A noninvasive method , currently available in most clinics and considered to be the preferred diagnostic modality. It is a relatively quick imaging method that allows the evaluation of the external contours of the uterus (Fig. 7.1) with MRI comparable results. Examples of TVS findings in various congenital uterine anomalies are presented in Figs. 7.2, 7.3, 7.4, and 7.5. The ability of 3D ultrasonography to visualize both the uterine cavity and the myometrium, as well its ability to differentiate subseptate from bicornuate uteri, makes it an accurate modality for the detection of uterine anomalies [22]. Szkodziak et al. [23] compared the performance of hysterosalpingography (HSG) and 3D transvaginal sonography (TVS) in diagnosing uterine anomalies. In 22 cases out of 155 the diagnosis of arcuate, septate, and bicornuate uterus was possible only after the use of 3D TVS. Importantly, in five patients the HSG exam could not be completed due to severe pain and lack of cooperation; a 3D TVS was performed and found all five cases to have normal uterus. The authors concluded that 3D TVS can accurately demonstrate uterine anomalies. Salim et al. [24] examined the reproducibility of the diagnosis of congenital uterine anomalies and the repeatability of the measurements of uterine cavity dimensions using 3D TVS. Two independent observers evaluated the data. Eighty-three 3D TVS volumes were examined and both investigators diagnosed 27 uteri as normal, 33 as arcuate, 19 as subseptate, and 3 as unicornuate; only a single uterine anomaly was classified by one as arcuate and by the other as subseptate (kappa 0.97). They concluded that 3D TVS is a reproducible method in diagnosing congenital uterine anomalies (Fig. 7.1).

Ghi et al. [25] studied the accuracy of 3D ultrasound in the diagnosis of congenital uterine anomalies among a group of women with RPL.

Ultrasound scan was performed using a machine equipped with a multi-frequency volume endovaginal probe. The insonation technique was standardized according to the following criteria: probe frequency set at 9 mHz, a midsagittal view of the uterus filling 75 % of the screen, three-dimensional (3D) box size including the uterus from fundus to the cervix, sweep angle of 90°, and sweep velocity adjusted to maximum quality. As shown in Fig. 7.1, the volume reconstruction technique was standardized according to the following criteria: the volume rendering box was as narrow as possible in the sagittal plane and adjusted on the uterine corpus in the coronal plane, cut plane scrolled in anterior-posterior fashion with slice thickness set at 1 cm, transparency low (<50 %), and volume rendering by a mix of surface and maximum mode. The analysis of uterine morphology was performed in a standardized reformatted section with the uterus in the coronal view using the interstitial portions of fallopian tubes as reference points. Specific ultrasound diagnosis of uterine anomalies was based on the classification system originally proposed by the American Fertility Society and subsequently modified according to 3D ultrasound landmarks [10] (Table 7.2).

Women with negative ultrasound findings subsequently underwent office hysteroscopy; a combined laparoscopic-hysteroscopic assessment was performed in cases of suspected Müllerian anomaly. A specific Müllerian malformation was sonographically diagnosed in 54 of the 284 women (19 %) included in the study group. All negative ultrasound findings were confirmed at office hysteroscopy. Among the women with abnormal ultrasound findings, the presence of a Müllerian anomaly was endoscopically confirmed in all. Concordance between ultrasound and endoscopy around the type of anomaly was verified in 52 of the 54 (96.3 %) cases, including all cases with a septate uterus and two out of three with bicornuate uterus. This important study concluded that volume TVS appears to be extremely accurate for the diagnosis and classification of congenital uterine anomalies and should conveniently become the first recommended step in the assessment of the uterine cavity in patients with a history of recurrent miscarriage. Three-dimensional ultrasound enables the clinician to comprehensively assess uterine morphology, thus alleviating the need for invasive tests.

Hysterosalpingography (HSG) is a radiographic procedure performed in order to mainly examine the patency of the Fallopian tubes and the morphology of the uterine cavity. It is usually indicated in the early stages of an infertility work-up [26]. The radio-opaque contrast medium fills the cavity, allowing the accurate identification of filling defects due to Müllerian malformations. However, this technique cannot accurately differentiate a septate uterus from a bicornuate uterus [22]. It is also unable to determine the myometrial thickness above the defect or the size of the defect itself. Therefore, the major limitation of this exam lies in its inability to evaluate the external uterine contour [5]. Another disadvantage is the exposure to ionizing radiation in typically young women.

