Donald Peter Goldstein, MD Dr. Goldstein is Senior Scientist, Division of Gynecologic Oncology, at Brigham and Women’s Hospital and Clinical Professor of Obstetrics, Gynecology, and Reproductive Biology at Harvard Medical School in Boston.

The author reports no fi nancial relationships relevant to this article.

When both müllerian ducts fail to fuse, the result is didelphys. The individual horns of the uterus develop ® Dowden Health Mediafully and are of nearly normal size. Copyright How toFor diagnosepersonal use only and repair congenital uterovaginal IN THIS ARTICLE ❙ Just what is normal malformations development? Knowing when and how these abnormalities become Page 54 apparent is the fi rst step toward correcting them ❙ Removing a transverse CASE 1 Fluid-fi lled abdominal mass are present at the dome of the mass. vaginal septum The kidneys are normal. Page 57 A 14-year-old girl complains of crampy, epi- What is the mass? sodic, lower abdominal pain of 3 months’ ❙ Unicornuate and duration and acute retention of urine. She A list of the processes involved in normal also reports back pain and dyschezia. She development of the female reproductive bicornuate uterus has never menstruated, but her breasts be- tract highlights its precarious complex- Page 60 gan developing 18 months earlier. Examina- ity: cellular differentiation, migration, ca- tion reveals normal Tanner stage 3 breast nalization, fusion, and programmed cell development and female hair distribution death. A failure in any of these processes and a large abdominal mass. No fetal heart can cause a malformation. When that tones are apparent. The external genitalia malformation becomes apparent depends appear to be normal except for a bulging on the stage of life of the patient and the mass at the introitus. nature of the abnormality. As you might Flynn

Imaging (FIGURE 1) reveals that the imagine, diagnosis and treatment are not Maura

mass is fl uid-fi lled. The uterus, tubes, and always straightforward. ©2008

52 OBG MANAGEMENT • March 2008

For mass reproduction, content licensing and permissions contact Dowden Health Media. In the patient just described, the FIGURE 1 likely diagnosis is imperforate or No exit for menstrual products transverse vaginal septum due to failed canalization of the vaginal plate. The patient has been menstruating internally for many months and now has a large he- matocolpos. Urinary retention develops when the amount of retained blood in the causes acute angulation of the urethrovesical junction. Evacuation of the blood restores the physiologic angle, enabling the patient to void normally. Most anomalies involving the exter- nal genitalia are apparent at birth (clito- romegaly, ), whereas An MRI shows a large hematocolpos that develops after obstructive and nonobstructive malfor- menarche in women who have outfl ow obstruction, such as imperforate hymen—as this patient had. mations may become evident at birth; during childhood, , or adoles- FIGURE 2 cence; or with menarche or childbearing. Treatment of these abnormalities has Imperforate hymen changed signifi cantly over the past few years—largely due to refi nements in diag- nostic imaging, surgical and nonsurgical techniques, and instrumentation. These advances have improved reproductive function and enhanced the psychosexual attitude of these patients. In this article, I review the most com- mon abnormalities and describe their FAST TRACK evaluation and management. Imperforate hymen is the most common Impaired canalization obstructive lesion Imperforate hymen of the female The most common obstructive lesion of reproductive tract the female reproductive tract is an im- perforate hymen. It can be diagnosed at birth with careful examination to ensure patency of both the and vagina. Not infrequently, the presents with a bulging introitus due to muco- colpos from vaginal secretions stimu- FIGURE 2 lated by maternal ( ). If Bulging hymen due to mucocolpos in a newborn (top) and diagnosis is delayed, the mucus usually hematocolpos in an adolescent (bottom). resorbs and the child remains asymp- tomatic until menarche, when she pres- is facilitated if the tissue has undergone ents with a bulging hymen and a large estrogen stimulation. Surgery is, there- hematocolpos, as in the opening case. fore, ideal in the neonatal, postpubertal, Management of imperforate hymen is and premenarchal periods. feasible for the generalist. Repair can be Repair involves incision of the mem- performed in a patient of any age, but brane near the hymeneal ring, followed

www.obgmanagement.com March 2008 • OBG MANAGEMENT 53 Congenital uterovaginal malformations

Just what is normal development? Vaginal canalization The sinovaginal bulbs are two solid evaginations originating A from the at the distal aspect of the müllerian tubercle, as shown at right (A). The sinovaginal bulbs prolifer- ate into the caudal end of the uterovaginal canal to become the solid vaginal plate (B). The lumen of the lower vagina is formed by degeneration of the central cells of this vaginal plate, which occurs in a cephalad direction (C). This process of canalization is complete by 20 weeks’ gestation.

