FERTILITY AND STERILITY
Vol. 57, No.4, April 1992 Printed on acid-free poper in U.S.A.
Copyright C> 1992 The American Fertility Society
Uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis: the University of Minnesota experience
Jacques P. Stassart, M.D.* Theodore C. Nagel, M.D.t Konald A. Prem, M.D. William R. Phipps, M.D.:!: Department of Obstetrics and Gynecology, University of Minnesota, Minneapolis, Minnesota
Objective: To present the experience of a large referral center with patients with the rare but specific syndrome of uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis. Design, Patients: Between 1953 and 1991, 15 patients with the syndrome were evaluated by the authors; each patient's records were carefully reviewed. Main Outcome Measures: For each patient, the clinical course, specific anatomic findings, treatment(s) offered, and obstetrical outcome are presented. Results: The specificity of the association of uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis was confirmed by our series, the largest in the literature to date. The findings suggest a specific developmental anomaly of the mUllerian ductal system, probably secondary to a wolffian duct anomaly. The most common clinical presentation was that of the onset of pelvic pain and/or dysmenorrhea shortly after menarche, in association with the finding of a vaginal/pelvic mass. When a communication between the two sides existed, symptoms of abnormal vaginal discharge and bleeding were common. Optimal outcome appears to have occurred for patients initially managed using a conservative surgical approach, i.e., simple vaginal septum resection combined with conservative treatment of associated endometriosis. Obstetrical outcome in our patients was similar to that in patients with the more common combination of uterus didelphys and sagittal vaginal septum. Conclusion: A greater awareness of the syndrome of uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis should lead to its prompt diagnosis, allowing for early and appropriate surgical intervention as well as decreased long-term morbidity. Fertil SterilI992;57:756-61 Key Words: Hematocolpos, mUllerian ducts, renal agenesis, uterus didelphys, vagina
The specific association of uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis was recognized as early as 1922 (1). Morgan et a1. (2) recently reviewed the English literature and
Received September 6, 1991; revised and accepted December 31,1991. * Reprint requests: Jacques P. Stassart, M.D., Department of Obstetrics and Gynecology, University of Minnesota, UMHC Box 395, Minneapolis, Minnesota 55455. t Present address: Reproductive Health Associates, St. Paul, Minnesota. :I: Present address: Department of Obstetrics-Gynecology, University of Rochester, Rochester, New York.
756
Stassart et aI.
Uterus didelphys/obstructed hemivagina
found 115 cases, to which they added one of their own. As did Rock and Jones (3), they noted a more common occurrence of the obstructed hemivagina and renal agenesis on the right side. In a minority of cases, a communication connecting the right and left sides at the level of the vagina or above the internal cervical ora was present (Fig. 1). Since the report of Morgan et a1. (2), over 50 additional cases have been reported in the world literature. To our knowledge, the two largest series to date have included 12 patients each (3, 4). We now report a series of 15 patients, including several with long-term obstetrical follow-up. Both embryologic considerations and clinical management issues are discussed. Fertility and Sterility
Figure 1 Illustration of associaton of uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis. Sites of communication between the two sides may occur either above the internal cervical ora (A), or essentially anywhere at the level of the vagina (B).
MATERIALS AND METHODS
Between 1953 and 1991, the authors evaluated 15 patients with the specific association of uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis. This report is based on a careful review of their records. When appropriate and possible, follow-up by telephone was obtained. In all but one case, the status of the reproductive organs was assessed by hysterosalpingogram, laparoscopy, and/or laparotomy, and the urinary system was evaluated by intravenous pyelogram (IVP) and/or cystoscopy. In our patient diagnosed at the age of 6 years, pelvic and renal ultrasound studies were used instead. RESULTS
A summary of our cases is presented in Table 1. In 11 of our 15 cases, the right side was the site of the obstructed hemivagina and renal agenesis, confirming previous reports showing a right-sided preponderance (2, 3). In all 11 cases in which cystoscopy was performed (all but cases 5, 7, 9, and 11), the findings included absence of the hemitrigone of the bladder and the ureteral orifice on the affected side. Vol. 57, No.4, April 1992
In most of our cases, menarche was shortly followed by pain and/or dysmenorrhea, related to the presence of hematocolpos, hematometra, and/or hematosalpinx. This then prompted the finding of a vaginal/pelvic mass. However, the three patients with a low isthmic or cervical communication (cases 11, 14, and 15) did not present until 3 to 8 years after menarche. Presumably, such a communication may to some extent diminish the occurrence of acute, obstruction-related symptoms. The three patients with a pinpoint vaginal communication (cases 8, 9, and 10) had symptoms of abnormal vaginal bleeding and/or discharge. Thus, in general, the nature and the chronology of the symptoms correlated well with the anatomical findings. Four patients had what was essentially an isolated vaginal/pelvic mucocele. These included two girls (cases 7 and 8) presenting before menarche, before the possibility of symptoms related to hematometra G8 and hematosalpinx. The other two cases with a mucocele (cases 1 and 5) were seen after hemihysterectomy and salpingo-oophorectomy. At least 7 of our 15 patients (cases 3, 4, 5, 8, 9, 10, and 13) had endometriosis noted at the time of laparosopy or laparotomy, including all 3 patients with a pinpoint vaginal communication. This can be explained on the basis of increased retrograde menstruation (5). Endometriosis was not found in any of the 3 patients with a low isthmic or cervical communication. One of our patients (case 13) presented with acute urinary retention and hydronephrosis, whereas another (case 2) had chronic hydronephorsis; obstructive uropathy has previously been reported in a few patients with this condition (6-9). In most of our cases, the patient was initially managed by another physician who failed to recognize the true nature of the syndrome. Thus, many of the patients underwent unnecessary and/or incomplete surgical procedures. Six of our 15 patients gave birth to a total of nine live infants after surgical treatment. Four other patients have not yet attempted to achieve a pregnancy, 1 was infertile, and 1 underwent a sterilization procedure at an early age because of renal disease. The remaining two have been lost to followup. The nine live births included two breech, seven cephalic presentations, and three cesarean sections. Obstetrical outcome did not appear to be adversely affected by leaving in place the affected hemiuterus and corresponding adnexa. In 1 patient (case 6), the affected side was the site of an intrauterine pregnancy (IUP), with a cesarean section performed at Stassart et al.
