- Author: Kassem Faraj; Chief Editor: Edward David Kim, MD, FACS more...
Causes of infertility in men can be explained by deficiencies in sperm formation, concentration, or transportation. This general division allows an appropriate workup of potential underlying causes of infertility and helps define a course of action for treatment.
The image below depicts male ductal anatomy.
Signs and symptoms
The initial step in the evaluation of an infertile male is to obtain a thorough medical and urologic history. Such a history should include consideration of the following:
Duration of infertility
Previous fertility in the patient and the partner
Timing of puberty (early, normal, or delayed)
Childhood urologic disorders or surgical procedures
Current or recent acute or chronic medical illnesses
Testicular cancer and its treatment
Social history (eg, smoking and alcohol use)
Environmental or occupational exposure
Spinal cord injury
The physical examination should include a thorough inspection of the following:
Testicles (for bilateral presence, size, consistency, symmetry)
Epididymis (for presence bilaterally, as well as any induration, cystic changes, enlargement, tenderness)
Vas deferens (for presence bilaterally, defects, segmental dysplasia, induration, nodularity, swelling)
Spermatic cord (for varicocele)
Penis (for anatomic abnormalities, strictures, or plaques)
Rectum (for abnormalities of the prostate or seminal vesicles)
Depending on the findings from the history, detailed examination of other body functions may also be warranted.
See Presentation for more detail.
The semen analysis is the cornerstone of the male infertility workup and includes assessment of the following:
Semen volume (normal, 1.5-5 mL)
Sperm density (normal, >15 million sperm/mL)
Total sperm motility (normal, >40% of sperm having normal movement)
Sperm morphology (sample lower limit for percentage of normal sperm is 4%)
Signs of infection – An increased number of white blood cells (WBCs) in the semen may be observed in patients with infectious or inflammatory processes
Other variables (eg, levels of zinc, citric acid, acid phosphatase, or alpha-glucosidase)
Other laboratory tests that may be helpful include the following:
Antisperm antibody test
Hormonal analysis (FSH, LH, TSH, testosterone, prolactin)
Genetic testing (karyotype, CFTR, AZF deletions if severe oligospermia (<5 million sperm/mL)
Imaging studies employed in this setting may include the following:
An abnormal postcoital test result is observed in 10% of infertile couples. Indications for performing a postcoital test include semen hyperviscosity, increased or decreased semen volume with good sperm density, or unexplained infertility.
If the test result is normal, consider sperm function tests, such as the following:
Acrosome reaction assay
Sperm penetration assay
Hypoosmotic swelling test
Inhibin B level
Testicular biopsy is indicated in azoospermic men with a normal-sized testis and normal findings on hormonal studies to evaluate for ductal obstruction, to further evaluate idiopathic infertility, and to retrieve sperm.
See Workup for more detail.
The following causes of infertility, if identified, can often be treated by medical means:
Poor semen quality or number
Surgical interventions to be considered include the following:
Vasovasostomy or vasoepididymostomy
Transurethral resection of the ejaculatory ducts
Sperm retrieval techniques
Assisted reproduction techniques
In vitro fertilization
Gamete intrafallopian transfer (GIFT) and zygote intrafallopian transfer (ZIFT)
Intracytoplasmic sperm injection
Infertility is defined as the inability to achieve pregnancy after one year of unprotected intercourse. An estimated 15% of couples meet this criterion and are considered infertile, with approximately 35% due to female factors alone, 30% due to male factors alone, 20% due to a combination of female and male factors, and 15% unexplained. Conditions of the male that affect fertility are still generally underdiagnosed and undertreated.
Causes of infertility in men can be categorized as obstructive or nonobstructive. Infertile men may have deficiencies in sperm formation, concentration (eg, oligospermia [too few sperm], azoospermia [no sperm in the ejaculate]), or transportation. This general division allows an appropriate workup of potential underlying causes of infertility and helps define a course of action for treatment.
The initial evaluation of the male patient should be rapid, noninvasive, and cost-effective, as nearly 70% of conditions that cause infertility in men can be diagnosed with history, physical examination, and hormonal and semen analysis alone. More detailed, expensive, and invasive studies can then be ordered if necessary.
Treatment options are based on the underlying etiology and range from optimizing semen production and transportation with medical therapy or surgical procedures to complex assisted reproduction techniques. Technological advancements have made conceiving a child possible with as little as one viable sperm and one egg. Although the workup was traditionally delayed until a couple was unable to conceive for 12 months, evaluation may be initiated at the first visit in slightly older couples.
