Septate Uterus

Etiology

The septate uterus is an anatomical anomaly resulting from the maldevelopment of the embryologic Müllerian, or paramesonephric, ducts. The specific cause of the anomaly is unknown. Attempts have been made to identify a genetic etiology of Müllerian anomalies, but a causal genetic relationship remains elusive. The etiology of Müllerian anomalies is thought to be multifactorial.[3]

Epidemiology

A septate uterus is the most commonly diagnosed congenital Müllerian anomaly, accounting for approximately 55% of such diagnoses.[4] The prevalence is estimated to be up to 1.5% in reproductive-age females. However, it is difficult to account for the prevalence of septate uteruses accurately; there are multiple accepted definitions, and many patients with the anomaly are asymptomatic.[5][6]

Pathophysiology

During the seventh week of female embryonic development, the absence of the Müllerian inhibitory factor triggers the regression of the mesonephric ducts and stimulates the development of two paramesonephric ducts.[7] These paramesonephric ducts eventually form the upper two-thirds of the vagina, cervix, uterus, and fallopian tubes.[8] The ovaries originate from the embryonic genital ridge.

In the eighth week of development, the paramesonephric ducts undergo a vertical fusion that creates a midline septum. By week 20 of embryonic development, the septum usually has undergone complete bidirectional resorption. If resorption is halted, the septum remains, and the uterus will be septate.[9] 

Resorption may be halted at any stage. If resorption is arrested early in development, the resulting septum creates a significant division of the endometrial cavity. If resorption is halted late in development, the septate uterus may only have a slight midline indentation; this is the arcuate or "heart-shaped" uterus, which appears to have no known clinical relevance.

Uterine septa may be partial, extending longitudinally from the uterine fundus without reaching the internal os, or they may be complete, extending from the uterine fundus to include the cervix. (Image 1, Partial and Complete Uterine Septa) Total resorption failure may result in a longitudinal vaginal septum with or without cervical duplication.

Thin uterine septa predominately comprise smooth muscle fibers and avascular fibrous tissue. Thickened muscular septa may have significant vasculature.[6]

Due to the timing of embryonic development, Müllerian anomalies are strongly associated with abnormalities of the upper and lower urinary tract; coexistence occurs in up to 40% of patients.[10] Although the concurrent incidence of uterine septa and renal anomalies lacks specific data, it is believed that renal anomalies are less frequently observed in cases involving impaired resorption rather than impaired fusion of the paramesonephric ducts. It is important to note that patients with isolated uterine septa do not require renal imaging unless otherwise indicated.[6]

History and Physical

A septate uterus is most likely to cause no symptoms and be found incidentally during pelvic imaging. Uterine septa are most likely to be identified after a first-trimester pregnancy loss, another adverse obstetrical outcome, or during cesarean section. A comprehensive obstetrical history is crucial when attempting to diagnose uterine septa.

There are no physical examination findings associated with isolated uterine septa.

Evaluation

The septate uterus may be visualized either directly during a diagnostic or therapeutic hysteroscopy or laparoscopy or indirectly via imaging studies such as ultrasonography (US), hysterosalpingography (HSG), or magnetic resonance imaging (MRI). 

Hysteroscopy

Hysteroscopy is the insertion of a rigid or flexible hysteroscope through the cervical canal into the endometrial cavity. Visualization of the entire endometrial cavity is accomplished using distention media. Hysteroscopy provides a complete view of the contour of the endometrial cavity, both tubal ostia; uterine septa are directly visualized if present.[11] However, hysteroscopy does not allow visualization of the contour of the serosal surface of the uterine fundus; a second imaging modality, such as concurrent ultrasound or laparoscopy, is needed to rule out a more significant uterine anomaly. 

Laparoscopy

Laparoscopy is a surgical procedure performed under general anesthesia that permits direct visualization of intraperitoneal abdominopelvic structures. Laparoscopy can be used in conjunction with hysteroscopy and HSG to visualize the fundal contour and identify the class of Mullerian anomaly. The method of using hysteroscopy and laparoscopy together has been shown to have the same diagnostic yield for a uterine septum as 3D ultrasound. Thus, 3D ultrasound is the preferable modality given the less invasive approach.[12]

Ultrasonography

A saline-infusion sonohystogram combines real-time uterine with the injection of sterile saline into the endometrial cavity to visualize its contour. [13] To measure a uterine septum during sonography, one line is drawn from cornu to cornu (line 1), and a second perpendicular line is drawn from line 1 to the tip of the septum (line 2). The length of line 2 is the septum measurement. In one study, sonohysterography was more sensitive and specific for a septate uterus than HSG and diagnostic hysteroscopy. There was no significant difference between HSG and diagnostic hysteroscopy.[4]

Hysterosalpingography (HSG) 

HSG is the radiologic imaging technique that facilitates structural evaluation of the endometrial cavity and fallopian tubes. Either oil- or water-based radiopaque contrast is delivered into the endometrial cavity under fluoroscopic guidance, and radiographs are taken.[14] A uterine septum may appear as an inverted triangular piece of tissue dividing the uterine cavity. However, the diagnostic accuracy of HSG in a septate uterus is low due to the difficulty distinguishing this finding from a bicornuate uterus.[6] Additionally, if the HSG reveals findings consistent with a septate uterus, this must be confirmed with 3D ultrasound, saline-infused sonogram, MRI, or laparoscopy to visualize the fundal contour and rule out a bicornuate uterus.

