Imaging of Male Infertility: Pictorial Review

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1 JR Integrative Imaging LIFELONG LERNING FOR RDIOLOGY Imaging of Male Infertility: Pictorial Review William L. Simpson, Jr. 1 and Dana R. Rausch STRCT Objective This article will review the workup of infertility in a male. The imaging of common conditions associated with infertility, including varicocele, ejaculatory duct obstruction, seminal vesicle agenesis, and undescended testis, will be shown, as well as other conditions that can be incidentally seen. Conclusion The analysis of infertility in males has become more common in recent years. The practicing radiologist should be familiar with the evaluation of the infertile man and the common radiologic findings and disease processes associated with infertility. INTRODUCTION In recent years, many couples have delayed starting a family to concentrate on careers. s a consequence, these older couples frequently have difficulty conceiving and are undergoing infertility investigations. Infertility is classified as primary when there has never been a pregnancy for the couple. Secondary infertility refers to the situation in which a prior pregnancy was possible involving at least one partner of the couple. Infertility is an issue for 15 20% of couples [1 3]. lthough many assume that infertility is predominantly related to the woman, the cause of infertility can rest with either the female or the male partner. male factor is involved in 50% of cases and is the sole cause of infertility in 30% [2 5]. Evaluation The evaluation of the infertile man begins with a detailed clinical history and physical examination. It is important to inquire about the man s reproductive history. With unprotected intercourse, if the woman has become pregnant with another partner but the man has not, or if there has been a significant intervening time period, interval surgery, or serious illness since the man s prior conception, then a male factor should be considered. t the physical examination, the physician should carefully examine the man s body habitus and perform a complete genitourinary examination [5]. Next, a semen analysis is performed. Normal semen is defined as a semen volume of greater than 2 ml, concentration of greater than 20 million/ml, motility of greater than 50%, and normal morphology of more than 30% [6]. These parameters constitute a routine semen analysis. More advanced testing can also be performed on the semen sample to detect abnormalities of the seminal fluid or sperm function [2, 5]. Furthermore, endocrine disorders can be detected with various hormonal assays. These include testosterone, follicle-stimulating hormone, luteinizing hormone, prolactin, and estradiol levels [2, 4]. Imaging can then be performed. Ultrasound and MRI are the techniques commonly performed. Scrotal ultrasound is useful in the evaluation of the testicles and extratesticular scrotal structures (i.e., epididymis, peritesticular veins, and spermatic cord). Transrectal ultrasound (TRUS) and MRI can yield pertinent information about the distal ductal system and prostate gland. MRI is also used to evaluate the brain and sella turcica in cases in which an abnormality of these areas is suspected on the basis of hormonal assays. Causes of Male Infertility The various causes of male infertility can be subcategorized as obstructive and nonobstructive azoo- or hypospermia. Nonobstructive disease includes varicocele, endocrinopathy, chromosomal abnormality, cryptorchidism, anabolic steroid abuse, gonadotoxin exposure, primary testicular failure, and ejaculatory disorders. Obstructive disorders include congenital bilateral absence of the vas deferens, ejaculatory duct obstruction, and prostatic cysts. The most common cause of correctable male infertility is a varicocele. These are best imaged with gray-scale and col- Keywords: conception, endocrine abnormality, infertility, reproductive organs, scrotal contents DOI: /JR Received June 30, 2008; accepted after revision ugust 12, oth authors: Department of Radiology, Mount Sinai Medical Center, ox 1234, New York, NY ddress correspondence to W. L. Simpson, Jr. JR 2009;192:S98 S X/09/1926 S98 merican Roentgen Ray Society S98 JR:192, June 2009

