Vaginal Agenesis: Diagnosis, Management, and Routine Care

Vaginal agenesis is an uncommon, but not rare, condition. Given an incidence ranging from 1 per 4,000 to 1 per 10,000 females (1), vaginal agenesis is a condition that general gynecologists will encounter once or twice during their professional careers. The most common cause of vaginal agenesis is congenital absence of the uterus and vagina, which also is referred to as mullerian aplasia, mullerian agenesis, or Mayer.Rokitansky.Kuster. Hauser syndrome. The term mullerian aplasia will be used to describe this congenital reproductive anomaly throughout this document. Mullerian aplasia is caused by embryologic growth failure of the mullerian duct, with resultant anomalies in the mullerian structures. With absence of the vagina, there is variation on the presence or absence of the uterus. A single midline uterus can be present or uterine horns (with or without an endometrial cavity) can exist. The ovaries, given their separate embryologic source, are normal in structure and function.

To manage vaginal agenesis effectively, correct diagnosis of the underlying condition is important. Evaluation for associated congenital, renal, or other anomalies also is essential. Both diagnosis and evaluation usually can be completed without surgery. Patient counseling should be provided before any treatment or intervention. Nonsurgical creation of the neovagina should be the first-line approach.

Differential Diagnosis
Patients with mullerian aplasia have a normal 46,XX karyotype, normal female phenotype, and normal ovarian hormonal and oocyte function. Puberty and development of secondary sexual characteristics progress normally except that menarche does not occur. Therefore, patients with mullerian aplasia typically present in adolescence with primary amenorrhea. The practitioner should remember that it is usually 2.3 years from the onset of breast development until the first period. If menarche has not occurred within 3 years of the onset of breast development, further evaluation is indicated. Mullerian aplasia is the second most common cause of primary amenorrhea, with gonadal dysgenesis being the most common cause (2).

On physical examination, patients with mullerian aplasia have normal breast development, normal secondary sexual body proportions, body hair, and hymenal tissue. A vagina is absent unless it has been created by sexual encounters. Differential diagnosis of vaginal agenesis includes congenital absence of the vagina (with or without uterine structures), androgen insensitivity (absence or alteration of androgen-receptor function), 17 ƒ¿-hydroxylase deficiency, a low transverse vaginal septum, and imperforate hymen.

In cases of androgen insensitivity, the gonads are testes, producing normal androgens in karyotypic 46,XY individuals. The lack of androgen tissue receptors results in sparse or no pubic and axillary hair. Patients with androgen insensitivity typically have normal breast development because of peripheral conversion of circulating androgens to estrogens. They may have a small lower vagina, or a normal length vagina can occur; however, no uterus or cervix is present. In pubertal females, the differential diagnosis between androgen insensitivity and mullerian aplasia is easily made by assessing serum testosterone levels. A testosterone level in the pubertal male range confirms the diagnosis of androgen insensitivity.

In postpubertal patients, the presence of functioning ovarian tissue seen on pelvic ultrasound examinations may serve as a secondary confirmation of the diagnosis of mullerian aplasia, excluding the diagnosis of androgen insensitivity. Chromosomal studies, although more costly than a serum testosterone level assessment, provide the diagnostic tool to differentiate between mullerian aplasia in genetic females and disorders of testosterone synthesis in genetic males. Chromosomal analysis also is helpful in prepubertal children who do not yet have postpubertal sex steroid production. In cases of 17 ƒ¿-hydroxylase deficiency, 46XY individuals will have complete male pseudohermaphroditism with female external genitalia, a blind short vaginal pouch, no uterus or fallopian tubes, and intraabdominal testes. Affected males are usually raised as girls, with the underlying disorder being recognized when the patient is evaluated for lack of pubertal development (3, 4).

The differential diagnosis of vaginal agenesis also includes imperforate hymen and low transverse vaginal septum. Patients with these latter conditions will have a normal cervix and uterus, both of which may be palpable on rectal examination. In contrast to most patients with mullerian aplasia, the patient with an imperforate hymen will not have the typical fringe of hymenal tissue. The patient with a low transverse vaginal septum will have a normal hymen, like the patient with mullerian aplasia. Conventional ultrasonography, three-dimensional ultrasonography, and magnetic resonance imaging can be used to better define the mullerian structures and are helpful in definitively defining anatomy.

