Current Clinical Urology Eric A. Klein, MD, Series Editor
For other titles published in the series, go to www.springer.com/series/7635
Male Infertility Problems and Solutions
Edited by
Edmund S. Sabanegh, Jr., M.D.
Editor Edmund S. Sabanegh, Jr., MD. Chairman, Department of Urology Glickman Urological and Kidney Institute Cleveland Clinic Cleveland, Ohio USA
[email protected] Series Editor Eric A. Klein, Md Professor of surgery Cleveland Clinic Lerner College of Medicine Head, Section of Urologic Oncology Glickman Urological and Kidney Institute Cleveland, OH
ISBN 978-1-60761-192-9 e-ISBN 978-1-60761-193-6 DOI 10.1007/978-1-60761-193-6 Springer New York Dordrecht Heidelberg London Library of Congress Control Number: 2010938366 © Springer Science+Business Media, LLC 2011 All rights reserved. This work may not be translated or copied in whole or in part without the written permission of the publisher (Humana Press, c/o Springer Science+Business Media, LLC, 233 Spring Street, New York, NY 10013, USA), except for brief excerpts in connection with reviews or scholarly analysis. Use in connection with any form of information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed is forbidden. The use in this publication of trade names, trademarks, service marks, and similar terms, even if they are not identified as such, is not to be taken as an expression of opinion as to whether or not they are subject to proprietary rights. Printed on acid-free paper Humana Press is part of Springer Science+Business Media (www.springer.com)
Preface
With almost 50% of infertility attributed either wholly or in part to male issues, it has become increasingly important to look at infertility from a couple’s perspective. Advances in assisted reproductive technologies allow more conceptions than ever before, but such treatments may come with significant financial and safety cost. These costs are certainly justifiable with the targeted use of these innovative advances, but they should not be applied in a blanket fashion to all causes of infertility. Thorough evaluation of the male with the correction of underlying issues can maximize the potential for natural reproduction. In this text, we have assembled world-renowned experts in the field to provide a clear and concise overview of state-of-the-art developments in male infertility for both the novice and experienced
p ractitioners in the field. We have placed special emphasis on diagnostic and treatment algorithms to allow the reader to obtain rapid answers to this challenging medical issue. The text is intended for general urologists, gynecologists, primary care providers, and allied health providers who manage infertility in both men as well as women. It is our sincere hope that this book allows rapid acquisition of pertinent background and development of management plans in this ever changing field. It is an exciting time to be involved in the treatment of infertility. We hope this book further stimulates your interest as together we manage couples in a compassionate, safe, and efficient fashion. Cleveland, OH, USA
Edmund S. Sabanegh, Jr.
v
Acknowledgments
Special thanks to my clinical fellows, Kashif Siddiqi, MD and John Kefer, MD for their diligent assistance throughout the preparation of this book and
to my children, Emily and Ned and my wife, Amy. Without their support, none of this would have been possible.
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Contents
Preface ..........................................................................................................................................................
v
Contributors ..................................................................................................................................................
xi
The Initial Consultation for Male Infertility ............................................................................................ Wayne Kuang
1
Interpretation of Basic Semen Analysis and Advanced Semen Testing ................................................. Ashok Agarwal and Tamer M. Said
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Azoospermia: Diagnosis and Management .............................................................................................. John C. Kefer and Dan B. French
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Ejaculatory Dysfunction............................................................................................................................. Dana A. Ohl, Susanne A. Quallich, Jens Sønksen, Nancy L. Brackett, and Charles M. Lynne
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Genetic Issues with Male Fertility ............................................................................................................. Robert D. Oates
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Endocrinopathies in Male Infertility......................................................................................................... Stephanie E. Harris, Hussein M.S. Kandil, and Craig S. Niederberger
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Female Fertility: Implications to Management of Male Factor.............................................................. Jeffrey M. Goldberg and Michelle Catenacci
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Varicocele: To Fix or Not to Fix ................................................................................................................. Fábio Firmbach Pasqualotto, Edson Borges, Felipe Roth, Luana Venturin Lara, and Eleonora Bedin Pasqualotto
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Medical Management of Male Infertility .................................................................................................. Eric E. Laborde, Vishal Bhalani, Neal Patel, and Robert E. Brannigan
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Surgical Reconstructions for Obstruction ................................................................................................ Edmund S. Sabanegh, Jr. and Kashif Siddiqi
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Techniques for Sperm Harvest................................................................................................................... Wayland Hsiao and Peter N. Schlegel
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Sperm Banking: When, Why, and How? .................................................................................................. Sajal Gupta, Lucky H. Sekhon, and Ashok Agarwal
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Assisted Reproduction and Male Factor Fertility: Which Type Is Right? ............................................ James Goldfarb and Nina Desai
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Ethical Dilemmas in Male Infertility......................................................................................................... Barbara Chubak and Anthony J. Thomas
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Index .............................................................................................................................................................
