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Guideline Summary
Guideline Title
Guidelines on male infertility.
Bibliographic Source(s)
Jungwirth A, Diemer T, Dohle GR, Giwercman A, Kopa Z, Tournaye H, Krausz C. Guidelines on male infertility. Arnhem (The Netherlands): European Association of Urology (EAU); 2013 Mar. 60 p. [362 references]
Guideline Status

This is the current release of the guideline.

This guideline updates a previous version: Jungwirth A, Diemer T, Dohle GR, Giwercman A, Kopa Z, Krausz C, Tournaye H. Guidelines on male infertility. Arnhem (The Netherlands): European Association of Urology (EAU); 2012 Feb. 64 p.

Scope

Disease/Condition(s)

Male infertility

Note: Infertility is the inability of a sexually active, non-contracepting couple to achieve spontaneous pregnancy in 1 year.

Guideline Category
Counseling
Diagnosis
Evaluation
Management
Risk Assessment
Treatment
Clinical Specialty
Endocrinology
Medical Genetics
Oncology
Psychiatry
Psychology
Surgery
Urology
Intended Users
Physicians
Guideline Objective(s)

To assist urologists and healthcare professionals from related specialties in the treatment of male infertility

Target Population

Men with, or suspected to have, infertility

Interventions and Practices Considered

Diagnosis/Evaluation

  1. History and physical examination of both partners
  2. Evaluation of fertility status of the female partner
  3. Examination for urogenital abnormalities
  4. Andrological investigations
  5. Semen analysis
  6. Determination of follicle-stimulating hormone (FSH) concentration
  7. Testicular biopsy
  8. Testing for Y chromosome (Yq) microdeletions
  9. Karyotype analysis for men with damaged spermatogenesis
  10. Testing for cystic fibrosis gene mutation
  11. Scrotal exploration
  12. Ultrasonography

Treatment/Management

  1. Genetic counselling
  2. Testicular sperm extraction (TESE) with cryopreservation of the spermatozoa
  3. Intracytoplasmic sperm injection (ICSI)
  4. Percutaneous epididymal sperm aspiration (PESA)
  5. Long-term endocrine follow-up
  6. Androgen replacement therapy
  7. Vasovasostomy
  8. Tubulovasostomy
  9. Microsurgical epididymal sperm aspiration (MESA)
  10. Microsurgical reconstruction
  11. Varicocele treatment/repair
  12. Drug therapy
  13. Testosterone substitution therapy
  14. Early orchidopexy
  15. Microsurgical reversal of vasectomy
  16. Referral of partners for evaluation and treatment of N. gonorrhoeae or C. trachomatis
  17. Orchidectomy
  18. Aetiological treatment for ejaculatory disorders
  19. Therapy for premature ejaculation disorders: topical anaesthetic creams or selective serotonin reuptake inhibitors (SSRIs)
  20. Vibrostimulation
  21. Electroejaculation

Note: Hormonal treatment of cryptorchidism was considered but not recommended.

Major Outcomes Considered
  • Incidence of male infertility
  • Frequency of chromosomal abnormalities
  • Accuracy of diagnostic tests
  • Value of prognostic factors
  • Risk of foetal abnormality
  • Measures of treatment success, including measures of fertility
  • Complications of treatment

Methodology

Methods Used to Collect/Select the Evidence
Searches of Electronic Databases
Description of Methods Used to Collect/Select the Evidence

General Search Strategy

A structured literature search is performed for all guidelines but this search is limited to randomised controlled trials and meta-analyses, covering at least the past three years, or up until the date of the latest text update if this exceeds the three-year period. Other excellent sources to include are other high-level evidence, Cochrane review and available high-quality guidelines produced by other expert groups or organizations. If there are no high-level data available, the only option is to include lower-level data. The choice of literature is guided by the expertise and knowledge of the Guidelines Working Group.

Specific Strategy for This Guideline

Data Identification

The recommendations provided in the current guidelines are based on a systemic literature search performed by the panel members. Medline, EMBASE, and Cochrane databases were searched to identify original and review articles. The controlled vocabulary of the Medical Subject Headings (MeSH) database was used alongside a free-text protocol, combining "male infertility" with the terms "diagnosis", "epidemiology", "investigations", "treatment", "spermatogenic failure", "genetic abnormalities", "obstruction", "hypogonadism", "varicocele", "cryptorchidism", "testicular cancer", "male accessory gland infection", "idiopathic", "contraception", "ejaculatory dysfunction", and "cryopreservation".

All articles published between January 2011 (previous update) and October 2012 were considered for review. The expert panel reviewed these records and selected articles with the highest evidence.

