Diagnosis And Treatment Of Infertility In Men: AUA/ASRM .
Diagnosis and treatment of infertilityin men: AUA/ASRM guideline part IPeter N. Schlegel, M.D.,a Mark Sigman, M.D.,b Barbara Collura,cChristopher J. De Jonge, Ph.D., H.C.L.D.(A.B.B).,d Michael L. Eisenberg, M.D.,eDolores J. Lamb, Ph.D., H.C.L.D.(A.B.B).,f John P. Mulhall, M.D.,g Craig Niederberger, M.D., F.A.C.S.,hJay I. Sandlow, M.D.,i Rebecca Z. Sokol, M.D., M.P.H.,j Steven D. Spandorfer, M.D.,fCigdem Tanrikut, M.D., F.A.C.S.,k Jonathan R. Treadwell, Ph.D.,l Jeffrey T. Oristaglio, Ph.D.,land Armand Zini, M.D.maNew York Presbyterian Hospital-Weill Cornell Medical College; b Brown University; c RESOLVE; d University of MinnesotaSchool of Medicine; e Stanford University School of Medicine; f Weill Cornell Medical College; g Memorial-Sloan KetteringCancer Center; h Weill Cornell Medicine, University of Illinois-Chicago School of Medicine; i Medical College of Wisconsin;jUniversity of Southern California School of Medicine; k Georgetown University School of Medicine; l ECRI; and m McGillUniversity School of MedicinePurpose: The summary presented herein represents Part I of the two-part series dedicated to the Diagnosis and Treatment of Infertilityin Men: AUA/ASRM Guideline. Part I outlines the appropriate evaluation of the male in an infertile couple. Recommendations proceedfrom obtaining an appropriate history and physical exam (Appendix I), as well as diagnostic testing, where indicated.Materials/Methods: The Emergency Care Research Institute Evidence-based Practice Center team searched PubMedÒ, EmbaseÒ, andMedline from January, 2000 through May, 2019. When sufficient evidence existed, the body of evidence was assigned a strengthrating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence ofsufficient evidence, additional information is provided as Clinical Principles and Expert Opinions. (Table 1) This summary is beingsimultaneously published in Fertility and Sterility and The Journal of Urology.Results: This Guideline provides updated, evidence-based recommendations regarding evaluation of male infertility as well as theassociation of male infertility with other important health conditions. The detection of male infertility increases the risk ofsubsequent development of health problems for men. In addition, specific medical conditions are associated with some causes formale infertility. Evaluation and treatment recommendations are summarized in the associated algorithm. (Figure 1)Conclusion: The presence of male infertility is crucial to the health of patients and its effects must be considered for the welfare ofsociety. This document will undergo updating as the knowledge regarding current treatments and future treatment options continuesto expand. (Fertil SterilÒ 2020;-:-–-. Ó2020 by American Urological Association Education and Research, Inc. and American Society for Reproductive Medicine.)Keywords: Male infertility, evaluation, chemotherapy, surgery, healthBACKGROUNDThe overall goal of the male evaluationis to identify conditions that may affectmanagement or health of the patient ortheir offspring. The specific goals of theevaluation of the infertile male are toidentify the following: potentially correctable conditions; irreversible conditions that areamenable to assisted reproductivetechnologies (ART)using the spermof the male partner; irreversible conditions that are notamenable to the above, and forwhich donor insemination or adoption are possible options; life- or health-threatening conditions that may underlie the infertilityor associated medical comorbiditiesthat require medical attention; and genetic abnormalities or lifestyle andage factors that may affect the healthof the male patient or of offspringparticularly if ART are to beemployed.In this guideline, the term ‘‘male’’ or‘‘men’’ is used to refer to biological orgenetic men.The complete unabridged version of the guideline is available at -committee-documents/.Fertility and Sterility Vol. -, No. -, - 2020 0015-0282/ 36.00Copyright 2020 by American Urological Association Education and Research, Inc. and American Society for Reproductive Medicine. Published by Elsevier 15VOL. - NO. - / - 2020GUIDELINE STATEMENTSAssessment1. For initial infertility evaluation,both male and female partnersshould undergo concurrent assessment. (Expert Opinion)2. Initial evaluation of the male forfertility should include a reproductive history. (Clinical Principle)Initial evaluation of the male shouldalso include one or more semen analyses (SAs). (Strong Recommendation; Evidence Level: Grade B)3. Men with one or more abnormalsemen parameters or presumed maleinfertility should be evaluated by amale reproductive expert for completehistory and physical examination aswell as other directed tests when indicated. (Expert Opinion)1