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Contributors
Ashok Agarwal, Ph.D., H.C.L.D. Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA
James Goldfarb, M.D., M.B.A. In-Vitro Fertilization Center, Cleveland Clinic, Cleveland, OH 44195, USA
Vishal Bhalani, M.D. Department of Urology, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA
Sajal Gupta, M.D. Center for Reproductive Medicine and Andrology Laboratory and Reproductive Tissue Bank, Glickman Urological & Kidney Institute, Cleveland Clinic, 9500 Euclid Avenue, Desk A19.1, Cleveland, OH 44195, USA
Edson Borges, Jr, M.D., Ph.D. Fertility - Center for Assisted Fertilization, São Paulo, SP, Brazil; Institute Sapientiae - Center of Post-Graduation in Human Assisted Reproduction Brazil Nancy L. Brackett, Ph.D. The Miami Project to Cure Paralysis, University of Miami School of Medicine, Miami, FL 33101, USA Robert E. Brannigan, M.D. Department of Urology, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA Michelle Catenacci, M.D. Obstetrics/Gynecology and Women’s Health Institute, Cleveland Clinic, Cleveland, OH, USA Barbara Chubak, M.D. Department of Bioethics, Cleveland Clinic, Cleveland, OH, USA Nina Desai, Ph.D., H.C.L.D. In-Vitro Fertilization Center, Cleveland Clinic, Cleveland, OH 44195, USA Dan B. French, M.D. Dallas Center for Pelvic Medicine, Suite 200, 10501 N Central Expressway, 75231 Dallas, TX, USA Jeffrey M. Goldberg, M.D. Obstetrics/Gynecology and Women’s Health Institute, Cleveland Clinic, Cleveland, OH, USA
Stephanie E. Harris, M.D. University of Illinois at Chicago, Chicago, IL, USA Wayland Hsiao, M.D. James Buchanan Brady Foundation, Starr 900, Department of Urology, Weill Cornell Medical College, The New York Presbyterian Hospital, 525 East 68th Street, New York, NY 10021, USA Hussein M.S. Kandil, M.D. University of Illinois at Chicago, Chicago, IL, USA John C. Kefer, M.D., Ph.D. Center for Male Fertility/Andrology, Glickman Urological and Kidney Institute, Mailcode Q10, 9500 Euclid Ave, 44113 Cleveland, OH, USA Wayne Kuang, M.D. Division of Urology, University of New Mexico, Albuquerque, NM, USA Eric E. Laborde, M.D. Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA Luana V. Lara, B.Sc. CONCEPTION - Center for Human Reproduction, Caxias do Sul, RS, Brazil
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Contributors
Charles M. Lynne, M.D. Department of Urology, University of Miami School of Medicine, Miami, FL, USA
Susanne A. Quallich, N.P.-C. Department of Sexual and Reproductive Medicine, University of Michigan, Ann Arbor, MI 48108, USA
Craig S. Niederberger, M.D. University of Illinois at Chicago, Chicago, IL, USA
Felipe Roth, M.D. CONCEPTION - Center for Human Reproduction, Caxias do Sul, RS, Brazil
Robert D. Oates, M.D. Boston University School of Medicine, Boston, MA 02118, USA Dana A. Ohl, M.D. Department of Sexual and Reproductive Medicine, University of Michigan, Ann Arbor, MI 48108, USA Eleonora B. Pasqualotto, M.D., Ph.D. CONCEPTION - Center for Advanced Research in Human Reproduction, Infertility & Sexual Function, Center for Biological and Health Sciences, University of Caxias do Sul, Caxias do Sul, RS, Brazil; Department of Obstetrics–Gynecology, General Hospital, University of Caxias do Sul, Caxias do Sul, RS, Brazil Fábio F. Pasqualotto, M.D., Ph.D. University of Caxias do Sul, RS, Brazil; Institute of Biotechnology, University of Caxias do Sul, RS, Brazil; Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Brazil; CONCEPTION - Center for Human Reproduction, Caxias do Sul, RS, Brazil; Rua Pinheiro Machado, 2569, sl 23/24, Bairro São Pelegrino, Caxias do Sul, RS, Brazil Neal Patel, B.S. Chicago Medical School at Rosalind Franklin University of Medicine and Science, North Chicago, IL 60061, USA