Correct diagnosis of the underlying condition affecting the genital anatomy is crucial before any surgical intervention. If the patient undergoes an operation because of an incorrect diagnosis (eg, an incorrect preoperative diagnosis of an imperforate hymen in cases of vaginal agenesis), it can be extremely difficult to correct the anomaly because of scar tissue.

Evaluation of the Patient With Mullerian Aplasia
Most patients with mullerian aplasia have small rudimentary mullerian bulbs without any endometrial activity. In 2.7% of patients with mullerian aplasia, active endometrium is found in these uterine structures (1). These patients will present with cyclic or chronic abdominal pain. Magnetic resonance imaging has been suggested to assess the reproductive anatomy, although it is rarely needed in the initial evaluation unless ultrasound evaluation for the presence of functional endometrium in a mullerian structure is equivocal (5). Although laparoscopy is not necessary to diagnose mullerian aplasia, it may be useful in the evaluation of patients with cyclic abdominal pain to exclude the possibility of endometrial activity in mullerian structures (6). When obstructed hemi-uteri are identified (uterine horns with the presence of active endometrium without associated cervix and upper vagina), then removal of the unilateral or bilateral obstructed uterine structures should be performed. The removal of the obstructed uterine structures can be accomplished laparoscopically (7, 8).

Patients with mullerian aplasia often have concomitant congenital malformations, especially of the abdominal wall, urinary tract, and skeleton. Inguinal hernias occur at an increased incidence in patients with mullerian aplasia. Ultrasonography can be used to screen for the more common findings of renal agenesis or a pelvic kidney. This evaluation can be performed during the study of ovarian and mullerian structures. The implications of ureteral duplication in the case of later abdominal or pelvic surgery can be discussed, or intravenous pyelography can be used to exclude this possibility. Scoliosis is the most common skeletal abnormality associated with mullerian aplasia. It also should be noted that there is an increased, but small, rate of hearing impairment in patients with mullerian aplasia.

After the diagnosis of mullerian aplasia, the adolescent should be offered counseling to emphasize that a normal sex life will be possible after a neovagina has been created. Ultimately, however, infertility may be a more difficult aspect of this disorder for the patient to accept. Future fertility options should be addressed with adolescents and their parent(s) or guardian(s). Discussion of assisted reproductive techniques and use of a gestational carrier (surrogate) is appropriate. Specifically, it is important to explain that eggs can be harvested from patients with mullerian aplasia and used in assisted reproductive technology; daughters of women with Mayer.Rokitansky.Kuster.Hauser syndrome conceived by assisted reproductive technology have been shown to have normal reproductive tracts (9). This information allows teens to understand their reproductive potential for becoming a biologic parent and may help them accept the diagnosis and its implications. Referral to a mental health professional is very worthwhile for some patients. The best predictor of good emotional outcome after diagnosis and vaginoplasty is a good relationship between the patient and her parents or guardians and the ability to share feelings with family and friends (7). Contact with a support group or young women with the same diagnosis may be helpful (6) (see Resources).

Patients should be given a brief, written medical summary of their condition, including a summary of concomitant malformations. This information may be useful if the patient requires urgent medical care or emergency surgery from a health care provider unfamiliar with mullerian aplasia.

Nonsurgical Creation of a Neovagina
Timing for nonsurgical or surgical creation of a neovagina is elective; however, it is best planned when the patient is emotionally mature. Nonsurgical creation of the vagina is the appropriate first-line approach in most patients because it is the least morbid procedure. In a recently reported series of patients with mullerian aplasia, more than 90% were able to achieve anatomic and functional success by vaginal dilation (10).

Patients are asked to manually place successive dilators on the perineal dimple for 30 minutes to 2 hours per day. Another option of sitting on a bicycle seat stool provides the perineal pressure and allows the patient to participate in simultaneous productive activities, such as doing homework or practicing a musical instrument (11). Many young women find that sitting on the bicycle seat stool is too uncomfortable or awkward, thus they may have better success using dilators while reclining on a bed after a relaxing bath. Use of dilators in the management of vaginal agenesis is appropriate and successful in most patients. Mature, highly motivated patients who wish to avoid surgery and are aware that it will take several months to achieve their goal are likely to be successful (11, 12). Because the nonoperative approach is noninvasive and usually successful, it is strongly recommended as first-line therapy.

Clinicians often use 'buddies,' other patients with vaginal agenesis who have successfully dilated, as support to the young woman attempting dilation. Young married patients make excellent buddies. If fertility issues are a major concern to the patient or her family, it may be helpful to find a buddy who has used assisted reproductive techniques to become a mother.