An image depicting male ductal anatomy can be seen below.
Gonadal and sexual functions are mediated by the hypothalamic-pituitary-gonadal axis, a closed-loop system with feedback control from the testicles. The hypothalamus, the primary integration center, responds to various signals from the central nervous system (CNS), pituitary gland, and testicles to secrete gonadotropin-releasing hormone (GnRH) in a pulsatile pattern approximately every 70-90 minutes. The half-life of GnRH is 2-5 minutes.
Release of GnRH is stimulated by melatonin from the pineal gland and inhibited by testosterone, inhibin, corticotropin-releasing hormone, opiates, illness, and stress. GnRH travels down the portal system to the anterior pituitary, located on a stalk in the sella turcica, to stimulate the release of the gonadotropins, luteinizing hormone (LH), and follicle-stimulating hormone (FSH). See the image below.
FSH and LH, glycopeptides with a molecular weight of 10,000 Daltons, are each composed of an alpha chain that is identical to that of human chorionic gonadotropin (HCG) and thyroid-stimulating hormone (TSH), but with a beta chain that is unique for each. FSH has a lower plasma concentration and longer half-life than LH, and it has less obvious pulsatile changes. The pulsatile nature of GnRH is essential to normal gonadotropin release; a continuous stimulation inhibits their secretion.
The hypothalamus also produces thyrotropin-releasing hormone (TRH) and vasoactive intestinal peptide (VIP), both of which stimulate prolactin release from the anterior pituitary, and dopamine, which inhibits prolactin release. Men with elevated prolactin levels present with gynecomastia, diminished libido, erectile dysfunction, and occasionally galactorrhea. Prolactin inhibits the production of GnRH from the hypothalamus and LH and FSH from the pituitary. Gonadotropin release is modulated by various other signals, such as estradiol (a potent inhibitor of both LH and FSH release), and inhibin from the Sertoli cell, which causes a selective decrease in FSH release.
FSH and LH are released into the systemic circulation and exert their effect by binding to plasma membrane receptors of the target cells. LH mainly functions to stimulate testosterone secretion from the Leydig cells of the testicle, while FSH stimulates Sertoli cells to facilitate germ cell differentiation.
Testosterone is secreted in a diurnal pattern, peaking a few hours after the man awakens from sleep. In the body, testosterone circulates 2% in the free form, 44% bound to sex hormone–binding globulin (SHBG), and 54% bound to albumin. Testosterone is converted to dihydrotestosterone (DHT) by the action of 5-alpha reductase, both locally and in the periphery, and to estrogen in the periphery. Testosterone and estradiol function as feedback inhibitors of gonadotropin release.
The testicle contains the Leydig cells and the Sertoli cells and is covered by the tunica albuginea, which also provides septae that divide it into approximately 200-350 pyramids (see image below). These pyramids are filled with the seminiferous tubules. A normal testicle contains 600-1200 seminiferous tubules with a total length of approximately 250 meters. The interstitium between the seminiferous tubules contains the Leydig cells, fibroblasts, lymphatics, blood vessels, and macrophages. Histologically, Leydig cells are polygonal with eosinophilic cytoplasm. Occasionally, the cytoplasm contains crystalloids of Reinke after puberty.
Seminiferous tubules are made up of Sertoli cells and germ cells and are surrounded by peritubular and myoid cells.
Sertoli cells are columnar, with irregular basal nuclei that have prominent nucleoli and fine chromatin. They rest on the basement membrane and serve mainly to support, nourish, and protect the developing germ cells and to provide a blood-testis barrier to provide a microenvironment that facilitates spermatogenesis and maintains the germ cells in an immunologically privileged location. Sertoli cells also secrete inhibin, which provides negative feedback on the hypothalamus, and androgen-binding protein, which helps modulate androgen activity in the seminiferous tubules. In addition to FSH, Sertoli cell function is modulated by intratesticular testosterone and signals from peritubular myoid cells.
Germ cells (precursors to spermatozoa) are derived from the gonadal ridge and migrate to the testicle before testicular descent. In response to FSH stimulation at puberty, germ cells become spermatogonia and undergo an ordered maturation to become spermatozoa. The entire process of development from spermatogonium to spermatid takes 74 days and is described in 14 steps; as they mature, the developing spermatids progress closer to the lumen of the seminiferous tubule.