Number of Source Documents

Not stated

Methods Used to Assess the Quality and Strength of the Evidence
Weighting According to a Rating Scheme (Scheme Given)
Rating Scheme for the Strength of the Evidence

Level of Evidence

Level Type of Evidence
1a Evidence obtained from meta-analysis of randomised trials
1b Evidence obtained from at least one randomised trial
2a Evidence obtained from one well-designed controlled study without randomisation
2b Evidence obtained from at least one other type of well-designed quasi-experimental study
3 Evidence obtained from well-designed non-experimental studies, such as comparative studies, correlation studies and case reports
4 Evidence obtained from expert committee reports or opinions or clinical experience of respected authorities
Methods Used to Analyze the Evidence
Review of Published Meta-Analyses
Systematic Review
Description of the Methods Used to Analyze the Evidence

References in the text have been assessed according to their level of scientific evidence (see the "Rating Scheme for the Strength of the Evidence" field) according to the Oxford Centre for Evidence-based Medicine Levels of Evidence.

Methods Used to Formulate the Recommendations
Expert Consensus
Description of Methods Used to Formulate the Recommendations

General Methods Used to Formulate the Recommendations

  • The first step in the European Association of Urology (EAU) guidelines procedure is to define the main topic.
  • The second step is to establish a working group. The working groups comprise about 4 to 8 members, from several countries. Most of the working group members are academic urologists with a special interest in the topic. Specialists from other medical fields are included as full members of the working groups as needed. In general, general practitioners or patient representatives are not part of the working groups. Each member is appointed for a four-year period, renewable once. A chairman leads each group.
  • The third step is to collect and evaluate the underlying evidence from the published literature.
  • The fourth step is to structure and present the information. All main recommendations are summarized in boxes and the strength of the recommendation is clearly marked in three grades (A–C), depending on the evidence source upon which the recommendation is based. Every possible effort is made to make the linkage between the level of evidence and grade of recommendation as transparent as possible.

Specific Methods Used for This Guideline

Guideline recommendations have been graded (see the "Rating Scheme for the Strength of the Recommendations" field) according to the Oxford Centre for Evidence-based Medicine Levels of Evidence. It should be noted that when recommendations are graded, the link between the level of evidence and grade of recommendation is not directly linear. Availability of randomised controlled trials may not necessarily translate into a grade A recommendation where there are methodological limitations or disparity in published results.

Alternatively, absence of high level of evidence does not necessarily preclude a grade A recommendation, if there is overwhelming clinical experience and consensus. There may be exceptional situations where corroborating studies cannot be performed, perhaps for ethical or other reasons and in this case unequivocal recommendations are considered helpful. Whenever this occurs, it is indicated in the text as "upgraded based on panel consensus". The quality of the underlying scientific evidence – although a very important factor – has to be balanced against benefits and burdens, values and preferences, and costs when a grade is assigned.

Rating Scheme for the Strength of the Recommendations

Grade of Recommendations

Grade Nature of Recommendations
A Based on clinical studies of good quality and consistency addressing the specific recommendations and including at least one randomised trial
B Based on well-conducted clinical studies, but without randomised clinical trials
C Made despite the absence of directly applicable clinical studies of good quality
Cost Analysis

The guideline developers reviewed published cost analyses.

Method of Guideline Validation
Internal Peer Review
Description of Method of Guideline Validation

There is no formal external review prior to publication.

The Appraisal of Guidelines for Research and Evaluation (AGREE) instrument was used to analyse and assess a range of specific attributes contributing to the validity of a specific clinical guideline.

The AGREE instrument, to be used by 2 to 4 appraisers, was developed by the AGREE collaboration (www.agreetrust.org External Web Site Policy) using referenced sources for the evaluation of specific guidelines (see the "Availability of Companion Documents" field for further methodology information).

Recommendations

Major Recommendations

Note from the European Association of Urology (EAU) and the National Guideline Clearinghouse (NGC): The following recommendations were current as of March 2013. However, because the EAU updates their guidelines frequently, users may wish to consult the EAU Web site External Web Site Policy for the most current version available.

Definitions for levels of evidence (LE) (1-4) and grades of recommendation (GR) (A-C) are provided at the end of the "Major Recommendations" field.

Epidemiology and Aetiology

Recommendations on Epidemiology and Aetiology

Recommendations

  • To categorise infertility, both partners should be investigated simultaneously (Grade of recommendation: C).
  • In the diagnosis and management of male subfertility, the fertility status of the female partner must also be considered, because this might determine the final outcome (Grade of recommendation: B).
  • The urologist/andrologist should examine any man with fertility problems for urogenital abnormalities. This applies to all men diagnosed with reduced semen quality. A diagnosis is mandatory to start appropriate therapy (drugs, surgery, or assisted reproduction) (Grade of recommendation: C).

