Vol. 28, No.3, March 1977 Printed in U.S.A.
FERTILITY AND STERILITY Copyright < 1977 The American Fertility Society
MALE MULLERIAN HERMAPHRODITISM: A CASE REPORT OF A RARE CAUSE OF MALE INFERTILITY
GAD POTASHNIK, M.D.* IVOR SOBER, M.B., F.R.C.S. ILANA INBAR, M.D. NOACH BEN-ADERET, M.D.
Infertility Clinic, Department of Obstetrics and Gynecology "A," Department of Urology, and Institute of Pathology, Soroka Medical Center, Faculty of Life Sciences, Ben Gurion University, Beersheba, Israel
The patient was operated on under general anesthesia via a midline scrotal incision. A single tunica vaginal is was found to contain both testes. The mass proved to be the fundus of an elongated uterus lying between the two testes (Fig. 1). Each fallopian tube lay alongside one of the testes at the site of the hydatid of Morgagni. Both vasa deferentia together with the body of the uterus ascended to the left inguinal canal. The uterus was freed as far as the internal ring via a left inguinal incision, and a supracervical hysterectomy was performed. The testes, which appeared normal, were left in the scrotum. A biopsy specimen was obtained from the left testis. Postoperative endocrine studies revealed a daily urinary excretion of 6.1 mg of hydroxycorticosteroids and 10.8 mg of keto steroids, both values being within the normal male range. Plasma luteinizing hormone and follicle-stimulating hormone levels were 6.8 and 9.7 mIU/ml, respectively, values regarded as normal for adult males. The plasma testosterone level was significantly low2.3 ng/ml as compared with normal values of 4 to 16 ng/ml. The buccal smear was chromatinnegative, and lymphocyte cultures showed a 46,XY karyotype. The resected specimen consisted of a uterus measuring 7 x 2.5 x 2 cm with normal-appearing fallopian tubes. No ovarian or cervical tissue was identified. The uterine cavity was normal and communicated with the fallopian tubes. Histologic sections showed a well-developed myometrium and a thin endometrium lined by pseudostratified columnar epithelium with very few
The presence of Mullerian duct derivatives in an otherwise normal male is a rare form of intersexuality, usually found during hernia repair or exploration of cryptorchism. The susceptibility for the undescended testis to malignant tumor formation and the desire to preserve spermatogenesis combine to present the surgeon with a delicate problem of management. In this paper we report a case of male Mullerian hermaphroditism in whom the presenting clinical manifestation was infertility; the appropriate management is discussed. CASE REPORT
I. I., a 26-year-old man, and his wife were investigated at our infertility clinic following 3 years of childless marriage. No obvious cause for infertility was found in the wife. The husband's past history was irrelevant. Semen analysis revealed severe oligospermia, with counts ranging from 1 x 106 to 7.5 X 106 spermatozoa/ml and repeated semen volumes of 2 to 3 ml/ejaculate. Physical examination revealed a well-developed male with normal secondary sex characteristics. An ill-defined, rounded mass of elastic consistency was present within the scrotum. It was situated above the left testis and extended toward the midline. The mass did not transmit light, nor did it change in size with straining. Accepted November 3, 1976. *Reprint requests: Gad Potashnik, M.D., Infertility Clinic, Department of Obstetrics and Gynecology "A," Soroka Medical Center, P.O. Box 151, Beersheba, Israel.
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FIG.1.1. Operative Operativefindings. findings. The Theuterus uterusand andfallopian fallopiantubes tubeshave havebeen beenelevated elevatedbybythe the FIG. surgeon. Note the normal-looking testes. surgeon. Note the normal-looking testes.