Uterus didelphys/obstructed hemivagina
757
Table 1
Summary of Presentation and Course of Patients With Uterus Agenesis Didelphys, Obstructed Hemivagina, and Ipsilateral Renal
Case
Affected side, communication
R*, none
Age at menarche
Age at presentation
y
y
15
26
Initial presentation
Pain, mass
Treatment
(1) R salpingo-oophectomy (26,1927)t (2) R hemihysterectomy (27,1928)t (3) Vaginal septum incision for
Obstetrical outcome
Comments
Infertility
abdominal pain and vaginal/pelvic mucocele (66, 1968)t (4) Vaginal septum resection
for vaginal/pelvic mucocele 2
R, none
10
12
Pain, mass
(67,1969) (1) Strassmann-type unification
procedure, vaginal septum incision (15, 1953) (2) Vaginal septum resection for vaginal mass and discharge after spontaneous closure of incision 3
R, none
11
16
Pain, mass
(21,1959) (1) R hemihysterectomYI
salpingo-oophectomy, vaginal septum resectionendometriosis noted 4
R, none
11
11
Pain, mass
(21,1967) (1) Vaginal septum incision (11,1973)t (2) R hemihysterectomyI
Sterilization at age 22 because of persistent L-sided hydronephrosis and urinary tract infections
L:j:-sided hydronephrosis first noted at age 15
First trimester loss, then term vaginal deliveries X 3 Term cesarean section (fetal distress)
salpingo-oophectomy, vaginal septum resectionendometriosis noted 5
R, none
14
14
Pain, mass
(11,1973) (1) R hemihysterectomyI
salpingo-oophectomy
No desire for pregnancy
(14,1975)t (2) Laparoscopy-pelvic massl
endometriosis noted (27,1988)t (3) Operative laparoscopy,
6
7
8
R, none
R, none
R, vaginal
14
NA§
12
14
6
11
Pain, mass
Pain, mass
Pain, mass, spontaneous vaginal drainage
vaginal septum resection for large vaginal/pelvic mucocele (28, 1989) (1) Exploratory laparotomy, hemivaginal aspiration (14,1976)t (2) Vaginal septum resection (15,1976) (1) Vaginal aspiration only-
surgical procedure limited by exposure (6, 1989) (1) Exploratory laparotomy, vaginal septum resection for hematopyocolpos (11,1967)t (2) Diagnostic laparoscopy-
Complete duplication of L ureter
Term cesarean section (breech)affected side NA§ (1) Vaginal
delivery at 36 weeks (2) Ltubal pregnancy
Asymptomatic 2 years after surgery Vaginal endometriosis noted in obtructed hemivagina
pelvic endometriosis
9
10
R, vaginal
R, vaginal
11
12
11
13
Pain, vaginal discharge, abnormal vaginal bleeding Abnormal bleeding
(23,1979) (3) LaparotomyIlysis of adhesions (25, 1981) (1) Operative laparoscopyendometriosis (13, 1989)t (2) Operative laparoscopy,
NA§
vaginal septum resection (13,1990) (1) Laparoscopy-
NA§
endometriosis noted (13,1991)t (2) Operative laparoscopy,
vaginal septum resection (13,1991)
758
Sta8Sart et aI.
Uterus didelphys/obstructed hemivagina
Fertility and Sterility
Table 1 (Continued) Age at menarche
Age at presentation
R,low isthmic or cervical
13
21
Vaginal discharge
12
L, none
15
15
Pain, mass
13
L,none
14
14
14
L, low isthmic or cervical
11
14
Urinary symptoms (dysuria, acute urinary distension) pain, mass Pain, mass
15
L, low isthmic or cervical
13
19
Case
Affected side, communication
11
Initial presentation
Abnormal bleeding, mass
• R, right. t Indicates surgery performed elsewhere. Values in parentheses are age and year.
term because of breech presentation; before resection of her septum, the affected hemiuterus had been noted to be 10 cm in diameter. The only tubal pregnancy in our series (case 8) occurred on the unaffected side in a patient who had previously undergone laparotomy for lysis of major pelvic adhesions secondary to severe endometriosis. She had had a prior live birth. DISCUSSION Embryologic Considerations
The constellation of findings in these patients may be the result of an abnormality in the development of the caudal portion of one of the wolffian (mesonephric) ducts with secondary involvement of the ipsilateral miillerian (paramesonephric) duct. Each wolffian duct originates in the vicinity of the pronephros about 3! weeks after conception (10). Each ureteric bud develops from the wolffian duct near the opening into the cloaca about 1! weeks later (11) and grows dorsocranially into the metanephric blastema, inducing the differentiation of the metaVol. 57, No.4, April 1992
Treatment
(1) Laparoscopy-pelvic adhesions noted (22, 1986)t (2) Vaginal septum resection (22,1986) (1) Rectal drainage of mass (15,1962)t (2) L hemihysterectomYI salpingo-oophectomyI hemicolpectomy for abscess after first surgery (15, 1962) (1) Exam under anesthesia (15,1983)t (2) Operative laparoscopy with lysis of adhesions, vaginal septum resection (15, 1983) (3) Operative laparoscopyendometriosis (16, 1984) (1) L salpingo-oophectomy for adnexal mass (14, 1967)t (2) Vaginal incision for recurrent mass (15, 1968)t (3) Vaginal septum resection (18,1971) (1) Vaginal septum resection (19,1974)t (2) Laparoscopy, hysteroscopy-obstruction within L hemiuterus noted (30,1986)
Obstetrical outcome Unknown
Comments
Pelvic adhesions sip gonococcal salpingitis
Unknown
No desire for pregnancy
R-sided hydronephrosis resolved after first surgery
(1) Vaginal delivery at 32 weeks (2) Cesarean section at 34 weeks (breech) Vaginal delivery at 27 weeks
:t: L, left. § NA, not applicable.
