Clinical Presentation

Müllerian agenesis (i.e., Mayer-Rokitansky-Küster-Hauser syndrome) was first described in 1829. Its incidence is reported to be 1 in every 5000 newborn females.⁶ Because the vagina and associated uterine structures do not develop with this disorder, it is a ASRM Class IA müllerian anomaly. Patients typically present during their adolescent years with complaint of primary amenorrhea. As a cause of primary amenorrhea, müllerian agenesis is second only to gonadal dysgenesis.⁷

Patients with müllerian agenesis will present with normal onset of puberty and appropriate secondary sexual characteristics, but apparently delayed menarche. They do not complain of cyclic pelvic pain like patients with obstructive müllerian anomalies. The external genitalia appear completely normal, with normal pubic hair growth and normal-size labia minora, which is in contrast to patients with complete androgen insensitivity syndrome. Hymeneal fringes may be evident, but the vaginal opening is absent. No pelvic masses suggestive of hematocolpos will be evident, which is in contrast to cases of complete transverse septum.

Because these patients have a 46,XX karyotype, normal ovaries will be present in the pelvis. Ovulation can be documented as a shift in basal body temperature. These patients’ hormonal levels are normal, and their cycle length based on hormonal studies varies from 30 to 34 days.⁸ In addition they may experience the monthly pain (mittelschmertz) that is indicative of ovulation.

Associated Anomalies

Some but not all anomalies described can be extrapolated from the embryology.^9–12 Hearing difficulties have been reported in patients with müllerian agenesis.^10,11 A higher rate of auditory defects have been noted in general in patients with müllerian anomalies compared to those with normal müllerian structures.¹²

Müllerian agenesis is associated with renal and skeletal system anomalies. Renal abnormalities are noted in 40% of these patients. These include complete agenesis of a kidney, malposition of a kidney, and changes in renal structure.¹³ Skeletal abnormalities are noted in 12% of patients and include primarily spine defects followed by limb and rib defects.¹⁴ Patients with müllerian agenesis should be actively assessed for these associated anomalies.

Etiology

The etiology of müllerian agenesis remains unknown. It appears to be influenced by multifactorial inheritance, and rare familial cases have been reported. It does not appear to be transmitted in an autosomal dominant inheritance pattern, because none of the female offspring of women with müllerian agenesis (born via in vitro fertilization [IVF] and surrogacy) have shown evidence of vaginal agenesis.⁹

Diagnosis

Vaginal Dilation

The simplicity and ease of vaginal dilation and its significantly lower complication rate than surgical techniques dictates its use as initial form of therapy for most patients with müllerian agenesis. The American College of Obstetricians and Gynecologists recently released a committee opinion that recommends nonsurgical management of müllerian agenesis as the first mode of treatment.¹⁶

Frank’s technique of dilation involves actively placing pressure with the dilators against the vaginal dimple (Fig. 51-1). The patient is not only in an awkward position, but the hand applying the pressure can also become tired. In 1981, Ingram proposed the concept of passive dilation, where pressure is placed on the dilator by sitting on a bicycle seat.¹⁷

Figure 51-1 Examples of vaginal dilators of different sizes.

Roberts reported a success rate of 92% in women who dilated the vagina via the Ingram technique for 20 minutes three times a day.¹⁸ The average time to creation of a functional vagina was 11 months. This series demonstrated that an initial dimple less than 0.5cm was all that was necessary to achieve adequate dilation. Interestingly, failure of this technique was not related to length of vaginal dimple but rather was more closely associated with the patient’s youth. Failure of this technique was more common in patients younger than age 18.

Procedure

When the patient expresses a desire to proceed with therapy, she is shown the exact location of her vaginal dimple. The axis of dilator placement is also demonstrated (Fig. 51-2). The process is initiated by placement of the smallest dilator against the dimple. Pressure is kept on the distal aspect of the dilator by sitting on a stool while leaning slightly forward. When the dilator fits comfortably she moves to the next size dilator. The patient is instructed to use this technique a minimum of 20 minutes a day, two to three times a day. In motivated patients, a functional vagina can be created in as short as 12 weeks.

Figure 51-2 Schematic drawing of angle of dilator placement. The patient is viewed in lithotomy position and the axis is directed away from the bladder.

