Global Advanced Research Journal of Medicine and Medical Science (ISSN: 2315-5159) Vol. 3(8) pp. 173-176, August 2014 Available online http://garj.org/garjmms/index.htm Copyright © 2014 Global Advanced Research Journals
Case Report
Olignecropermia infertility associated with Reifenstein syndrome in a Sudanese patient Bedawi Said Bedawi1, Eltayeb Tayrab2* and A.Latief Ashmaig3 1
Department of Andrology, Reproductive Health Care Center, Khartoum, Sudan. Department of Chemical Pathology, Faculty of Medical Laboratory Sciences, the National Ribat University, P.O. Box 55, Khartoum, Sudan. 3 Department of Obstetrics and Gynecology, Faculty of Medicine, the National Ribat University, P.O. Box 55, Khartoum, Sudan. P.O. Box 55, Khartoum, Sudan.
2
Accepted 28 July, 2014
Reifenstein syndrome is a familial form of male pseudohermaphroditism characterized by ambiguous genitalia or hypospadias, postpubertal, abnormally large breasts, and infertility associated with sclerosis of the seminal tubules. In the present study, a Sudanese man was visited andrology clinic in Reproductive Health Care Center (RHCC) in Khartoum, Sudan. The patient complains of primary infertility for 5 years. He has the history of bilateral undescended testes for which he underwent a surgery of orchiopexy. The scrotum is not well formed, the penis is small in size, and external urethral meatus is not present at the tip of penis but inpenoscrotal (hypospadias). His semen showed oligonecropermia. The patient was diagnosed with infertility due to oligonecrosprmia. Artificial testosterone supplementation, have a good response on semen volume, concentration and motility, increasing the chance of success in assisted reproduction techniques for a man with Reifenstein syndrome Keywords: oligonecrospermia, infertility, Reifenstein syndrome.
INTRODUCTION Male pseudohermaphrodites have a 46, XY chromosome complement, and their cells are usually chromatinnegative. Reduced production of androgenic hormones and müllerian inhibiting substance are responsible for this condition internal and external characteristic vary considerably, depending on the degree of development of external genitalia and the presence of paramesonephric derivatives (Sadler, 2003). Reifenstein syndrome; also known as partial androgen insensitivity syndrome
*Corresponding Author E-mail:
[email protected]; Phone: 00249912278825
(Sadler, 2003), is one of a group of diseases in which the body is unable to respond appropriately to the male sex hormones especially testosterone (Reifenstein, 1947). The characteristics of the Reifenstein syndrome are abnormal male genitals, hypospadias, small penis, small scrotum, undescended testicles, breast development, gynaecomastia, decreased body hair, but normal pubic, low sperm concentration, normal or high testosterone level as well as normal male chromosomal karyotyping, with no remote ovaries. The incidence of Reifenstein syndrome is estimated to be1 in 99,000,or 1 in 130,000 (Gottlieb et al., 2005; Sadler, 2003). More than 400 different AR gene mutations have thus far been reported but the receptor structure-function relationship and its
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Figure 1. small penis and malformed scortum, supra pubic surgical scar (for bilateral Orchiopexy) is seen.