nephric nephrons (12). If the ureteric bud fails either to form or make contact with the metanephric blastema, the kidney on that side will not develop (13). The caudal portions of wolffian ducts are then incorporated into the bladder (14). In the process, the ureters acquire their own openings into the bladder, whereas the openings of the wolffian ducts shift into a urethral position. The trigone is formed between the openings of the ureters and that of the wolffian ducts bilaterally. The miillerian duct may be recognized as early as 44 to 48 days after conception (14). Its cells contact the wolffian duct and grow caudally using its epithelium as a guide. Interruption of the wolffian duct or its failure to form results in interruption or failure of formation of the miillerian duct (14). Caudal to the mesonephric ridges the miillerian ducts cross the wolffian ducts ventrally and approach each other in the midline, running caudally between the wolffian ducts. The caudal ends of the miillerian ducts then contact the endodermal epithelium of the urogenital sinus without breaking through at 55 to 60 days after conception. The caudal portions normally fuse to form a single canal. The direct contact at Stassart et al.
Uterus didelphys/obstructed hemivagina
759
r the tip of the canal is thought to induce the development of the vaginal plate, the caudal one fifth of which is generally considered to be endodermal in origin. The origin of the upper four fifths of the vaginal plate and the precise manner in which the vaginal plate contributes to the vagina is controversial (15). In the cases presented, the presence of mullerian structures bilaterally indicates that wolffian duct formation has occurred. On the affected side, however, the ureteric bud has either failed to form or has formed aberrantly, as suggested by reported cases (16, 17) in which a rudimentary pelvic kidney was found. Failure of normal ureteric bud formation would result in failure of differentiation of the mesonephric blastema into the kidney and absence of the bladder hemitrigone, as confirmed in most of our cases. An aberrant location of the wolffian duct might account for failure of ureteric budding as well as an abnormal location of the mullerian duct on the affected side. The result would be failure of the aberrant mullerian duct to fuse with both its opposite counterpart and with the urogenital sinus, the latter in turn leading to failure of formation of the vaginal plate on the affected side. This would account for the finding that, unless a spontaneous or surgical communication between the two hemivaginas has been established, the obstructed hemivagina is invariably lined by columnar epithelium, presumably of mullerian origin (3). The presence of such epithelium may lead to the development of a mucocele, as seen in four of our patients (cases 1, 5, 7, and 8). In patients with the more common syndrome of uterus didelphys associated with a sagittal vaginal septum, renal agenesis is seldom present (3). Our cases may represent a variant of that syndrome. However, although the precise mechanisms involved remain undefined, the constancy of the association of unilateral renal agenesis and the obstructed hemivagina in the patients under discussion makes it more likely that the syndrome represents a distinct aberrancy of wolffian duct development. Three of our patients (cases 11, 14, and 15) had a low isthmic or cervical communication and, thus, despite the presence of two cervices and two distinct uterine horns, might be considered not to have a true uterus didelphys. This was also true for 2 of the 12 patients described by Rock and Jones (3) and an unspecified number of the 12 patients described by Intaraprasert and Benchakan (4) (6 of whom had either a vaginal or a low isthmic/cervical communication). We do not believe that the presence of a 760
Stassart et al.