Edmund S. Sabanegh, Jr., M.D. Center for Male Fertility, Glickman Urological and Kidney Institute, Cleveland, OH, USA Tamer M. Said, M.D., Ph.D. The Toronto Institute for Reproductive Medicine – ReproMed, Toronto, ON, Canada Peter N. Schlegel, M.D. James Buchanan Brady Foundation, Starr 900, Department of Urology, Weill Cornell Medical College, The New York Presbyterian Hospital, 525 East 68th Street, New York, NY 10021, USA Lucky H. Sekhon, B.Sc. Center for Reproductive Medicine and Andrology Laboratory and Reproductive Tissue Bank, Glickman Urological & Kidney Institute, Cleveland Clinic, 9500 Euclid Avenue, Desk A19.1, Cleveland, OH 44195, USA Kashif Siddiqi, M.D. Center for Male Fertility, Glickman Urological and Kidney Institute, Cleveland, OH, USA Jens Sønksen, M.D., Ph.D. Department of Urology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark Anthony J. Thomas Jr., M.D. Department of Bioethics, Cleveland Clinic, Cleveland, OH, USA
The Initial Consultation for Male Infertility Wayne Kuang MD
Contents Introduction....................................................................................................................................................................... Male Infertility.................................................................................................................................................................. Sexual History................................................................................................................................................................... Developmental and Childhood History............................................................................................................................. Infection History............................................................................................................................................................... Medical History................................................................................................................................................................ Surgical History................................................................................................................................................................ Social History.................................................................................................................................................................... Medications....................................................................................................................................................................... Physical Exam................................................................................................................................................................... Summary........................................................................................................................................................................... References.........................................................................................................................................................................
1 1 3 4 4 5 7 7 8 8 9 9
Abbreviations
Introduction
AAS Anabolic androgenic steroids CAH Congential adrenal hyperplasia CF Cystic fibrosis Gy Gray HPG Hypothalamic – gonadal – axis IHH Isolated hypogonadotropic hypogonadism IVF In vitro fertilization LH Luteinizing hormone
A thorough history and physical exam is a critical stepping stone towards the diagnosis and treatment of male infertility. This review focuses on obtaining a sexual, developmental, infection, medical, surgical and social history, providing an overview of medications that may impair a man’s fertility potential and performing a careful physical exam (see Table 1). The interpretation of hormonal, seminal and genetic testing is discussed in later chapters in association with specific disease entities.