Surgical Creation of a Neovagina
Surgery becomes an option for patients who are unsuccessful with dilators or patients who prefer surgery after a thorough discussion with the patient and her parent(s) or guardian(s) of the risks and benefits of the procedure and the available nonsurgical alternatives. It should be stressed to the young woman that a surgical vaginoplasty is not a 'quick fix' and that she will still need to use vaginal dilators postoperatively to maintain her surgically created vagina. The aim of surgery is the creation of a vaginal canal in the correct axis of adequate size and secretory capacity to allow intercourse to occur without the need for continued postoperative dilation. The timing of the surgery depends on the patient and the type or procedure planned. Surgeries often are performed in late adolescence (ages 17.21 years) when the patient is more mature and better able to adhere to postoperative dilation or instructions. Surgery usually is scheduled during summer vacation to allow for an adequate recovery time without missing school and to reduce questions from peers (6, 13).

A number of operations are appropriate for the correction of vaginal agenesis. The approach usually is based on the experience of the operating surgeon. Pediatric surgeons are more likely to use bowel segments for the creation of a neovagina; gynecologists are more likely to use a perineal approach. Whatever technique is chosen, the surgeon must be experienced with the procedure because the initial surgery is more likely to succeed than follow-up procedures. Reoperation in these cases increases the chance of operative injury to surrounding tissues and the possibility of a poor functional outcome. At present, there is no consensus in the literature regarding the best option for surgical correction (14).

The most common surgical procedure used by U.S. gynecologists to create a neovagina is the Abbe.McIndoe operation. This involves the dissection of a space between the rectum and bladder, placement of a mold covered with a split-thickness skin graft into the space, and the diligent use of vaginal dilation postoperatively. Postoperative dilation must be continued to prevent significant skin graft contracture. This surgery is inappropriate if the patient rejects the nonsurgical technique because she has concerns about or objections to dilation. If postoperative dilation is not done, the patient will have a nonfunctional vagina. The dilators are used long-term on a less frequent basis until the woman is having vaginal intercourse because at that time the penis will act as a dilator to maintain the length of the vagina.

Other procedures for the creation of the neovagina are the Vecchietti procedure and laparoscopic modifications of operations previously performed by laparotomy. The Vecchietti procedure involves the creation of a neovagina via dilation with a traction device attached to the abdomen, sutures placed subperitoneally via laparotomy, and a plastic 'olive' placed on the vaginal dimple. In the laparoscopic modification, traction sutures are placed laparoscopically. The two techniques are comparable in terms of producing a functional neovagina (15). Davydov developed a three-stage operation involving dissection of the rectovesical space with abdominal mobilization of the peritoneum, with creation of the vaginal fornices and attachment of the peritoneum to the introitus. The newer adaptation involves dissection of the rectovaginal space, with mobilization of the peritoneum from below and laparoscopic assistance from above. This is followed by closure of the abdominal end of the neovagina with a laparoscopically placed pursestring suture (8, 16, 17).

General Gynecologic Care
Women who have a history of mullerian agenesis and have created a functional vagina do require routine gynecologic care. Annual pelvic examinations should be performed to examine for vaginal stricture or stenosis. Women with mullerian agenesis should be aware that the neovagina has the same risk as a native vagina for sexually transmitted diseases and thus they should be appropriately screened. In addition, vaginal speculum examination and inspection should be performed to look for possible malignancies (in cases of skin graft or bowel vaginas), colitis or ulceration (in cases of bowel vaginas), or other problems. No data exists regarding the need or lack of need for routine Pap testing in women with a neovagina. It is reasonable to consider these women in the same category as women without a cervix because of hysterectomy for the treatment of benign disease. Thus, annual cytologic screening for cancer can be considered unnecessary, although no data are available to support or oppose this concept.

Conclusion
The most important steps in the effective management of mullerian aplasia are correct diagnosis of the underlying condition; evaluation for associated congenital, renal, or other anomalies; and preparation of the patient before any treatment or intervention. If any of these are neglected, the success of the intervention will be compromised.

Laparoscopy is seldom required to make the diagnosis but may be appropriate in the patient presenting with pelvic pain. Nonsurgical creation of the neovagina should be the first-line approach. In cases in which surgical intervention is required, referrals to centers with expertise in this area should be considered. Few surgeons have extensive experience in construction of the neovagina, and the initial surgery has the greatest chance for success. In addition, experts at these centers may be more successful in promoting the nonsurgical approach, given their experience.

