Imperforate hymen is the most frequent anomaly of the female reproductive tract, occurring in 1/2000 girls [32] and it represents a persistent portion of the urogenital membrane. Familial inheritance has been reported; however, no common genetic trait has been recognized. Some reports suggest a dominant transmission [33], while others suggest a recessive trait [34] or a multifactorial transmission. Antenatal diagnosis of imperforate hymen and hydrocolpos has been reported as early as the second trimester [35]. In this case, drainage of the fluid should be the immediate intervention in the neonatal period, postponing the final surgical procedure. Occasionally, prepubertal girls can be referred with no obvious hymenal opening or with a poorly visible microperforation (Fig. 3.3). In the absence of a collection, definitive surgery should be deferred until the child is peripubertal. The imperforate hymen is usually seen in girls in their early teens. On the clinical examination, the hymen may be visualized as a bluish bulge at the perineum. Transabdominal or translabial US may be used to confirm the diagnosis [36]. Depending on the circumstance, an imperforate hymen may not be detected until an adolescent girl has recurrent bouts of lower abdominal crampy pain but does not menstruate. The problem may persist through several cycles until a pelvic mass becomes evident. This finding is diagnostic and no further investigation is needed. A simple cruciate incision of the hymen will release the menstrual flow and allow further normal menstruations. Some authors prefer a U-shaped incision at the base of the hymenal membrane as it maintains a normal hymenal remnant and avoids incision into the vaginal walls, which can cause bleeding [37].

Vaginal atresia is a rare congenital defect resulting in uterovaginal outflow tract obstruction. It occurs when the caudal portion of the vagina, contributed by the urogenital sinus, fails to form. The caudal portion of the vagina is replaced with fibrous tissue. Although not Müllerian in origin, vaginal atresia can clinically mimic vaginal agenesis and imperforate hymen. Vaginal atresia, secondary adrenogenital syndrome, and cloacal anomalies are beyond the aim of this chapter. Fifteen percent of young patients with vaginal agenesis have segmental vaginal atresia [38] which is usually referred to as complete or partial vaginal atresia (lower vaginal atresia) (Fig. 3.4). Complete vaginal atresia is frequently associated with uterine agenesis, known as the Mayer–Rokitansky–Küster–Hauser syndrome (MRKHS). The fallopian tubes are normal, and the ovaries demonstrate normal endocrine function. Partial vaginal agenesis is rarer and is characterized by normal uterus, normal cervix, and small vaginal pouch distal to the cervix. Each examination of a newborn should include an inspection of the genitalia, as absence of the vagina or complete atresia could be detected during this simple evaluation. Complete vaginal atresia or agenesis is usually diagnosed at puberty when young adolescents present with primary amenorrhea. In infancy, partial vaginal agenesis can present as hydrocolpos or hydrometrocolpos; however, more commonly it occurs after menarche as a result of trapped menstrual secretions and, similarly to imperforate hymen, the adolescent girls are often in severe pain after only a few months of obstructed flow. Such pain may be either cyclic or noncyclic, and is located in the pelvis or in the vagina, depending on the patient’s anatomy. An abdominal mass can be sometimes palpated and upon rectal exam a bulge is felt. 2D- and 3D-US and/or MRI confirm the presence of an obstructed upper vagina with hematocolpos and exclude the diagnosis of cervical agenesis [40]. Percutaneous drainage may be temporarily necessary to allow relief of pain and the facilitation of transfer of care to a tertiary center. Definitive surgical correction is the therapy of choice. This goal can be established by a vaginal pull-through procedure to create a new vaginal canal, with undermining and approximation of mucosal edges [41]. Postoperatively, wearing a vaginal mold or initiating early vaginal dilation may further decrease the risk of vaginal stenosis [10]. Incorrect diagnosis of the vaginal obstruction may result in excising of the obstruction without mucosal approximation. This will lead to local scar formation, recurrent partial or total obstruction, and difficulty in performing a second surgical procedure.