Male Infertility W. Kuang () Division of Urology, University of New Mexico, Southwest Fertility Center for Men, Albuquerque, NM, USA
Infertility is defined as failure to conceive after 12 or more months of regular unprotected intercourse (Practice Committee of the American Society for
From: Current Clinical Urology: Male Infertility: Problems and Solutions, Edited by: E.S. Sabanegh, DOI: 10.1007/978-1-60761-193-6_1, Springer Science+Business Media, LLC 2011
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Table 1. Male infertility history. Infertility history Duration Previous partner Previous pregnancies Previous infertility therapy Partner’s fertility status Sexual history Timing and frequency of sex Libido and erectile function Lubricants Ejaculatory status and volume Developmental and childhood history Undescended testicles Pre-pubertal hypogonadism Congenital syndromes Infection history Viral febrile infection Sexually transmitted HIV Gonorrhea Chlamydia Bacterial Atypical (mycoplasma) Prostatitis Epididymitis Tuberculosis Post-pubertal mumps orchitis Medical history Systemic illnesses Diabetes Chronic liver disease Renal failure Thyroid disease Malnutrition Metabolic syndrome Blood dyscrasias Neurologic disease Multiple sclerosis Transverse myelitis Spinal cord injury Cancer Cystic fibrosis Post-pubertal hypogonadism Klinefelter’s syndrome
IHH Pituitary diseases/tumour Surgical history Trauma Penis Chordee Hypospadias Urethroplasty Scrotum Orchiopexy Orchiectomy Torsion Vasectomy Inguinal Orchidopexy Hernia Pelvis Bladder neck surgery TURP Retroperitoneum Fibrosis RPLND Social history Environmental exposures Chemicals Radiation Recreational drugs Tobacco use Heat exposure Stress Anabolic-androgenic steroids Family history Cystic fibrosis Male infertility Hypogonadism Medications Review of systems Headache Visual field changes Galactorrhea Gynecomastia Anosmia
Reproductive Medicine 2008). A comprehensive male infertility evaluation should be pursued sooner than at 1 year if there is a previous history of infertility, a known risk factor, advanced female age or a specific request by the couple. In the USA, 7.5% of sexually experienced men reported that they had sought assistance in having a child (Anderson et al. 2009). Conception rates for fertile couples can be as high as 30% per month and approximately 85% within 1 year (Spira 1986; Ford et al. 2000; Thonneau et al. 1991). When left untreated, 20–35% of couples can conceive naturally even after a 2-year period of infertility (Collins
et al. 1983; Aafjes et al. 1978). While fecundity begins to decline for both men and women at the age of 31, the rate of decline is faster for women starting at the age of 37 (Ford et al. 2000; van Noord-Zaadstra et al. 1991; Schwartz and Mayaux 1982). A growing body of evidence suggests an association between advanced paternal age and miscarriage, genetic abnormalities (Down’s), autism spectrum disorder (ASD) as well as schizophrenia (Durkin et al. 2008; Fisch 2009; Belloc et al. 2008; Weiser et al. 2008). A contributory male infertility factor is identified in almost 50% of infertile couples while it is the sole
TURP transurethral resection of the prostate; RPLND retroperitoneal lymph node dissection; IHH isolated hypogonadotropic hypogonadism
The Initial Consultation for Male Infertility
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Table 2. Distribution of diagnoses for male infertility (World Health Organization; n = 7,057) Adapted from EAU guidelines on male infertility 2005; with permission Diagnosis Percentage (%) Idiopathic Idiopathic abnormal semen analysis Varicocele Infection Immunologic factor Other abnormalities Acquired factor Congenital anomaly Coital factor Endocrine abnormality
48.5 26.4 12.3 6.6 3.1 3.0 2.6 2.1 1.7 0.6
cause in 20–30% of infertile couples (Thonneau et al. 1991; Hull et al. 1985). These factors range from being correctable to irreversible. Significant medical pathologies that threaten a man’s overall health or life (endocrinopathies, testicular and prostate cancer, brain and spinal cord tumours) can be identified in up to 6% of infertile men (Honig et al. 1994; Kolettis and Sabanegh 2001; Walsh et al. 2009; Peng et al. 2009). The distribution of diagnoses seen in a male infertility clinic reveals that 75% of men will have idiopathic infertility with or without an abnormal semen analysis (see Table 2) Dohle et al. 2005. The goal of a comprehensive male infertility evaluation is to optimize a man’s reproductive potential while maximizing his overall health. In close colla boration with the female fertility specialists, a male fertility specialist should help a couple identify the treatment option that best resonates with their reproductive philosophy, needs and timetable. For the infertile man, the best reproductive option may involve rectifying correctable causes with surgical or medical therapy. Alternatively, sperm retrieval in conjunction with assisted reproductive techniques can overcome irreversible factors. Options of having non-biological children (donor insemination or adoption) or staying as they are should also be presented. It is important to be aware that the reproductive journey towards building a family can be emotionally taxing and lead to issues of depression, sexual dysfunction and relationship problems (Shindel et al. 2008).