endometrialglands glands(Fig. (Fig.2). 2). The Thefallopian fallopiantubes tubes endometrial were normal. normal. InInthe thetesticular testicularbiopsy, biopsy,some someofof were thetubules tubuleswere werelined linedwith withSertoli Sertolicells cellsonly, only,but but the most showed showed several several layers layersofofspermatocytes spermatocytes most withsmall smallnumbers numbersofofspermatids spermatidsand andvery veryococwith casionalspermatozoa spermatozoa(Fig. (Fig.3).3).There Therewas wasa aslight slight casional thickeningofofthe thetubular tubularbasement basementmembranes. membranes. thickening
Groups of Leydig cells were present in the interGroups of Leydig cells were present in the interstitialtissue tissueand andappeared appearednormal normalininnumber. number. stitial DISCUSSION DISCUSSION
Thepatient patientdescribed describedrepresents representsa arare rareform formofof The a male hermaphroditism characterized the a male hermaphroditism characterized bybythe presence of Miillerian duct structures (uterus and presence of Mullerian duct structures (uterus and
FIG. Uterine cavity lined inactive endometrium (hematoxylin eosin, FIG. 2. 2.Uterine cavity lined by by inactive endometrium (hematoxylin andand eosin, x 80). X 80).
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FIG. 3. Testicular biopsy showing seminiferous tubules with diminished spermatogenesis and occasional small groups of Leydig cells (hematoxylin and eosin, x 80).
fallopian tubes) in a well-developed male with masculine external genitalia.! This syndrome appears to be due to absence of the Mullerian duct inhibitory factor (a peptide secreted by the fetal Sertoli cells), to a defective inhibitory factor, or to unresponsiveness of the Mullerian ducts to this fetal testicular factor. 2 A possible inheritance linkage has been suggested. Almost without exception this syndrome has been discovered accidentally in the course of operation for inguinal hernia or cryptorchism.! None of the above features were present in our patient, who presented because of infertility, and the indication for surgical exploration was the presence of a scrotal mass. Although fertility has been claimed in some cases, the evidence seems somewhat questionable. 3 Infertility seems to be the rule and is attributed to the hypoplastic testes usually associated with these cases. Endocrine studies are not helpful for the purpose of diagnosis. Since these patients usually have a normal male physique, adequate body hair, and normal libido, their androgen function seems to be adequate. The Mullerian duct inhibitory factor normally disappears at 28 weeks of in utero development,4 thus its absence during extrauterine life cannot be used for diagnostic purposes. The low plasma testosterone level (2.3 nglml) in the presence of normal levels of circulating lutein-
izing hormone and follicle-stimulating hormone (6.8 mIU/ml and 9.7 mIU/ml, respectively) suggests diminished testicular activity but is of no specific value in establishing the diagnosis of the rare syndrome of male Mullerian hermaphroditism. The role of the surgeon when confronted with this syndrome in a young male presenting with infertility is somewhat controversial. While it is agreed that there is an increased incidence of seminomas, teratomas, and gonadoblastomas in male hermaphrodite patients,! this increase may merely be related to the ectopic situation of the testes. 3 Therefore, we recommend that, as in the treatment of ectopic testes, the .testes should be preserved, provided they can be brought into the scrotum. If the testes are already scrotal, they should be left in order to preserve possible fertility. Removal of the uterus would seem desirable to reduce the blood flow in the testicular area, as in the treatment of varicoceles in oligospermic patients. However, removal of the whole uterus and vagina would jeopardize the vasa deferentia, the urethra, and conceivably the nervous mechanism of potency. In the absence of demonstrable urinary tract disturbance, such a radical excision is therefore unjustified. Hence, in our case, the testes were left in the scrotum while the body of the uterus and both tubes were excised.
COMMUNICATIONS-IN-BRIEF
276 REFERENCES
1. Jones HW, Scott WW: Male hermaphroditism (non-
familial-masculinizing). In Hermaphroditism, Genital Anomalies and Related Endocrine Disorders, Second Edition. Baltimore, Williams & Wilkins Co, 1971, p 97 2. Grumbach MM, Van Wyk JJ: Female genital ducts in otherwise normal men. In Textbook of Endocrinology, Fifth Edition, Edited by RH Williams. Philadelphia, WB Saunders Co, 1974, p 488
March 1977
3. Brook GD, Wagner H, Zachmann M, Prader A, Armendares S, Frenk S, Aleman P, Naijar SS, Slim MS, Genton N, Bozic C: Familial occurrence of persistent MUllerian structures in otherwise normal males. Br Med J 1:771, 1973 4. Josso N: Evolution of the Mullerian-inhibiting activity of the human testis: effect of fetal, peri-natal and post-natal human testicular tissue on the Mullerian duct of the fetal rat in organ culture. BioI Neonate 20:368, 1972
FERTILITY AND STERILITY Copyright < 1977 The American Fertility Society
MALE MULLERIAN HERMAPHRODITISM: A CASE REPORT OF A RARE CAUSE OF MALE INFERTILITY
GAD POTASHNIK, M.D.* IVOR SOBER, M.B., F.R.C.S. ILANA INBAR, M.D. NOACH BEN-ADERET, M.D.