Congenital absence of the uterine cervix associated with a functioning endometrium is an extremely rare müllerian anomaly and occurs in 1 in 80,000 to 100,000 births [42]. Rock et al. have organized cervical agenesis (or atresia) and dysgenesis (or dysplasia) into four categories: cervical agenesis, cervical fragmentation, fibrous cervical cord, and cervical obstruction [43]. When this anomaly occurs, it is known to be associated in half of the cases with vaginal aplasia and with renal anomalies [44]. Amenorrhea and cyclic lower abdominal pain are the first symptoms presenting in an adolescent, and can be associated also with upper abdominal pain and fever if diagnosis is delayed. Endometriosis or pelvic infection may result from the chronic hematometra. In some cases, hematosalpinx may also be present. Transrectal ultrasonography and MRI can aid in defining anatomy [45]. Menstrual suppression with GnRH analogues may be helpful in controlling symptoms while planning surgery. The diagnosis and management of this Müllerian anomaly are both challenging and controversial. In the past, the surgical management of cervical agenesis has been debated and the solutions offered have gone from hysterectomy with the creation of a neovagina [46], to the recanalization around stents of the rudimentary cervix [47]. The surgical perspective in cases of cervical agenesis has evolved in time. Early literature reports different attempts of canalization of cervical atresia through cervical drilling or through catheter or pessary placement between the uterus and vaginal vault, with or without simultaneous vaginoplasty [48–50]. Some successful cases have been reported but the risks of conservative surgery (deadly peritonitis, high failure rates, and poor functional results) far outweighed the benefits. Consequently, it is not, thus, surprising that total hysterectomy with ovarian conservation still offers numerous benefits and is supported as a treatment option by several authors. Recent advances in reproductive technology and laparoscopic surgical techniques mean that conservative surgery is a possibility and perhaps should be considered as the first-line treatment option. Two series of patients treated for this rare Müllerian anomaly with uterovaginal anastomosis have been reported. Deffarges et al. [51] described 18 patients with cervical atresia, 7 of whom had associated vaginal aplasia, and Chakravarty et al. [52] described 18 patients with cervicovaginal atresia. In both series, menstruation was restored in all the patients. In each of those series, two pregnancies were reported, both with delivery of viable neonates. Complications reported by Deffarges et al. were two low vaginal stenoses that were easily resolved and one cervical stenosis treated with multiple canalization procedures leading to a pyosalpinx requiring salpingo-oophorectomy. In the largest published series of 30 patients with cervical dysgenesis, Rock et al. [43] recommended hysterectomy, as first-line of treatment option, in patients with complete cervical agenesis and described successful creation of an adequate cervical outflow tract in the subset of patients with cervical obstruction. An Italian study performed in 12 adolescents (10 with complete cervical agenesis and 2 with cervical dysgenesis) confirmed that laparoscopically assisted uterovaginal anastomosis may be considered the treatment of choice for patients with cervicovaginal atresia [53]. The technique adopted by the authors was unique in performing hysterotomy at the caudal end of the uterine corpus to ensure direct communication of the vaginal mucosa to the endometrial lining. In conclusion, careful preoperative workup is essential so that an accurate diagnosis is made prior to surgery. This congenital condition is very rare and should be managed in specialist or tertiary centers with not only surgical expertise but also access to multidisciplinary and wide-ranging clinical support services.

The unicornuate uterus is caused by complete development of only one of the Müllerian ducts, with absent development of the contralateral side. In cases where the contralateral Müllerian duct develops only partially, the unicornuate uterus is associated with a rudimentary horn, which may be cavitated or not cavitated and may or may not communicate with the unicornuate uterus. A solitary uterine horn can be observed in up to 35% of patients. More commonly (in 65% of cases), a small rudimentary horn is seen arising from the primary single horn. A cavitated non-communicating rudimentary uterine horn (class II-b according to the ASRM classification) can be found in about 20–25% of women with unicornuate uterus. There is a higher incidence of unicornuate horns on the right side which is not fully understood [54]. A unicornuate uterine malformation is estimated to account for 5% of all uterine anomalies, occurring in 1 in 4020 to 5400 women [55, 56]. Patients can have an associated 40% risk of renal anomalies usually ipsilateral to the anomalous side [57], 15% endometriosis, and, rarely, extrapelvic or absent ovaries [56]. Patients with cavitated non-communicating rudimentary horn present shortly after menarche with increasing dysmenorrhea that is refractory to any treatment except complete suppression with either combination hormonal therapy or GnRH analogue with add-back therapy. Ultrasonographic imaging typically reveals a mass [58], but anatomical assessment of the uterine structures is best accomplished through MRI [59]; however, 3D-US has increased the sensitivity and specificity of this diagnosis [60]. Laparoscopy is utilized to confirm the diagnosis and remove the non-communicating functional rudimentary horn as treatment for dysmenorrhea, and to prevent possible endometriosis caused by transtubal menstrual reflux and conception in an obstructed horn [55, 61].

