Andrology in the Nineties, 1997
The third edition of Andrology in the Nineties, an international symposium on male infertility, was held at the Jones Institute for Reproductive Medicine, Norfolk, Virginia, on March 13-14, 1997. The objective of the symposium was to present information on recent developments in the rapidly advancing field of human reproduction and male infertility. This two-day program was designed to provide general practitioners, gynecologists, urologists, reproductive endocrinologists, andrologists, technical personnel, medical students and residents with current information in the field of andrology.
The symposium covered the general areas of sperm interaction and fertilization, diagnostic methods for the evaluation of infertile men, and state-of-the-art medical, surgical and ART strategies currently used to treat male infertility. The symposium was preceded by a one-day, hands-on workshop on strict morphology directed by Professor Thinus Kruger (South Africa) and a simultaneous workshop on ICSI directed by Susan Lanzendorf (USA). The symposium directors were Susan Lanzendorf, Sergio Oehninger (USA), Willem Ombelet (Belgium) and Andre Van Steirteghem (Belgium). Excellent presentations and discussions ensured the success of the meeting which was attended by more than 120 participants from over 14 countries.
Ryuzo Yanagimachi (USA) discussed recent advances in the biology of fertilization. He also demonstrated the usefulness of different animal models for micromanipulation and the lessons to be learned from these models which can be applied to the human. Particularly important were his results using the mouse model. Normal fertile offspring were obtained by ICSI using not only mature (epididymal) spermatozoa, but also round spermatids as well as secondary spermatocytes. This suggests that general imprinting of male germ cells is completed prior to spermatogenesis. Examination of human sperm chromosomes after sperm injection into mouse oocytes revealed that human spermatozoa with abnormal head morphology have significantly higher incidence of chromosomal abnormalities than those with normal heads, yet the majority of abnormal spermatozoa have normal chromosomal constitutions. His findings suggested that the spermatozoa with aberrant morphology and/or motility are not necessarily genomically abnormal.
Patricia Saling (USA) discussed her elegant results on the expression of human recombinant ZP3 in COS cells. This product is active in competition binding assays, triggers acrosomal exocytosis and stimulates sperm protein tyrosine phosphorylation. Klaus Hinsch (Germany) discussed the mechanisms known thus far that trigger acrosomal exocytosis. He presented data in the bovine model suggesting the importance of AP3 derived synthetic peptides triggering acrosome reaction under capacitating conditions. John Aitken (UK) elegantly discussed the physiological regulators of sperm capacitation. He highlighted the fact that the induction of tyrosine phosphorylation appears to be an important component of capacitation that primes the cell in such a way that it can respond to the calcium transients induced by physiological agonists such as progesterone and ZP3 by undergoing the acrosome reaction.
David Page (USA) discussed the present status of the relationship between the Y chromosome and male infertility. Of particular interest were his results on the co-deletions of the Y chromosome that have been observed in 13% of men with nonobstructive azoospermia and in a smaller percentage of men with severe oligozoospermia. These deletions define a region in which should be found one or more genes required for spermatogenesis (and an Azoospermia Factor, AZF). These infertile men are otherwise healthy, suggesting that this AZF is a "pure male sterile" locus. The deletions encompass a string of very closely related genes, the DAZ (Deleted in AZoospermia) gene cluster, which is expressed specifically in spermatogonia and appears to encode an RNA binding protein.
Several diagnostic tests were discussed, including the present status of the general consensus on the use of strict criteria for sperm morphology (Thinus Kruger, South Africa). Mary Mahony (USA) discussed the present status of the clinical use of computer assisted semen analysis (CASA) and the need for further standardization for a more universal application of this method. She presented data in the nonhuman primate model for assessment of hyperactivated motility and the effects of cAMP-dependent cellular events involving primate capacitation and fertilization in vitro. Daniel Franken (South Africa) demonstrated the usefulness of sperm-zona pellucida binding tests (both the hemizona assay and the whole egg binding assay) and their high predictive value for fertilization under in vitro conditions. Dr. Franken discussed data on sperm zona penetration assay and the lack of uniformity in terms of the results of the zona free hamster egg penetration assay. Christopher De Jonge (USA) examined the significance of total quality management in the clinical andrology laboratory. Quality control essentially represents the mechanism of technique for ensuring the delivery of a quality protocol service and is only a subset of a much larger philosophy.
Sergio Oehninger (USA) discussed the current status of the clinical management of male infertility. He stressed that, following completion of a thorough history and physical examination as well as the appropriate endocrine and urologic work-up, extended by repeated semen analysis, a clinical diagnosis should be established. This should be followed by the development of an etiologic and a pathophysiologic diagnosis based upon the use of a sequential diagnostic scheme in order to detect specific sperm abnormalities. Presently, dysmorphic characteristics should lead toward disclosing different cellular disorders such as immaturity as well as identification of abnormalities at the molecular level including those of membrane components, intracellular signaling cascades, modulator and effector mechanisms of acrosomal exocytosis and hyperactivated motility, release of egg-activating factor, and chromosomal-genetic abnormalities and thier origin.
Gabor Huszar (USA) presented data on the identification of two objective biochemical markers of sperm maturation: (a) sperm creatine kinase concentration, and (b) spermiogenesis-related changes of CK-isoforms from the B-type to the M-type. He also presented data on the expression of plasma membrane receptors for hyaluronic acid and that sperm selectively bind to hyaluronic acid-coated beads as long as the sperm are viable.
Robert Aitken (U.K.) discussed medical strategies for the treatment of male infertility, stressing the fact that empirical administration of different medical treatments to patients with no demonstrable endocrinological disorder has no proven therapeutic value. He also discussed the potential use of antioxidants for treatment of oxidative stress. Marc Goldstein (USA) presented data on surgical treatment of male infertility, including varicocele corrective surgery and obstructive corrective surgery. He stressed the value of testicular sperm aspiration and microsurgical epididymal extraction combined with ICSI for cases with obstructive and nonobstructive azoospermia. Johannes Evers (The Netherlands) emphasized the need for controlled clinical trials in his lecture of evidence-based medicine in andrology. Willem Ombelet (Belgium) presented interesting data on the role of intrauterine insemination to treat subfertile men.
Andre Van Steirteghem (Belgium) discussed the latest results from his program using ICSI with ejaculated, epididymal and testicular sperm. He also presented the outcome of chromosomal studies performed on children born following ICSI. Thus far, the results indicate a slight increase in de novo mainly sex chromosomal aberrations, which is probably related to the characteristics of the infertile men treated. The percentage of major congenital malformations was within the expected range when compared to most registers of children born in the general population or after assisted reproduction. Martine Nijs (Belgium) presented her current experience with the use of spermatids (round and elongated) for ICSI. Clearly, this is a developing field that needs further experimentation. Susan Lanzendorf (USA) discussed the use of micromanipulation techniques in the clinical setting, including ICSI, assisted hatching and embryo biopsy.
Jacques Cohen (USA) examined the role of different experimental techniques in the areas of (a) single sperm cell freezing (using hamster and human empty zona pellucida) and (b) cytoplasmic transfusion in order to improve egg quality. Finally, Williams Gibbons (USA) and Suheil Muasher (USA) discussed state-of-the art techniques used during in vitro fertilization and embryo transfer procedures as well as preimplantation genetic diagnosis.
Following lectures by the leading researchers and clinicians, a large part of the meeting was devoted to discussion. Abstracts from these lectures and other submitted papers are available in a syllabus published for the symposium. These may be obtained by contacting Sheila Robinson, fax (757) 446-8998.
Sergio Oehninger, USA