Magnetic Resonance Imaging (MRI) 

MRI of the pelvis using T2 images in three planes can measure a uterine septum. Long- and short-axis views are prescribed relative to the endometrium in the sagittal plane. The long-axis view allows visualization of the uterine fundal contour, while the short-axis view allows measurement of the uterine septum. To measure the uterine septum on MRI, you again measure from cornu to cornu (line 1) and measure from the caudal end of the uterine septum to the midpoint of line 1. A study by Ata et al determined that the ability of 3D ultrasound to diagnose a uterine septum is comparable to that of MRI but is the more cost-effective option.[15]

Treatment / Management

When a uterine septum is diagnosed in patients with infertility or a history of poor obstetrical outcomes, the recommended treatment is hysteroscopic resection of the septum. Many observational studies support this therapeutic regimen.[16] (A1)

However, there has been only one randomized controlled trial comparing hysteroscopic resection with expectant management in patients with a septate uterus. The Randomized Uterine Septum Transection (TRUST) trial randomized 80 patients with a septate uterus who desired pregnancy and had a history of subfertility, pregnancy loss, or preterm birth to either expectant management or septum resection. The two groups did not differ in time to pregnancy or live birth rate. The TRUST trial was limited by its small sample size, which included only 7 patients with a complete uterine septum. The study did not distinguish between septate and arcuate uteruses, which may have confounded their results.[17] (A1)

When a septate uterus is diagnosed in the absence of infertility or a history of a poor obstetrical outcome, septum resection can be considered with the appropriate patient counseling and shared decision-making.[6] The ideal timing of septum resection is during the early follicular phase of the menstrual cycle; the uterine lining is thin and does not obscure the hysteroscopic view. Medications such as progestins, danazol, or gonadotropin-releasing hormone (GnRH) agonists can suppress endometrial growth and facilitate hysteroscopic visualization of the uterine septum.

The goal of the hysteroscopic septal resection is to incise the uterine septum. Transection can be accomplished using cold scissors, unipolar or bipolar cautery, or argon lasers; success rates are similar for each.[18][19][20] Complications of this procedure are infrequent. A staged procedure is sometimes required if patients have a thick or complete uterine septum or a concurrent vaginal septum. [21] Ultrasound or fluoroscopic guidance can be used as an adjunct to prevent incising the myometrium.(A1)

Many techniques have been implemented to prevent intrauterine adhesions and septum reformation after hysteroscopic resection; no significant evidence suggests for or against any of these methods. Methods have included balloon stenting via intrauterine foley catheter placement, intrauterine injection of crosslinked hyaluronic gel, copper, or hormonal intrauterine device placement, and oral administration of estradiol or progestin.[22][23][24](A1)

Neither the Jones nor Tompkins metroplasty is frequently performed in current clinical practice; abdominal hysterotomy with subsequent resection of the uterine septum and metroplasty is an invasive procedure with significant surgical and obstetrical risk.[25]

Differential Diagnosis

The differential diagnosis of a septate uterus includes an arcuate uterus, bicornuate uterus, or uterus didelphys.

Prognosis

Uterine septa are associated with poor reproductive outcomes, including recurrent pregnancy loss and preterm delivery. There is conflicting evidence regarding the association of uterine septa with infertility. However, observational studies have indicated that surgical septum resection can improve clinical pregnancy rates in infertile couples and improve pregnancy outcomes in those with prior miscarriages or preterm deliveries.[6][25]

Complications

Many patients with a septate uterus do not experience any adverse reproductive sequelae. However, the most common adverse reproductive outcome of a septate uterus is infertility or preterm delivery. For each pregnancy that develops within a septate uterus, there is a 26% to 94% chance of miscarriage and a 6% to 16% chance of preterm labor.[4]

A review article found that congenital anomalies were identified in 12.6% of patients with recurrent pregnancy loss.[26] In observational studies, patients with a septate uterus were found to have higher rates of first-trimester miscarriage than those with a normal uterine cavity (42% vs 12%); however, a septate uterus did not increase the risk of a second-trimester miscarriage or preterm labor.[27]

There is some observational evidence that a septate uterus may increase the risk for fetal malpresentation, intrauterine growth restriction, placental abruption, and perinatal mortality. However, there have not been large randomized controlled trials to evaluate these outcomes.[6]

The complications of a hysteroscopic septum resection include uterine perforation, resulting injury to surrounding pelvic structures, and intrauterine adhesion formation. The risk of uterine perforation can be minimized by using intraoperative ultrasound guidance. The formation of postoperative intrauterine adhesions may be minimized with prophylactic hormone replacement therapy or intrauterine balloon placement; data is inclusive.

Case reports have described intrapartum uterine rupture following hysteroscopic septum resection; uterine rupture may have been due to inadvertent myometrial incision during the resection procedure. A recent 20-year retrospective analysis in Slovenia found 4 cases of uterine rupture in patients who achieved term pregnancy after undergoing hysteroscopic uterine septum resection.[28] Avoiding myometrial incision through judicious septal transection may prevent this catastrophic complication.