Investigations

Recommendations for Investigations in Male Infertility

Recommendations

  • According to World Health Organization (WHO) criteria, andrological investigations are indicated if semen analysis is abnormal in at least 2 tests (Grade of recommendation: A).
  • Assessment of andrological status must consider the suggestions made by WHO for the standardised investigation, diagnosis, and management of the infertile couple; this will result in implementation of evidence-based medicine in this interdisciplinary field of reproductive medicine (Grade of recommendation: C).
  • Semen analysis must follow the guidelines of the WHO Laboratory Manual for the Examination and Processing (5th edn.) (Grade of recommendation: A) (upgraded following panel consensus).

Testicular Deficiency (Primary Spermatogenic Failure)

Conclusions and Recommendations for Testicular Deficiency

Conclusions

  • Impaired spermatogenesis is often associated with elevated follicle-stimulating hormone (FSH) concentration (Level of evidence: 3).
  • Spermatozoa are found in about 50% of patients with non-obstructive azoospermia (NOA) (Level of evidence: 2a).
  • Pregnancies and live births are achieved in 30% to 50% of couples with NOA, when spermatozoa has been found in the testicular biopsy (Level of evidence: 3).

Recommendations

  • Men who are candidates for sperm retrieval must receive appropriate genetic counselling (Grade of recommendation: A).
  • Testicular biopsy is the best procedure to define the histological diagnosis and possibility of finding sperm. Spermatozoa should be cryopreserved for use in intracytoplasmic sperm injection (ICSI) (Grade of recommendation: A).
  • For patients with NOA who have spermatozoa in their testicular biopsy, ICSI with fresh or cryopreserved spermatozoa is the only therapeutic option (Grade of recommendation: A).
  • Men with NOA can be offered testicular sperm extraction (TESE) with cryopreservation of the spermatozoa to be used for ICSI (Grade of recommendation: A).
  • To increase the chances of positive sperm retrieval in men with NOA, TESE (single, multiple, or microsurgical) should be used rather than percutaneous epididymal sperm aspiration (PESA) (Grade of recommendation: B).

Genetic Disorders in Infertility

Y-chromosome and Male Infertility

Clinical Implications of Y Microdeletions

Conclusions and Recommendations

Conclusions

  • gr/gr deletion has been confirmed as a significant risk factor for impaired sperm production, whereas further evidence of the prognostic significance of gr/gr and development of a testicular germ cell tumour is needed (Level of evidence: 2b).
  • A son who inherits a complete AZF deletion will have abnormal spermatogenesis because these deletions have not been reported in normozoospermic men (Level of evidence: 2a).

Recommendations

  • Testing for microdeletions is not necessary in men with obstructive azoospermia (OA) (with normal FSH) when ICSI is used because spermatogenesis should be normal (Grade of recommendation: A).
  • Men with severely damaged spermatogenesis (spermatozoa <5 million/mL) should be advised to undergo Yq microdeletion testing for both diagnostic and prognostic purposes. Yq microdeletion also has important implications for genetic counseling (Grade of recommendation: A).
  • If complete AZFa or AZFb microdeletions are detected, micro-TESE is not necessary because it is extremely unlikely that any sperm will be found (Grade of recommendation: A).
  • If a man with Yq microdeletion and his partner wish to proceed with ICSI, they should be advised that microdeletions will be passed to sons, but not to daughters (Grade of recommendation: A).

Conclusions and Recommendations for Genetic Disorders in Male Infertility

Conclusions

  • New insights into the genetic basis of infertility and the advent of ICSI require a good understanding of genetics by clinicians and the general public (Level of evidence: 3).
  • Diagnostic advances will allow clinicians to identify the genetic basis of more disorders and diagnose known disorders at a lower cost. For some of these disorders, gene therapy might be practical in the future (Level of evidence: 2a).

Recommendations

  • Standard karyotype analysis should be offered to all men with damaged spermatogenesis (spermatozoa <10 million/mL) who are seeking fertility treatment by in vitro fertilisation (IVF) (Grade of recommendation: B).
  • Genetic counselling is mandatory in couples with a genetic abnormality found in clinical or genetic investigation and in patients who carry a (potential) inheritable disease (Grade of recommendation: A).
  • All men with Klinefelter's syndrome need long-term endocrine follow-up and may require androgen replacement therapy (Grade of recommendation: A).
  • For men with severely damaged spermatogenesis (spermatozoa <5 million/mL), testing for Yq microdeletions is strongly advised (Grade of recommendation: A).
  • When a man has structural abnormalities of the vas deferens (unilateral or bilateral absence), he and his partner should be tested for cystic fibrosis (CF) gene mutations (Grade of recommendation: A).