2 Male Infertility or Doppler sonography (Fig. 1). Varicoceles are defined as internal spermatic veins that are dilated to greater than 3 mm. Valsalva maneuvers can be used during ultrasound to evaluate the change in size of the veins with increased abdominal pressure. Varicoceles are found in 40% of men with primary infertility and between 45 and 80% of men with secondary infertility [4, 5]. Even a subclinical varicocele can have negative effects on spermatogenesis [7]. When unilateral, varicoceles are more commonly left-sided. If isolated right-sided varicoceles are detected, which is uncommon, the possibility of a retroperitoneal process compressing the right gonadal vein should be considered. Gonadotropin-releasing hormone from the thalamus promotes the release of luteinizing hormone and follicle-stimulating hormone from the pituitary gland. Luteinizing hormone stimulates the production of testosterone, which is needed for sperm production in the testis, and follicle-stimulating hormone controls spermatogenesis. Various abnormalities of this hypothalamic pituitary gonadal axis can result in male infertility [4, 5]. nabolic steroid use interferes with the normal feedback loop of the hypothalamic pituitary gonadal axis because of the introduction of exogenous androgens. Pituitary adenoma, including pro lactinoma (Fig. 2), is a rare cause of infertility. In addition, disorders of androgen function (e.g., congenital adrenal hyperplasia) can also interfere with the hypothalamic pituitary gonadal axis. Idiopathic hypogonadotropic hypogonadism results from abnormal synthesis and release of gonadotropin-releasing hormone. Kallmann s syndrome and Prader-Willi syndrome are examples of such endocrinopathies. In fact, Kallmann s syndrome is the most common X-linked disorder in male infertility, with an incidence of 1 in 10,000 60,000 live births [4, 5]. Chromosomal abnormalities can lead to altered spermatogenesis, decreased sperm motility, impaired genital tract development, and decreased fertilization capacity. Fig year-old man with low sperm count undergoing evaluation for infertility. and, Sagittal sonograms of the superior aspect of the left hemiscrotum show multiple dilated peritesticular veins on color Doppler imaging () and an individual vein on gray-scale imaging () that measures 4.2 mm when Valsalva maneuver is used. These findings are compatible with a varicocele. When infertility is chromosomally mediated, it is more likely to be related to the sex chromosomes than to the autosomal chromosomes [4]. Klinefelter s syndrome is the most common sex chromosome disorder [4, 5]. Male patients may be tall or obese and may have a female hair distribution, low intelligence, or diabetes. These men have small, firm testes and are azoospermic (or severely oligospermic) and are rarely able to initiate a pregnancy through natural conception. Less common abnormalities include mixed gonadal dysgenesis and XX male (46,XX) and XYY male (47,XYY) karyotypes. Undescended testes, or cryptorchidism, leads to infertility [4, 5, 8], but the cause is unclear. Even after its detection and subsequent orchiopexy, men may be subfertile. When the testis fails to descend into the scrotum, it is usually found in the inguinal canal, but it may be intraabdominal. Ultrasound is most commonly used for evaluation and may show a small testis of heterogeneous echotexture outside the hemiscrotal sac (Figs. 3 and 4). The most common abnormality of the extratesticular ductal system is congenital bilateral absence of the vas deferens [4, 5], which occurs in 1 2% of infertile men. It is considered a genital manifestation of cystic fibrosis [4, 5, 9, 10]. It also is seen in association with unilateral renal agenesis when it is not related to cystic fibrosis [4, 5, 9, 11]. This diagnosis can be suspected on the basis of a physical examination in which the vas deferens is not palpable. t sonographic evaluation, the epididymal heads are prominent and the rete testis is dilated [9, 11] (Fig. 5). On MRI, low signal throughout the peripheral zone of the prostate gland is always seen [11]. The seminal vesicles may be absent, as noted on transabdominal sonography or MRI (Fig. 6). Obstruction of the ejaculatory ducts is another cause of male infertility. It can be congenital and associated with midline cysts or acquired in relation to postinflammatory stenosis, typically from a prior sexually transmitted disease JR:192, June 2009 S99

3 Simpson and Rausch [9 11]. When an obstruction is suspected, MRI or TRUS is performed (Fig. 7). Male infertility may be related to prostatic cysts. These are midline in location and are embryologically of müllerian or wolffian origin [1, 9 11]. Those of müllerian derivation C Fig year-old man with mildly elevated prolactin level. D, Coronal T1-weighted (), coronal T2-weighted (), and coronal (C) and sagittal (D) T1-weighted contrast-enhanced MR images show adenoma on the right side of the pituitary gland (arrow) that has a central area of fluid or necrosis. are more common, do not contain sperm, and are usually utricle cysts. Those of wolffian origin usually contain sperm. It is common for these midline cysts to compress the ejaculatory ducts and cause obstruction. This process can be imaged with either MRI or TRUS (Fig. 8). D S100 JR:192, June 2009

