Introduction

Congenital uterine anomalies (CUAs) comprise of structural disorders of the female genital tract that arise because of abnormal fusion or resorption of the Müllerian ducts.

The prevalence of CUAs is estimated to be at 5.5% in the general population, while up to 8.0% in infertile women, 13.3% in women with a history of miscarriage, and 24.5% in those who were infertile that have suffered a miscarriage [1]. The past few years, a combination of three-dimensional (3D) ultrasound, magnetic resonance imaging (MRI), laparoscopy, and hysteroscopy had contributed significantly to the classification these anomalies. In contemporary medicine, most cases can be diagnosed by a less invasive approach because of the increasing use of MRI and 3D ultrasound [2].

CUAs are mostly asymptomatic and fortuitously diagnosed during the annual check-up or investigation of recurrent pregnancy loss or infertility. The reproductive outcomes in women with such anomalies range widely, from normal to severe adverse outcomes, including preterm birth or miscarriage [1].

In this work, we present three cases of women upon patient consent with complex genital tract anomalies classified as per the ESHRE consensus (U2bC2V1), including complete uterine septum, cervical duplication, and vaginal septum respectively, with different reproductive outcomes.

Case Presentation

1st Case

A 51-year-old G2P1 (natural conception, no history of miscarriages, vaginal delivery) presenting with severe worsening menorrhagia attributed to multiple leiomyomas was referred to our clinic. Pelvic examination revealed an enlarged uterus, small vertical vaginal septum in the upper third of vagina and two external cervical orifices (Fig. 1). Complete septate uterus and cervical duplication were found during 2D (two dimensional) transvaginal ultrasound (TVUS) and confirmed by MRI (Fig. 2). The patient reported that she had already undergone three myomectomies in the past (at the age of 20, 28, and 40) due to persistent fibroid-related symptoms, including excessive bleeding and consequent anemia. All of them were performed by laparotomy and more than 8 intramural and subserosal fibroids (1–8 cm) were removed at each operation. After the exclusion of endometrial pathology, by conducting endometrial biopsy, hysterectomy was recommended. Those findings were also confirmed intraoperatively. The histopathology report mentioned the presence of two intracervical canals, 3.5 cm each, and two external cervical orifices.

Fig. 1
figure 1

Cervical duplication as per case 1. Patient consent for photography and educational use of their history was sought and obtained

Full size image
Fig. 2
figure 2

MRI image, 1st case. Enlarged fibroid uterus, presence of complete septate uterus and cervical duplication

Full size image

2nd Case

A 25-year-old G0P0 woman, without significant medical history, presented with dyspareunia. The gynecological examination revealed a longitudinal non-obstructing vaginal septum with a well-formed cervix in the left and a hypoplastic one in the right side. During 2D ultrasound, complete septate uterus was identified (Fig. 3) and MRI was suggested to confirm this finding. The MRI results confirmed the diagnosis and classified the identified congenital anomaly as U2bC2V1 (Fig. 4). The patient underwent resection of the vaginal septum and diagnostic hysteroscopy from both cervical orifices. Laparoscopy was performed simultaneously due to a persistent ovarian cyst of 6 cm in diameter, which was resected, and confirmed normal contour of uterus (Fig. 5). The reproductive outcome in this case could not be evaluated at the time, since the patient was not desiring to conceive.

Fig. 3
figure 3

Ultrasound image of septate uterus, 2nd case

Full size image
Fig. 4
figure 4

MRI image, 2nd case. Presence of complete septate uterus and vaginal septum

Full size image
Fig. 5
figure 5

Well-formed cervix in the left and a hypoplastic one in the right side as per case 2. Patient consent for photography and educational use of their history was sought and obtained