Counseling and psychological support is integral to successful treatment.^19–21 Patients are requested to return to the office frequently to monitor their progress, provide guidance, and have an opportunity to answer questions. Intercourse may be attempted when the largest dilator fits comfortably.

Multiple types of graduated dilators, made of various materials, are present on the market. None have been found superior to the others. Patients may stop and reinitiate the dilation at any time without any negative long-term sequelae. Although most patients appear interested in initiating this therapy the summer before college when they are mature enough and motivated to create the vagina, the timing of therapy is purely dependent on the patient’s desires. The median age of starting treatment is 17 years.²² For appropriately selected motivated patients, the reported success rates are as high as 90%.²³

Vecchietti Procedure

Giuseppe Vecchietti described this method of creating a neovagina in 1965.²⁴ Similar to vaginal dilation, this method avoids the use of a graft. The Vecchietti procedure is a one-step procedure in which a neovagina is created in 7 days by continuous pressure on the vaginal dimple using an acrylic olive connected by retroperitoneal sutures to a spring-tension device on the lower abdomen. Although the original description of the Vecchietti procedure utilized laparotomy, this technique is currently performed laparoscopically.^25,26

Vaginoplasty Techniques

The traditional surgical management of vaginal agenesis is to create a vaginal space followed by placement of a lining to prevent stenosis. Multiple tissues and at least one manmade material have been used to line this cavity with varying degrees of success in preventing subsequent stenosis of the neovagina (Table 51-2).

Table 51-2 Surgical Methods of Creating a Neovagina

McIndoe Procedure

The most widely used surgical technique for creation of a neovagina is the McIndoe operation. The first step of the procedure is obtaining the split-thickness skin graft. The plastic surgery team typically acquires the skin graft from the buttock area, a location usually covered by clothing. The patient is placed in the prone position and the site is cleansed with an antiseptic solution and then soaked with an epinephrine saline gauze to allow vasoconstriction of small punctate bleeding sites. Mineral oil is applied to the donor site and the skin is held taut while the electrodermatome device is used to obtain a thick split-thickness skin graft. The skin graft should be 0.015 to 0.018 inch thick. After application of antiseptic solution, the donor site is covered with Op-Site, which is fixed in place by several stitches. Within 2 to 3 weeks the area heals with acceptable scarring.

The skin graft is placed through a 1:5 ratio skin mesher. The purpose of meshing the skin is not to stretch it but rather to allow escape of any underlying blood clots or serous fluids. This skin graft is sutured around the mold with 4-0 absorbable suture (Fig. 51-3). The mold is covered completely, because any uncovered sites, whether due to lack of enough tissue or a gaping hole in the line of suture, tend to result in the formation of granulation tissue. Thus great care must be taken to obtain a sufficient amount of graft for this procedure.

Figure 51-3 Skin graft is sutured around a mold.

The patient is placed in the dorsolithotomy position. A transverse incision is made in the vaginal vestibule, between the rectum and urethral openings (Fig. 51-4). In a patient who has not had prior surgery or radiation in the area, areolar tissue is now encountered. This tissue is easily dissected with either fingers or a Hagar dilator on either side of a median raphe (Fig. 51-5). The dissection is continued for at least the length of the mold without entering the peritoneal cavity. By cutting the median raphe, the two channels are then connected. If the dissection is performed in this manner, minimal bleeding is encountered. Any bleeding sites must be controlled meticulously to avoid lifting of the graft from the newly created vaginal wall and subsequent nonadherence and necrosis.

Figure 51-4 The initial transverse cut was made on the fibrous tissue and an initial space developed.

Figure 51-5 Placement of Hagar dilator to create space for the graft. The direction of the Hagar dilators is posterior.

After creation of the vaginal space, the mold covered with the skin graft is placed inside the cavity (Fig. 51-6). At the introitus, the skin graft is attached with several separate 3-0 absorbable stitches. To hold the mold in place, several loose nonreactive sutures such as 2-0 silk are used to approximate the labia minor in the midline.

Figure 51-6 The mold with the graft is placed in the space. Notice that the space to be created must accommodate the mold completely.

