THE WORK-UP OF AZOOSPERMIC MALES

Participants:

Dr. Ross MacMahon, Winnipeg
Dr. Keith Jarvi, Toronto
Dr. John Grantmyre, Halifax
Dr. Michael Carter, Kelowna
Dr. Gerald Brock, London

INTRODUCTION

The Canadian Urology Association created a guidelines committee to establish practice guidelines for its membership. The evolution of therapeutics and diagnostic testing for male infertility has evolved at a rapid rate over the past decade. In many cases, treatment options and diagnostic tests not available two or three years ago are now becoming the standard of practice. The guidelines committee proposed a consensus group with geographic representation across Canada allowing for diversity of experience and variation of current practice patterns.

Variation of opinion exists in the appropriate work-up and management of men with azoospermia depending on a number of key factors. The presence of an in vitro-fertilization program able to perform ICSI (intra-cytoplasmic sperm injection) and the availability of experienced healthcare workers (reproductive endocrinologists, geneticists, psychologists and others) is a major determinant of the current work-up. The financial resources of the presenting patient, coupled to the training and experience of the urologist are also important elements in determining the most appropriate management steps. In this report, we outline the major diagnostic categories, evaluation techniques and therapeutic options available to Canadian men with azoospermia in 1998.

This document should be viewed as a guideline based on consensus agreement of the authors. The standard of care for the work-up and management of azoospermia must be established locally, determined by local resources, personnel and other factors. Our objectives are to: provide a concise algorithm allowing for the diagnosis and treatment of azoospermia indicate the management steps where specialized testing or therapies may impact positively on fertility and identify consensus views on the most appropriate timing and indications for testes biopsy. The initial focus of management of the azoospermic male relies heavily on a thorough history. Attached to this document is an algorithm. We believe this is a useful tool providing a framework for the careful work-up of azoospermia. It should not be viewed, as totally inclusive and best results will be achieved when the management steps are individualized to the needs of the specific patient.

A detailed questionnaire, which provides important historical information, should be reviewed with the couple and present on the chart, forming an essential component of the diagnostic approach. The important elements of the history include previous surgery, history of cryptorchidism as a child or other inguinal surgery including herniorrhaphy, hydrocelectomy previous scrotal surgery such as vasectomy, varicocelectomy or spermatocele excision. The duration of infertility and history of previous pregnancies, history of medication uses, chemotherapeutic treatment or a history of cystic fibrosis, are all important. Description of a change in the ejaculate (volume and consistency), history of sexually transmitted diseases. General medical conditions such as diabetes, which may predispose to retrograde ejaculation, bladder neck surgery or genito-urinary trauma / mumps, should all be elicited from the history.

Physical examination should encompass a general physical examination directed towards the secondary male sexual characteristics and genitalia. Evaluation of male hair distribution, gynecomastia, evaluation of genitalia (palpation of the testicles for consistency, size and location) and presence or absence of vasa. It should also encompass palpation of the epididymis, evaluating for possible tenderness, spermatoceles and varicoceles on valsalva.

There exists no absolute standard hormonal screen, however most commonly a serum FSH and testosterone are requested to rule out hypogonadism. The need for genetic testing and karyotyping in men with testicular failure is most appropriate in those situations where the couple will be proceeding onto ICSI (this is currently a standard of practice). However interestingly, findings of Kleinfelters on karyotype, does not exclude the possibility of proceeding with ICSI. Thus, the utility of performing a karyotype is mainly in that it provides the physician and patient with greater information to assess risk.

The semen analysis evaluating bulk sperm parameters represents an important step in the evaluation of the azoospermic man. Two sperm analyses, obtained following a three day abstinence, should be done whenever possible. Should one semen analysis be significantly different from the other, a third specimen should be performed. The essential components of the consensus group are depicted on the attached algorithms and serve as a means of selecting the management arm within the algorithms.

Low semen volume is <1.5 cc. The finding of decreased ejaculate volume would prompt the search for a hormonal cause (lowered testosterone) or possibly retrograde ejaculation (testing post-ejaculate urine for sperm). Failure to demonstrate sperm within the urine (after attempting to contract the internal sphincter with an alpha agonist (Ornade TM) would prompt an evaluation for ejaculatory duct obstruction. Dilated ejaculatory ducts were felt by the panel to be >2 mm as detected by trans rectal ultrasound (TRUS).

The algorithm of patient management for azoospermia with normal ejaculate volume is presented in Fig.2. The work-up for the couple interested in proceeding to ICSI contrasts with the evaluation suggested for the infertile azoospermic male without access or resources to proceed to advanced reproductive technologies.

The indications for performing vasograms were felt by the panel to be very limited as this procedure may predispose to vasal stricture. In experienced hands it was felt that the TRUS ultrasound is reliable and provides a sensitive evaluation able to identify partial or complete ejaculatory duct obstruction, which would require subsequent therapy. A cut-off value of 2 mm was felt to be most sensitive and specific.

The presence of an inguinal scar noted at the time of reconstruction in which attempts at a saline vasogram or methylene blue dye fail to demonstrate patency remains an indication for a formal vasogram.

Testicular biopsy remains a controversial issue and is used in different ways in the armamentarium urn of the evaluation of the azoospermic man depending on regional resources. In those cases where IVF facilities are available a testicular biopsy can be indicated in men whose FSH level is greater than two times normal for detection of foci of spermatogenesis. In addition, variation exists within the ICSI community. Some urologists feel that biopsy of the testicle when a normal consistency and volume is present even in the presence of an elevated FSH, greater than two times normal, is not necessary and can be performed at the same time as ICSI. Alternatively, establishing the presence of sperm on biopsy before ICSI allows the physician to confidently assure the couple that in all likelihood sperm will be available at the time of the egg harvesting during the procedure. However it should be noted that a significant interval between diagnostic biopsy and sperm retrieval for ICSI may be necessary (4-12 weeks).

Where IVF and ICSI are not yet available, testicular biopsy is reserved for men with azoospermia and FSH levels within the normal range or less than two times the upper limit of normal. The objective of the procedure is to rule out obstructive azoospermia versus nonobstructive causes (sertoli cell only, hypospermatogenesis or spermatogenic arrest). In these cases, testicular biopsy performed unilaterally will provide the urologists with information about possibility of reconstruction. The need for bilateral testes biopsies is very limited. Should the testicles be asymmetrical in size, biopsy of the larger testicle is suggested.

TECHNIQUES

Ejaculatory duct resection remains a technique, which is infrequently used by most Canadian Urologists. The fertility literature describes strong evidence that incision or resection of the ejaculatory ducts is in wide spread in centers with great experience in infertility. The need to perform a vasogram was felt to be very limited. Transrectal-ultrasound demonstrating either ejaculatory duct cyst or ejaculatory duct dilatation very often are amenable to incision and resection. Use of simultaneous ultrasound to evaluate the depth of the incision is not uniformly used across Canada, but may be of value. A vasogram at the time of resection using methylene blue or other contrast material is of benefit in some cases. It is important that the urologist performing these procedures be aware of the possibility of complications and side effects secondary to the procedure.

VASOEPIDIDYMOSTOMY

Over the past decade dramatic improvement in the success rate obtained in men with azoospermia secondary to vaso-epididymal obstruction has occurred. Centers with extensive experience have demonstrated superior results with up to 75% of postoperative cases demonstrating sperm. This procedure is now considered as a standard option in reconstructive cases but may require 12-18 months of time for viable sperm to be seen on sperm analyses.