4. In couples with failed ART cycles or recurrent pregnancylosses (RPL) (two or more losses), evaluation of the maleshould be considered. (Expert Opinion)Couple infertility may be due to male factors, female factors or a combination of male and female factors thereforeparallel evaluation of both partners is always required. Tointerpret male infertility studies in isolation from female factors is not appropriate for these couples. Maternal age is thestrongest predictor of fertility outcome for couples. A malein an infertile couple should have an initial SA and malereproductive history evaluation. The reproductive historyassessment provides important information about functionalsexual, lifestyle and medical history including medicationsthat can contribute to reduced fertility or sterility. The SA isan important component in the initial clinical evaluation ofthe male and his reproductive health. Semen parameter valuesfalling above or below the lower limit do not by themselvespredict either fertility or infertility (1). In the interpretationof the SA, the clinician should remember that semen parameters are highly variable biological measures and may varysubstantially from ejaculate to ejaculate. Therefore, at leasttwo SAs, ideally obtained at least one month apart, are important to obtain, especially if the first SA has abnormal parameters. Evaluation and treatment of the male can improve SAand fertility outcomes allowing some couples to conceivenaturally and potentially lower treatment costs. In additionto treatment benefits, 1-6% of men evaluated for infertilityhave significant undiagnosed medical pathology includingmalignancies even when they have so-called ‘‘normal’’ SAs(2, 3). Just as all infertile women are treated by those withspecialized gynecologic training and expertise, all infertilemen be evaluated by specialists in male reproduction (4).Lifestyle Factors and Relationships BetweenInfertility and General Health5. Clinicians should counsel infertile men or men withabnormal semen parameters of the health risks associatedwith abnormal sperm production. (Moderate Recommendation; Evidence Level: Grade B)6. Infertile men with specific, identifiable causes of maleinfertility should be informed of relevant, associatedhealth conditions (Moderate Recommendation; EvidenceLevel: Grade B)7. Clinicians should advise couples with advanced paternalage (R40) that there is an increased risk of adverse healthoutcomes for their offspring. (Expert Opinion)8. Clinicians may discuss risk factors (i.e., lifestyle, medication usage, environmental exposures) associated withmale infertility, and patients should be counseled thatthe current data on the majority of risk factors are limited.(Conditional Recommendation; Evidence Level: Grade C)It is increasingly recognized that male reproductive andoverall health are related with infertile subjects having morecomorbidities compared to fertile controls (5). Men withabnormal semen parameters have higher rates of testicularcancer (6–9) and men with azoospermia have higher ratesof cancer in general than fertile men (10). In addition,2mortality rates have been positively associated withabnormal SAs (11).Over 50% of the time, the cause of a man’s infertility canbe attributed to one of several conditions many of which havehealth implications beyond fertility. It is important for theclinician to understand the various etiologies of male infertility and provide adequate counseling regarding associatedconditions or consider referral to a specialist for the diagnosedconditions (Table 2). Data indicate that advanced paternal ageincreases de novo intra- and inter-genic germline mutations,sperm aneuploidy, structural chromosomal aberrations,sperm DNA fragmentation, birth defects, and geneticallymediated conditions (e.g., chondrodysplasia, schizophrenia,autism) in the offspring. Genetic counseling may be considered for couples with advanced paternal age to discuss thelow absolute risk (but high relative risk) of increased paternalage on at least certain genetic risks in their offspring,including de novo gene mutations as well as multiple medicalconditions including schizophrenia and autism.While a number of putative risk factors for male factorinfertility (e.g., demographic, lifestyle, medical