Spermatogonia rest on the basement membrane and contain dense nuclei and prominent nucleoli. Three types are described: A dark (Ad), A pale (Ap), and B cells. Ad cells (stem cells) divide to create more Ad cells (stem cell renewal) or differentiate into daughter Ap cells every 16 days. Ap cells mature into B spermatogonia, which then undergo mitotic division to become primary spermatocytes, which are recognized by their large centrally located nuclei and beaded chromatin. The mitotic division does not result in complete separation; rather, daughter cells maintain intracellular bridges, which have functional significance in cell signaling and maturation.
Primary spermatocytes undergo meiosis as the cells successively pass through the preleptotene, leptotene, zygotene, and pachytene stages to become secondary spermatocytes. During this time, the cells cross from the basal to the adluminal compartments. Secondary spermatocytes contain smaller nuclei with fine chromatin. The secondary spermatocytes undergo a second meiosis and become spermatids. This reduction division (ie, meiosis) results in a haploid chromosome number. Therefore, a total of 4 spermatids are made from each spermatocyte.
Next, the spermatids undergo the process of spermiogenesis (through stages named Sb1, Sb2, Sc, Sd1, and Sd2), which involves the casting of excess cytoplasm away as a residual body, the formation of the acrosome and flagella, and the migration of cytoplasmic organelles to their final cellular location. The acrosome, a derivative of the Golgi process, surrounds the nucleus anteriorly and contains enzymes necessary to penetrate the ovum. The mature spermatid is then located adjacent to the tubule lumen and contains dark chromatin with an oval-shaped nucleus.
After their release from the Sertoli cells into the lumen of the seminiferous tubules, the spermatids successively pass through the tubuli recti, rete testis, ductuli efferentes, and, finally, the epididymis (see image below). The epididymis is a 3- to 4-cm long structure with a tubular length of 4-5 m. As sperm move from the head to the tail, they mature and acquire fertilization capacity. Sperm from the head move with immature wide arcs and are generally unable to penetrate the egg, while those from the tail propel forward and have better penetration capacity. The transit time varies with age and sexual activity but is usually from 1-12 days. The epididymis additionally secretes substances for sperm nutrition and protection such as glycerophosphorylcholine, carnitine, and sialic acid.
Sperm next enter the vas deferens, a 30- to 35-cm muscular conduit of Wolffian duct origin. The vas is divided into the convoluted, scrotal, inguinal, retroperitoneal, and ampullary regions and receives its blood supply from the inferior vesical artery. In addition to functioning as a conduit, the vas also has absorptive and secretory properties.
During emission, sperm are propelled forward by peristalsis. After reaching its ampullary portion behind the bladder, the vas joins with the seminal vesicles, at the ejaculatory duct, which empties next to the verumontanum of the prostate.
During ejaculation, the ejaculate is propelled forward by the rhythmic contractions of the smooth muscle that surrounds the ducts and by the bulbourethral muscles and other pelvic muscles. Bladder neck closure during ejaculation is vital to ensure antegrade ejaculation.
Normal ejaculate volume ranges from 1.5 to 5 mL and has a pH level of 7.05-7.8. The seminal vesicles provide 40-80% of the semen volume, which includes fructose for sperm nutrition, prostaglandins and other coagulating substances, and bicarbonate to buffer the acidic vaginal vault. Normal seminal fructose concentration is 120-450 mg/dL, with lower levels suggesting ejaculatory duct obstruction or absence of the seminal vesicles.
The prostate gland contributes approximately 10-30% (0.5 mL) of the ejaculate. Products include enzymes and proteases to liquefy the seminal coagulum. This usually occurs within 20-25 minutes. The prostate also secretes zinc, phospholipids, phosphatase, and spermine. The testicular-epididymal component includes sperm and comprises about 5% of the ejaculate volume.
In addition to the components already listed, semen is also composed of secretions from the bulbourethral (Cowper) glands and the (periurethral) glands of Litre, each producing 2-5% of the ejaculate volume, serving mainly to lubricate the urethra and to buffer the acidity of the residual urine. The ordered sequence of release is important for appropriate functioning.
For conception, sperm must reach the cervix, penetrate the cervical mucus, migrate up the uterus to the fallopian tube, undergo capacitation and the acrosome reaction to digest the zona pellucida of the oocyte, attach to the inner membrane, and release its genetic contents within the egg. The cervical mucus changes consistency during the ovulatory cycle, being most hospitable and easily penetrated at mid cycle. After fertilization, implantation may then take place in the uterus. Problems with any of these steps may lead to infertility.