Didelphys uterus is a class III Müllerian anomaly based on the ASRM classification. In the general population, the true incidence is unknown, but has been reported to be between 0.1 and 3.8% [62]. For unknown reasons, anomalies of this type are more common in the Finnish population, with an incidence of 0.5% [63]. This disorder occurs as a result of a complete or near-complete failure of the Müllerian ducts to fuse. Each duct develops into an independent hemiuterus and cervix, although partial cervical fusion is generally seen. A longitudinal vaginal septum can be seen in up to 75% of cases [64] (see below Sect. 3.8). Without obstruction, didelphys uterus is asymptomatic. However, 6% of cases of vaginal septum with duplicated cervix and uterus are characterized by unilateral obstruction of one hemivagina by vaginal septum [65]. Didelphys uterus with obstructed hemivagina is associated with ipsilateral renal agenesis [66–68]. This association has been first described in the literature as Herlyn-Werner-Wunderlich syndrome. More recently, an acronym OHVIRA (Obstructed Hemivagina and Ipsilateral Renal Anomaly) has been proposed to describe this condition [69]. Patients may present at menarche with progressive dysmenorrhea secondary to hematometrocolpos, hematosalpinx, and endometriosis, [70]. Occasionally, patients present with fever, peritonitis, purulent vaginal discharge, and leukocytosis, leading to a presumptive diagnosis of PID [71]. It is only the finding of a double uterus and the absence of a kidney that will lead to the correct diagnosis. In general, examination reveals an anterolateral bulge in the vagina that makes it impossible to reach the cervix. In these cases, persistent postmenstrual hemorrhage (sometimes malodorous) is characteristic before the patient presents with pyocolpos in the obstructed vaginal canal. There is sometimes limited inter-uterine (at the level of the isthmus) or inter-vaginal (at the vaginal apex) communication. Furthermore careful examination of the vagina in these cases will sometimes reveal a small opening in the otherwise obstructed vaginal septum that may have allowed the migration of pathogenic bacteria. In the majority of cases, regular menses from the communicating hemiuterus result in misdiagnosis and increase the risk of unindicated procedures at the time of presentation [68, 69]. Occasionally, the condition can be diagnosed following acute urinary retention [72]. There are also some cases described in girls under 5 years of age [73]. Ultrasound has proven to be accurate in the differential diagnosis of double uteri. In a study of 39 patients with technically adequate sonographic visualization of the uterus, transabdominal US demonstrated a sensitivity of 100% and a specificity of 100% in reaching the correct diagnosis of double uteri [74] (Fig. 3.5). MRI has been demonstrated to be also accurate in discriminating between the various types of double uteri. Fedele et al. reported a sensitivity of 100% and a specificity of 79% when using MRI to differentiate between bicornuate, didelphic, and septate uteri [75]. Currently, 3D-US and especially MRI are the primary diagnostic tools but they are limited to tertiary care centers (Fig. 3.6). In the meantime, MRI correctly anticipates the diagnosis, but it is unable to accurately assess the presence of endometriosis, pelvic infection, or adhesions that would affect future fertility. In these selected patients, laparoscopy is highly recommended. In general, a single transvaginal surgical procedure, including removal of the obstructed vaginal septum and marsupialization of the blind hemivagina, solves the symptoms of this pathology. After the septum has been excised (Fig. 3.7), laparoscopy can be performed for potential treatment of associated endometriosis, adhesions, or both. In certain cases, hysteroscopic metroplasty has been performed with simultaneous abdominal ultrasound to evacuate and correct a complete septate uterus with unilateral hematometra [76, 77]. More recently, to avoid damage to hymen or cervices, vaginoscopy with resectoscope has been suggested [78, 79]. Women with non-obstructed didelphys uterus are usually not candidates for surgical unification. The decision to perform metroplasty should be individualized, and only selected patients may benefit from surgical reconstruction. Most reports of metroplasty in this setting are anecdotal and lack the statistical power of randomized studies. Therefore, the apparent benefits of surgery are not clear.