Hymen usually ruptures before birth The vaginal hymen is separated from the urogenital sinus by the hymeneal membrane. The hymen usually ruptures before birth B with the degeneration of central epithelial cells (i.e., canaliza- tion), leaving a thin fold of around the vaginal introitus.

Uterus, fallopian tubes develop from solid tissue The müllerian ducts are fi rst identifi able at approximately 6 weeks of gestation, when they begin to elongate caudally and cross the metanephric ducts medially to meet in the midline. By the sev- enth week, the has developed, separating the rectum from the urogenital sinus. Around 12 weeks’ gestation, the caudal portion of the müllerian ducts fuses to form the uterovagi- C nal canal, which inserts into the dorsal wall of the urogenital sinus at Müller’s tubercle. The two müllerian ducts are initially solid tissue and lie side by side. Subsequently, internal canalization of each duct pro- duces two channels divided by a septum that is reabsorbed in a cephalad direction by 20 weeks. The cranial unfused portions of the müllerian ducts develop into the fi mbria and fallopian tubes, whereas the caudal, fused portions form the uterus and upper vagina. Flewell Rob ©2008

by evacuation of accumulated blood. The malodorous discharge due to partial ob- may appear to be fl ush with the struction and poor drainage. vaginal apex, owing to compression, but Treatment of microperforate, cribri- this condition usually corrects itself with- form, or septate hymen entails resec- in 2 or 3 weeks. Extra hymeneal tissue is tion of excess hymeneal tissue to create excised to create an orifi ce of normal size, a functional hymeneal ring. and the vaginal mucosa is intermittently sutured to the hymeneal ring using ab- Transverse vaginal septum sorbable material (FIGURE 3, page 57). A transverse septum represents failed ca- nalization of the vaginal plate. This con- Incomplete hymeneal fenestration dition occurs in approximately one of This condition often goes undiagnosed every 18,000 to 30,000 women.1,2 The until the patient seeks evaluation for an septum can be located at any of various inability to insert or medica- levels in the vagina; approximately 46% tion or because of coital diffi culty. Young are found in the upper vagina, 35% to girls with microperforate hymen may 40% in the middle portion, and 15% to present with postmenstrual spotting or 20% in the lower vagina.1,2 Lower septa

54 OBG MANAGEMENT • March 2008 Congenital uterovaginal malformations

appear to be thinner than those in the FIGURE 3 proximal vagina; thinness may be due Hymenectomy restores vaginal orifi ce to the pressure of accumulated fl uid. If a small perforation is present, the patient will experience irregular spotting. Examination. The external genitalia appear to be normal, but the vagina is shortened. Children may present with mucocolpos, whereas adolescents devel- op hematocolpos. If a small perforation is present, pyohematocolpos may result from ascending infection. A mass can be palpated on rectal examination. Ultrasonography (US) or magnetic resonance imaging (MRI) helps defi ne the location and thickness of the septum Extra hymeneal tissue is excised to create an orifi ce of normal size. The vaginal mucosa is and distinguish a high septum from con- intermittently sutured to the hymeneal ring. ©2008 Rob Flewell genital absence of the cervix. FIGURE 4 Treatment. Resect a small septum and perform end-to-end anastomosis of the Removing a transverse vaginal septum upper and lower edges of the vaginal wall (FIGURE 4). Only an experienced surgeon should excise a thick septum. Reanastomo- sis is easier if the upper vagina is distended with menstrual blood. To ensure healing without stricture, mobilize the vaginal edge circumferentially before suturing the raw edges. Outfl ow obstruction caused by a transverse septum in the distal vagina almost never leads to hematometra or hematosalpinx. However, septa that arise in the proximal vagina are usually thicker and, if left untreated, can cause refl ux that damages the upper reproduc- tive tract. These cases are almost always The septum is resected from the distal vagina. This is followed by end-to-end anastomosis of associated with severe dysmenorrhea mucosal edges. ©2008 Rob Flewell and should be referred to an experienced vaginal surgeon. Pelvic MRI is recom- nal septum. A slight midline septum with mended to assess the thickness and pre- minimal fundal indentation is classifi ed cise anatomy of the defect before repair. by some as a septate uterus; by others, as a bicornuate uterus. Uterine septum A higher risk of recurrent miscarriage A septate uterus has a normal external is associated with longer septa. surface but two endometrial cavities. It is Surgical repair with hysteroscopic resec- caused by a defect in fusion or resorption tion of the septum yields excellent results. of the midline septum between the two müllerian ducts. The degree of septation CASE 2 The problem of agenesis varies from a small midline septum to a total failure of resorption that produces An 18-year-old patient consults a gynecolo- a septate uterus with a longitudinal vagi- gist because she has never menstruated

www.obgmanagement.com March 2008 • OBG MANAGEMENT 57 Congenital uterovaginal malformations