An estimated 10-15% of couples are considered infertile, defined by the World Health Organization (WHO) as the absence of conception after at least 12 months of unprotected intercourse. In American men, the risk correlates to approximately 1 in 25. Low sperm counts, poor semen quality, or both account for 90% of cases; however, studies of infertile couples without treatment reveal that 23% of these couples conceive within 2 years, and 10% more conceive within 4 years. Even patients with severe oligospermia (<2 million sperm/mL) have a 7.6% chance of conception within 2 years.
Patterns of male infertility vary greatly among regions and even within regions. The highest reported fertility rates are in Finland, while Great Britain has a low fertility rate. A combination of social habits, environmental conditions, and genetics is suspected to contribute to this variation.
Recent debate has occurred in the literature regarding a poorer semen quality, decreased sperm counts (113 million/mL in 1940 compared with 66 million/mL in the 1990s), and decreased fertility in men today compared with fertility 50 years ago. Investigators hypothesize that environmental conditions and toxins have led to this decline; however, others argue that this is solely because of differences in counting methods, laboratory techniques, and geographic variation.
Many patients who present with infertility as their primary symptom have a serious underlying medical disease, such as pituitary adenomas, hormonally active tumors, testicular cancer, liver and renal failure, and cystic fibrosis (CF). Evaluating patients for life-threatening or life-altering conditions during the workup is important.
In addition, the risk of cancer appears to be increased in infertile men. In a study of 2238 infertile men, 451 with azoospermia and 1787 without, male infertility was associated with an increased risk of developing cancer in comparison with the general population.[4, 5] Median age at initial evaluation was 35.7 years, and median follow-up was 6.7 years.
Overall, 29 men developed some type of cancer, including 10 (2.2%) with azoospermia and 19 (1.1%) without azoospermia. Compared with the general population of Texas, infertile men had a higher risk of overall cancer (standardized incidence ratio [SIR], 1.7; 95% confidence interval [CI], 1.2-2.5).
The risk was significantly higher in azoospermic men than in nonazoospermic men (SIR, 2.9; 95% CI, 1.4-5.4). The risk of cancer in nonazoospermic infertile men was similar to that in the general population (SIR, 1.4; 95% CI, 0.9-2.2), although there was a trend toward an elevated risk.
The men who developed cancer in the study developed a variety of malignancies, including prostate cancer, testicular cancer, CNS cancer, melanoma, and stomach cancer.
Isolated conditions of the female are responsible for infertility in 35% of cases, isolated conditions of the male in 30%, conditions of both the male and female in 20%, and unexplained causes in 15%. Even if one partner has an obvious cause for the infertility, a thorough evaluation of both partners for completeness is prudent. In addition, both partners may be aided by evaluation of their sexual practices.
The effect of aging on fertility is unclear. As men age, their testosterone levels decrease, while estradiol and estrone levels increase. Studies have shown that, as men age, their sperm density decreases. Young men have spermatids present in 90% of seminiferous tubules, which decreases to 50% by age 50-70 years and to 10% by age 80 years. Additionally, 50% of Sertoli cells are lost by age 50 years, 50% of Leydig cells are lost by age 60 years. Despite this, aging men may achieve fertility rates similar to those in younger men, although conception often takes longer.
Palermo G, Joris H, Devroey P, Van Steirteghem AC. Pregnancies after intracytoplasmic injection of single spermatozoon into an oocyte. Lancet. 1992 Jul 4. 340(8810):17-8. [Medline].
Matorras R, Diez J, Corcóstegui B, Gutiérrez de Terán G, García JM, Pijoan JI, et al. Spontaneous pregnancy in couples waiting for artificial insemination donor because of severe male infertility. Eur J Obstet Gynecol Reprod Biol. 1996 Dec 27. 70(2):175-8. [Medline].
Carlsen E, Giwercman A, Keiding N, Skakkebaek NE. Evidence for decreasing quality of semen during past 50 years. BMJ. 1992 Sep 12. 305(6854):609-13. [Medline].
Mulcahy N. Male infertility increases overall cancer risk. Medscape Medical News. June 21, 2013; Accessed July 30, 2013. Available at http://www.medscape.com/viewarticle/806619.