Sexual History The best chance for conception is within the 7-day window that ends on the day of ovulation and is highest within 2 days of ovulation (Wilcox et al. 1995). Given
that abstinence intervals of 2 days are associated with normal sperm densities and that moving sperm can live in the cervical mucus for more than 2 days, the following frequency of intercourse is suggested for couples seeking to optimize coitus: every other day starting 7 days before ovulation, including the day of and the day after (Wilcox et al. 2001; Perloff and Steinberger 1964). Strict timing of intercourse can escalate the stress of infertility (Lenzi et al. 2003). Couples should be advised to find a coital frequency that maximizes fecundity but minimizes emotional distress. Specific coital positions are not associated with increased fertility. Regardless of position, sperm can be found within the oviduct within 5 min after deposition of sperm in the proximal vagina (Settlage et al. 1973). There are no data to support an association of orgasm with increased fertility or specific coital practices with gender selection. An assessment of libido as well as erectile and ejaculatory function is critical since it may be the only symptoms of hypogonadism or ejaculatory dysfunction. Commercially available water-based lubricants which include KY Jelly, Surgilube, Astroglide, Replens and Touch have been found to be spermicidal (Kutteh et al. 1996). After a 30-min incubation with KY Jelly or Surgilube, no moving or viable sperm are found in in vitro studies (Tagatz et al. 1972). Natural products such as vegetable oils (canola, vegetable, olive, safflower and peanut) as well as glycerin and petroleum jelly only cause a mild decrease in sperm motility (Kutteh et al. 1996; Goldenberg and White 1975). While saliva is often thought of as a “more natural” lubricant, mild impairment of sperm motility has been seen (Tulandi et al. 1982). In 2008, in vitro studies suggest that a newer commercially available hydroxyethylcellulose-based lubricant, such as PreSeed, has minimal deleterious effects on mobility and sperm chromatin integrity (Agarwal et al. 2008). Obviously, the optimal artificial lubricant for vaginal dryness has yet to be identified based on more than just in vitro studies. While lubricants are not recommended by male fertility specialists, it may be a necessity for successful intercourse. In these situations, couples are advised to use the minimal amount necessary, to avoid water-based lubricants and to consider using vegetable oils, saliva, glycerin, petroleum jelly as well as hydroxyethylcellulose-based lubricants. Men with low or absent ejaculate volumes may have an anatomic (partial or complete) or functional obstruction of the ejaculatory ducts, and often present with infertility, hematospermia or painful ejaculation. The etiology may be congenital or acquired. After retrograde
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ejaculation, hypogonadism, absent vas deferens, and suspect medications are ruled out, seminal vesicle aspiration, chromotubation or seminovesiculography will help further characterize the obstruction (Smith et al. 2008). The finding of three sperm per high-powered field with seminal vesicle aspiration is consistent with obstruction. The injection of the seminal vesicles with contrast (seminovesiculography) or indigo carmine/ methylene blue (chromotubation) can confirm patency with radiographic imaging or cystoscopy, respectively. All three of these diagnostic studies are performed under transrectal ultrasound guidance. Other acquired causes of ejaculatory include systemic illnesses (diabetes), neurologic disorders (multiple sclerosis, transverse myelitis, spinal cord injury), retroperitoneal surgeries or fibrosis, as well as bladder neck surgeries (transurethral resection of the prostate or bladder neck incision) (Smith et al. 2008; Arafa and El Tabie 2008; Chally et al. 1998; Fisch et al. 2002; Jewett and Groll 2007; Ralph and Wylie 2005; Witt and Grantmyre 1993). Medications, including anti-hypertensives (prazosin, phentolamine, thiazides), anti-depressants (imipramine, amitriptyline), anti-psychotics (thioridazine, haloperidol), 5a-reductase inhibitors and a-blockers, may be contributory factors to ejaculatory dysfunction (Smith et al. 2008; Hellstrom and Sikka 2006; Narayan and Lepor 2001; Carbone and Hodges 2003). Selective a-adrenergic blockers, such as tamsulosin, may result in decreased ejaculatory volume in almost 90% of men, and ejaculatory dysfunction can be seen in almost 8% of men on a 5a-reductase inhibitors such as finasteride (Hellstrom and Sikka 2006; Narayan and Lepor 2001; Carbone and Hodges 2003).