Uterus didelphys/obstructed hemivagina
small communication between the two sides, either at the level of the vagina or just above the cervical ora, warrants a separate classification or suggests a distinct teratogenic process because of the constancy of the other findings. It is possible, in fact, that such communications may not be congenital in nature but, rather, represent acquired lesions. Mullerian anomalies in general clearly represent a spectrum of anatomical variants, as suggested by the classification of Toaff et al. (18), dividing communicating uteri into nine basic groups, including five with subtypes. Clinical Management Issues
The association under discussion needs to be considered in patients presenting with pain and/or dysmenorrhea who, on physical examination, are noted to have a vaginal/pelvic mass. In particular, the identification of an absent functional kidney in a patient experiencing pain shortly after menarche should alert the practitioner to the strong possibility of the diagnosis. This syndrome should also be included in the differential diagnosis of acute and chronic obstructive uropathies, as well as that of a pelvic or abdominal mass in the prepubertal or even newborn child (19). In some patients, the presence of a persistent vaginal discharge, with or without abnormal vaginal bleeding, may suggest the less common situation in which a communication between the two sides exists (Fig. 1). It should be remembered that a unicornuate uterus with a noncommunicating but functional horn may also have an essentially identical clinical presentation, including unilateral renal agenesis. In these patients, however, the diagnosis should become clear at the time of a vaginal examination (under anesthesia if necessary) when the typical paravaginal cystic mass seen in our patients is not found. The combination of uterus didelphys and obstructed hemivagina appears to be virtually always associated with ipsilateral renal agenesis or dysgenesis. For these patients, renal imaging, generally an IVP, is necessary not only to confirm the absence of a normal kidney on the affected side but also to detect abnormalities ofthe contralateral kidney and/ or ureter. Identification of the proper diagnosis allows for appropriate surgical therapy, which in general should involve resection of the vaginal septum. A single procedure should be performed, rather than incising the septum first and then resection it 2 to 3 months later, as previously recommended (2). Incision and drainage alone may lead to the developFertility and Sterility
ment of pyocolpos after spontaneous closure. Operative laparoscopy, allowing for surgical treatment of associated endometriosis and/or adhesions if needed, can be performed at the time the septum is resected. If proper surgical therapy has been delayed, hemihysterectomy with or without salpingo-oophorectomy may become necessary because of continued retrograde menstruation leading to hematometra, hematosalpinx, endometriosis, and pelvic adhesions. However, such surgery should only rarely be needed because once the obstruction has been surgically relieved, both the dilated hemiuterus and its corresponding tube may largely regain their normal anatomic appearance as well as normal function. This normalization clearly occurred in case 6, in which a term pregnancy in the affected side was achieved after the affected hemiuterus has been noted to be 10 cm in diameter. Two of our patients (cases 1 and 5) presented with a vaginal/pelvic mucocele after hemihysterectomy and salpingo-oophorectomy; this stresses the importance of either establishing a long-lasting communication between the obstructed hemivagina and its patent counterpart or, alternatively, excising the hematocolpos at the time of hemihysterectomy, should the latter be necessary. As is the case for other patients with uterus didelphys, there is generally no role for a unification procedure in the management of these patients. The obstetrical outcome in our patients was quite favorable. Of the 10 IUPs that occurred, 5 resulted in term deliveries, 4 in preterm deliveries, and 1 in an early spontaneous pregnancy loss. This set of outcomes is quite comparable with that reported for the more common syndrome of uterus didelphys associated with a sagittal vaginal septum (20). In conclusion, a greater awareness of the syndrome of uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis should lead to its prompt diagnosis. This in tum should allow for early and appropriate surgical intervention and decreased long-term morbidity. REFERENCES 1. Purslow CEo A case of unilateral haematocolpos, haematometra and haematosalpinx. J Obstet Gynaecol Br Emp 1922;29:643.
Vol. 57, No.4, April 1992
2. Morgan MA, Thurnau GR, Smith ML. Uterus didelphys with unilateral hematocolpos, ipsilateral renal agenesis and menses. A case report and literature review. J Reprod Med 1987;32: 47-58. 3. Rock JA, Jones HJ. The double uterus associated with an obstructed hemivagina and ipsilateral renal agenesis. Am J Obstet Gynecol 1980;138:339-42. 4. Intaraprasert S, Benchakan V. Milllerian duct anomalies and unilateral renal agenesis: report of 21 cases from Ramathibodi Hospital. J Med Assoc Thai 1985;68:183-9. 5. Olive DL, Henderson DY. Endometriosis and miillerian anomalies. Obstet Gynecol 1987;69:412-5. 6. Andersen HH, Folke K, Frimodt MC, Berget A. Didelphic uterus, atretic unilateral vagina communicating with a double vagina, ipsilateral renal hypoplasia and ectopic ureter. Acta Obstet Gynecol Scand 1986;65:799-801. 7. Adams GW. Uterus didelphys with unilateral imperforate vagina: a rare cause of urinary retention. J Urol 1979;121: 131-2. 8. Broseta E, Boronat F, Dominguez C, Alonso M, Ruiz JL. Retencion aguda de orina por hematocolpos asociado a utero didelfo y agenesia renal ipsilateral. Arch Esp Urol 1989;42: 885--8. 9. Gasser F, Gasser G, Rasmussen P. Uterus didelphys med unilateral haematocolpos, haematometra, haematosalpinx, ipsilateral renal agenesi and kontralateral hydroureter og hydronefrose. Ugeskr Laeger 1983;145:3263-4. 10. Torrey TW. The early development of the human nephros. Carnegie Inst Contrib EmbryoI1954;35:175-97. 11. Gyllensten L. Contributions to embryology of the uroinary bladder: development of definitive relations between openings of Wolffian ducts and ureters. Acta Anat (Basel) 1949;7:30544. 12. Grobstein C. Some transmission characteristics of the tubule inducing influence on mouse metanephrogenic mesenchyme. Exp Cell Res 1957;13:575-87. 13. Hamilton W J, Mossman HW. Prenatal development of form and function. In: Human embryology. Baltimore: The Williams and Wilkins Co., 1972:377-436. 14. Streeter GL. Developmental horizons in human embryos. Carnegie Inst Contrib Embryol 1951;34:165-96. 15. Langman J, Wilson DB. Embryology and congenital malformations of the female genital tract. In: Blaustein A, editor. Pathology of the female genital tract. 2nd ed. New York: Springer-Verlag, 1982:1-12. 16. Denis X, Aubineau JM, Rousseau 0, Mazeman E. uterus didelphe avec hemivagin borgne et agenesie renale homolaterale. Ann Urol (Paris) 1989;23:31-4. 17. Miller NF. Clinical aspects of uterus didelphys. Am J Obstet Gynecol 1922;4:398-408. 18. ToaffME, Lev-Toaff AS, ToaffR. Communicating uteri: review and classification with introduction of two previously unreported types. Fertil Steril1984;41:661-79. 19. Burbige KA, Hensle TW. Uterus didelphys and vaginal duplication with unilateral obstruction presenting as a newborn abdominal mass. J Urol 1984;132:1195--8. 20. Stein AL, March CM. Pregnancy outcome in women with miillerian duct anomalies. J Reprod Med 1990;35:411-4.