Eisenberg ML, Betts P, Herder D, Lamb DJ, Lipshultz LI. Increased risk of cancer among azoospermic men. Fertil Steril. 2013 Jun 12. [Medline].
Ventimiglia E, Capogrosso P, Boeri L, Serino A, Colicchia M, Ippolito S, et al. Infertility as a proxy of general male health: results of a cross-sectional survey. Fertil Steril. 2015 Jul. 104 (1):48-55. [Medline].
Baker HW. Reproductive effects of nontesticular illness. Endocrinol Metab Clin North Am. 1998 Dec. 27(4):831-50. [Medline].
Alshahrani S, Ahmed AF, Gabr AH, Abalhassan M, Ahmad G. The impact of body mass index on semen parameters in infertile men. Andrologia. 2016 Feb 5. [Medline].
Jacobsen KD, Ous S, Waehre H, Trasti H, Stenwig AE, Lien HH, et al. Ejaculation in testicular cancer patients after post-chemotherapy retroperitoneal lymph node dissection. Br J Cancer. 1999 Apr. 80(1-2):249-55. [Medline].
Gundersen TD, Jørgensen N, Andersson AM, Bang AK, Nordkap L, Skakkebæk NE, et al. Association Between Use of Marijuana and Male Reproductive Hormones and Semen Quality: A Study Among 1,215 Healthy Young Men. Am J Epidemiol. 2015 Sep 15. 182 (6):473-81. [Medline].
El Osta R, Almont T, Diligent C, Hubert N, Eschwège P, Hubert J. Anabolic steroids abuse and male infertility. Basic Clin Androl. 2016. 26:2. [Medline].
Wang C, McDonald V, Leung A, Superlano L, Berman N, Hull L, et al. Effect of increased scrotal temperature on sperm production in normal men. Fertil Steril. 1997 Aug. 68(2):334-9. [Medline].
Schatte EC, Orejuela FJ, Lipshultz LI, Kim ED, Lamb DJ. Treatment of infertility due to anejaculation in the male with electroejaculation and intracytoplasmic sperm injection. J Urol. 2000 Jun. 163(6):1717-20. [Medline].
Brackett NL, Lynne CM, Aballa TC, Ferrell SM. Sperm motility from the vas deferens of spinal cord injured men is higher than from the ejaculate. J Urol. 2000 Sep. 164(3 Pt 1):712-5. [Medline].
da Silva BF, Meng C, Helm D, Pachl F, Schiller J, Ibrahim E, et al. Towards understanding male infertility after spinal cord injury using quantitative proteomics. Mol Cell Proteomics. 2016 Jan 26. [Medline].
Talebi AR, Khalili MA, Vahidi S, Ghasemzadeh J, Tabibnejad N. Sperm chromatin condensation, DNA integrity, and apoptosis in men with spinal cord injury. J Spinal Cord Med. 2013 Mar. 36 (2):140-6. [Medline].
Takihara H, Sakatoku J, Fujii M, Nasu T, Cosentino MJ, Cockett AT. Significance of testicular size measurement in andrology. I. A new orchiometer and its clinical application. Fertil Steril. 1983 Jun. 39(6):836-40. [Medline].
Bouloux P, Warne DW, Loumaye E; FSH Study Group in Men's Infertility. Efficacy and safety of recombinant human follicle-stimulating hormone in men with isolated hypogonadotropic hypogonadism. Fertil Steril. 2002 Feb. 77(2):270-3. [Medline].
Whitten SJ, Nangia AK, Kolettis PN. Select patients with hypogonadotropic hypogonadism may respond to treatment with clomiphene citrate. Fertil Steril. 2006 Dec. 86(6):1664-8. [Medline].
Rucker GB, Mielnik A, King P, Goldstein M, Schlegel PN. Preoperative screening for genetic abnormalities in men with nonobstructive azoospermia before testicular sperm extraction. J Urol. 1998 Dec. 160(6 Pt 1):2068-71. [Medline].
Yoshida A, Miura K, Nagao K, Hara H, Ishii N, Shirai M. Sexual function and clinical features of patients with Klinefelter's syndrome with the chief complaint of male infertility. Int J Androl. 1997 Apr. 20(2):80-5. [Medline].
Aiman J, Griffin JE, Gazak JM, Wilson JD, MacDonald PC. Androgen insensitivity as a cause of infertility in otherwise normal men. N Engl J Med. 1979 Feb 1. 300 (5):223-7. [Medline].