Obstructive Azoospermia (OA)

Conclusion and Recommendations for OA

Conclusion

  • Obstructive lesions of the seminal tract should be suspected in azoospermic or severely oligozoospermic patients with normal-sized testes and normal endocrine parameters (Level of evidence: 3).

Recommendations

  • In azoospermia caused by epididymal obstruction, standard procedures include vasovasostomy and tubulovasostomy (Grade of recommendation: B).
  • Sperm retrieval techniques, such as microsurgical epididymal sperm aspiration (MESA), TESE, and PESA, can be used additionally. These methods should be used only when cryostorage of the material obtained is available (Grade of recommendation: B).
  • In azoospermia caused by epididymal obstruction, scrotal exploration with microsurgical epididymal sperm aspiration and cryopreservation of spermatozoa should be performed. Microsurgical reconstruction should be performed, if applicable. Results of reconstructive microsurgery depend on the cause and location of the obstruction, and the surgeon's expertise (Grade of recommendation: B).

Varicocele

Conclusions and Recommendations for Varicocele

Conclusions

  • Current information supports the hypothesis that the presence of varicocele in some men is associated with progressive testicular damage from adolescence onwards and consequent reduction in fertility (Level of evidence: 2a).
  • Although the treatment of varicocele in adolescents may be effective, there is a significant risk of overtreatment (Level of evidence: 3).
  • Varicocele repair may be effective in men with subnormal semen analysis, a clinical varicocele and otherwise unexplained infertility (Level of evidence: 1a).

Recommendations

  • Varicocele treatment is recommended for adolescents with progressive failure of testicular development documented by serial clinical examination (Grade of recommendation: B).
  • No evidence indicates benefit from varicocele treatment in infertile men who have normal semen analysis or in men with subclinical varicocele. In this situation, varicocele treatment cannot be recommended (Grade of recommendation: A).
  • Varicocele repair should be considered in case of a clinical varicocele, oligospermia, infertility duration of ≥2 years, and otherwise unexplained infertility in the couple (Grade of recommendation: A).

Hypogonadism

Conclusion and Recommendation for Hypogonadism

Conclusion

  • It is generally agreed that patients with primary or secondary hypogonadism associated with hypoandrogenism should receive testosterone substitution therapy (Level of evidence: 1b).

Recommendations

  • Effective drug therapy is available to achieve fertility in men with hypogonadotropic hypogonadism (Grade of recommendation: A) (upgraded following panel consensus).
  • Testosterone replacement is strictly contraindicated for the treatment of male infertility (Grade of recommendation: A) (upgraded following panel consensus).

Cryptorchidism

Conclusions and Recommendations for Cryptorchidism

Conclusions

  • Cryptorchidism is multifactorial in origin and can be caused by genetic factors and endocrine disruption early in pregnancy (Level of evidence: 3).
  • Cryptorchidism is often associated with testicular dysgenesis and is a risk factor for infertility and germ cell tumours (GCT) (Level of evidence: 2b).
  • Whether early surgical intervention can prevent germ cell loss is still debatable, but in a randomised study it improved testicular growth in boys treated at the age of 9 months compared to those aged 3 years at the time of orchidopexy.
  • Paternity in men with unilateral cryptorchidism is almost equal to that in men without cryptorchidism (Level of evidence: 3).
  • Bilateral cryptorchidism significantly reduces the likelihood of paternity (Level of evidence: 3).

Recommendations

  • Hormonal treatment of cryptorchidism in adults is not recommended (Grade of recommendation: A).
  • Early orchidopexy (6–12 months of age) might be beneficial for testicular development in adulthood (Grade of recommendation: B).
  • If undescended testes are corrected in adulthood, testicular biopsy for detection of intratubular germ cell neoplasia of unclassified type (ITGCNU) (formerly CIS) is recommended at the time of orchidopexy (Grade of recommendation: B).

Idiopathic Male Infertility

Empirical Treatments

Recommendation

  • Medical treatment of male infertility is recommended only for cases of hypogonadotropic hypogonadism (Grade of recommendation: A).

Male Contraception

Conclusions and Recommendations for Male Contraception

Conclusions

  • Vasectomy is considered the gold standard for the male contribution to contraception (Level of evidence: 1).
  • All available data indicate that vasectomy is not associated with any serious, long term side effects (Level of evidence: 1b).
  • Pregnancy is still achievable after successful vasectomy reversal (Level of evidence: 2a).
  • Methods of male contraception other than vasectomy are associated with high failure rates or are still experimental (e.g., hormonal approach) (Level of evidence: 3).