An expensive, powerful but noninvasive and accurate technique. It has displayed promising results in the diagnosis and categorization of uterine malformations with an accuracy of up to 100 % in the evaluation of Müllerian anomalies [5]. In a study by Bermejo et al. [27], a high degree of concordance between 3D TVS and MRI was reported for the diagnosis of uterine malformations. The structural relationship between the uterine cavity and fundus was equally well visualized with both techniques. Currently MRI is indicated as a complementary imaging modality to 3D ultrasound only in cases of complex abnormalities that involve in addition to the uterus both the cervix and the vagina [22].

Hysteroscopy has become the gold standard for the evaluation of the uterine cavity and is a reliable and safe method in an office setting [22]. This technique allows visualization of the inner part of the cervix and uterus, offering direct vision of the uterine cavity and its internal structures and allows guided biopsies to be obtained if necessary [28]. However, it is also an invasive method that may cause patient discomfort. Hysteroscopy alone is unable to differentiate a septate uterus from a bicornuate uterus [22]. In a retrospective analysis performed by Valli et al. [29], 344 women with RPL and 922 controls were referred for diagnostic hysteroscopy. There was a significantly higher rate of major and minor uterine anomalies (septate and unicornuate uterus) in the RPL group compared to the control group (32 % vs. 6 %, p < 0.001). There was no significant difference in uterine adhesions between the two groups. Another retrospective analysis by Weiss et al. [30] compared the prevalence of uterine anomalies between women referred to hysteroscopy for RPL after two or more consecutive miscarriages. There was no significant difference in uterine abnormality rates between the 67 patients with 2 RPLs and the 98 patients with 3 or more RPLs (32 % vs. 28 %, respectively).

This modality gives the surgeon the ability to assess the outer surface of the uterus as well as other pelvic structures. Nonetheless, it is more expensive and invasive [5] compared to the previously reviewed modalities. Currently, diagnostic laparoscopy is generally reserved for women in whom interventional therapy is likely to be undertaken and rarely used for uterine anatomic evaluation purposes [22]. As shown by some, the high accuracy of 3D TVS or MRI allows a noninvasive diagnosis and characterization of uterine anomalies without the need for diagnostic laparoscopy [28].

A transvaginal sonogram used in combination with a saline contrast medium injected into the uterine cavity. This is a simple and quick procedure with minimal discomfort to the patient and is now being increasingly used for a routine evaluation of the uterine cavity [22]. Goldberg et al. [26] performed transvaginal sonohysterography on 40 consecutive patients with infertility or RPL previously diagnosed with uterine abnormalities by HSG. The study found that sonohysterography was more accurate than HSG and provided more information about uterine abnormalities. It also provides additional information on the relative proportion of the intracavitary and intramyometrial components of submucous myomas, as well as extracavitary myomas and adhesions [26].

Septated uterus is the most common Müllerian anomaly, accounting for about 55 % of all Müllerian duct anomalies [5]. It is also the most common major uterine anomaly in women with RPL [32], with a reported prevalence of 15–26 %.

The etiology of RPL in a septated uterus was originally attributed to the fibrous and vascular nature of the septum, despite the lack of histologic data [33, 34]. However, thanks to the use of MRI and histology it is now clear that the septum is composed primarily of smooth muscle and not fibrous tissue [5].

The increased risk of pregnancy loss is most probably related to the decreased connective tissue of the septum that may result in poor decidualization and reduced implantation rate, while increased muscular tissue may result in increased contractility of the tissue. In addition to the inherent deficiencies of the composition of the septum, the overlying endometrium has been shown to be defective [35]. Studies employing electron microscopy reported that the septal endometrium was found to be irregular in morphology, with a decreased sensitivity to preovulatory hormonal changes [36]. Morphologic narrowing of the cavity by the septum, causing a reduction in endometrial capacity, is also believed to play a role in the pathophysiology of adverse reproductive outcome [37].

Finally, inadequate vascularization within the septum and altered relationships between the endometrial, myometrial vessels and myometrial nerves are also considered to be associated with RPL [33, 34]. If this is true, the likelihood of miscarriage caused by septal implantation should increase with the severity of the disruption of uterine morphology [24].

Adverse pregnancy outcome seems to be increased in women with septate uterus as shown in several studies with fetal survival between 6 and 28 % [2]. Ghi et al. [38] reported on pregnancy outcome in women with incidental diagnosis of septate uterus at first trimester scan. They found that in 24 patients diagnosed at a median gestational age of 8.2 weeks, the cumulative pregnancy progression rate was 33.35 % due to the occurrence of early (≤13 weeks) or late (14–22 weeks) miscarriages in 13 and 2 cases, respectively.