TVS results from failure of fusion between the müllerian ducts and the urogenital sinus or abnormal vaginal canalization. A TVS can divide the vagina into two segments and thereby reduce its functional length. A TVS can be imperforate or perforate, and vary in its thickness and location in the vagina. Most of them are located in the superior vagina (46%). The next most common locations are the mid vagina, at a rate of 40%, and the inferior vagina, at a rate of 14% [80]. A TVS is relatively uncommon, with a reported incidence varying greatly from 1 in 2100 to 1 in 84,000 females [81–83]. Unlike other Müllerian duct anomalies, TVS is only occasionally associated with urologic defects but it has been associated with other structural anomalies, including imperforate anus, bicornuate uterus, coarctation of the aorta, atrial septal defect, and malformations of the lumbar spine. TVS is rarely diagnosed in the neonate or infant unless the obstruction causes a significant hydromucocolpos. Hydromucocolpos can be diagnosed in utero during a third-trimester transabdominal ultrasound. Early delivery and drainage of the obstructed vagina and uterus are indicated when other organs are compromised [84]. In infants, the vaginal septum is usually thin (<1 cm thick) and can be corrected without extensive procedures. Clinical follow-up is necessary because vaginal stenosis with subsequent accumulation of fluid may develop postoperatively. In adolescence, imperforate septum presents with obstructed menstruation and hematocolpos [85]. A presence of a palpable pelvic mass and a perineal bulge can be often revealed depending on level and location of the imperforation during the physical examination. In these patients, cyclic abdominal pain, vaginal discharge, amenorrhea, or abnormal menstruation, and occasionally urinary retention may be present at the postpubertal stage. Moreover, retrograde blood flow through the uterus and the fallopian tubes resulting from imperforation may predispose these patients to develop severe endometriosis in 2–56% of cases [65, 86]. Women with a perforate septum often have normal menses and usually present with dyspareunia and difficulty in inserting tampons into the vagina [85]. Initial evaluations should include an abdominal US of the pelvis [87]. Imaging should include an assessment of the renal anatomy since up to 20% of cases have associated renal anomalies. The diagnosis can be confirmed on MRI, especially if a strong clinical suspicion exists. MRI can also be useful to determine the thickness of the vaginal septum preoperatively. It is also extremely important to identify a cervix on US or MRI in order to differentiate between a high septum and cervical atresia. The surgical approach to TVS excision depends on the character, thickness, and location of the septum. The TVS is most frequently less than 1 cm thick and can be treated by excision and end-to-end anastomosis of the vaginal mucosa. The TVS can be thick in the adulthood, rendering its removal more difficult than in the infant. While thick septa require complex surgery often necessitating reconstruction using grafts or flaps, thin TVS can be managed considerably more easily [88]. Treatment involves surgical resection of the septum and anastomosis of the upper and lower vaginal mucosa, usually followed by vaginal dilatation. It can be performed vaginally, laparoscopically, or via an abdominoperineal approach, depending on the location and thickness of the septum [80, 88]. Common problems of these techniques include shortening of the vagina due to septal tissue excision and postoperative stenosis of the vagina owing to the formation of constricting fibrous bands during the healing process. A Z-plasty technique may help to prevent circumferential scar formation [89–91]. More recently, Arkoulis et al. have proposed a simple technique for the surgical management of thin septa, utilizing two interdigitating Y-plasties, without the need for excision of any septal tissue. The authors presented their small series of eight consecutive cases where this technique was used, with no major complications or any case of vaginal re-stenosis [92]. In general, regardless of the technique used for postoperative dilation, it is very important to do an entire septum resection and to try to prevent stenosis and scarring, which is common after a transverse septum resection. For difficult cases, a probe can be passed transfundally through the uterus, down through the endocervical canal, and into the upper vagina so as to tent up the septum and aid in the resection. For more extreme and complex cases, vaginoplasty may be indicated. Complications may be significant and include vaginal stenosis and re-obstruction (recurrence), dyspareunia, endometriosis, infertility, obstetric complications, and psychological difficulties. It is essential that accurate information on the septum is available to ensure that the correct operative approach is chosen.

In conclusion, transverse vaginal septum should be managed within specialist centers for complex gynecology with experience in managing congenital gynecological anomalies. However, knowledge of the clinical presentation and management of these abnormalities is important, as it can prevent misdiagnosis and unnecessary delays in specialist referrals.