Davis-Dao CA, Tuazon ED, Sokol RZ, Cortessis VK. Male infertility and variation in CAG repeat length in the androgen receptor gene: a meta-analysis. J Clin Endocrinol Metab. 2007 Nov. 92 (11):4319-26. [Medline].
Vicdan A, Vicdan K, Günalp S, Kence A, Akarsu C, Isik AZ, et al. Genetic aspects of human male infertility: the frequency of chromosomal abnormalities and Y chromosome microdeletions in severe male factor infertility. Eur J Obstet Gynecol Reprod Biol. 2004 Nov 10. 117(1):49-54. [Medline].
Colombo JB, Naz RK. Modulation of insulin-like growth factor-1 in the seminal plasma of infertile men. J Androl. 1999 Jan-Feb. 20 (1):118-25. [Medline].
Naderi G, Mohseni Rad H, Tabassomi F, Latif A. Seminal insulin-like growth factor-I may be involved in the pathophysiology of infertility among patients with clinical varicocele. Hum Fertil (Camb). 2015 Jun. 18 (2):92-5. [Medline].
Tollner TL, Venners SA, Hollox EJ, Yudin AI, Liu X, Tang G, et al. A common mutation in the defensin DEFB126 causes impaired sperm function and subfertility. Sci Transl Med. 2011 Jul 20. 3 (92):92ra65. [Medline].
Diao R, Fok KL, Chen H, Yu MK, Duan Y, Chung CM, et al. Deficient human β-defensin 1 underlies male infertility associated with poor sperm motility and genital tract infection. Sci Transl Med. 2014 Aug 13. 6 (249):249ra108. [Medline].
Smith HC. Fertility in men with cystic fibrosis assessment, investigations and management. Paediatr Respir Rev. 2010 Jun. 11 (2):80-3. [Medline].
Zahalsky MP, Berman AJ, Nagler HM. Evaluating the risk of epididymal injury during hydrocelectomy and spermatocelectomy. J Urol. 2004 Jun. 171(6 Pt 1):2291-2. [Medline].
Purohit RS, Wu DS, Shinohara K, Turek PJ. A prospective comparison of 3 diagnostic methods to evaluate ejaculatory duct obstruction. J Urol. 2004 Jan. 171(1):232-5; discussion 235-6. [Medline].
Cooper TG, Noonan E, von Eckardstein S, Auger J, Baker HW, Behre HM, et al. World Health Organization reference values for human semen characteristics. Hum Reprod Update. 2010 May-Jun. 16(3):231-45. [Medline].
Pierik FH, Dohle GR, van Muiswinkel JM, Vreeburg JT, Weber RF. Is routine scrotal ultrasound advantageous in infertile men?. J Urol. 1999 Nov. 162(5):1618-20. [Medline].
Raman JD, Nobert CF, Goldstein M. Increased incidence of testicular cancer in men presenting with infertility and abnormal semen analysis. J Urol. 2005 Nov. 174(5):1819-22; discussion 1822. [Medline].
Yanagimachi R, Yanagimachi H, Rogers BJ. The use of zona-free animal ova as a test-system for the assessment of the fertilizing capacity of human spermatozoa. Biol Reprod. 1976 Nov. 15(4):471-6. [Medline].
Finkel DM, Phillips JL, Snyder PJ. Stimulation of spermatogenesis by gonadotropins in men with hypogonadotropic hypogonadism. N Engl J Med. 1985 Sep 12. 313 (11):651-5. [Medline].
Santi D, Granata AR, Simoni M. FSH treatment of male idiopathic infertility improves pregnancy rate: a meta-analysis. Endocr Connect. 2015 Sep. 4 (3):R46-58. [Medline].
Pavlovich CP, King P, Goldstein M, Schlegel PN. Evidence of a treatable endocrinopathy in infertile men. J Urol. 2001 Mar. 165 (3):837-41. [Medline].
Whitten SJ, Nangia AK, Kolettis PN. Select patients with hypogonadotropic hypogonadism may respond to treatment with clomiphene citrate. Fertil Steril. 2006 Dec. 86 (6):1664-8. [Medline].
Chua ME, Escusa KG, Luna S, Tapia LC, Dofitas B, Morales M. Revisiting oestrogen antagonists (clomiphene or tamoxifen) as medical empiric therapy for idiopathic male infertility: a meta-analysis. Andrology. 2013 Sep. 1 (5):749-57. [Medline].
