Human Reproduction, Vol. 16, No. 6, 1218-1220,
June 2001
© 2001 European Society of Human Reproduction and Embryology
Azoospermia due to testicular amyloidosis in a patient with familial Mediterranean fever: Case report
1 Department of Obstetrics and Gynecology, 2 Department of Pathology, Hadassah University Hospital, Mount Scopus and 3 Department of Medicine, Hadassah University Hospital, Ein-Kerem, Jerusalem, Israel
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Abstract |
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We describe a patient suffering from familial Mediterranean fever (FMF) who presented to our clinic with secondary infertility of 2 years due to amyloid A amyloidosis. His spermiogram disclosed azoospermia. A testicular biopsy revealed hyalinized tubules devoid of full spermatogenesis and containing abundant amyloid, confirmed by Congo red stain. We suggest that testicular amyloidosis be taken into consideration when dealing with azoospermic FMF patients. In view of the progressive nature of amyloid accumulation in the testis we propose to follow routinely the spermiogram of FMF patients with renal amyloidosis. Furthermore, consideration of sperm cryopreservation is suggested in these cases. In FMF patients with azoospermia consideration of testicular biopsy is recommended as early as possible in order to increase the chance of sperm retrieval.
Key words: amyloidosis/azoospermia/recurrent polyserositis/testicular biopsy
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Introduction |
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Familial Mediterranean fever (FMF) is an hereditary disease characterized by recurrent attacks of fever, peritonitis, pleuritis, arthritis and erysipelas-like skin lesions. The disease is prevalent among populations originating in the Mediterranean basin. One of the main complications of FMF is the development of amyloidosis, primarily in the kidneys, leading to chronic renal failure. Following renal amyloidosis some FMF patients may have amyloid deposits in their liver, spleen and heart. Testicular amyloidosis is relatively rare but can also occur, typically being asymptomatic. However, it may lead to azoospermia. We present an FMF patient with secondary infertility due to azoospermia associated with testicular amyloid deposition. We wish to discuss the importance of checking spermiograms along the course of the disease and performing an early testicular biopsy in these FMF patients once azoospermia ensues.
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Case report |
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A 46 year old man, a father of five children, came to our clinic for evaluation of secondary infertility. The patient suffered from rheumatic fever in childhood and at the age of 14 years an additional diagnosis of familial Mediterranean fever (FMF) was made. The patient was non-compliant and neither took prophylactic antibiotics nor colchicine for FMF. At the age of 40 years he had an aortic valve replacement due to significant aortic stenosis with regurgitation. A year later, he had kidney transplantation because of end-stage renal failure due to amyloidosis. Since then, he had been treated with cyclosporin A (Novartis, Basel, Switzerland), azathioprine (Glaxo-Wellcome, Uxbridge, UK) and prednisone (Vitamed, Bat-Yam, Israel). After renal transplantation and while on these medications, the patient fathered a child. Amyloid deposition was detected in rectal and kidney biopsies and in his replaced aortic valve.
On physical examination the testes, vas deferens and epipidymides were found to be normal. Varicocele was not palpated. The serum follicle-stimulating-hormone (FSH) concentration was elevated 17 mIU/ml (normal range 1–12 mIU/ml) and the serum testosterone was normal. Scrotal ultrasound scan was normal as well. His semen analysis disclosed azoospermia.
The patient underwent an uneventful open testicular biopsy. The biopsy specimen revealed decreased spermatogenesis with spermatogenic arrest to the stage of spermatocytes (Figure 1
). The seminipherous tubules and the blood vessels showed focal amyloid deposits (Figure 2), which subsequently stained positively with Congo red (Figure 3).
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Discussion |
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The present patient illustrates the consequences of non- compliance in colchicine treatment in FMF. One of the most notorious complications of FMF is amyloidosis that may affect primarily the kidneys, leading to renal failure. Later it can be deposited in other organs such as the liver, spleen and heart. The finding of amyloidosis in the testes is less commonly known. The amyloid in FMF is formed from serum amyloid A (SAA), an acute phase protein produced in response to inflammation (Falk et al., 1997
).