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Vol. 57, No.4, April 1992 Printed on acid-free poper in U.S.A.
Copyright C> 1992 The American Fertility Society
Uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis: the University of Minnesota experience
Jacques P. Stassart, M.D.* Theodore C. Nagel, M.D.t Konald A. Prem, M.D. William R. Phipps, M.D.:!: Department of Obstetrics and Gynecology, University of Minnesota, Minneapolis, Minnesota
Objective: To present the experience of a large referral center with patients with the rare but specific syndrome of uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis. Design, Patients: Between 1953 and 1991, 15 patients with the syndrome were evaluated by the authors; each patient's records were carefully reviewed. Main Outcome Measures: For each patient, the clinical course, specific anatomic findings, treatment(s) offered, and obstetrical outcome are presented. Results: The specificity of the association of uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis was confirmed by our series, the largest in the literature to date. The findings suggest a specific developmental anomaly of the mUllerian ductal system, probably secondary to a wolffian duct anomaly. The most common clinical presentation was that of the onset of pelvic pain and/or dysmenorrhea shortly after menarche, in association with the finding of a vaginal/pelvic mass. When a communication between the two sides existed, symptoms of abnormal vaginal discharge and bleeding were common. Optimal outcome appears to have occurred for patients initially managed using a conservative surgical approach, i.e., simple vaginal septum resection combined with conservative treatment of associated endometriosis. Obstetrical outcome in our patients was similar to that in patients with the more common combination of uterus didelphys and sagittal vaginal septum. Conclusion: A greater awareness of the syndrome of uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis should lead to its prompt diagnosis, allowing for early and appropriate surgical intervention as well as decreased long-term morbidity. Fertil SterilI992;57:756-61 Key Words: Hematocolpos, mUllerian ducts, renal agenesis, uterus didelphys, vagina
The specific association of uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis was recognized as early as 1922 (1). Morgan et a1. (2) recently reviewed the English literature and
Received September 6, 1991; revised and accepted December 31,1991. * Reprint requests: Jacques P. Stassart, M.D., Department of Obstetrics and Gynecology, University of Minnesota, UMHC Box 395, Minneapolis, Minnesota 55455. t Present address: Reproductive Health Associates, St. Paul, Minnesota. :I: Present address: Department of Obstetrics-Gynecology, University of Rochester, Rochester, New York.
756
Stassart et aI.
Uterus didelphys/obstructed hemivagina
found 115 cases, to which they added one of their own. As did Rock and Jones (3), they noted a more common occurrence of the obstructed hemivagina and renal agenesis on the right side. In a minority of cases, a communication connecting the right and left sides at the level of the vagina or above the internal cervical ora was present (Fig. 1). Since the report of Morgan et a1. (2), over 50 additional cases have been reported in the world literature. To our knowledge, the two largest series to date have included 12 patients each (3, 4). We now report a series of 15 patients, including several with long-term obstetrical follow-up. Both embryologic considerations and clinical management issues are discussed. Fertility and Sterility
Figure 1 Illustration of associaton of uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis. Sites of communication between the two sides may occur either above the internal cervical ora (A), or essentially anywhere at the level of the vagina (B).
MATERIALS AND METHODS
Between 1953 and 1991, the authors evaluated 15 patients with the specific association of uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis. This report is based on a careful review of their records. When appropriate and possible, follow-up by telephone was obtained. In all but one case, the status of the reproductive organs was assessed by hysterosalpingogram, laparoscopy, and/or laparotomy, and the urinary system was evaluated by intravenous pyelogram (IVP) and/or cystoscopy. In our patient diagnosed at the age of 6 years, pelvic and renal ultrasound studies were used instead. RESULTS
A summary of our cases is presented in Table 1. In 11 of our 15 cases, the right side was the site of the obstructed hemivagina and renal agenesis, confirming previous reports showing a right-sided preponderance (2, 3). In all 11 cases in which cystoscopy was performed (all but cases 5, 7, 9, and 11), the findings included absence of the hemitrigone of the bladder and the ureteral orifice on the affected side. Vol. 57, No.4, April 1992
In most of our cases, menarche was shortly followed by pain and/or dysmenorrhea, related to the presence of hematocolpos, hematometra, and/or hematosalpinx. This then prompted the finding of a vaginal/pelvic mass. However, the three patients with a low isthmic or cervical communication (cases 11, 14, and 15) did not present until 3 to 8 years after menarche. Presumably, such a communication may to some extent diminish the occurrence of acute, obstruction-related symptoms. The three patients with a pinpoint vaginal communication (cases 8, 9, and 10) had symptoms of abnormal vaginal bleeding and/or discharge. Thus, in general, the nature and the chronology of the symptoms correlated well with the anatomical findings. Four patients had what was essentially an isolated vaginal/pelvic mucocele. These included two girls (cases 7 and 8) presenting before menarche, before the possibility of symptoms related to hematometra G8 and hematosalpinx. The other two cases with a mucocele (cases 1 and 5) were seen after hemihysterectomy and salpingo-oophorectomy. At least 7 of our 15 patients (cases 3, 4, 5, 8, 9, 10, and 13) had endometriosis noted at the time of laparosopy or laparotomy, including all 3 patients with a pinpoint vaginal communication. This can be explained on the basis of increased retrograde menstruation (5). Endometriosis was not found in any of the 3 patients with a low isthmic or cervical communication. One of our patients (case 13) presented with acute urinary retention and hydronephrosis, whereas another (case 2) had chronic hydronephorsis; obstructive uropathy has previously been reported in a few patients with this condition (6-9). In most of our cases, the patient was initially managed by another physician who failed to recognize the true nature of the syndrome. Thus, many of the patients underwent unnecessary and/or incomplete surgical procedures. Six of our 15 patients gave birth to a total of nine live infants after surgical treatment. Four other patients have not yet attempted to achieve a pregnancy, 1 was infertile, and 1 underwent a sterilization procedure at an early age because of renal disease. The remaining two have been lost to followup. The nine live births included two breech, seven cephalic presentations, and three cesarean sections. Obstetrical outcome did not appear to be adversely affected by leaving in place the affected hemiuterus and corresponding adnexa. In 1 patient (case 6), the affected side was the site of an intrauterine pregnancy (IUP), with a cesarean section performed at Stassart et al.