phenotypic outcome is not yet fully understood (Galani et al., 2008), due to its subtle presentation, mild androgen insensitivity syndrome mild androgen sensitivity syndrome MAIS is not typically investigated except in the case of male infertility, and thus its true prevalence is unknown (Galani et al., 2008). Androgen insensitivity syndrome (AIS) is typically characterized by evidence of feminization (i.e., undermasculinization) of the external genitalia at birth, abnormal secondary sexual development in puberty, and infertility in individuals with a 46, XY karyotype. AIS represents a spectrum of defects in androgen action and can be subdivided into three broad phenotypes; complete androgen insensitivity syndrome (CAIS), with typical female external genitalia; partial androgen insensitivity syndrome (PAIS) with predominantly female, predominantly male, or ambiguous external genitalia, Mild androgen insensitivity syndrome (MAIS) with typical male external genitalia (Diamond and Beh, 2008; Douglas et al., 2010; Pasterski et al., 2010; Wiesemann et al., 2010). Semen analysis is a principal test for assessment of male infertility. Some rare conditions the couple infertility may be due to a familial form of male pseudohermaphroditism characterised by varying degrees of ambiguous genitalia or hypospadias, postpubertal development of gynaecomastia, and infertility associated with seminiferous tubular sclerosis; cryptorchidism may be present, and Leydig cell hypofunction may lead to impotence in later years;
chromosomal studies are usually normal; X-linked recessive or autosomal dominant male-linked trait (Stedman's Medical Spellchecker © 2006, 1974). partial androgen sensitivity; a familial form of male pseudohermaphroditism characterized by varying degrees of ambiguous genitalia or hypospadias, postpubertal development of gynecomastia, and infertility associated with seminiferous tubular sclerosis; cryptorchidism may be present, and Leydig cell hypofunction may lead to impotence in later years; chromosomal studies show 46,XY karyotype; X-linked recessive inheritance, caused by mutation in the androgen receptor gene (AR) on Xq (Jean et al., 1974). CASE REPORT A 28-years old farmer was seen at the clinic of andrology in the Reproductive Health Care Center (RHCC) in Khartoum- Sudan. He was complaining of primary infertility after five years of marriage. He has the history of bilateral undescended testes for which he underwent a surgery of bilateral orchiopexy at age of 8 years old.Puberty was reached spontaneously by age of 17 (nocturnal emission, increase in pubic and axillary hair and higher voice pitch). Concerning sexual life; he has good sexual life, good libido, good erection, and ejaculation as he claimed. On examination; the scrotum is not well developed, the
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Figure 2. penoscortal urethral meatus
Figure 3. absent of facial hair and gyneacomatsia
penis is small in size (figure 1), external urethral meatus is not present at the tip of penis but is penoscrotal (hypospadias) see figure (2). Right scrotal examination revealed that; the right testis is of an average size and consistent, right epididymis is normal, vas deferens is felt on right side. Left testis is absent in scrotum, palpable at the external inguinal ring, smaller in size. Left syntheyic testis is implanted and fixed in scrotum. No virilization sign with decreased body and absent facial
hair figure (3), decrease body muscles. The breasts were enlarged with Feminine like (Gynaecomastia). The density of auxiliary and pubic hair seem normal (figure 3). He is non - smoker, neither diabetic nor hypertensive. He has no history of medical illness, or exposed to any type of radiation or gonadotoxins. He showed no family history of infertility. Laboratory data showed that serum FSH, prolactin and estradiol (E2) were within the normal limits, while testosterone and LH levels were elevated.
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Peripheral blood cell chromosomal karyotyping revealed (46XY) or normal male karyotying. Masturbated semen analysis, on more than one occasions, using the standard procedure showed low concentrations of spermatozoa in semen, and computerized semen analyzer (CASA WELY 900); showed approximated (0.6) ml volume, (0.8x106) sperm/ml concentration, with zero per cent motility (100% class D), using WHO standard eosin procedure for viability test; 43% of immotile sperms were viable (WHO, 2010). Pelvi-abdominal CT imaging, denied the presence of remote ovaries, or uterus. The patient was put on treatment for three months using Cidotestone 250mg (testosterone) injections intramuscularly given every 3 weeks, beside