During the ensuing week, the patient is maintained on bed rest, broad-spectrum antibiotics, a low-residue diet, and an agent to decrease bowel motility. She also has an indwelling urinary catheter in place. On return to the operating room in 1 week, the mold is carefully removed. The vaginal cavity is irrigated with warm saline solution and the graft site is carefully assessed for any signs of necrosis or underlying hematoma. Another soft mold is then reinserted and kept in place for the next 3 months except during defecation and urination. Nighttime usage of the mold is recommended for the next 6 months. To prevent contracture of the vagina, the patient is instructed to reinsert the mold during extended times of sexual inactivity.

Difficulty in dissecting the neovagina and increased probability of bleeding and fistula formation is encountered in the patient with a prior surgical procedure. Other problems that may be encountered include narrow subpubic arch, strong levators, shorter perineum, prior hymenectomy, and congenitally deep cul-de-sac.³¹

Because of concern regarding tissue necrosis from mold pressure and subsequent fistula formation, both rigid and soft molds have been used for this procedure (Figs. 51-7 and 51-8). Theoretically, soft molds decrease the risk of fistula formation that can result from avascular necrosis. A soft mold can be created by covering a foam rubber block with a condom.³² The foam is able to expand and fit the neovaginal space, thereby providing equal pressure throughout the canal. However, a report on the use of a rigid mold on 201 patients who underwent the McIndoe operation demonstrated a fistula formation rate of less than 1%.³³ There is no study comparing the outcomes of soft versus rigid molds in this operation. Typically a rigid mold is used initially, but the patient is sent home with a soft mold in place.

Figure 51-7 Hard glass mold.

Figure 51-8 Adjustable vaginal mold (Mentor, Minneapolis).

An 80% success rate has been reported with this procedure.³⁴ Because success rates are highest in those patients that have not undergone prior vaginoplasty, patients must be counseled extensively before surgery regarding the need for prolonged use of the mold. Indeed, part of the presurgical assessment involves determination of patient maturity and motivation concerning the use of dilators. Lack of compliance with postoperative use of dilators will lead to contracture and diminishment of vaginal length.

Surgical complications include postoperative infection and hemorrhage, failure of graft and formation of granulation tissue, and fistula formation. In general the incidence of complications are low: a rectal perforation rate of 1%, graft infection in 4%, and graft site infection of 5.5%.³³ In a review of 50 patients, 2 rectovaginal fistulas and 1 graft failure were reported.³¹ Five patients required an additional operative procedure. Eighty-five percent of these patients considered their surgery to be a success.

Long-term data on the McIndoe procedure, although limited, consistently indicate an improvement in quality of life. In a series of 44 patients who underwent a surgical procedure to create the vagina, 82% achieved a functional satisfactory postoperative result.³⁵ Vaginal length varied from 3.5 to 15cm. In another long-term study of women who underwent a McIndoe procedure, 79% of the patients reported improved quality of life, 91% remained sexually active, and 75% regularly achieved orgasm.³⁶

The newly created vagina must be inspected at the time of the yearly pelvic examination and regular pap tests. Hair growth has been reported to be a problem with some skin grafts. Transformation to squamous cell carcinoma from skin graft has been described.^37,38

Peritoneal Graft: Davydov Procedure

Use of the peritoneum to line the newly created vaginal space was popularized by Davydov, a Russian gynecologist, and first described by Rothman in the United States in 1972.^39–41 In his original description, a laparotomy is performed after creation of the vaginal space, as described with the McIndoe operation.

A cut is made on the peritoneum overlying the new vagina. Long sutures are applied to the anterior posterior and lateral sides of this peritoneum. The sutures are then pulled down through the vaginal space, thus pulling the peritoneum to the introitus. The edge of the peritoneum is then stitched to the mucosa of the introitus. Closing the peritoneum on the abdominal side then forms the top of the vagina. Several investigators have also described the laparoscopic modification of this procedure.^42–44

This procedure may have several advantages compared to the traditional McIndoe. Contrary to skin grafts that leave visible scarring at the donor site, there is no outward sign of using a graft in the Davydov procedure. There appears to be no danger of lack of graft takes and no problem with hair growth.