Recommendations

  • Vasectomy meets best the criteria for the male contribution to contraception, with regard to efficacy, safety, and side effects. Cauterisation and fascial interposition are the most effective techniques (Grade of recommendation: A).
  • Patients seeking consultation about vasectomy must be informed about the surgical method, risk of failure, irreversibility, the need for post-procedure contraception until clearance, and the risk of complications (Grade of recommendation: A) (upgraded following panel consensus).
  • Microsurgical vasectomy reversal is a low-risk and (cost-) effective method of restoring fertility (Grade of recommendation: B).
  • MESA/TESE/PESA and ICSI should be reserved for failed vasectomy reversal surgery (Grade of recommendation: A).
  • For couples wanting to achieve pregnancy, sperm aspiration together with ICSI is a second-line option for selected cases and in those with failed vasovasostomy (Grade of recommendation: B).

Male Accessory Gland Infections and Infertility

Conclusions and Recommendations for Male Accessory Gland Infections

Conclusions

  • Urethritis and prostatitis are not associated clearly with male infertility (Level of evidence: 3).
  • Antibiotic treatment often only eradicates microorganisms; it has no positive effect on inflammatory alterations, and cannot reverse functional deficits and anatomical dysfunction (Level of evidence: 2a).
  • Although antibiotic treatment for male accessory gland infection (MAGI) might provide improvement in sperm quality, it does not necessarily enhance the probability of conception (Level of evidence: 2a).

Recommendations

  • Patients with epididymitis that is known or suspected to be caused by Neisseria gonorrhoea or Chlamydia trachomatis must be instructed to refer their sexual partners for evaluation and treatment (Grade of recommendation: B).

Germ Cell Malignancy and Testicular Microcalcification

Recommendations for Germ Cell Malignancy and Testicular Microcalcification

Recommendations

  • As for all men, patients with testicular microlithiasis (TM) and without special risk factors (see below) should be encouraged to perform self-examination because this might result in early detection of testicular germ cell tumour (TGCT) (Grade of recommendation: B).
  • Testicular biopsy should be offered to men with TM, who belong to one of the following high-risk groups: infertility and bilateral TM, atrophic testes, undescended testes, a history of TGCT, or contralateral TM (Grade of recommendation: B).
  • If there are suspicious findings on physical examination or ultrasound in patients with TM and associated lesions, surgical exploration with testicular biopsy or orchidectomy should be considered (Grade of recommendation: B).
  • Testicular biopsy, follow-up scrotal ultrasound, routine use of biochemical tumour markers, or abdominal or pelvic computed tomography (CT) is not justified for men with isolated TM without associated risk factors (e.g., infertility, cryptorchidism, testicular cancer, atrophic testis) (Grade of recommendation: B).
  • Men with TGCT are at increased risk of developing hypogonadism and sexual dysfunction and should therefore be followed up (Grade of recommendation: B).

Disorders of Ejaculation

Conclusion and Recommendations for Disorders of Ejaculation

Conclusion

  • Ejaculation disorders can be treated using a wide range of drugs and physical stimulation, with a high level of efficacy (Level of evidence: 3).

Recommendations

  • Aetiological treatments for ejaculatory disorders should be offered before sperm collection and assisted reproduction technique (ART) is performed (Grade of recommendation: B).
  • Premature ejaculation can be treated successfully with either topical anaesthetic creams or selective serotonin reuptake inhibitors (SSRIs) (Grade of recommendation: A).
  • In men with spinal cord injury, vibrostimulation and electroejaculation are effective methods of sperm retrieval (Grade of recommendation: B).

Semen Cryopreservation

Conclusions and Recommendations for Semen Cryopreservation

Conclusions

  • The purpose of sperm cryopreservation is to enable future ART procedures (Level of evidence: 1b).
  • Cryopreservation techniques are not optimal, and future efforts are needed to improve the outcome of sperm banking (Level of evidence: 3).

Recommendations

  • Cryopreservation of semen should be offered to all men who are candidates for chemotherapy, radiation or surgical interventions that might interfere with spermatogenesis or cause ejaculatory disorders (Grade of recommendation: A).
  • If testicular biopsies are indicated, sperm cryopreservation is strongly advised (Grade of recommendation: A).
  • If cryopreservation is not available locally, patients should be advised about the possibility of visiting, or transferring to, the nearest cryopreservation unit before therapy starts (Grade of recommendation: C).
  • Consent for cryopreservation should include a record of the man's wishes for his samples if he dies or is otherwise untraceable (Grade of recommendation: C).
  • Precautions should be taken to prevent transmission of viral, sexually transmitted or any other infection by cryostored materials from donor to recipient, and to prevent contamination of stored samples. These precautions include testing of the patient and the use of rapid testing and quarantine of samples until test results are known. Samples from men who are positive for hepatitis virus or human immunodeficiency virus (HIV) should not be stored in the same container as samples from men who have been tested and are free from infection (Grade of recommendation: C).