4 Male Infertility Several substances such as certain drugs, alcohol, tobacco, and others have been proven to be gonadotoxic (ppendix 1). Exposure to these substances can affect spermatogenesis and result in infertility. C Fig year-old man with bilateral cryptorchidism., Midline transverse sonogram of the scrotum through the median raphe reveals no testis in the scrotal sac. and C, Sagittal sonograms show both testes to be located in the inguinal canals and diminutive. Testicular volume measured 2 3 ml each (normal range, ml). In the course of the infertility evaluation, clinically significant disorders will be detected in an estimated 1.1% of patients [2]. These abnormalities can be categorized as scrotal and nonscrotal. Fig year-old man with history of left cryptorchidism after orchiopexy at age 6 years. and, Sagittal sonograms of both testes show that the left testis () is smaller than the right () and markedly heterogeneous. JR:192, June 2009 S101

5 Simpson and Rausch Scrotal abnormalities include testicular tumors, hydroceles, microlithiasis, and epididymal cysts. Malignant germ cell tumors account for 90 95% of intratesticular primary tumors; seminoma is the most common subtype [8] (Fig. 9). Fig year-old man with no palpable vas deferens on physical examination. Midline transverse sonogram of both testes shows dilatation of the rete testis in the medial aspect of each testis. These findings are typical of congenital bilateral absence of the vas deferens. They are most commonly imaged with sonography and appear as hypoechoic masses. In addition, the incidence of tumors in the undescended testis is increased. hydrocele is an accumulation of fluid in the tunica vaginalis (Fig. 10); it is commonly related to trauma or infection. Studies have shown an increased prevalence of hydroceles in infertile men compared with their fertile counterparts [12, 13]. Microlithiasis is an uncommon condition in which calcifications form in the seminiferous tubules. The calcifications are generally 3 mm or smaller and do not shadow on sonography (Fig. 11). Microlithiasis has been associated with several conditions such as Klinefelter s syndrome, cryptorchidism, varicocele, testicular atrophy, torsion, tumors, and infertility [8, 12]. The mechanism by which microlithiasis affects spermatogenesis is unknown [12]. Epididymal cysts are common and can be simple cysts containing clear fluid or spermatoceles that contain sperm (Fig. 12). Epididymal cysts are frequently seen in both fertile and infertile men. It has been postulated that compression of the ductal system in the epididymis by such cysts can lead to infertility [12]. Nonscrotal abnormalities include renal agenesis associated with urologic disorders (Fig. 13), spinal or brain tumors, and Peyronie disease. Neurologic tumors can be incidentally found when infertile men undergo brain MRI in a search for endocrine abnormalities. Peyronie disease is due to fibrosis, often with calcification, of the tunica albuginea surrounding the Fig year-old hypospermic male. and, xial () and coronal () T2-weighted MR images using an endorectal coil show a normal left seminal vesicle (arrows) but none on the right. S102 JR:192, June 2009

6 Male Infertility Fig. 7 Obstruction of ejaculatory ducts., In 28-year-old man, axial 3D T2-weighted MR image shows two normal ejaculatory ducts entering the prostate gland (arrows)., In 33-year-old man, axial 3D T2-weighted MR image shows a normal left ejaculatory duct (arrow). The right ejaculatory duct is absent. C Fig. 8 Prostatic cysts. and, xial () and sagittal () T2-weighted MR images using an endorectal coil (asterisk) in a 26-year-old man show a large midline cyst (arrow) limited to the prostate gland. C, xial T2-weighted MR image using endorectal coil in a 29-year-old man shows a small utricle cyst (arrow). JR:192, June 2009 S103

7 Simpson and Rausch Fig year-old asymptomatic, hypospermic man undergoing infertility evaluation. Transverse sonogram of the right testicle shows multiple hypoechoic masses in the parenchyma, consistent with multifocal tumor. Pathology at surgical resection revealed seminoma. Fig. 11 Longitudinal sonogram of a testicle of a 25-year-old man undergoing scrotal sonography as part of an infertility evaluation shows multiple punctate calcifications scattered throughout the parenchyma, consistent with testicular microlithiasis. penile shaft. lthough Peyronie disease is frequently seen in older men, it can be found in younger men and be a source for infertility secondary to erectile dysfunction. The plaques of Peyronie disease can be imaged with sonography, especially when they are calcified, or with MRI when enhancement of the plaques suggests an active inflammatory process (Fig. 14). Fig year-old man after scrotal trauma 1 week previously who presents with swelling of the scrotum. Transverse sonogram of the scrotum reveals a large amount of fluid surrounding the testicle, consistent with a hydrocele. Fig year-old asymptomatic man undergoing sonography as part of an infertility evaluation. Longitudinal sonogram of the epididymal head shows a cyst with posterior through-transmission. Conclusion Given the prevalence of male infertility, the radiologist s familiarity with its appropriate imaging workup and recognition of the commonly involved pathologic processes is critical. Imaging plays a key role in the evaluation of the hypospermic or azoospermic man. It can detect correctable abnormalities, which can lead to a successful conception. S104 JR:192, June 2009