Full size image

3rd Case

A 38-year-old G0P0 infertile women presented to our clinic for fertility counseling and management of dyspareunia. The patient was evaluated by pelvic examination, TVUS and hormonal blood test assessment for ovarian reserve markers. Gynecological examination revealed a vertical vaginal septum on the left side of vagina with a well-defined cervix in the right side. The left part of the vagina was too small to allow left cervix examination. TVUS revealed 2 well-developed cervixes and 2 endometrial cavities completely separated by the septum (Fig. 6). The external contour of the uterus, according to 2D ultrasound and MRI (Fig. 7), was found to be normal. Hysterosal**ography was performed only from the right side and revealed well-formed right side of the uterine cavity and that right fallopian tube was unobstructed. After TVUS and blood test assessment, the patient was diagnosed with poor ovarian reserve. The AFC (antral follicle count) was 4 and her AMH (anti-Mullerian hormone) was 0.9 ng/ml. Partners’ sperm count was found to be within normal range. Therefore, patient’s infertility was attributed primarily to poor ovarian reserve and the option of in vitro fertilization (IVF) was offered. The woman underwent diagnostic hysteroscopy of both cavities and resection only of the vaginal septum (Fig. 8).

Fig. 6
figure 6

Ultrasound image of septate uterus, 3rd case

Full size image
Fig. 7
figure 7

3rd case. MRI image. Presence of two endometrial cavities completely separated by uterine septum

Full size image
Fig. 8
figure 8

Two well-developed cervixes as per case 3. Patient consent for photography and educational use of their history was sought and obtained

Full size image

Of note, none of the above-described cases was found to have any other associated genetic or congenital anomalies, such as renal, skeletal, or abdominal wall abnormalities.

Discussion

Septate uterus is believed to develop due to the failed fusion or resorption of the Müllerian ducts, during the period of embryologic development [3,4,5]. According to the new ESHRE (European Society of Human Reproduction and Embryology)/ESGE (European Society for Gynecological Endoscopy) classification system of female genital tract congenital anomalies, septate uterus involves all those cases with a normal external contour and an internal indentation extending >50% of the uterine wall thickness [3].

During the last few years, an increasing number of congenital anomalies cases have been reported. The increasing incidence of these presentations may be due to the widespread use of transvaginal ultrasound and MRI. The different types of CUAs have been associated with varying degrees of suboptimal reproductive outcomes. Women with canalization defects seem to have the poorest reproductive performance, including reduced conception rates, which often are linked to implantation failure [4, 6,7,8]. The present study describes three cases of women with duplicated cervices and septate uteri. A complete uterine septum with double “normal” cervix may have a wide spectrum of reproductive outcomes. We advised nulliparous and infertile women to complete their evaluation by performing hysteroscopy. This provides reliable information of the anatomical status of the vagina, cervix, uterine cavity, and tubal ostia. There is no doubt that women with dyspareunia should undergo resection of vaginal septum. In cases of infertility or recurrent pregnancy loss, the dilemma remains as to whether to proceed with the resection of the uterine septum in combination with resection of the vaginal section.

Several studies have evaluated the association between congenital anomalies and reproductive outcomes with controversial conclusions since they are associated with both acceptable as well as adverse outcomes [9]. Septate uterus seems to be associated with infertility as well as with an increased risk of miscarriages and preterm births. A systematic review of 3805 women with both canalization and unification defects reported decreased pregnancy rates in the canalization defect group and significant higher risk for preterm birth, miscarriage, and fetal malpresentation. Additionally, women with septate uterus appear to have poorer outcomes when compared with those with subseptate uterus [8]. Naeh et al. compared the course of 167 pregnancies of women with CUAs to the general population. Overall, higher rates of major adverse outcomes were reported in the CUAs group but safe conclusions regarding the CUAs subtype could not be drawn [10]. Although the exact mechanism that causes infertility in women with septate uterus remains obscure, implantation alterations seem present the most plausible explanation [11]. Conversely, as infertility is a multifactorial condition, it is hard to be exclusively attributed to septate uteri [5]. These findings were confirmed by the first case of 51-year-old woman, who had no history of infertility and had one normal delivery.