Definitions:

Level of Evidence

Level Type of Evidence
1a Evidence obtained from meta-analysis of randomised trials
1b Evidence obtained from at least one randomised trial
2a Evidence obtained from one well-designed controlled study without randomisation
2b Evidence obtained from at least one other type of well-designed quasi-experimental study
3 Evidence obtained from well-designed non-experimental studies, such as comparative studies, correlation studies and case reports
4 Evidence obtained from expert committee reports or opinions or clinical experience of respected authorities

Grade of Recommendations

Grade Nature of Recommendations
A Based on clinical studies of good quality and consistency addressing the specific recommendations and including at least one randomised trial
B Based on well-conducted clinical studies, but without randomised clinical trials
C Made despite the absence of directly applicable clinical studies of good quality
Clinical Algorithm(s)

None provided

Evidence Supporting the Recommendations

Type of Evidence Supporting the Recommendations

The type of supporting evidence is identified and graded for each recommendation (see the "Major Recommendations" field).

Benefits/Harms of Implementing the Guideline Recommendations

Potential Benefits

Appropriate diagnosis and management of male infertility

Potential Harms
  • Percutaneous epididymal sperm aspiration (PESA): PESA may result in more tubular and vascular damage than testicular sperm extraction (TESE).
  • Fertility treatment in men with genetic disorders causing infertility: The spermatozoa of infertile men show an increased rate of aneuploidy, structural chromosomal abnormalities, and deoxyribonucleic acid (DNA) damage, carrying the risk of passing genetic abnormalities to the next generation.
  • Fertility treatment in men autosomal karyotype abnormality: Genetic counselling should be offered to all couples seeking fertility treatment (including in vitro fertilisation [IVF]/intracytoplasmic sperm injection [ICSI]) when the male partner is known or found to have an autosomal karyotype abnormality. The most common autosomal karyotype abnormalities are Robertsonian translocations, reciprocal translocations, paracentric inversions, and marker chromosomes. It is important to look for these structural chromosomal anomalies because there is an increased associated risk of aneuploidy or unbalanced chromosomal complements in the foetus.
  • Fertility treatment in men with AZF deletions
    • After conception, any Y-deletions are transmitted obligatorily to the male offspring, and genetic counselling is therefore mandatory. In most cases, father and son have the same microdeletion, but occasionally the son has a larger one. The extent of spermatogenic failure (still in the range of azoo-/oligozoospermia) cannot be predicted entirely in the son, due to the different genetic background and the presence or absence of environmental factors with potential toxicity for reproductive function. A significant proportion of spermatozoa from men with complete AZFc deletion are nullisomic for sex chromosomes, indicating a potential risk for any offspring to develop 45,X0 Turner's syndrome and other phenotypic anomalies associated with sex chromosome mosaicism, including ambiguous genitalia. The screening for Y-chromosome microdeletions in patients bearing a mosaic 46,XY/45,X0 karyotype with sexual ambiguity and/or Turner stigmata has shown a relatively high incidence of AZFc deletions (33%). There are data to support the association of Yq microdeletions with an overall Y-chromosomal instability, which leads to the formation of 45,X0 cell lines. Despite this theoretical risk, babies born from fathers affected by Yq microdeletions are phenotypically normal. This could be due to the reduced implantation rate and a likely higher risk of spontaneous abortion of embryos bearing a 45,X0 karyotype.
    • When ICSI is used in the presence of a Y microdeletion, long-term follow up of any male children is needed with respect to their fertility status and cryopreservation of spermatozoa at a young age can be considered.
  • Fertility treatment in men with Y-chromosome 'gr/gr' deletion: For genetic counselling it is worth noticing that partial AZFc deletions (gr/gr and b2/b3) may predispose to complete AZFc deletion in the next generation.
  • Fertility treatment in men with congenital bilateral absence of the vas deferens (CBAVD): When a man has CBAVD, it is important to test him and his partner for cystic fibrosis mutations. If the female partner is found to be a carrier of cystic fibrosis transmembrane conductance regulator (CFTR) mutations, the couple must consider very carefully whether to proceed with ICSI using the husband's sperm, as the risk of a having a child with cystic fibrosis or CBAVD will be 50%, depending on the type of mutations carried by the parents. If the female partner is negative for known mutations, the risk of being a carrier of unknown mutations is ~0.4%.
  • ICSI in men with genetic disorders causing infertility: Use of ICSI has led to concern that children may be born with a foetal abnormality, because ICSI may enable defective sperm to bypass the selective processes of the female genital tract and egg covering. Alternatively, eggs may be fertilised that would otherwise not be. Intracytoplasmic sperm injection babies have a higher risk of de novo sex chromosomal aberrations (about a threefold increase compared with natural conceptions) and paternally inherited structural abnormalities. Treatment with assisted reproductive technology was associated with increased risks of cardiovascular, musculoskeletal, urogenital, and gastrointestinal defects and cerebral palsy. When both partners are known to carry defects (e.g., CFTR mutations), there is up to a 50% chance of the child developing a clinical condition.
  • Transurethral resection of the ejaculatory ducts (TURED): Complications following TURED include retrograde ejaculation due to bladder neck injury and urine reflux into the ejaculatory ducts, seminal vesicles and vasa (causing poor sperm motility, acid semen pH, and epididymitis).
  • Varicocele treatment: Complications associated with treatments for varicocele:
    • Antegrade sclerotherapy: Complication rate 0.3% to 2.2%; testicular atrophy; scrotal haematoma; epididymitis; left-flank erythema
    • Retrograde sclerotherapy: Adverse reaction to contrast medium; flank pain; persistent thrombophlebitis; vascular perforation
    • Retrograde embolisation: Pain due to thrombophlebitis; bleeding haematoma; infection; venous perforation; hydrocele; radiological complication (e.g., reaction to contrast media); misplacement or migration of coils; retroperitoneal haemorrhage; fibrosis; ureteric obstruction
    • Open operation:
      • Scrotal operation: Testicular atrophy; arterial damage with risk of devascularisation and gangrene of testicle, scrotal haematoma, post-operative hydrocele
      • Inguinal approach: Possibility of missing out a branch of testicular vein
      • High ligation: 5% to 10% incidence of hydrocele
      • Microsurgical, inguinal or subinguinal: Post-operative hydrocele; arterial injury; scrotal haematoma
      • Laparoscopy: Injury to testicular artery and lymph vessels; intestinal, vascular, and nerve damage; pulmonary embolism; peritonitis; bleeding; postoperative pain in right shoulder (due to diaphragmatic stretching during pneumoperitoneum); pneumoscrotum; wound infection
  • Orchidopexy: Vascular damage is the most severe complication following orchidopexy and can cause testicular atrophy in 1% to 2% of cases. In men with non-palpable testes, the postoperative atrophy rate was 12% in those cases with long vascular pedicles that enabled scrotal positioning. Post-operative atrophy in staged orchidopexy has been reported in up to 40% of patients.
  • Vasectomy
    • Acute local complications associated with vasectomy include haematoma, wound infection, and epididymitis in up to 5% of cases. The potential long-term complications (e.g., chronic testicular pain), must be discussed with the patient before the procedure. Epididymal tubal damage is common, and is associated with consequent development of sperm granuloma and time-dependent secondary epididymal obstruction, which limits vasectomy reversal.
    • The chance of secondary epididymal obstruction after vasectomy increases with time. After an interval of 10 years, 25% of men appear to have epididymal blockage. If secondary epididymal obstruction occurs, tubulovasostomy is needed to reverse the vasectomy.

