Key Questions

1. What are the general health implications (malignancies, overall survival) and conditions commonly associated (syndromes, varicocele, CAVD, testicular dysgenesis) with male infertility?
2. What are the sensitivities/specificities/yields of available testing for identifying underlying conditions associated with and treatments for male infertility (semen analysis subfactors and ability to predict spontaneous pregnancy and success with assisted reproductive technique outcomes, chromosomal testing in azoospermic/oligospermic males, hormonal testing [predictive ability of FSH, LH, testosterone for detecting primary testicular failure versus obstruction], prolactin/pituitary MRI for detecting pituitary pathologies, DNA fragmentation index and pregnancy outcomes, other specialized testing)?
3. How does the treatment of varicoceles (grade 0-3) impact fertility outcomes (semen analysis, spontaneous pregnancy, IUI, IVF, ICSI)?
4. What are the outcomes of medical therapies (SERMs, aromatase inhibitors, multivitamins/nutritional supplements, LH analogues, FSH analogues) on semen analysis, spontaneous pregnancy outcomes, and assisted reproductive technique outcomes?
5. What are success rates of assisted reproductive techniques (IUI, IVF, ICSI) in men with azoospermia (yields of identifying sperm and successful pregnancy outcomes after TESE/microTESE based on underlying condition), oligospermia and normospermia?
6. What are the comparative success rates of sperm retrieval methods (Microsurgical epididymal sperm aspiration, percutaneous epididymal sperm aspiration, testicular sperm extraction (TSE) and microTSE, and percutaneous testicular sperm aspiration) in men with azoospermia?

Relevant patients, group(s) or subgroups of people

This topic nomination is primarily concerned with looking at research that is relevant to men of childbearing age who have failed to conceive after 12 months of regular, unprotected intercourse or 6 months with a known condition contributing to infertility.

Infertility evaluations should commence before 12 months if: 1.) male infertility risk factors such as a history of bilateral cryptorchidism are present; 2.) female infertility risk factors are present; and 3.) the couple questions the male partner s fertility.

Subgroups of patients that your question might apply to:

1. Oligospermic patients
2. Varicocele patients
3. Azoospermic patients (including prior vasectomy)
4. Idiopathic infertility patients

Oligospermia is defined as sperm densities lower than 15 million/mL or 39 million per ejaculate. This condition can be difficult to manage because unlike obstructive azoospermia, there are a number of potential etiologies, including testicular damage; hormonal deficiencies; exogenous agents; and idiopathic conditions. Oligospermia is also seen in conjunction with motility and morphology dysfunctions, making the management of this condition complex Treatment options include several available hormonal therapies, lifestyle modification, variococelectomy, and referral to ART.

Varicoceles may occur in up to 42% of all male infertility cases, and these patients may be able to improve their chances of conception with varicocelectomy.

There has been a long-standing debate in the urologic field with respect to the necessity of varicocele repair and its effect on fertility. The urologic medical community needs a concise, evidence-based document that will provide guidance regarding treatment and outcomes of variococele repair.

Patients who suffer obstructive azoospermia, approximately 14.3% of all male infertility patients, warrant particular attention because the only manner of treatment is surgical repair or sperm extraction. Vasectomy is the most common cause of obstructive azoospermia, but CBAVD, epididymitis, and ejaculatory duct obstruction are also forms of obstructive azoospermia.

Health-related benefits

Improvement in fertility rates (pregnancy / live births) in male-only infertility patients;

Improvement in positive outcomes of surgical procedures used to reverse obstruction by providing comparative analysis;

Improvement in the consistency in the approach to the treatment of varicoceles;

Improvement in the management of male infertility.

With so many options available in terms of diagnosis and treatment, urologists will greatly benefit from a guideline created from an AHRQ evidence report that covers all aspects of the detection, management, and treatment of male infertility. It will provide physicians with the information necessary to make important decisions about patient options, particularly in areas that have not yet been addressed in a formal way. This is particularly relevant given the relative paucity of information available on evidence-based management of male-factor infertility.

Health-related risks

Infertility is associated with higher rates of malignancies, including testicular, prostate, colorectal, and melanoma, among others.

Other known etiologies of male-factor infertility, including CBAVD, is associated with cystic fibrosis, which has implications for the individual as well as for the partner and future progeny. In the case of a man with known absence of one or both vasa deferentia, both partners should be tested for CFTR abnormalities, considering there is a chance that the female partner is a carrier of the mutation as well. Conception under these conditions is not only a risk and a concern for the couple seeking medical treatment, but also for their siblings, as these traits can be shared within families.

There are several different treatment options to reverse obstructive azoospermia and to repair variococeles. These all come with inherent risk, and there is no guarantee that surgery will improve semen parameters, patency, rates of spontaneous pregnancy, or quality of life. If variococele surgery is not performed properly there is a chance that the condition could return.