Septate uterus is the most frequent congenital anomaly accounting for 35% of all uterine anomalies. Despite that, there is still no consensus regarding the proper management [12]. The most frequent intervention in these women includes hysteroscopic septum resection. Various observational studies report that the restoration of the anatomy of the uterus improves live birth rates [13, 14]. Bendifallah et al. have analyzed pregnancy rates among 128 women with primary infertility or recurrent miscarriage and septate uterus. After metroplasty, via hysteroscopy, 60.9% of women became pregnant while the birth rate in this group was reported at 53.1% and the miscarriage rate significantly decreased [13]. However, the outcome seems to be acceptable even without an intervention. Rikken et al. report the lack of evidence to support the surgical intervention and the need for relevant RCTs. From nine comparative studies regarding miscarriages and live birth rates with and without metroplasty, three supported better outcomes after surgery while six found expectant management safer and equally effective [14]. Furthermore, the possibility of intrauterine synechiae after hysteroscopic resection of uterine septum should also be considered. Recently, an international-multicenter-open-label, randomized controlled trial, compared reproductive outcomes in women with septate uterus using either expectant management or septum resection in 80 patients was published by Rikken et al. According to their findings, live birth rates, miscarriages, and preterm birth rates were not improved by the septum resection. More specifically, live birth rate was 31% in the metroplasty group and 35% in the expectant group [15].

Recently, Noventa et al. performed a systematic review and meta-analysis to evaluate the impact of hysteroscopic septum resection on pregnancy rate, live birth rate, spontaneous abortion, and preterm labor in patients with history of infertility or miscarriages. Hysteroscopic metroplasty seemed to significantly improve the live birth rates and reduce the possibility for spontaneous abortions compared to women with untreated uterine septum. Although the efficacy of metroplasty regarding the likelihood of pregnancy in women with history of infertility remained controversial [16]. Furthermore, Manchado et al. [17] in their recent prospective study showed that office hysteroscopic metroplasty by diode laser improved pregnancy and cumulative live birth rate (CLBR) in women with septate uterus. This study included 41 nulliparous women diagnosed with septate uterus and a history of primary infertility or recurrent miscarriage. The pregnancy rate was 78.9% and CLBR 63.2%, concluding that it is safe alternative techniques in terms of reproductive outcomes.

Consequently, hysteroscopic metroplasty is a common and safe procedure routinely offered to women with congenital anomalies. Therefore, it is crucial to mention that, whether performed in a surgical setting or in an office, hysteroscopy is associated with minimal complications. Miklavcic et al. report that hysteroscopic septum resection should not be considered a risk factor for preterm delivery to women with singleton pregnancies [18]. As for uterine rupture in pregnancy followed by a hysteroscopic metroplasty, it is a life-threatening complication that has been extremely rarely reported [19].

In our institution, we suggest all patients with complete uterine septum to perform diagnostic hysteroscopy. We used to adopt the expectant management in women without history of infertility if at least one endometrial cavity was found to be “normal” during diagnostic hysteroscopy. In infertile women, as well as women with the history of recurrent pregnancy losses, after excluding all possible causes of infertility (male factor, poor ovarian reserve etc.) and miscarriages (thrombophilia, karyotype, etc.), the possibility of resection of uterine septum should be considered. Royal college of Obstetricians and Gynecologists (RCOG) suggests that among women with several types of CUAs, surgical treatment should be offered to those who have had recurrent miscarriages and have a septate uterus [2]. Although further evidence, preferably, from randomized controlled trials with sufficient power is required to clarify further the guidelines.

Conclusion

Congenital uterine anomalies and especially a septate uterus are very common. The association of these anomalies with the woman’s fertility status remains controversial issue as their impact may vary from asymptomatic presentation to severe reproductive adverse outcomes. Literature controversies make the appropriate management of these patients challenging. The available research remains limited and consequently insufficient to allow for any safe conclusions to be drawn. However, here, we suggest that patients with septate uterus and history of infertility or poor pregnancy outcome to complete their investigation with hysteroscopy and proceed with resection of septum.