treatments,environmental exposures) have been studied, data are limitedon the specific factors that actually affect male fertility. Thereis low-quality evidence for some association between diet andmale infertility. Most of these studies have suggested that menwith a diet lower in fats and meats (with more fruits andvegetables) is preferable to a higher-fat diet. Similarly,low-quality evidence (due to high risk of bias) exists to linksmoking with a small impact on sperm concentration,motility, and morphology. Ongoing use of anabolic steroidssuppresses spermatogenesis and interferes with fertility. It isrecommended that if there is concern about the influence ofa particular medication on fertility, clinicians may consult reviews on this subject or databases with data on reproductiveeffects of medications for additional information (12).Diagnosis/Assessment/Evaluation9. The results from SA should be used to guide managementof the patient. In general, results are of greatest clinicalsignificance when multiple SA abnormalities are present.(Expert Opinion)10. Clinicians should obtain hormonal evaluation includingfollicle-stimulating hormone (FSH) and testosterone forinfertile men with impaired libido, erectile dysfunction,oligozoospermia or azoospermia, atrophic testes, or evidence of hormonal abnormality on physical evaluation.(Expert Opinion)11. Azoospermic men should be clinically evaluated todifferentiate genital tract obstruction from impairedsperm production initially based on semen volume, physical exam, and FSH levels. (Expert Opinion)12. Karyotype and Y-chromosome microdeletion analysisshould be recommended for men with primary infertilityand azoospermia or severe oligozoospermia ( 5 millionsperm/mL) with elevated FSH or testicular atrophy or apresumed diagnosis of impaired sperm production asthe cause of azoospermia. (Expert Opinion)VOL. - NO. - / - 2020
Fertility and Sterility FIGURE 1One year of failure to conceive if female 35 years old orif female 35 years old, 6 months of failure to conceivePostVasectomyMale and female evaluatedin parallel including malereproductive historyPostVasectomyCounselling re:post-vasectomyfertility optionsAt least one abnormal semen analysis or abnormalmale reproductive historyNoPrimary evaluation/management offemale partnerYesFailed ARTOligozoospermiaInitial hormonalevaluation(FSH, T)Complete male evaluationwith history and physicalNormozoospermiaTreatment of abnormalfactors or managementwith ARTFurther egorizeazoospermia withFSH, examObstructiveGenetic testing (karyotypeand Y microdeletion)Genetic (CF) testing forcongenital cases of obstructionOption for microTESE andICSISperm retrieval ormicrosurgical reconstructionConsider diagnotic and therapeuticbiopsy if FSH & testicular volume normalbut no clinical evidence of obstruction 2020 American Urological Association Education and Research, Inc. and AmericanSociety for Reproductive Medicine All Rights Reserved.Male Infertility Algorithm.Schlegel. AUA/ASRM guideline part I. Fertil Steril 2020.13. Clinicians should recommend Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) mutation carriertesting (including assessment of the 5T allele) in menwith vasal agenesis or idiopathic obstructive azoospermia. (Expert Opinion)14. For men who harbor a CFTR mutation, genetic evaluationof the female partner should be recommended. (ExpertOpinion)VOL. - NO. - / - 202015. Sperm DNA fragmentation analysis is not recommended in the initial evaluation of the infertilecouple. (Moderate Recommendation; Evidence Level:Grade C)16. Men with increased round cells on SA ( 1million/mL)should be evaluated further to differentiate whiteblood cells (pyospermia) from germ cells. (ExpertOpinion)3
Schlegel. AUA/ASRM guideline part I. Fertil Steril 2020.Benefits Risks/Burdens (or vice versa)Benefits Risks/Burdens (or vice versa)Benefits Risks/Burdens (or vice versa)Net benefit (or net harm) is substantialNet benefit (or net harm) is substantialNet benefit (or net harm) appears substantialApplies to most patients in most circumstancesApplies to most patients in most circumstances butApplies to most patients in most circumstances butand future research is unlikely to changebetter evidence could change confidencebetter evidence is likely to change confidenceconfidence(rarely used to support a Strong Recommendation)Moderate RecommendationBenefits Risks/Burdens (or vice versa)Benefits Risks/Burdens (or vice versa)Benefits Risks/Burdens (or vice versa)(Net benefit or harmNet benefit (or net harm) is moderateNet