Developmental and Childhood History Unilateral cryptorchidism has been associated with a mildly decreased paternity rate of 90%, whereas bilateral cryptorchidism significantly decreases paternity rates to 65% with an associated decreased sperm concentration (Lee 2005). Preliminary data suggest that earlier orchiopexy is associated with lower folliclestimulating hormone (FSH) levels with potential benefits to spermatogenesis (Coughlin et al. 1999). Vanishing testes syndrome (anorchia) in a newborn is a rare condition where undescended testicles must be ruled out. Another rare cause of impaired testicular function is seen in autoimmune testicular failure (Tsatsoulis and Shalet 1991).
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Men with pre-pubertal onset of hypogonadism may present to a male infertility clinic with a known endocrinopathy, including various clinical syndromes (Prader-Willi, Lawrence-Moon-Biedl, Familial Cerebral Ataxia) or the classic form of Isolated Hypogonadotropic Hypogonadism (IHH) which is called Kallman’s syndrome when anosmia is evident (Fechner et al. 2008). Pre-pubertal onset of hypogonadism may require hormonal stimulation to initiate or complete puberty and spermatogenesis (Kulin 1997; Pozo and Argente 2003). Eunuchoid features (arm span exceeds height by more than 5 cm) with small “infantile” testes and penis may be seen. Other rare diseases that present in early childhood and impair a man’s reproductive capacity are 5a-reductase deficiency, androgen resistance, congenital adrenal hyperplasia (CAH) and isolated gonadotropin deficiencies of the pituitary. 5a-reductase deficiency results in ambiguous genitalia with abnormal prostate development due to the relative absence of dihydrotestosterone while virilization at puberty is maintained due to elevated testosterone (Chan et al. 2009; Wilson et al. 1993). Androgen resistance is due to a defect in the androgen receptor that prevents negative-feedback inhibition of luteinizing hormone secretion by the pituitary, and androgenization is abnormal. Consequently, complete androgen insensitivity presents as a phenotypic female (testicular feminization), whereas partial androgen insensitivity presents with ambiguous genitalia (Reifenstein syndrome) (Cheikhelard et al. 2008; Griffin 1992; Boehmer et al. 2001). The two major types of CAH are 21-hydroxylase and 11b-hydroxylase deficiencies. An inability to produce cortisol results in an overproduction of androgens that suppress gonadotropin secretion. The resulting hypogonadotropic hypogonadism with elevated adrenal androgens leads to precocious puberty and small testicles with suppressed spermatogenesis (Antal and Zhou 2009; Speiser and White 2003; Stikkelbroeck et al. 2001). Finally, isolated LH deficiency leads to abnormal androgenization with spermatogenesis whereas isolated FSH deficiency causes infertility with normal androgenization (Giltay et al. 2004; Trarbach et al. 2007).