In Davydov’s first reported series, sexual intercourse was initiated within several weeks of surgery in all but one of his 30 patients. On follow-up, the length of the vagina was noted to be 8 to 11cm. In a series of 18 patients who underwent the laparoscopic modification of this procedure, 85% reported being sexually satisfied during an 8- to 40-month follow-up. Although there was one report of a rectovaginal fistula 18 months after the surgery, there was no evidence of vault prolapse or enterocele formation. Minor granulation tissue was noted at the vaginal cuff, but the vault was primarily covered with squamous epithelium tissue.

Adhesion Barrier Lining

Jackson first described the use of an adhesion barrier to line the neovagina in 1994.⁴⁵ Oxidized regenerated cellulose (Interceed; Johnson and Johnson Patient Care Inc, New Brunswick, N.J.) forms a gelatinous barrier on raw surfaces and thus prevents adhesion formation. After creation of the vaginal space, sheets of clothlike oxidized regenerated cellulose are wrapped around the mold and placed in the vagina in a manner similar to the McIndoe. The neovaginal space must be free of any bleeding. Epithelialization is noted to occur within 3 to 6 months. Small areas of granulation tissue may be seen at the apex of the vagina and resolve after application of silver nitrate. Average vaginal depth ranges from 6 to 12cm. Continuous use of the mold is encouraged until complete epithelilization has occurred.

A case series assessed the outcome of this technique on 10 patients with vaginal agenesis.⁴⁶ Complete squamous epithelialization was noted within 1 to 4 months. When compared to a normal vagina, fern formation was noted and the vaginal pH was always acidic. However, none of the women complained of vaginal dryness or foul-smelling discharge. Patients who were sexually active did not report any problems.

The advantages of use of oxidized regenerated cellulose include avoidance of any scars, readily available product, and low expense. In addition, the surgical procedure is simplified into a one-stage procedure. Although the reported data appear encouraging, confirmatory studies are required before use of oxidized regenerated cellulose can be recommended without any reservations.

Amnion Lining

Amnion has also been used to line the neovagina cavity.⁴⁷ Advantages include lack of a graft site, potential antibacterial effect, and lack of expression of histocompatibility antigens.^48,49 Eight to 10 weeks after placement of amnion into the vaginal canal, the resulting epithelium was found to be “identical” to normal vaginal epithelium.⁵⁰ However, concern about transmission of an infection with use of amnion has limited its use in the United States.

Muscle and Skin Flap

These approaches are not procedures of choice for women with vaginal agenesis. However, they may be used for those who require vaginal reconstruction after exposure to radiation or multiple surgical procedures. The advantage of using a full-thickness skin flap is that it avoids the problem of contracture encountered with split-thickness grafts.

The use of gracilis myocutaneous flaps and rectus abdominis myocutaneous flaps for vaginal reconstruction has been reported.^51,52 This approach has been associated with a conspicuous scar and a higher failure rate. Wee and Joseph in Singapore designed flaps that maintained good blood supply and innervation.⁵³ Known as a pudendal–thigh flap vaginoplasty, this technique has been particularly successful in patients with vulvar anomalies.⁵⁴ In one study of patients with müllerian agenesis, 100% success in creating a functional vagina was reported.⁵⁵

The patient’s own labia majora and labia minora have also been used to create a vagina.⁵⁶ Tissue expansion has also been advocated to create labiovaginal flaps, which are then used to line the neovagina.^57,58 Other modifications of this procedure have been reported.^59,60

Bowel Vaginoplasty

This is not a procedure of choice in women with vaginal agenesis. For this procedure, also known as a colocolpopoiesis, a portion of large bowel with its preserved vascular pedicle is sutured into the neovagina. In recent years, sigmoid colon use has been recommended.

Continuous use of dilators is not considered necessary, although constriction has been noted when ilium has been used. Success rates of up to 90% have been reported. Reported complications include profuse vaginal discharge, prolapse, introital stenosis, bowel obstruction, and colitis.^61,62 Finally there is a report of a mucinous adenocarcinoma arising in a neovagina lined with the sigmoid colon.⁶³

A laparoscopic modification of this procedure has also been described.^64,65 Given the increased complication rates, it seems appropriate to reserve this treatment modality for complex situations where a prior vaginoplasty technique has failed or when there are multiple urogenital malformations.