Infertility Clinic, Department of Obstetrics and Gynecology "A," Department of Urology, and Institute of Pathology, Soroka Medical Center, Faculty of Life Sciences, Ben Gurion University, Beersheba, Israel
The patient was operated on under general anesthesia via a midline scrotal incision. A single tunica vaginal is was found to contain both testes. The mass proved to be the fundus of an elongated uterus lying between the two testes (Fig. 1). Each fallopian tube lay alongside one of the testes at the site of the hydatid of Morgagni. Both vasa deferentia together with the body of the uterus ascended to the left inguinal canal. The uterus was freed as far as the internal ring via a left inguinal incision, and a supracervical hysterectomy was performed. The testes, which appeared normal, were left in the scrotum. A biopsy specimen was obtained from the left testis. Postoperative endocrine studies revealed a daily urinary excretion of 6.1 mg of hydroxycorticosteroids and 10.8 mg of keto steroids, both values being within the normal male range. Plasma luteinizing hormone and follicle-stimulating hormone levels were 6.8 and 9.7 mIU/ml, respectively, values regarded as normal for adult males. The plasma testosterone level was significantly low2.3 ng/ml as compared with normal values of 4 to 16 ng/ml. The buccal smear was chromatinnegative, and lymphocyte cultures showed a 46,XY karyotype. The resected specimen consisted of a uterus measuring 7 x 2.5 x 2 cm with normal-appearing fallopian tubes. No ovarian or cervical tissue was identified. The uterine cavity was normal and communicated with the fallopian tubes. Histologic sections showed a well-developed myometrium and a thin endometrium lined by pseudostratified columnar epithelium with very few
The presence of Mullerian duct derivatives in an otherwise normal male is a rare form of intersexuality, usually found during hernia repair or exploration of cryptorchism. The susceptibility for the undescended testis to malignant tumor formation and the desire to preserve spermatogenesis combine to present the surgeon with a delicate problem of management. In this paper we report a case of male Mullerian hermaphroditism in whom the presenting clinical manifestation was infertility; the appropriate management is discussed. CASE REPORT
I. I., a 26-year-old man, and his wife were investigated at our infertility clinic following 3 years of childless marriage. No obvious cause for infertility was found in the wife. The husband's past history was irrelevant. Semen analysis revealed severe oligospermia, with counts ranging from 1 x 106 to 7.5 X 106 spermatozoa/ml and repeated semen volumes of 2 to 3 ml/ejaculate. Physical examination revealed a well-developed male with normal secondary sex characteristics. An ill-defined, rounded mass of elastic consistency was present within the scrotum. It was situated above the left testis and extended toward the midline. The mass did not transmit light, nor did it change in size with straining. Accepted November 3, 1976. *Reprint requests: Gad Potashnik, M.D., Infertility Clinic, Department of Obstetrics and Gynecology "A," Soroka Medical Center, P.O. Box 151, Beersheba, Israel.
273
274
March 1977
COMMUNICATIONS-IN-BRIEF
FIG.1.1. Operative Operativefindings. findings. The Theuterus uterusand andfallopian fallopiantubes tubeshave havebeen beenelevated elevatedbybythe the FIG. surgeon. Note the normal-looking testes. surgeon. Note the normal-looking testes.