Contraindications

Contraindications

Testosterone replacement is strictly contraindicated for the treatment of male infertility.

Qualifying Statements

Qualifying Statements
  • The aim of clinical guidelines is to help clinicians to make informed decisions about their patients. However, adherence to a guideline does not guarantee a successful outcome. Ultimately, healthcare professionals must make their own treatment decisions about care on a case-by-case basis, after consultation with their patients, using their clinical judgment, knowledge, and expertise. A guideline is not intended to take the place of physician judgment in diagnosing and treatment of an individual patient.
  • Guidelines may not be complete or accurate. The European Association of Urology (EAU) and their Guidelines Office, and members of their boards, officers and employees disclaim all liability for the accuracy or completeness of a guideline, and disclaim all warranties, express or implied to their incorrect use.
  • Guidelines users always are urged to seek out newer information that might impact the diagnostic and treatment recommendations contained within a guideline.
  • Due to their unique nature – as international guidelines, the EAU Guidelines are not embedded within one distinct healthcare setting – variations in clinical settings, resources, or common patient characteristics, are not accounted for.

Implementation of the Guideline

Description of Implementation Strategy

The European Association of Urology (EAU) Guidelines long version (containing all EAU guidelines) is reprinted annually in one book. Each text is dated. This means that if the latest edition of the book is read, one will know that this is the most updated version available. The same text is also made available on a CD (with hyperlinks to PubMed for most references) and posted on the EAU website Uroweb (http://www.uroweb.org/guidelines/online-guidelines External Web Site Policy).

Condensed pocket versions, containing mainly flow-charts and summaries, are also printed annually. All these publications are distributed free of charge to all (more than 17,000) members of the Association. Abridged versions of the guidelines are published in European Urology as original papers. Furthermore, many important websites list links to the relevant EAU guidelines sections on the association websites and all, or individual, guidelines have been translated to some 25 languages.