Uterus didelphys/obstructed hemivagina
757
Table 1
Summary of Presentation and Course of Patients With Uterus Agenesis Didelphys, Obstructed Hemivagina, and Ipsilateral Renal
Case
Affected side, communication
R*, none
Age at menarche
Age at presentation
y
y
15
26
Initial presentation
Pain, mass
Treatment
(1) R salpingo-oophectomy (26,1927)t (2) R hemihysterectomy (27,1928)t (3) Vaginal septum incision for
Obstetrical outcome
Comments
Infertility
abdominal pain and vaginal/pelvic mucocele (66, 1968)t (4) Vaginal septum resection
for vaginal/pelvic mucocele 2
R, none
10
12
Pain, mass
(67,1969) (1) Strassmann-type unification
procedure, vaginal septum incision (15, 1953) (2) Vaginal septum resection for vaginal mass and discharge after spontaneous closure of incision 3
R, none
11
16
Pain, mass
(21,1959) (1) R hemihysterectomYI
salpingo-oophectomy, vaginal septum resectionendometriosis noted 4
R, none
11
11
Pain, mass
(21,1967) (1) Vaginal septum incision (11,1973)t (2) R hemihysterectomyI
Sterilization at age 22 because of persistent L-sided hydronephrosis and urinary tract infections
L:j:-sided hydronephrosis first noted at age 15
First trimester loss, then term vaginal deliveries X 3 Term cesarean section (fetal distress)
salpingo-oophectomy, vaginal septum resectionendometriosis noted 5
R, none
14
14
Pain, mass
(11,1973) (1) R hemihysterectomyI
salpingo-oophectomy
No desire for pregnancy
(14,1975)t (2) Laparoscopy-pelvic massl
endometriosis noted (27,1988)t (3) Operative laparoscopy,
6
7
8
R, none
R, none
R, vaginal
14
NA§
12
14
6
11
Pain, mass
Pain, mass
Pain, mass, spontaneous vaginal drainage
vaginal septum resection for large vaginal/pelvic mucocele (28, 1989) (1) Exploratory laparotomy, hemivaginal aspiration (14,1976)t (2) Vaginal septum resection (15,1976) (1) Vaginal aspiration only-
surgical procedure limited by exposure (6, 1989) (1) Exploratory laparotomy, vaginal septum resection for hematopyocolpos (11,1967)t (2) Diagnostic laparoscopy-
Complete duplication of L ureter
Term cesarean section (breech)affected side NA§ (1) Vaginal
delivery at 36 weeks (2) Ltubal pregnancy
Asymptomatic 2 years after surgery Vaginal endometriosis noted in obtructed hemivagina
pelvic endometriosis
9
10
R, vaginal
R, vaginal
11
12
11
13
Pain, vaginal discharge, abnormal vaginal bleeding Abnormal bleeding
(23,1979) (3) LaparotomyIlysis of adhesions (25, 1981) (1) Operative laparoscopyendometriosis (13, 1989)t (2) Operative laparoscopy,
NA§
vaginal septum resection (13,1990) (1) Laparoscopy-
NA§
endometriosis noted (13,1991)t (2) Operative laparoscopy,
vaginal septum resection (13,1991)
758
Sta8Sart et aI.
Uterus didelphys/obstructed hemivagina
Fertility and Sterility
Table 1 (Continued) Age at menarche
Age at presentation
R,low isthmic or cervical
13
21
Vaginal discharge
12
L, none
15
15
Pain, mass
13
L,none
14
14
14
L, low isthmic or cervical
11
14
Urinary symptoms (dysuria, acute urinary distension) pain, mass Pain, mass
15
L, low isthmic or cervical
13
19
Case
Affected side, communication
11
Initial presentation
Abnormal bleeding, mass
• R, right. t Indicates surgery performed elsewhere. Values in parentheses are age and year.
term because of breech presentation; before resection of her septum, the affected hemiuterus had been noted to be 10 cm in diameter. The only tubal pregnancy in our series (case 8) occurred on the unaffected side in a patient who had previously undergone laparotomy for lysis of major pelvic adhesions secondary to severe endometriosis. She had had a prior live birth. DISCUSSION Embryologic Considerations
The constellation of findings in these patients may be the result of an abnormality in the development of the caudal portion of one of the wolffian (mesonephric) ducts with secondary involvement of the ipsilateral miillerian (paramesonephric) duct. Each wolffian duct originates in the vicinity of the pronephros about 3! weeks after conception (10). Each ureteric bud develops from the wolffian duct near the opening into the cloaca about 1! weeks later (11) and grows dorsocranially into the metanephric blastema, inducing the differentiation of the metaVol. 57, No.4, April 1992
Treatment
(1) Laparoscopy-pelvic adhesions noted (22, 1986)t (2) Vaginal septum resection (22,1986) (1) Rectal drainage of mass (15,1962)t (2) L hemihysterectomYI salpingo-oophectomyI hemicolpectomy for abscess after first surgery (15, 1962) (1) Exam under anesthesia (15,1983)t (2) Operative laparoscopy with lysis of adhesions, vaginal septum resection (15, 1983) (3) Operative laparoscopyendometriosis (16, 1984) (1) L salpingo-oophectomy for adnexal mass (14, 1967)t (2) Vaginal incision for recurrent mass (15, 1968)t (3) Vaginal septum resection (18,1971) (1) Vaginal septum resection (19,1974)t (2) Laparoscopy, hysteroscopy-obstruction within L hemiuterus noted (30,1986)
Obstetrical outcome Unknown
Comments
Pelvic adhesions sip gonococcal salpingitis
Unknown
No desire for pregnancy
R-sided hydronephrosis resolved after first surgery
(1) Vaginal delivery at 32 weeks (2) Cesarean section at 34 weeks (breech) Vaginal delivery at 27 weeks
:t: L, left. § NA, not applicable.