References

1. Evans TN, Poland ML, Boving RL. Vaginal malformations. Am J Obstet Gynecol 1981;141:910.20.
2. Reindollar RH, Byrd JR, McDonough PG. Delayed sexual development: a study of 252 patients. Am J Obstet Gynecol 1981;140:371.80.
3. New MI. Male pseudohermaphroditism due to 17 alphahydroxylase deficiency. J Clin Invest 1970;49:1930.41.
4. Nieman LK, Kovacs WJ. Uncommon causes of congenital adrenal hyperplasia. In: Rose BD, editor. UpToDate. Waltham (MA); 2006.
5. Fedele L, Dorta M, Brioschi D, Giudici MN, Candiani GB. Magnetic resonance imaging in Mayer-Rokitansky- Kuster-Hauser syndrome. Obstet Gynecol 1990;76: 593.6.
6. Laufer MR, Goldstein DP, Hendren WH. Structural abnormalities of the female reproductive tract. In: Emans SJ, Laufer MR, Goldstein DP, editors. Pediatric and adolescent gynecology. 5th ed. Philadelphia (PA): Lippincott Williams & Wilkins; 2005. p. 334.416.
7. Poland ML, Evans TN. Psychologic aspects of vaginal agenesis. J Reprod Med 1985;30:340.4.
8. Adamyan LV. Laparoscopic management of vaginal aplasia with or without functional noncommunicating rudimentary uterus. In: Arregui ME, Fitzgibbons RJ Jr, Katkhouda N, McKernan JB, Reich H, editors. Principles of laparoscopic surgery: basic and advanced techniques. New York (NY): Springer.Verlag; 1995. p. 646.51.
9. Petrozza JC, Gray MR, Davis AJ, Reindollar RH. Congenital absence of the uterus and vagina is not commonly transmitted as a dominant genetic trait: outcomes of surrogate pregnancies. Fertil Steril 1997;67:387.9.
10. Roberts CP, Haber MJ, Rock JA. Vaginal creation for mullerian agenesis. Am J Obstet Gynecol 2001; 185:1349.52; discussion 1352.3.
11. Williams JK, Lake M, Ingram JM. The bicycle seat stool in the treatment of vaginal agenesis and stenosis. J Obstet Gynecol Neonatal Nurs 1985;14:147.50.
12. Rock JA, Breech LL. Surgery for anomalies of the Mullerian ducts. In: Rock JA, Jones HW 3rd, editors. Te Linde's operative gynecology. 9th ed. Philadelphia (PA): Lippincott Williams & Wilkins; 2003. p. 705.52.
13. Templeman CL, Lam AM, Hertweck SP. Surgical management of vaginal agenesis. Obstet Gynecol Surv 1999;54:583.91.
14. Laufer MR. Congenital absence of the vagina: in search of the perfect solution. When, and by what technique, should a vagina be created? Curr Opin Obstet Gynecol 2002;14:441.4.
15. Borruto F, Chasen ST, Chervenak FA, Fedele L. The Vecchietti procedure for surgical treatment of vaginal agenesis: comparison of laparoscopy and laparotomy. Int J Gynaecol Obstet 1999;64:153.8.
16. Davydov SN, Zhvitiashvili OD. Formation of vagina (colpopoiesis) from peritoneum of Douglas pouch. Acta Chir Plast 1974;16:35.41.
17. Adamyan LV. Therapeutic and endoscopic perspectives. In: Nichols DH, Clarke-Pearson DL, editors. Gynecologic, obstetric, and related surgery. 2nd ed. St. Louis (MO): Mosby; 2000. p. 1209.17.

Resources
MRKH.org, Inc.
PO Box 301494
Jamaica Plain, MA 02130
Web: http://www.mrkh.org

The Center for Young Women's Health
Children's Hospital Boston
333 Longwood Avenue, 5th Floor
Boston, MA 02115
(617) 730-0192
Web:http://www.youngwomenshealth.org

A guide to vaginal agenesis in teens. Available at http://www.youngwomenshealth.org/vaginalagenesis.html MRKH (Mayer Rokitansky Kuster Hauser Syndrome) and vaginal agenesis: a guide for parents and guardians. Available at http://www.youngwomenshealth.org/mrkh_parent.html