In patients with FMF complicated by renal failure, azoospermia could be ascribed to several causes. Exposure to chemotoxic agents such as cyclosporin A and azathioprine could lead to testicular failure (Lazowski et al., 1982). Advanced uraemia may impair testicular function leading to oligo- or azoospermia (Prem et al., 1996). Colchicine, which is the treatment of choice for FMF since 1972, has been encountered as a possible cause of azoospermia (Haimov-Kochman and Ben-Chetrit, 1998). Amyloidosis of the testes is the least known and the most controversial cause of azoospermia. Testicular amyloid infiltration was reported usually in association with diffuse long-standing disease. Lazowski et al. (1982) reported 11 men with chronic rheumatoid arthritis complicated by systemic amyloidosis (Lazowski et al., 1982). Azoospermia and oligoteratoasthenospermia were detected in seven of them. Nevertheless, amyloid deposits were identified in the vascular walls and in the rete testis in only three of them. Handelsman et al. (1983) reported a patient with azoospermia, hypogonadism and massive testicular infiltration due to amyloidosis (Handelsman et al., 1983). Recently, Schrepferman et al. (2000) reported an azoospermic patient with familial amyloidosis associated with abnormal production of apolipoprotein A1, in whom amyloid deposition in the testes was detected along with normal spermatogenesis (Schrepferman et al., 2000).
In a previous report we described two FMF patients with azoospermia. Testicular biopsy revealed abundant amyloid and marked germ cell aplasia in one, and maturation arrest of the spermatocytes with amyloid deposition in the blood vessels in the other patient (Ben Chetrit et al., 1998). Two other reports of isolated testicular amyloidosis have been reported, but in each case the finding was incidental (Erkun, 1945; Tripathi and Desautels, 1969).
The association between testicular amyloidosis and secondary azoospermia remains unclear. It is still unknown whether amyloid disturbs sperm transport by obliteration of intra-testicular cannaliculi, causing obstructive azoospermia, or disrupts sperm production by its direct effect on the seminipherous tubules. Incidental disclosure of amyloid in the testicles of an asymptomatic man along with its finding in testicular biopsies of azoospermic patients suggest that progressive parenchymal replacement with amyloid probably plays a role. The array of pathological results of testicular biopsies from complete germ cell aplasia to normal spermatogenesis could be viewed as different stages in the accumulation of amyloid in the testes.
In the light of the present case and our previous two cases (Haimov-Kochman and Ben-Chetrit, 1998), we recommend a routine spermiogram follow up in young FMF patients with renal or other organ amyloidosis. Furthermore, sperm cryopreservation should also be advised in these patients in order to circumvent developing azoospermia in the future.
The possibility of testicular amyloidosis should be taken into account when dealing with azoospermia in FMF patients, especially in those who are non-compliant or already have renal amyloidosis. Testicular biopsy should be kept only for azoospermic men with FMF who have not cryopreserved spermatozoa prior to this stage and it should be considered for diagnostic purposes and for sperm retrieval. The chances of successful testicular sperm retrieval are probably better in cases of obstructive azoospermia due to cannaliculi obliteration by amyloid than in cases of testicular failure due to parenchymal distortion by amyloid. It is suggested that the longer the process of amyloid deposition in the testis the more meagre the chance of successful sperm retrieval. Testicular sperm cryopreservation and micromanipulation techniques could allow the use of IVF later on.
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Notes |
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4 To whom correspondence should be addressed. E-mail: eldad{at}hadassah.org.il
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References |
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TopAbstractIntroductionCase reportDiscussionReferences |
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Ben Chetrit, E., Backenroth, R., Haimov-Kochman, R. et al. (1998) Azoospermia in familial Mediterranean fever patients: the role of colchicine and amyloidosis. Ann. Rheum Dis., 57, 259–260.
Erkun, S. (1945) Amyloid tumor of left testis. Turk. Tip. Cemiy. Mecm., 11, 392–393.
Falk, R.H., Comenzo, R.L. and Skinner, M. (1997) The systemic amyloidoses. N. Engl. J.Med., 337, 898–909.
Haimov-Kochman, R. and Ben Chetrit, E. (1998) The effect of colchicine treatment on sperm production and function: a review. Hum. Reprod., 13, 360–362.
Handelsman, D.J., Yo, D.K. and Turtle, J.R. (1983) Hypogonadism and massive testicular infiltration due to amyloidosis. J. Urol., 129, 610–612.[Medline]
Lazowski, Z., Janczewski, Z. and Polowiec, Z. (1982) The effect of alkylating agents on the reproductive and hormonal testicular function in patients with rheumatoid arthritis. Scand. J. Rheumatol., 11, 49–54.[Medline]
Prem, A.R., Punekar, S.V., Kalpana, A.R. et al. (1996) Male reproductive function in uremia: efficacy of haemodialysis and renal transplantation. Br. J. Urol., 78, 635–638.
Schrepferman, C.G., Lester, D.R. and Sandlow, J.I. (2000) Testicular amyloid deposition as a cause of secondary azoospermia. Urology., 55, 145i–145ii.
Tripathi, V.N.P. and Desautels, R.E. (1969) Primary amyloidosis of the urogenital system: a study of 16 cases and brief review. J. Urol., 102, 96–101.[Medline]
Submitted on August 8, 2000; accepted on March 3, 2001.
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