benefit (or net harm) is moderateNet benefit (or net harm) appears moderatemoderate)Applies to most patients in most circumstancesApplies to most patients in most circumstances butApplies to most patients in most circumstances butand future research is unlikely to changebetter evidence could change confidencebetter evidence is likely to change confidenceconfidenceBenefits ¼ Risks/BurdensBalance between Benefits & Risks/Burdens unclearConditional Recommendation Benefits ¼ Risks/BurdensBest action appears to depend on individual patientAlternative strategies may be equally reasonable(No apparent net benefit Best action depends on individual patientcircumstancesBetter evidence likely to change confidenceor harm)circumstancesBetter evidence could change confidenceFuture research unlikely to change confidenceClinical PrincipleA statement about a component of clinical care that is widely agreed upon by urologists or other clinicians for which there may or may not be evidence in themedical literatureExpert OpinionA statement, achieved by consensus of the Panel, that is based on members clinical training, experience, knowledge, and judgment for which there is no evidenceStrong Recommendation(Net benefit or harmsubstantial)Evidence Strength C (Low Certainty)Evidence Strength B (Moderate Certainty)Evidence Strength A (High Certainty)AUA Nomenclature Linking Statement Type to Level of Certainty, Magnitude of Benefit or Risk/Burden, and Body of Evidence Strength.TABLE 1417. Patients with pyospermia should be evaluated for thepresence of infection. (Clinical Principle)18. Antisperm antibody (ASA) testing should not be done inthe initial evaluation of male infertility. (Expert Opinion)19. For couples with RPL, men should be evaluated with karyotype (Expert Opinion) and sperm DNA fragmentation.(Moderate Recommendation; Evidence Level: Grade C)20. Diagnostic testicular biopsy should not routinely be performed to differentiate between obstructive azoospermiaand non-obstructive azoospermia (NOA). (Expert Opinion)SA and a male reproductive history should be obtainedfor all couples interested in fertility. Abnormalities in anyone or more semen parameters can compromise a man’s ability to naturally impregnate his female partner except in casesof azoospermia, some types of teratozoospermia (e.g., complete globozoospermia), necrozoospermia, or complete asthenozoospermia. With the exception of the aforementionedanomalies (which clearly cause infertility), none of the individual sperm parameters (e.g., concentration, morphology,motility) are highly predictive of fertility or diagnostic ofinfertility. The odds ratio for infertility increases as the number of abnormal parameters increases (13). Clinicians managing results from a SA should counsel patients that multiplesignificant abnormalities in semen parameters increase theirRR for infertility. An endocrine evaluation of the infertilemale with serum FSH and testosterone is not recommendedas a primary first-line test in the evaluation of male infertility,but is indicated if oligospermia ( 10 million sperm/mL) ispresent. Further evaluation of the male with luteinizing hormone is indicated for men with low serum testosterone ( 300ng/dL) as well as PRL evaluation for men with hypogonadotropic hypogonadism or decreased libido.Azoospermia is defined as the absence of sperm in theejaculate, including the absence of sperm after examinationof a centrifuged semen pellet. The history, physical examination and hormonal studies can help differentiate obstructiveazoospermia from NOA (Table 3). Men with azoospermiaand small volume testes, elevated FSH and normal semen volume will typically have NOA (azoospermia due to impairedsperm production). Men with normal testis volume (e.g., testislength 4.6 cm), FSH 7.6 and/or semen volume 0.5 or 1.0mL most likely have obstructive azoospermia, especially if theproximal epididymis is enlarged on physical examination orthe vasa deferentia are absent on exam.Men with severe oligospermia ( 5 M/mL) including NOAshould be evaluated with a karyotype and Y microdeletionstudies (14). The most common abnormal karyotypic patternis Klinefelter syndrome (the presence of extra X chromosomes). There may be rare foci of spermatogenesis foundupon microdissection-testicular sperm extraction in at least50%-60% of 47, XXY men. Y chromosome microdeletionsare the second most common known genetic cause of infertility in the male. Although sperm may be found in the ejaculate of some men and through testicular sperm extraction inat least 50% of men with an AZFc deletion, sperm have notbeen retrieved by testicular sperm extraction in men withcomplete AZFa and/or AZFb microdeletions, so surgical intervention is not indicated.VOL. - NO. - / - 2020