Incomplete resorption of the Müllerian ducts and urogenital sinus may cause the formation of a longitudinal vaginal septum. A longitudinal vaginal septum is associated with a uterine anomaly (septate or didelphys uterus) in 95% of cases [86]. Conversely (as previously stated), patients with uterine duplication have a concurrent longitudinal vaginal septum in 75% of cases [64]. The presence of a duplicated cervix is indicative of either didelphys or complete uterine septum. The septum may be complete or partial. In some cases where the septum is complete, it may be bilaterally (uterus didelphys, bicollis, with complete vaginal septum with bilateral obstruction) or unilaterally imperforate and symptomatic (see didelphys uterus). Non-obstructed longitudinal partial vaginal septum is typically asymptomatic and, occasionally, the patient will complain of bleeding despite the placement of a tampon. Currently, it may not present at all until pregnancy when it is an incidental finding. In some cases the patient may complain of a hooked tampon or pain with coital activity, which may be secondary to bruising of the septum [83]. The partial septum should be removed only if symptomatic or if the woman desires restoration of a normal vaginal canal. Prior to initiating the surgery, a Foley catheter is placed in the bladder. Since these septa are typically well vascularized, Kelly clamps are systematically applied to the anterior and posterior portion of the septum and then cut with a knife or electrocautery device. It is not usually necessary to excise the complete septum as the tissue retracts and leaves a narrow ridge that is of no consequence. Hemostasis is secured by placing a continuous locking suture, absorbable (00) on each edge of the divided septum [93]. As the tissue can be very thick, attention to hemostatic control is always essential.

Vaginal agenesis, also known as Müllerian aplasia or MRKHS, is the congenital absence of the vagina with variable Müllerian duct in otherwise phenotypically normal 46, XX females. The uterus and cervix in such patients are more often absent; however, 7–10% of such women have a rudimentary uterus with functional endometrium [94], and as many as 25% have cavitated müllerian remnants [95, 96]. The fallopian tubes are frequently normal; however, they may be hypoplastic or malformed [97]. The ovaries demonstrate normal endocrine function [98]. The prevalence of MRKHS is given as 1 in 4500–5000 newborn females [99]. This is based on a single study from Finland and does not allow similar predictions for other populations. MRKHS is generally divided into three subtypes: MRKHS (typical or type I), MRKHS (atypical or type II), and MURCS (Müllerian Renal Cervical Somite) association or type III. Anatomic examination is required for differential diagnosis of specific MRKHS types. MRKHS type I accounts for approximately 44% of MRKHS cases and is characterized by complete uterus aplasia in the presence of two symmetric rudimentary horns linked by a peritoneal fold, normal fallopian tubes, ovaries, and renal system [100]. MRKHS type I is rarely associated with clinical signs of hyperandrogenism [101]. MRKHS type II is the most frequent form of MRKHS, accounting for approximately 56% of cases [100]. It is characterized by uterine symmetric or asymmetric hypoplasia, accompanied by aplasia of one of the two horns or by a size difference between the two rudimentary horns, with or without dysplasia of one or both of the fallopian tubes. MURCS association, which represents the most severe form of MRKHS, is characterized by Müllerian duct aplasia/hypoplasia, renal agenesis/ectopy (in 25–50% of patients), and cervicothoracic somite dysplasia (Klippel–Feil syndrome) (30–40%)[102]. In this form, other less common associated anomalies such as heart defects, hearing impairment, syndactyly or polydactyly are often observed [103]. MRKHS is mainly sporadic; however, familial cases have been described indicating that, at least in a subset of patients, MRKHS may be an inherited disorder [104, 105]. The syndrome appears to demonstrate an autosomal dominant inheritance pattern, with incomplete penetrance and variable expressivity. The etiology of MRKHS is still largely unknown, probably because of its intrinsic heterogeneity. Several candidate causative genes have been investigated, but to date only WNT4 has been associated in a few cases with MRKHS patients with hyperandrogenism [106]. The development of secondary sexual characteristics occurs normally, thus the diagnosis of MRKHS is generally made late, at the beginning of puberty, due to the lack of onset of menstruation (primary amenorrhea) or, seldom, due to the impossibility of sexual intercourse. Indeed, vaginal agenesis is the second most common cause of primary amenorrhea in adolescents [107]. Functional endometrial tissue in an obstructed uterine remnant can rarely cause cyclic pelvic pain from hematometra, hematosalpinx, and endometriosis [108]. When it is expected to have a suspicion of Müllerian anomalies, 2D-US and renal US represent the first assessment survey to exclude urinary tract anomalies [37]. An MRI may be more accurate in the evaluation of müllerian structures, but given the expense, it can be reserved for when ultrasound is indeterminate [19]. Because transabdominal 2D-US and MRI are not always reliable in providing a clear-cut diagnosis on the presence of endometrium in the uterine horns, Fedele et al. have recently demonstrated the use of an endoscopic ultrasound probe in the evaluation of the structure of the rudimentary uterine horns in MRKHS, with specific regard to the identification of the endometrial cavity and its localization inside the myometrial structure, as well as the identification of the vascular structures of the rudiment [108].