nephric nephrons (12). If the ureteric bud fails either to form or make contact with the metanephric blastema, the kidney on that side will not develop (13). The caudal portions of wolffian ducts are then incorporated into the bladder (14). In the process, the ureters acquire their own openings into the bladder, whereas the openings of the wolffian ducts shift into a urethral position. The trigone is formed between the openings of the ureters and that of the wolffian ducts bilaterally. The miillerian duct may be recognized as early as 44 to 48 days after conception (14). Its cells contact the wolffian duct and grow caudally using its epithelium as a guide. Interruption of the wolffian duct or its failure to form results in interruption or failure of formation of the miillerian duct (14). Caudal to the mesonephric ridges the miillerian ducts cross the wolffian ducts ventrally and approach each other in the midline, running caudally between the wolffian ducts. The caudal ends of the miillerian ducts then contact the endodermal epithelium of the urogenital sinus without breaking through at 55 to 60 days after conception. The caudal portions normally fuse to form a single canal. The direct contact at Stassart et al.
Uterus didelphys/obstructed hemivagina
759
r the tip of the canal is thought to induce the development of the vaginal plate, the caudal one fifth of which is generally considered to be endodermal in origin. The origin of the upper four fifths of the vaginal plate and the precise manner in which the vaginal plate contributes to the vagina is controversial (15). In the cases presented, the presence of mullerian structures bilaterally indicates that wolffian duct formation has occurred. On the affected side, however, the ureteric bud has either failed to form or has formed aberrantly, as suggested by reported cases (16, 17) in which a rudimentary pelvic kidney was found. Failure of normal ureteric bud formation would result in failure of differentiation of the mesonephric blastema into the kidney and absence of the bladder hemitrigone, as confirmed in most of our cases. An aberrant location of the wolffian duct might account for failure of ureteric budding as well as an abnormal location of the mullerian duct on the affected side. The result would be failure of the aberrant mullerian duct to fuse with both its opposite counterpart and with the urogenital sinus, the latter in turn leading to failure of formation of the vaginal plate on the affected side. This would account for the finding that, unless a spontaneous or surgical communication between the two hemivaginas has been established, the obstructed hemivagina is invariably lined by columnar epithelium, presumably of mullerian origin (3). The presence of such epithelium may lead to the development of a mucocele, as seen in four of our patients (cases 1, 5, 7, and 8). In patients with the more common syndrome of uterus didelphys associated with a sagittal vaginal septum, renal agenesis is seldom present (3). Our cases may represent a variant of that syndrome. However, although the precise mechanisms involved remain undefined, the constancy of the association of unilateral renal agenesis and the obstructed hemivagina in the patients under discussion makes it more likely that the syndrome represents a distinct aberrancy of wolffian duct development. Three of our patients (cases 11, 14, and 15) had a low isthmic or cervical communication and, thus, despite the presence of two cervices and two distinct uterine horns, might be considered not to have a true uterus didelphys. This was also true for 2 of the 12 patients described by Rock and Jones (3) and an unspecified number of the 12 patients described by Intaraprasert and Benchakan (4) (6 of whom had either a vaginal or a low isthmic/cervical communication). We do not believe that the presence of a 760
Stassart et al.