Infection History A history of sexually transmitted diseases (STDs), urinary tract infections (UTIs) or other genitourinary inflammatory processes may impair the production and quality of sperm and may cause obstruction of the reproductive tract (Keck et al. 1998). Viral orchitis can
The Initial Consultation for Male Infertility
be seen in up to 40% of men with post-pubertal mumps (Philip et al. 2006). Systemic therapy with interferonalpha 2B can prevent infertility and testicular atrophy associated with bilateral orchitis (Erpenbach 1991). STDs, such as Chlamydia and Mycoplasma, are associated with decreased sperm counts and higher sperm DNA fragmentation that improves with antibiotics (Gallegos et al. 2008; Joki-Korpela et al. 2009). Infertility may be identified in 1–2% of men with a history of Chlamydia (Trei et al. 2008). Gonorrhea can result in obstructive urethral strictures that impair proper vaginal deposition of semen or epididymorchitis affecting sperm quality (Ochsendorf 2008). Tuberculosis can lead to the obstruction of the epididymides and vas deferens by granuloma formation and its associated fibrosis (Kumar 2008). Chronic prostatitis or epididymorchitis due to either atypical or typical bacterial infections can lead to leukocytospermia. The presence of these white blood cells in the semen can result in increased sperm DNA fragmentation thought to be the result of increased reactive oxygen species (Gdoura et al. 2008). While the DNA of herpes viruses can be found in semen of infertile men, no association has been found with abnormal semen parameters (Neofytou et al. 2009). Recent data show that HIV-1 infected men can ejaculate sperm that contain HIV-1 DNA, and this infection may be associated with increased sperm DNA fragmentation (Cardona-Maya et al. 2009; Muciaccia et al. 2007).
Medical History Systemic illnesses may adversely affect a man’s reproductive capacity. Various degrees of hypogonadism can be seen in chronic liver disease, renal failure, thyroid disease, malnutrition, metabolic syndrome and blood dyscrasias (sickle cell anemia, hemachromatosis and thalassemia) (Sokol 2009; Kasturi et al. 2008). Febrile illnesses have been known to decrease sperm concentration that may take 3–4 months from which to recover (Buch and Havlovec 1991). Primary ciliary dyskinesia (disorder of ciliary motility) that includes Kartagener’s (infertility and situs inversus) and Young’s syndrome (azoospermia with epididymal obstruction) present with chronic sinopulmonary infections (Cowan et al. 2001; Ichioka et al. 2006; Wilton et al. 1991). Historically, patients with cystic fibrosis (CF) rarely survived beyond adolescence. With medical advancements, CF men are now surviving into their reproductive years, and fertility is an important survivorship issue. While the vas deferens are absent
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(congenital bilateral absence of the vas deferens or CBAVD) in 99% of CF men, spermatogenesis is normal within the testicles which allows in vitro fertilization (IVF) to be a viable reproductive option (Taussig et al. 1972; Sokol 2001; Jarzabek et al. 2004; Kaplan et al. 1968). Endocrinopathies may be found in up to 10% of men who undergo a comprehensive male infertility evaluation (Sigman and Jarow 1997). Infertile men with post-pubertal onset of hypogonadism (sexual dysfunction, decreased libido, impaired spermatogenesis, decreased bone and muscle mass, fatigue, decreased facial and body hair, thinning facial skin) may be suffering from a late-onset form of IHH or various pituitary diseases. With normal pubertal development, men with late-onset IHH may report recent-onset impotence or decreased libido (Nachtigall et al. 1997; Ascoli and Cavagnini 2006). The hypogonadism for these men may have gone undiagnosed and untreated for years. Pituitary diseases that may result in hypogonadotropic hypogonadism include craniopharyngioma, prolactinproducing micro- and macroadenomas, infiltrative diseases such as sarcoidosis, amyloidosis, granulomatous diseases of histiocytosis X as well as iron-depositing conditions such as hemochromatosis and transfusionrequiring sickle cell anemia or thalassemia (Sokol 2009). Headaches, galactorrhea and impaired visual fields may be the presenting signs and symptoms of a prolactin-producing pituitary tumour (Mascarell and Sarne 2007; Verhelst and Abs 2003). Of note, infertile men who have the mildest form of androgen resistance will have normal male development and present with only an abnormal semen analysis. Klinefelter’s syndrome is the most common genetic cause of azoospermia. The prevalence is 40 in 100,000 and is found in up to 3% of infertile men. Unfortunately, less than 10% are diagnosed before puberty (Bojesen et al. 2003; Bojesen and Gravholt 2007). The diagnosis is often significantly delayed since few physical abnormalities are seen before puberty and since the presentation of hypogonadism can be insidious with various degrees of virilization that can be quite mild. Unfortunately, the small testes that are firm due to hyalinization of tubules are often overlooked during routine medical exams and only detected during a male infertility examination (Sokol 2009). Presenting with hypergonadotropic hypogonadism and non-obstructive azoospermia, these men may be able to use testicular sperm found by microdissection for IVF with intracytoplasmic sperm injection (ICSI) (Ramasamy et al. 2009; Paduch et al. 2009).