Tamoxifen10mg film-coated tablets (tamoxifen citrate) given twice per week. After finished the course of the treatment; following results were obtained. Ejaculated semen volume reached (4ml). Sperm concentration elevated to 26x106, with relatively good motility of 27.5% (Class A 0.4%, Class B 5.3%, Class C 21.8%, and Class D 72.5%). Sperm morphology and (TZI and SDI) became within the normal accepted limits. DISCUSSION Several case studies of fertile 46, XY males with androgen insensitivity have been published, although this group is thought to be a minority. Characterized by gynecomastia and hormonal levels in serum indicating androgen insensitivity (high LH levels, despite extremely high testosterone concentration), which is in agreement with the finding of this case report (Giwercman et al., 2000; Gottlieb et al., 2005). Additionally, some infertile males with MAIS have been able to conceive children after increasing their sperm count through the use of supplementary testosterone (Yong et al., 1994). Even author like Sadler (2003); mentioned that, in general; androgen insensitivity syndrome patient with a 46,XY karyotyping have no chance of spermatogenesis and hence production of any type of sperms (Sadler, 2003), this case study gave an example of some type of androgen insensitivity which is typical Reifenstein syndrome (Reifenstein, 1947), which is capable of producing very small amount of semen volume (0.6ml), and containing only (0.8x106) per milliliter (oligospermia), with completely immotile sperm (zero%) or (necrospermia); while the normal characteristic of semen volume, concentration and motility are more than 6 (1.5ml, 15x10 , 40%) consequently; according to WHO laboratory manual for the examination and processing of human semen (WHO, 2010). This condition may give the chance for the patient of Reifenstein syndrome to have a child using the reproductive techniques especially intra-
cytoplasmic injection (ICSI), which is a new presentation and solution for this type of patients, as observed here after Cidotestone 250 mg artificial testosterone supplementation, good response was observed where the semen volume became 4ml per ejaculate, the concentration and motility were 26x106, 27% motile sperm type (B+C) successively, these results increase the chance of success in assisted reproduction techniques for a man with Reifenstein syndrome . REFRENCES Ahmed SF, Cheng A, Hughes IA (1999). Assessment of the gonadotrophin-gonadal axis in androgen insensitivity syndrome. Arch. Dis. Child. 80 (4): 324–329. Diamond M, Beh HG (2008). Changes in the management of children with intersex conditions. Available online. Accessed 9-30-11. Douglas G, Axelrad ME, Brandt ML, el al (2010). Consensus in guidelines for evaluation of DSD by the Texas Children’s Hospital multidisciplinary gender medicine team. Available online. Accessed 9-30-11. Galani A, Kitsiou-Tzeli S, Sofokleous C, et al (2008). Androgen insensitivity syndrome: clinical features and molecular defects. Hormones (Athens). 7 (3): 217–29. Giwercman A, Kledal T, Schwartz M, et al (2000). Preserved male fertility despite decreased androgen sensitivity caused by a mutation in the ligand-binding domain of the androgen receptor gen. J. Clin. Endocrinol. Metab. 85 (6): 2253–2259. Gottlieb B, Lombroso R, Beitel LK, Trifiro MA (2005). Molecular pathology of the androgen receptor in male (in) fertility. Reprod. Biomedecine. Online10 (1): 42–48. Jean D Wilson, Mary J Harrod, Joseph L Goldstein, David L Hemsell, Paul C (1974). MacDonald.Familial incomplete male pseudohermaphroditism, type 1-evidence for androgen resistance and variable clinical manifestations in a family with the Reifenstein syndrome, N. Engl. J. Med. 290:1097-1103 Mazen I, El-Ruby M, Kamal R, et al (2010). Screening of genital anomalies in newborns and infants in two Egyptian governorates. Horm. Res. Paediatr. 73 (6): 438–442. Pasterski V, Prentice P, Hughes IA (2010). Impact of the consensus statement and the new DSD classification system. Accessed 9-30-11. Reifenstein EC Jr (1947). Hereditary familial hypogonadism: Proc. Am. Fed. Clin. Res. 3: 86. Sadler TW (2003). Langman’s medical embryology. 9th ed. Lippincott Williams and Wilkins. pp. 353-356. WHO laboratory manual for the examination and processing of human semen, prepublication version 2010. Wiesemann C, Ude-Koeller S, Sinnecker GH, Thyen U (2010). Ethical principles and recommendations for the medical management of differences of sex development (DSD)/intersex in children and adolescents. Accessed 9-30-11. Yong EL, Ng SC, Roy AC, Yun G, Ratnam SS (1994). Pregnancy after hormonal correction of severe spermatogenic defect due to mutation in androgen receptor gene. Lancet. 344 (8925): 826–827.