endometrialglands glands(Fig. (Fig.2). 2). The Thefallopian fallopiantubes tubes endometrial were normal. normal. InInthe thetesticular testicularbiopsy, biopsy,some someofof were thetubules tubuleswere werelined linedwith withSertoli Sertolicells cellsonly, only,but but the most showed showed several several layers layersofofspermatocytes spermatocytes most withsmall smallnumbers numbersofofspermatids spermatidsand andvery veryococwith casionalspermatozoa spermatozoa(Fig. (Fig.3).3).There Therewas wasa aslight slight casional thickeningofofthe thetubular tubularbasement basementmembranes. membranes. thickening
Groups of Leydig cells were present in the interGroups of Leydig cells were present in the interstitialtissue tissueand andappeared appearednormal normalininnumber. number. stitial DISCUSSION DISCUSSION
Thepatient patientdescribed describedrepresents representsa arare rareform formofof The a male hermaphroditism characterized the a male hermaphroditism characterized bybythe presence of Miillerian duct structures (uterus and presence of Mullerian duct structures (uterus and
FIG. Uterine cavity lined inactive endometrium (hematoxylin eosin, FIG. 2. 2.Uterine cavity lined by by inactive endometrium (hematoxylin andand eosin, x 80). X 80).
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FIG. 3. Testicular biopsy showing seminiferous tubules with diminished spermatogenesis and occasional small groups of Leydig cells (hematoxylin and eosin, x 80).
fallopian tubes) in a well-developed male with masculine external genitalia.! This syndrome appears to be due to absence of the Mullerian duct inhibitory factor (a peptide secreted by the fetal Sertoli cells), to a defective inhibitory factor, or to unresponsiveness of the Mullerian ducts to this fetal testicular factor. 2 A possible inheritance linkage has been suggested. Almost without exception this syndrome has been discovered accidentally in the course of operation for inguinal hernia or cryptorchism.! None of the above features were present in our patient, who presented because of infertility, and the indication for surgical exploration was the presence of a scrotal mass. Although fertility has been claimed in some cases, the evidence seems somewhat questionable. 3 Infertility seems to be the rule and is attributed to the hypoplastic testes usually associated with these cases. Endocrine studies are not helpful for the purpose of diagnosis. Since these patients usually have a normal male physique, adequate body hair, and normal libido, their androgen function seems to be adequate. The Mullerian duct inhibitory factor normally disappears at 28 weeks of in utero development,4 thus its absence during extrauterine life cannot be used for diagnostic purposes. The low plasma testosterone level (2.3 nglml) in the presence of normal levels of circulating lutein-
izing hormone and follicle-stimulating hormone (6.8 mIU/ml and 9.7 mIU/ml, respectively) suggests diminished testicular activity but is of no specific value in establishing the diagnosis of the rare syndrome of male Mullerian hermaphroditism. The role of the surgeon when confronted with this syndrome in a young male presenting with infertility is somewhat controversial. While it is agreed that there is an increased incidence of seminomas, teratomas, and gonadoblastomas in male hermaphrodite patients,! this increase may merely be related to the ectopic situation of the testes. 3 Therefore, we recommend that, as in the treatment of ectopic testes, the .testes should be preserved, provided they can be brought into the scrotum. If the testes are already scrotal, they should be left in order to preserve possible fertility. Removal of the uterus would seem desirable to reduce the blood flow in the testicular area, as in the treatment of varicoceles in oligospermic patients. However, removal of the whole uterus and vagina would jeopardize the vasa deferentia, the urethra, and conceivably the nervous mechanism of potency. In the absence of demonstrable urinary tract disturbance, such a radical excision is therefore unjustified. Hence, in our case, the testes were left in the scrotum while the body of the uterus and both tubes were excised.
COMMUNICATIONS-IN-BRIEF
276 REFERENCES
1. Jones HW, Scott WW: Male hermaphroditism (non-
familial-masculinizing). In Hermaphroditism, Genital Anomalies and Related Endocrine Disorders, Second Edition. Baltimore, Williams & Wilkins Co, 1971, p 97 2. Grumbach MM, Van Wyk JJ: Female genital ducts in otherwise normal men. In Textbook of Endocrinology, Fifth Edition, Edited by RH Williams. Philadelphia, WB Saunders Co, 1974, p 488
March 1977
3. Brook GD, Wagner H, Zachmann M, Prader A, Armendares S, Frenk S, Aleman P, Naijar SS, Slim MS, Genton N, Bozic C: Familial occurrence of persistent MUllerian structures in otherwise normal males. Br Med J 1:771, 1973 4. Josso N: Evolution of the Mullerian-inhibiting activity of the human testis: effect of fetal, peri-natal and post-natal human testicular tissue on the Mullerian duct of the fetal rat in organ culture. BioI Neonate 20:368, 1972