ART can also be a burden on a woman s health, which carries risks related to ovarian hyperstimulation syndrome; multiple births, including higher rates of caesarian sections; prematurity; low birth weight; infant death; and disability. There is also a high rate of failure with ART, leading to emotional distress in both female and male partners. As such, attempting to correct any possible male barriers to conception should be exhausted.

Of all couples who try to conceive, approximately 15% will fail in the first year, 50% of those will fail in the second year, and 86% of the remaining childless couples will fail to conceive in the third year. Approximately 7% of all couples remain infertile, 20% of which can be attributed to male-only infertility.

Infertility continues to be a harbinger of testicular cancer and other malignancies, undetected infections of the genital tract, chromosomal abnormalities, and in some cases, mutations to the CTFR gene. Therefore, the field of male infertility remains significant, considering the management and treatment of infertility can reveal serious diseases that have previously gone undetected.

Varicoceles represent the most common attributable cause of male infertility with the condition being observed in approximately 40% of men with primary fertility and 80% of those with secondary fertility. Varicocele repair represents the most commonly performed surgery for the correction of male infertility, yet there has not been a consensus in the urologic community on how variococele treatment can improve fertility.

Oligospermia is commonly present in male infertility patients and it is difficult to determine etiology. Semen parameters for density, morphology, and motility (the latter two being often associated with the former) vary widely, and there are large grey areas in which one is not clinically fertile or clinically subfertile; it is within this range that a careful search for remediable causes and co-morbidities, of which there are numerous possibilities, must be undertaken.

ART is generally the last option for couple who have exhausted all other fertility solutions. An estimated $18 billion is spent per year on ART, which is a financial burden on families since many of these procedures are to be covered out-of-pocket. There are also risks inherent in ART procedures to a woman s health; therefore it is imperative that there are concise statements from the AUA regarding the diagnosis and management of male fertility before ART is proposed.

The AUA Guideline produced from the proposed evidence report has the potential to streamline diagnosis, improve management, provide guidance on contentious topics, and increase positive outcomes of male infertility treatments. The urologic community and the patients they treat will benefit from a new AUA guideline that summarizes the conditions that lead to male infertility, the treatment of these conditions, and provides a comparative analysis of interventions. There is a need in the male infertility subfield of urology that the AUA can meet by composing a guideline using evidence culled from the proposed AHRQ report.

The AUA intends to use this systematic report developed by AHRQ as the basis for a comprehensive evidence-based guideline product on male infertility. The creation of an evidence report on this topic would allow the AUA to create a clinical practice guideline in a relatively short timeframe as the data collection, extraction, and analysis would have already been completed in adherence with the highest standards of systematic review.

Following a guideline s publication, a summary manuscript is published in the Journal of Urology, which has extensive readership spanning both national and international clinical communities. Additionally, the AUA widely disseminates information about its guidelines through its annual meeting, the AUA Health Policy Brief, AUA News and through its Board of Directors and members. In addition, AUA is utilizing informaticists to help make guideline statements more actionable and relevant for electronic health records (EHRs).

The creation of an AHRQ evidence report on male infertility will enable the AUA to develop a guideline to enhance physician knowledge and reduce treatment inequalities among both the urologic and primary care medical communities.

The AUA Guidelines Department works closely with the AUA Foundation, committed to patient education and advocacy, to develop patient guides from its clinical practice guidelines. The AUA continues its dedication to providing quality; evidence-based education through the dissemination of pocket guides to both urologic specialists and primary care physicians in addition to patients in easy to access formats. The development of a newly-updated clinical practice guideline on male infertility would enable the AUA to develop additional material with a strong focus on the importance of patient counseling and education, which is essential for a condition that relies heavily on shared decision making when discussing treatment options.

The AUA has previously partnered with AHRQ in the development of evidence reports on the Management of Female Overactive Bladder (OAB), Urinary Retention, Medical Recurrent Nephrolithiasis, Cryptorchidism, and Bladder Cancer. Following the publication of guidelines on each of these topics, the AUA has increased its previous dissemination efforts to include production of high-quality videos for the purposes of continuing medical education (CME), patient and medical provider trifolds, Clinical Problem Solving Protocols, and a compendium of all AUA guidelines in both App and Pocket-Guide formats. The AUA is also pleased to partner with additional organizations to enhance dissemination efforts to include both the urology community as well as primary care. Using the AHRQ produced male infertility evidence report, the AUA is prepared to continue such efforts for the topic of male infertility.

Please choose a description that best describes your role or perspective: (you may select more than one category if appropriate)

Professional Society

If you are you making a suggestion on behalf of an organization, please state the name of the organization

American Urological Association

Please tell us how you heard about the Effective Health Care Program