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Table 3. Medications and male infertility. Medication class Direct effects on sperm or testicle Chemotherapy
Radiation Anti-hypertensives Anti-inflammatories
Antibiotics
Anti-depressants
Examples
References
Cyclophosphamide Chlorambucil Melphalan Busulfan Cisplatin Procarbazine >0.2 Gy Nifedipine Spirinolactone Colchicine
Meistrich (2009), Amory (2007) Meistrich (2009), Amory (2007) Meistrich (2009), Amory (2007) Meistrich (2009), Amory (2007) Meistrich (2009), Amory (2007) Meistrich (2009), Amory (2007) Howell and Shalet (2005), Rowley et al. (1974) Enders (1997), Hershlag et al. (1995) Caminos-Torres et al. (1977) Haimov-Kochman and Ben-Chetrit (1998), Mijatovic et al. (2003) Moody et al. (1997), Heetun et al. (2007) Albert et al. (1975), Reproductive toxicology (1997) Hargreaves et al. (1998) Hargreaves et al. (1998) Hargreaves et al. (1998) Hargreaves et al. (1998) Schlegel et al. (1991) Kumar et al. (2006), Tanrikut et al. (2009) Kumar et al. (2006)
Sulfasalazine Nitrofurantion Erythromycin Tetracycline Co-Trimazole Chloraquine Minocycline Paroxetine Fluoxetine
Indirect effect by altering the HPG axis 5a-Reductase inhibitor Finasteride Dutasteride Anti-androgens Ketoconazole H2 blocker Cimetidine GnRH analogues Leuprolide Goserelin Opiates Methadone Morpheine Anti-psychotics Lithium Chlorpromazine Anti-depressants Imipramine Androgens Testosterone
Selective a-blockers
Anabolic Steroids Tamsulosin
Amory et al. (2007), Liu et al. (2008) Amory et al. (2007) Pont et al. (1984) Van Thiel et al. (1979), Wang et al. (1982) Pace et al. (1991), Wilson et al. (2007) Pace et al. (1991) Daniell (2002), Ragni et al. (1985) Roberts et al. (2002), Singer et al. (1986), Abs et al. (2000) Gibbons and Gibbons (1984), Shen et al. (1992) Levin et al. (1981) Levin et al. (1981) Contraceptive efficacy of testosterone-induced azoospermia in normal men (1990) Holma (1977), Torres-Calleja et al. (2000) Hellstrom and Sikka (2009)
HPG hypothalamic-pituitary-gonadal; GnRH gonadotropin releasing hormone; H2 histamine H2 receptor
Cancer treatments using chemotherapy or radiotherapy may impair spermatogenesis resulting in permanent oligospermia or azoospermia. Prior to cancer therapy, men with testicular cancer have increased sperm DNA fragmentation, and almost 50% of these men with testicular cancer will have subfertile sperm concentrations (