FIGURE 5 drome is unknown. These patients have Uterine agenesis normal female karyotypes and pheno- types with normal ovaries and ovarian Round Rudimentary function—although there is evidence uterus that they are prone to early menopause. They develop secondary sexual charac- teristics. They usually present with pri- mary amenorrhea at 15 to 17 years of age. Vaginal agenesis is the second Fallopian most common cause of primary amen- tube orrhea after gonadal dysgenesis. Most patients have a rudimentary, nonfunc- This depiction of uterine agenesis shows small, nonfunction- tioning uterus, but 2% to 7% have a ing müllerian remnants and normal tubes and ovaries. uterus with functioning and present with cyclic or chronic ab- and is unable to have . dominopelvic pain secondary to ob- She appears to be phenotypically normal, struction or endometriosis, hematocol- with normal upon examination, but pos, or hematometra. no hymeneal opening is found. Pelvic US Imaging. US examination facilitates eval- reveals absence of the uterus with ovaries uation of the kidneys and confi rms the that appear to be normal. presence of ovaries and absence of the How should her condition be managed? uterus. MRI may be useful to confi rm the presence of functioning endometrium. Uterovaginal agenesis, also known as The differential diagnosis of vaginal müllerian aplasia or Mayer–Rokitan- agenesis includes androgen insensitivity sky–Küster–Hauser (MRKH) syndrome, and low-lying transverse vaginal septum. refers to congenital absence of the va- Treatment includes psychosocial support FAST TRACK gina with variable uterine development to reassure the patient that a normal First-line therapy (FIGURE 5). It arises from agenesis of the sex life will be possible after treatment.5 müllerian duct system, although the Construction of a neovagina, using for vaginal agenesis underlying cause is unknown. Vaginal vaginal dilators (the fi rst-line strategy) is creation of a agenesis is usually accompanied by cer- or surgical placement of split-thickness neovagina using vical and uterine agenesis. However, skin graft or artifi cial skin (Abbe–McIn- vaginal dilators 7% to 12% of patients with this syn- doe procedure), is the treatment. In one drome have a normal but obstructed case series, more than 90% of patients or rudimentary uterus with functional with vaginal agenesis were successfully endometrium. This condition occurs in treated using vaginal dilation.6 roughly one of every 5,000 females.1,3 The American College of Obstetri- In addition, these girls often ex- cians and Gynecologists (ACOG) recom- hibit extragenital anomalies.1,4 Ap- mends that patients be referred to centers proximately 25% to 50% have a uro- with expertise in surgical creation of a logic anomaly, such as unilateral renal neovagina.5 agenesis, pelvic or horseshoe kidneys, or irregularities of the collecting sys- Agenesis of the lower vagina tems; 10% to 15% have another type This malformation is caused by a failure of anomaly, such as congenital heart of canalization of the sinovaginal bulbs disease, abnormalities of the hands, and vaginal plate. The tubes, ovaries, congenital deafness, cleft palate, and cervix, and upper vagina are normal, but inguinal or femoral hernia. the lower vagina is replaced by fi brous The genetic basis of MRKH syn- tissue. Adolescents present with primary

58 OBG MANAGEMENT • March 2008 Congenital uterovaginal malformations

FIGURE 6 This is a classic description of utero- Uterus didelphys vaginal duplication that arises when the müllerian ducts fail to fuse (FIGURE 6). In this case, the right-sided vagina failed to canalize as well, causing a large he- matocolpos. Generally, duplication is limited to the uterus and cervix (uterus didelphys bicollis), although duplica- tion of the , bladder, , va- gina, and anus have been described. Women with a didelphic uterus of- ten have a good reproductive outcome. A septated vagina occurs in 75% of cases