Reynolds JC, McCall A, Kim ED, Lipshultz LI. Bladder neck collagen injection restores antegrade ejaculation after bladder neck surgery. J Urol. Apr 1998. 159(4):1303. [Medline].
Safarinejad MR, Safarinejad S, Shafiei N, Safarinejad S. Effects of the reduced form of coenzyme q(10) (ubiquinol) on semen parameters in men with idiopathic infertility: a double-blind, placebo controlled, randomized study. J Urol. 2012 Aug. 188(2):526-31. [Medline].
Binsaleh S, Lo KC. Varicocelectomy: microsurgical inguinal varicocelectomy is the treatment of choice. Can Urol Assoc J. 2007 Sep. 1 (3):277-8. [Medline].
Huang HC, Huang ST, Chen Y, Hsu YC, Chang PC, Hsieh ML. Prognostic factors for successful varicocelectomy to treat varicocele-associated male infertility. Reprod Fertil Dev. 2014 Mar. 26 (3):485-90. [Medline].
Kondo Y, Ishikawa T, Yamaguchi K, Fujisawa M. Predictors of improved seminal characteristics by varicocele repair. Andrologia. 2009 Feb. 41 (1):20-3. [Medline].
Al Bakri A, Lo K, Grober E, Cassidy D, Cardoso JP, Jarvi K. Time for improvement in semen parameters after varicocelectomy. J Urol. 2012 Jan. 187(1):227-31. [Medline].
Abdel-Meguid TA, Al-Sayyad A, Tayib A, Farsi HM. Does Varicocele Repair Improve Male Infertility? An Evidence-Based Perspective From a Randomized, Controlled Trial. Eur Urol. 2010 Dec 21. [Medline].
Wang J, Xia SJ, Liu ZH, Tao L, Ge JF, Xu CM, et al. Inguinal and subinguinal micro-varicocelectomy, the optimal surgical management of varicocele: a meta-analysis. Asian J Androl. 2015 Jan-Feb. 17 (1):74-80. [Medline].
Parekattil SJ, Gudeloglu A. Robotic assisted andrological surgery. Asian J Androl. 2013 Jan. 15 (1):67-74. [Medline].
Trost L, Parekattil S, Wang J, Hellstrom WJ. Intracorporeal robot-assisted microsurgical vasovasostomy for the treatment of bilateral vasal obstruction occurring following bilateral inguinal hernia repairs with mesh placement. J Urol. 2014 Apr. 191 (4):1120-5. [Medline].
Gudeloglu A, Brahmbhatt JV, Parekattil SJ. Robotic microsurgery in male infertility and urology-taking robotics to the next level. Transl Androl Urol. 2014 Mar. 3 (1):102-12. [Medline].
Belker AM, Thomas AJ, Fuchs EF. Results of 1,469 microsurgical vasectomy reversals by the Vasovasostomy Study Group. J Urol. 1991 Mar. 145(3):505-11. [Medline].
Fenig DM, Kattan MW, Mills JN, et al. Nomogram to preoperatively predict the probability of requiring epididymovasostomy during vasectomy reversal. J Urol. 2012 Jan. 187(1):215-8. [Medline].
Hsiao W, Sultan R, Lee R, Goldstein M. Increased Follicle-Stimulating Hormone is Associated With Higher Assisted Reproduction Use After Vasectomy Reversal. J Urol. 2011 Jun. 185(6):2266-71. [Medline].
Anger JT, Goldstein M. Intravasal "toothpaste" in men with obstructive azoospermia is derived from vasal epithelium, not sperm. J Urol. 2004 Aug. 172(2):634-6. [Medline].
Berger RE. Triangulation end-to-side vasoepididymostomy. J Urol. 1998 Jun. 159(6):1951-3. [Medline].
Hauser R, Yogev L, Paz G, Yavetz H, Azem F, Lessing JB, et al. Comparison of efficacy of two techniques for testicular sperm retrieval in nonobstructive azoospermia: multifocal testicular sperm extraction versus multifocal testicular sperm aspiration. J Androl. 2006 Jan-Feb. 27(1):28-33. [Medline].
Lewis R. Freezing sperm a viable option in azoospermic men. Medscape Medical News. August 12, 2013. [Full Text].
Omurtag K, Cooper A, Bullock A, et al. Sperm recovery and IVF after testicular sperm extraction (TESE): effect of male diagnosis and use of off-site surgical centers on sperm recovery and IVF. PLoS One. 2013. 8(7):e69838. [Medline]. [Full Text].