8 Male Infertility Fig year-old man found to have an absent left seminal vesicle on physical examination and transrectal ultrasound (not shown). Transverse T2-weighted MR image through mid abdomen shows a normal right kidney and bowel in the left renal fossa. No left kidney was identified in the remainder of the abdomen or in pelvis, consistent with left renal agenesis. Fig year-old man with infertility and painful erections who was found on physical examination to have a palpable abnormality along the shaft of the penis., Transverse sonogram through the shaft of the penis reveals a large calcification along the anterior aspect of the left corpus cavernosum (arrow) and a smaller calcification along the right corpora (arrowhead), consistent with Peyronie disease. (Fig. 14 continues on next page) JR:192, June 2009 S105

9 Simpson and Rausch It can also reveal potentially life-threatening disorders in the course of an infertility evaluation. References 1. Parsons R, Fisher M, ar-chama N, Mitty H. MR imaging in male infertility. RadioGraphics 1997; 17: Spitz, Kim ED, Lipshultz LI. Contemporary approach to the male infertility evaluation. Obstet Gynecol Clin North m 2000; 27: Collins JI, Woodward PJ. Radiological evaluation of infertility. Semin Ultrasound CT MR 1995; 16: rugh VM, Matschke HM, Lipshultz LI. Male factor infertility. Endocrinol Metab Clin N m 2003; 32: rugh VM, Lipshultz LI. Male factor infertility: evaluation and management. Med Clin N m 2004; 88: World Health Organization. WHO laboratory manual for the examination of human semen and sperm cervical mucus interaction, 4th ed. Cambridge, UK: Cambridge University Press, 1999 Fig. 14 (continued) 37-year-old man with infertility and painful erections who was found on physical examination to have a palpable abnormality along the shaft of the penis. and C, Contrast-enhanced axial () and sagittal (C) T1-weighted MR images of the penis show enhancing plaque (arrows) along the anterior aspect of both the corpora cavernosum in and the anterior and posterior aspects of the left corpus cavernosum in C. 7. Kondoh N, Meguro N, Matsumiya K, Namiki M, Kiyohara H, Okuyama. Significance of subclinical varicocele detected by scrotal sonography on male infertility: a preliminary report. J Urol 1993; 150: Ragheb D, Higgins JL. Ultrasonography of the scrotum: technique, anatomy and pathologic entities. J Ultrasound Med 2002; 21: Cornud F, mar E, Hamida K, Thiounn N, Hélénon O, Moreau JF. Imaging in male hypofertility and impotence. JU Int 2000; 86[suppl 1]: Raviv G, Mor Y, Levron J, et al. Role of transrectal ultrasonography in the evaluation of azoospermic men with low-volume ejaculate. J Ultrasound Med 2006; 25: Cornud F, elin X, Delafontaine D, mar T, Hélénon O, Moreau JF. Imaging of obstructive azoospermia. Eur Radiol 1997; 7: Qublan HS, l-okoor K, l-ghoweri S, bu-qama. Sonographic spectrum of scrotal abnormalities in infertile men. J Clin Ultrasound 2007; 35: Dandapat MC, Padhi NC, Patra P. Effect of hydrocele on testis and spermatogenesis. r J Surg 1990; 77: C ppendix 1 appears on the next page. S106 JR:192, June 2009

10 Male Infertility PPENDIX 1: Gonadotoxic Substances Drugs Spironolactone Ca++ channel blockers α-blockers Nitrofurantoin Erythromycin Tetracycline Cimetidine Colchicine llopurinol Sulfasalazine Cyclosporin Thiazide ß-blockers ntipsychotics Chemotherapy agents FOR YOUR INFORMTION Other Substances lcohol Tobacco Cocaine Marijuana Organic solvents Pesticides Heavy metals Printing attery manufacturing Radiation Therapeutic radiation Nuclear power plant workers Heat Prolonged hot tub use The reader s attention is directed to the Self-ssessment-Module for this article, which appears on the following pages. JR:192, June 2009 S107

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