Fertility and Sterility TABLE 2Summary of Evidence on Medical Comorbidities from Systematic Review.MULTIPLE studies indicateincreased riskConditionKlinefelter syndrome Testosterone deficiencyCystic fibrosis Tooth enamel defects of permanent teeth Pulmonary PancreaticHypospadiasCryptor-chidismTestosterone Deficiency Testicular cancerDiabetesMetabolic syndromeCVDHypertensionAll-cause mortalityCVD mortalityCVD morbidityAlzheimer’s diseaseSINGLE study indicatesincreased riskEvidence is UNCLEAR orCONFLICTING All-cause mortality Specific-cause mortality (perinatal disorders, congenitalanomalies and genetic disorders, respiratory diseases,cardiovascular diseases,endocrine diseases, and malignant neoplasms) Other specific-cause mortality(infections, nervous systemdiseases, digestive diseases,musculoskeletal diseases,trauma, other causes) Metabolic syndrome Peripheral artery diseaseIntima-media thicknessRapid bone lossLung cancerTesticular cancer Dental cariesPlaqueGingival bleedingDental calculusUrinary anomalies Charlson Comorbidity IndexPeriodontal diseaseIschemic heart diseaseProstate cancerColorectal cancerSchlegel. AUA/ASRM guideline part I. Fertil Steril 2020.Men with congenital obstructive azoospermia, includingcongenital bilateral absence of the vas deferens (CBAVD)should have cystic fibrosis (CF) testing. Mutations in theCFTR gene are present in up to 80% of men with CBAVD,20% of men w
Primary evaluation/ management of female partner Initial hormonal evaluation (FSH, T) Further evaluation/ management Consider diagnotic and therapeutic biopsy if FSH & testicular volume normal but no clinical evidence of obstruction Treatment of abnormal factors or management with ART Categorize azoospermia with FSH, exam
invalidate the diagnosis of infertility. When the cause of complete infertility is known, the one-year guideline may not be applicable. We cover services for members who are presumably healthy, for whom fertility would naturally be expected. Services must be authorized, and de
This review was conducted to renew public interest on the chromo-somal basis of infertility, testing, and management. Main text: Meiotic and post-zygotic mitotic errors may cause infertility-predisposing chromosomal abnormalities, including Klinefelter syndrome, Jacob syndrome, Triple X syndrome, Turner syndrome, and Down syndrome. Chromo-
the Medical Policy Statement, Limitations, and/or Applicable Coding sections of this policy. 1. Artificial insemination: Intracervical or intrauterine when done with donor sperm (i.e., the partner has a male factor infertility diagnosis; or donor sperm is being used as an alternative to preimplantation genetic diagnosis [PGD] when
provided as Clinical Principles and Expert Opinions. Guideline Statements Assessment 1. For initial infertility evaluation, both male and female partners should undergo concurrent assessment. (Expert Opinion) Approved by the AUA Board of Directors October 2020 Authors' disclosure of po-tential conflicts of interest and author/staff contribu-
PART V – BENEFITS AND MEMBER MANAGEMENT SECTION M: EARLY PERIODIC SCREENING, DIAGNOSIS, AND TREATMENT M-1 SECTION M – EARLY PERIODIC SCREENING, DIAGNOSIS, AND TREATMENT M.1 Describe your system for tracking each member's screening, diagnosis, and treatment including, at a
Medical Treatment Guideline for Shoulder Diagnosis and Treatment -updated May 2018 I. Review Criteria for Shoulder Surgery A request may be appropriate for If the patient has AND the diagnosis is supported by these clinical findings: AND this has been done Surgical Procedure Diagnosis Subjective Objective Imaging Non-operative care
minimally invasive interventions. Healthy living. Prevention. Diagnosis. Treatment. Home care. 3. user data. Towards precision medicine. user data. Key characteristics. 1 . of Diagnosis & Treatment businesses. 4. 1. Based on last twelve months September 2016. Diagnosis & Treatment businesses 9% . of sales invested in R&D. Image-Guided Therapy .
Section 1: Understand the diagnosis of Specific Learning Difficulties. 4. LCG 2017 . In this section, you will learn about diagnosis of Specific Learning Difficulties. You will . find out about the importance of gaining a diagnosis and gaining diagnosis as early as possible, and the impact of delayed or non-diagnosis. You will look at how diagnosis