Schlegel PN. Testicular sperm extraction: microdissection improves sperm yield with minimal tissue excision. Hum Reprod. 1999 Jan. 14 (1):131-5. [Medline].
Belker AM, Sherins RJ, Dennison-Lagos L, Thorsell LP, Schulman JD. Percutaneous testicular sperm aspiration: a convenient and effective office procedure to retrieve sperm for in vitro fertilization with intracytoplasmic sperm injection. J Urol. 1998 Dec. 160(6 Pt 1):2058-62. [Medline].
Mathieu C, Ecochard R, Bied V, Lornage J, Czyba JC. Cumulative conception rate following intrauterine artificial insemination with husband's spermatozoa: influence of husband's age. Hum Reprod. 1995 May. 10 (5):1090-7. [Medline].
Bellver J, Garrido N, Remohí J, Pellicer A, Meseguer M. Influence of paternal age on assisted reproduction outcome. Reprod Biomed Online. 2008 Nov. 17 (5):595-604. [Medline].
Olson CK, Keppler-Noreuil KM, Romitti PA, Budelier WT, Ryan G, Sparks AE, et al. In vitro fertilization is associated with an increase in major birth defects. Fertil Steril. 2005 Nov. 84(5):1308-15. [Medline].
Silver RI, Rodriguez R, Chang TS, Gearhart JP. In vitro fertilization is associated with an increased risk of hypospadias. J Urol. 1999 Jun. 161(6):1954-7. [Medline].
Jakab A, Sakkas D, Delpiano E, Cayli S, Kovanci E, Ward D, et al. Intracytoplasmic sperm injection: a novel selection method for sperm with normal frequency of chromosomal aneuploidies. Fertil Steril. 2005 Dec. 84 (6):1665-73. [Medline].
Van Steirteghem AC, Liu J, Joris H, Nagy Z, Janssenswillen C, Tournaye H, et al. Higher success rate by intracytoplasmic sperm injection than by subzonal insemination. Report of a second series of 300 consecutive treatment cycles. Hum Reprod. 1993 Jul. 8(7):1055-60. [Medline].
Wald M, Ross LS, Prins GS, Cieslak-Janzen J, Wolf G, Niederberger CS. Analysis of outcomes of cryopreserved surgically retrieved sperm for IVF/ICSI. J Androl. 2006 Jan-Feb. 27(1):60-5. [Medline].
Rehman R, Fatima SS, Hussain M, Khan R, Khan TA. Effect of endometrial thickness on pregnancy outcome after intracytoplasmic sperm injection. J Pak Med Assoc. 2015 May. 65 (5):448-51. [Medline].
Scott R, MacPherson A, Yates RW, Hussain B, Dixon J. The effect of oral selenium supplementation on human sperm motility. Br J Urol. 1998 Jul. 82(1):76-80. [Medline].
Klemetti R, Gissler M, Sevon T, Koivurova S, Ritvanen A, Hemminki E. Children born after assisted fertilization have an increased rate of major congenital anomalies. Fertil Steril. 2005 Nov. 84(5):1300-7. [Medline].
Agbugui JO, Omokhudu O. Posterior urethral valve: an unusual cause of primary male infertility. J Reprod Infertil. 2015 Apr-Jun. 16 (2):113-5. [Medline].
Mechlin C, Mccullough A. V1590 robotic microsurgical varicocele repair: initial experience and surgical outcomes from a single academic center. J Urol. 2013. 189:e652-3. [Full Text].
|Ejaculate volume||Low (< 1.5 mL)||Postejaculation urine (retrograde ejaculation)
TRUS (absence of vas deferens)
Hormonal evaluation (hypogonadism)
|High (>5 mL)||Likely contaminant|
|Semen quality||Does not coagulate||TRUS (ejaculatory duct obstruction)|
|Does not liquefy||Hormonal analysis|
|Sperm density||Oligospermia (< 20 million per mL)
Severe oligospermia (< 5 million per mL)
|TRUS (partial ejaculatory duct obstruction)
Antisperm antibody evaluation
Physical examination for varicocele
|Azoospermia||Sperm centrifuged to verify azoospermia
Postejaculation urine (retrograde ejaculation)
Testicular biopsy (testicular failure)
TRUS (ejaculatory duct obstruction)
Physical examination for varicocele
|*All semen analyses with abnormal results should be repeated.|