more traditional treatment of penile prosthetic devices.
Potential candidates for pharmacologic erection treatment require careful evaluation. This includes a thorough history physical examination, nocturnal penile tumescence studies, as well as endocrine and penile vascular studies. The patient must also receive a full explanation of the treatment process; including a detailed description of the genital anatomy, physiology, action of drugs to be used, and the self-injection technique. At this time, the patient is informed about potential complications of the treatment. Most candidates eligible for pharmacologic erection have documented evidence of organic impotence; however, under certain considerations, some patients with impotence secondary to performance anxiety may also be considered for pharmacotherapy.
Papaverine alone as well as in combination with Phentolamine or Prostaglandin E1 alone had been the main pharmacologic agents used. Fibrosis of the corporal bodies has been noted with long term use of papaverine while penile discomfort after injection has been found in up to 30% of patients after injection with prostaglandin E1. These side effects have resulted in many investigators trying various combinations in an attempt to maximize the response and minimize the side effects. Currently, a tri-mix appears to extremely effective and well tolerated. The tri-mix is a combination of Papaverine, Phentolamine and Prostaglandin E1. In 0.2 cc of this mixture ( a usual dose) there is 3.52 mg of Papaverine, 0.12 mg of Phentolamine and 1.18 mcg of Prostaglandin E1.

Late Breaking News:

A majority of men with Peyronie's disease were found to have "venous leak"

95 men with peyronie's disease underwent vascular study by duplex sonography. A subgroup of 25 men underwent cavernosometry/cavernosography (DICC) in addition (6 potent, 19 impotent). 59% of men with Peyronie's disease were found to have evidence of veno-occlusive disease while only 36% had evidence of arterial disease. All impotent men with normal cavernosal arteries were found to have veno-occlusive dysfunction. Lopez & Jarow;J.Urol, 149:53,1993.

Imaging of the seminal vesicles and ejaculatory ducts yields diagnoses

15 of 26 of men (58%) presenting with either hematospermia, hypospermia, oligospermia or painful ejaculation were found to have ejaculatory duct or seminal vessicle abnormalities by MR imaging with an endorectal surface coil. These abnormalities included mullerian cysts (4 cases), wolffian cysts (3 cases), anaplastic prostatic ca (1 case), and the remainder had either ejaculatory duct obstruction or seminal vesiculitis. Schnall et al; AJR, 159:337, 1992.