GUIDELINES

ON INFERTILITY

G. M. Colpi, T. B. Hargreave, G. K. Papp, J. M. Pomerol, W. Weidner.

TABLE OF CONTENTS PAGE

INTRODUCTION 5

1. ANDROLOGICAL INVESTIGATIONS AND SPERMATOLOGY 5

1. Ejaculate analysis 5

2. Advanced diagnostic spermatological tests 5

3. Andrological status 5

4. References 5

2. GENETIC DISORDERS IN INFERTILITY 6

1. Chromosomal abnormalities 6

2. Sperm chromosomal abnormalities 6

3. Sex chromosome abnormalities 6

4. Autosomal abnormalities 6

5. Genetic defects 7

6. Cystic fibrosis mutations and male infertility 10

7. Unilateral or bilateral absence or abnormalilty of the vas and renal anomalies 11

8. Unknown genetic disorders 11

9. Genetic counselling and ICSI 11

10. Conclusions 11

11. References 11

3. PRIMARY SPERMATOGENIC FAILURE 14

3.1 Definition 14

2. Aetiology 15

3. Testicular morphology 15

4. Biopsy techniques 18

5. Treatment 18

6. TESE techniques 19

7. ICSI with cryopreserved testicular spermatozoa 19

8. TESA and ICSI in Klinefelter's syndrome 20

9. Testicular spermatid injection in combination with ICSI 20

10. Conclusions 20

11. References 20

4. OBSTRUCTIVE AZOOSPERMIA 24

1. Definition 24

2. Classification 24

3. Diagnostic management 25

4. Treatment 26

5. Conclusions 28

6. References 28

5. VASECTOMY AND VASECTOMY REVERSAL 30

1. Conclusion 30

2. Vasectomy reversal 30

3. References 31

6. SPECIAL PROBLEMS IN THE TREATMENT OF MALE INFERTILITY 32

6.1 Varicocele 32

1. Introduction 32

2. Classification 32

3. Diagnosis 32

4. Basic considerations 32

5. Treatment 33

6. Conclusions 34

7. Recommendations 34

8. References 34

6.2 Hypogonadism 36

1. Introduction 36

2. Hypogonadotrophic hypogonadism 36

3. Hypergonadotrophic hypogonadism 36

4. Conclusion 37

5. References 37 6.3 Cryptochidism 37

1. Impact on fertility 37

2. References 38

7. IDIOPATHIC OLIGOASTHENOTERATOZOOSPERMIA 38

1. Introduction 38

2. Diagnosis 38

3. Treatment 38

4. Conclusions 41

5. References 41

8. UROGENITAL INFECTIONS AND DISTURBED MALE FERTILITY 42

8.1 Urethritis and prostatitis 42

1. Introduction 42

2. Urethritis 42

3. Prostatitis 43

4. Therapy 45

5. Conclusions 46

6. References 46

8.2 Orchitis and epididymitis 48

1. Orchitis 48

2. Epididymitis 49

3. References 50

9. DISORDERS OF EJACULATION 51

1. Definition 51

2. Classification and aetiology 51

3. Diagnosis 53

4. Treatment 54

5. Conclusions 56

6. References 56

10. ABBREVIATIONS USED IN THE TEXT 57

Introduction

The following guidelines are aimed at providing a consensus view on special topics in urological andrology, which seem to the EAU Infertility Group to be key points in the daily work of urologists dealing with infertility. These topics reflect our literature review and rating, debates of the pros and cons, and final recommendations of our expert group, with special focus on the different national views and clinical practice in European countries.

The group is aware of the fact that infertility in particular has to be discussed as an original interdisciplinary subject, with paternity in a sterile partnership being the primary goal of all clinical work. This understanding implies the cooperation with non-urologists in all aspects of infertility in daily work, and knowledge of other pertinent guidelines, issued by well-accepted authorities such as WHO, the ESHRE Andrology Special Interest Group and the European Academy of Andrology. Accepting these recommendations, our group is convinced that the following guidelines will help European urologists in their interdisciplinary situation to focus on their special skills and knowledge and to understand better the outcome for the patient and the couple.

W. Weidner (Chairman)

1. Andrological investigations and spermatology

1.1 Ejaculate analysis

Ejaculate analysis has been standardized by the World Health Organization (WHO) and propagated by continuing work and publications in the Laboratory Manual for Human Semen and Sperm-Cervical Mucus Interaction, which is in its fourth edition [1]. The consensus is that modern spermatology has to follow these guidelines without exclusions.

1.2 Advanced diagnostic spermatological tests

Computer-assisted sperm analysis (CASA), acrosome reaction tests, zona-free hamster egg penetration tests and sperm-zona pellucida bindings tests are not covered in toto by these guidelines, but are discussed with regard to relevance and clinical importance [2]. A critical assessment of these specialized tests using standardized laboratory techniques is absolutely necessary for given diagnostic situations.

1.3 Andrological status

Andrological status assessment has to consider the suggestions for the standardized investigation, diagnosis and management of the infertile man made by the WHO [3], so implementing evidence-based medicine in this interdisciplinary field of reproductive medicine.

1.4 References

1. World Health Organization.

WHO laboratory manual for the examination of human semen and sperm-cervical mucus interaction. 4^th edition, Cambridge, Cambridge University Press, 1999.

2. ESHRE Andrology Special Interest Group.

Consensus workshop on advanced diagnostic andrology techniques. Hum Reprod 1996; 11:1463-1479.

3. World Health Organization.

WHO manual for the standardized investigation, diagnosis and management of the infertile male. Cambridge, Cambridge University Press, 2000.

2. GENETIC DISORDERS IN INFERTILITY¹

A knowledge of genetic abnormalities in infertility is mandatory for every urologist working in andrology.

2.1 Chromosomal abnormalities

In a survey of pooled data from 11 publications, including a total of 9,766 infertile men, the incidence of chromosomal abnormalities was found to be 5.8% [1]. Of these, sex chromosome abnormalities accounted for 4.2% and autosomal abnormalities for 1.5%. In comparison, the incidence of abnormalities in pooled data from three series totalling 94,465 newborn male infants was 0.38%, of which 131 (0.14%) were sex chromosome abnormalities and 232 (0.25%) were autosomal abnormalities [2]. The possibility of abnormalities increases with increasing severity of impaired spermatogenesis [1,3]. By means of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) it is now possible for men with very low sperm counts to be given a reasonable chance of paternity (see below Idiopathic oligoasthenoteratozoospermia).

Standard karyotype analysis should be offered to all men with damaged spermatogenesis who are seekingfertility treatment by IVF/ICSI.

¹ With support by Ch. Gosk, Dept of Urology, Western General Hospital Edinburgh, UK.