Uterus didelphys/obstructed hemivagina
small communication between the two sides, either at the level of the vagina or just above the cervical ora, warrants a separate classification or suggests a distinct teratogenic process because of the constancy of the other findings. It is possible, in fact, that such communications may not be congenital in nature but, rather, represent acquired lesions. Mullerian anomalies in general clearly represent a spectrum of anatomical variants, as suggested by the classification of Toaff et al. (18), dividing communicating uteri into nine basic groups, including five with subtypes. Clinical Management Issues
The association under discussion needs to be considered in patients presenting with pain and/or dysmenorrhea who, on physical examination, are noted to have a vaginal/pelvic mass. In particular, the identification of an absent functional kidney in a patient experiencing pain shortly after menarche should alert the practitioner to the strong possibility of the diagnosis. This syndrome should also be included in the differential diagnosis of acute and chronic obstructive uropathies, as well as that of a pelvic or abdominal mass in the prepubertal or even newborn child (19). In some patients, the presence of a persistent vaginal discharge, with or without abnormal vaginal bleeding, may suggest the less common situation in which a communication between the two sides exists (Fig. 1). It should be remembered that a unicornuate uterus with a noncommunicating but functional horn may also have an essentially identical clinical presentation, including unilateral renal agenesis. In these patients, however, the diagnosis should become clear at the time of a vaginal examination (under anesthesia if necessary) when the typical paravaginal cystic mass seen in our patients is not found. The combination of uterus didelphys and obstructed hemivagina appears to be virtually always associated with ipsilateral renal agenesis or dysgenesis. For these patients, renal imaging, generally an IVP, is necessary not only to confirm the absence of a normal kidney on the affected side but also to detect abnormalities ofthe contralateral kidney and/ or ureter. Identification of the proper diagnosis allows for appropriate surgical therapy, which in general should involve resection of the vaginal septum. A single procedure should be performed, rather than incising the septum first and then resection it 2 to 3 months later, as previously recommended (2). Incision and drainage alone may lead to the developFertility and Sterility
ment of pyocolpos after spontaneous closure. Operative laparoscopy, allowing for surgical treatment of associated endometriosis and/or adhesions if needed, can be performed at the time the septum is resected. If proper surgical therapy has been delayed, hemihysterectomy with or without salpingo-oophorectomy may become necessary because of continued retrograde menstruation leading to hematometra, hematosalpinx, endometriosis, and pelvic adhesions. However, such surgery should only rarely be needed because once the obstruction has been surgically relieved, both the dilated hemiuterus and its corresponding tube may largely regain their normal anatomic appearance as well as normal function. This normalization clearly occurred in case 6, in which a term pregnancy in the affected side was achieved after the affected hemiuterus has been noted to be 10 cm in diameter. Two of our patients (cases 1 and 5) presented with a vaginal/pelvic mucocele after hemihysterectomy and salpingo-oophorectomy; this stresses the importance of either establishing a long-lasting communication between the obstructed hemivagina and its patent counterpart or, alternatively, excising the hematocolpos at the time of hemihysterectomy, should the latter be necessary. As is the case for other patients with uterus didelphys, there is generally no role for a unification procedure in the management of these patients. The obstetrical outcome in our patients was quite favorable. Of the 10 IUPs that occurred, 5 resulted in term deliveries, 4 in preterm deliveries, and 1 in an early spontaneous pregnancy loss. This set of outcomes is quite comparable with that reported for the more common syndrome of uterus didelphys associated with a sagittal vaginal septum (20). In conclusion, a greater awareness of the syndrome of uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis should lead to its prompt diagnosis. This in tum should allow for early and appropriate surgical intervention and decreased long-term morbidity. REFERENCES 1. Purslow CEo A case of unilateral haematocolpos, haematometra and haematosalpinx. J Obstet Gynaecol Br Emp 1922;29:643.
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2. Morgan MA, Thurnau GR, Smith ML. Uterus didelphys with unilateral hematocolpos, ipsilateral renal agenesis and menses. A case report and literature review. J Reprod Med 1987;32: 47-58. 3. Rock JA, Jones HJ. The double uterus associated with an obstructed hemivagina and ipsilateral renal agenesis. Am J Obstet Gynecol 1980;138:339-42. 4. Intaraprasert S, Benchakan V. Milllerian duct anomalies and unilateral renal agenesis: report of 21 cases from Ramathibodi Hospital. J Med Assoc Thai 1985;68:183-9. 5. Olive DL, Henderson DY. Endometriosis and miillerian anomalies. Obstet Gynecol 1987;69:412-5. 6. Andersen HH, Folke K, Frimodt MC, Berget A. Didelphic uterus, atretic unilateral vagina communicating with a double vagina, ipsilateral renal hypoplasia and ectopic ureter. Acta Obstet Gynecol Scand 1986;65:799-801. 7. Adams GW. Uterus didelphys with unilateral imperforate vagina: a rare cause of urinary retention. J Urol 1979;121: 131-2. 8. Broseta E, Boronat F, Dominguez C, Alonso M, Ruiz JL. Retencion aguda de orina por hematocolpos asociado a utero didelfo y agenesia renal ipsilateral. Arch Esp Urol 1989;42: 885--8. 9. Gasser F, Gasser G, Rasmussen P. Uterus didelphys med unilateral haematocolpos, haematometra, haematosalpinx, ipsilateral renal agenesi and kontralateral hydroureter og hydronefrose. Ugeskr Laeger 1983;145:3263-4. 10. Torrey TW. The early development of the human nephros. Carnegie Inst Contrib EmbryoI1954;35:175-97. 11. Gyllensten L. Contributions to embryology of the uroinary bladder: development of definitive relations between openings of Wolffian ducts and ureters. Acta Anat (Basel) 1949;7:30544. 12. Grobstein C. Some transmission characteristics of the tubule inducing influence on mouse metanephrogenic mesenchyme. Exp Cell Res 1957;13:575-87. 13. Hamilton W J, Mossman HW. Prenatal development of form and function. In: Human embryology. Baltimore: The Williams and Wilkins Co., 1972:377-436. 14. Streeter GL. Developmental horizons in human embryos. Carnegie Inst Contrib Embryol 1951;34:165-96. 15. Langman J, Wilson DB. Embryology and congenital malformations of the female genital tract. In: Blaustein A, editor. Pathology of the female genital tract. 2nd ed. New York: Springer-Verlag, 1982:1-12. 16. Denis X, Aubineau JM, Rousseau 0, Mazeman E. uterus didelphe avec hemivagin borgne et agenesie renale homolaterale. Ann Urol (Paris) 1989;23:31-4. 17. Miller NF. Clinical aspects of uterus didelphys. Am J Obstet Gynecol 1922;4:398-408. 18. ToaffME, Lev-Toaff AS, ToaffR. Communicating uteri: review and classification with introduction of two previously unreported types. Fertil Steril1984;41:661-79. 19. Burbige KA, Hensle TW. Uterus didelphys and vaginal duplication with unilateral obstruction presenting as a newborn abdominal mass. J Urol 1984;132:1195--8. 20. Stein AL, March CM. Pregnancy outcome in women with miillerian duct anomalies. J Reprod Med 1990;35:411-4.
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