This patient has uterus didelphys with an obstructed hemi- and may cause diffi culty with sexual in- vagina. tercourse or vaginal delivery. Symptom- atic women usually opt for resection of amenorrhea accompanied by cyclic pel- the vaginal septum. vic pain. A vaginal dimple may be appar- Women who have an obstructed ent on external inspection. hemivagina and ipsilateral renal agen- Because these girls have normal esis have regular menses because men- cyclic pituitary–ovarian–endometrial strual blood from one uterus can exit function at menarche, the upper vagi- through its unobstructed side. na will distend with blood and secre- Treatment involves resection of the tions, and a mass can be palpated on wall of the obstructed vagina, creat- rectoabdominal examination. US con- ing a single . If both vagi- fi rms the presence of a fl uid-fi lled mass, nas have failed to canalize, the patient and MRI further defi nes the length of will present much earlier, with primary obstruction. amenorrhea and cyclic pelvic pain—a FAST TRACK Treatment. Surgery (by an experienced presentation similar to that of trans- Women with vaginal surgeon) is best performed when verse septum. Reconstructive surgery a large hematocolpos is present because of the uterus is not recommended for a didelphic uterus distention increases the amount of tissue complete duplication of the uterus.1,7 often have a good available for pull-through. reproductive Unicornuate and bicornuate uterus outcome CASE 3 Fusion failure A unicornuate uterus represents an asym- metric lateral fusion defect. One cavity is A 17-year-old woman complains of lower usually normal, with a and abdominal pain and an enlarging abdo- cervix, but the failed müllerian duct can men. Menarche occurred at 13 years. The have various confi gurations. The affected patient began to notice right-sided lower müllerian duct may fail to develop, or it abdominal pain and abdominal swelling may develop partially as a horn on the about 2 years ago, but denies any other uterus or a separate structure that may or symptoms. may not communicate with the uterus. Examination reveals a mass arising Most rudimentary horns are asymp- from the right lateral vaginal wall. The cervix tomatic, but others contain functional appears to be normal. US shows a large, endometrium that is shed cyclically. If the predominantly right-sided, fl uid-fi lled mass rudimentary horn is obstructed, as is usu- arising from the pelvis. The uterus appears ally the case, the woman develops cyclic or to be didelphic, with normal ovaries and an chronic abdominopelvic pain that necessi- absent right kidney. tates surgical excision of the horn. Endo- What is the mass? metriosis, a result of refl ux, is common. CONTINUED

60 OBG MANAGEMENT • March 2008 Congenital uterovaginal malformations

In a bicornuate uterus, the fundus FIGURE 7 is indented and the vagina is normal. Gartner’s duct cysts This anomaly occurs when the mülle- rian ducts fuse only partially. The result is varying degrees of separation of the . outcomes appear to be similar to those of the general popula- tion. However, some women develop early pregnancy loss, preterm labor, in- competent cervix, or malpresentation. Treatment is open surgical reunifi cation.

CASE 4 Embryonic rest cells

A 55-year-old woman complains of “fullness” in the vagina, especially during intercourse. Upon examination, a 4- to 5-cm fl uid-fi lled These bilateral cysts developed from embryonic rest cells. cyst is visible at the right posterior fornix. What type of cyst is it? cause these embryonic rest cells may ex- tend deep into the retroperitoneum. ■ Gartner’s duct cysts from embryonic rest References cells arise from remnants of the meta- 1. Emans SJ, Laufer MR, Goldstein DP. Pediatric and nephric duct system. They usually devel- Adolescent Gynecology. 5th ed. Chapter 10. Philadel- phia: Lippincott Williams & Wilkins; 2005:334–416. op on the lateral vaginal walls or fornix 2. Acién P. Incidence of Müllerian defects in fertile and (FIGURE 7), unlike epidermal inclusion infertile women. Hum Reprod. 1997;12:1372–1376. 3. Evans TN, Poland ML, Boving RL. Vaginal malforma- cysts, which are generally located on the tions. Am J Obstet Gynecol. 1981;141:910–920. posterior wall or at the cervical–vesi- 4. Fedele L, Bianchi S, Agnoli B, Tozzi L, Vignali M. Urinary tract anomalies associated with unicornuate cal junction. Although they sometimes uterus. J Urol. 1996;155:847–858. FAST TRACK cause or make it diffi cult 5. Vaginal agenesis: diagnosis, management, and rou- tine care. Committee Opinion No. 355. Washington, Marsupialization for the patient to insert a , they DC: ACOG; December 2006. are usually asymptomatic unless they 6. Roberts CP, Haber MJ, Rock JA. Vaginal cre- rather than excision ation for müllerian agenesis. Am J Obstet Gynecol. are large. Intervention is not indicated 2001;185:1349–1353. is the treatment of unless the patient is symptomatic. 7. Stassart JP, Nagel TC, Prem KA, Phipps WR. Uterus choice for embryonic Treatment. Marsupialization rather than didelphys, obstructed hemivagina, and ipsilateral re- nal agenesis: the University of Minnesota experience. rest cells excision is the treatment of choice be- Fertil Steril. 1992;57:756–761.

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