Implementation Tools
Foreign Language Translations
Pocket Guide/Reference Cards
For information about availability, see the Availability of Companion Documents and Patient Resources fields below.

Institute of Medicine (IOM) National Healthcare Quality Report Categories

IOM Care Need
Getting Better
Living with Illness
IOM Domain
Effectiveness
Patient-centeredness

Identifying Information and Availability

Bibliographic Source(s)
Jungwirth A, Diemer T, Dohle GR, Giwercman A, Kopa Z, Tournaye H, Krausz C. Guidelines on male infertility. Arnhem (The Netherlands): European Association of Urology (EAU); 2013 Mar. 60 p. [362 references]
Adaptation

Not applicable: The guideline was not adapted from another source.

Date Released
2010 Apr (revised 2013 Mar)
Guideline Developer(s)
European Association of Urology - Medical Specialty Society
Source(s) of Funding

European Association of Urology

Guideline Committee

Guidelines Panel on Male Infertility

Composition of Group That Authored the Guideline

Panel Members: A. Jungwirth (Chair); T. Diemer; G.R. Dohle; A. Giwercman; Z. Kopa; H. Tournaye; C. Krausz

Financial Disclosures/Conflicts of Interest

All members of the Male Infertility Guidelines Working Group have provided disclosure statements of all relationships that they have that might be perceived as a potential source of a conflict of interest. This information is publicly accessible and can be viewed online at the European Association of Urology (EAU) Web site (http://www.uroweb.org/guidelines/eau-guidelines-board-and-working-panels/ External Web Site Policy). This guidelines document was developed with the financial support of the European Association of Urology. No external sources of funding and support have been involved. The EAU is a non-profit organisation, and funding is limited to administrative assistance and travel and meeting expenses. No honoraria or other reimbursements have been provided.

Guideline Status

This is the current release of the guideline.

This guideline updates a previous version: Jungwirth A, Diemer T, Dohle GR, Giwercman A, Kopa Z, Krausz C, Tournaye H. Guidelines on male infertility. Arnhem (The Netherlands): European Association of Urology (EAU); 2012 Feb. 64 p.

Guideline Availability

Electronic copies: Available in Portable Document Format (PDF) from the European Association of Urology (EAU) Web site External Web Site Policy. Also available in a variety of translations from the EAU Web site External Web Site Policy.

Print copies: Available from the European Association of Urology, PO Box 30016, NL-6803, AA ARNHEM, The Netherlands.

Availability of Companion Documents

The following are available:

  • Guidelines for the investigation and treatment of male infertility. Pocket guideline. Arnhem (The Netherlands): European Association of Urology; 2013 Feb. 12 p. Electronic copies: Available in Portable Document Format (PDF) from the European Association of Urology (EAU) Web site External Web Site Policy. Also available in a variety of translations from the EAU Web site External Web Site Policy.
  • Jungwirth A, Giwercman A, Tournaye H, Diemer T, Kopa Z, Dohle G, Krausz C. European Association of Urology guidelines on male infertility: the 2012 update. Eur Urol. 2012 Aug;62(2):324-32. Electronic copies: Available in PDF from the EAU Web site External Web Site Policy.
  • Dohle GR, Diemer T, Kopa Z, Krausz C, Giwercman A, Jungwirth A. European Association of Urology guidelines on vasectomy. Eur Urol. 2012 Jan;61(1):159-63. Electronic copies: Available in PDF from the EAU Web site External Web Site Policy.
  • The European Association of Urology (EAU) guidelines office manual. Arnhem (The Netherlands): European Association of Urology (EAU); 2012. 35 p. Electronic copies: Available in PDF from the EAU Web site External Web Site Policy.

Print copies: Available from the European Association of Urology, PO Box 30016, NL-6803, AA ARNHEM, The Netherlands.

Patient Resources

None available

NGC Status

This NGC summary was updated by ECRI Institute on January 17, 2012. The information was verified by the guideline developer on February 17, 2012. This NGC summary was updated by ECRI Institute on July 30, 2012. The updated information was verified by the guideline developer on August 19, 2012. This NGC summary was updated by ECRI Institute on July 25, 2013. The updated information was verified by the guideline developer on August 26, 2013.

Copyright Statement

This summary is based on the original guideline, which is subject to the guideline developer's copyright restrictions.

Downloads are restricted to one download and print per user, no commercial usage or dissemination by third parties is allowed.

Disclaimer

NGC Disclaimer

The National Guideline Clearinghouse™ (NGC) does not develop, produce, approve, or endorse the guidelines represented on this site.

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