Uterine Septum
The most frequent type of congenital uterine anomaly is the septate uterus, which is caused by the imperfect or complete failure of Müllerian duct fusion. The complete septate uterus, in which the septum separates the entire uterine cavity, and the subseptate uterus, in which a partial split of the uterine cavity does not reach the cervix, are both described. Failure of fusion may occur at a lower level, resulting in the presence of two cervices and even a vaginal septum. A new revised classification system for congenital uterine defects has been created by the European Society of Human Reproduction and Embryology (ESHRE) and the European Society for Gynecological Endoscopy (ESGE). The uterine septum was defined as a uterus that has a regular shape and an inner depression at the fundal centerline that was greater than half the thickness of the uterine wall. This indentation is known as a septum, and it can partition the uterine chamber partially or fully, including the cervix and/or vaginal canal in some circumstances (cervical and vaginal coexistent anomalies). In the general population, the true prevalence of Müllerian abnormalities is unknown. The paucity of diagnostic instruments hampered early investigations on congenital uterine defects, which were primarily focused on clinical examination. A meta-analysis of 94 observational studies involving approximately 91,000 women found a prevalence of 5% in the general population, 8.5 percent in infertile women, 13 percent in women who have had a miscarriage, and 24 percent in women who have had a miscarriage and are infertile. Canalization anomalies (subseptate or septate uteri) were also seen in 3% of the general population but were found substantially more commonly among women who had previously miscarried. Furthermore, a septate uterus is linked to a higher rate of abortion in the first and second trimesters, as well as premature labor, atypical labor, intrauterine growth restriction, and infertility. Reduced blood supply, uterine cavity deformation, increased intrauterine pressure with resulting cervical insufficiency, and altered estrogen and progesterone receptor expression are all possible causes of these disorders. When indications exist, surgical repair of a septate uterus should be regarded as a first-line treatment.
Embryology and Genetics
The Mullerian ducts are seen in the embryo at 5 to 6 weeks of gestation. They begin as a groove of the coelomic epithelium on the urogenital ridge, grow caudally, connect in the midline around 9 weeks, and eventually join the endodermal evaginations of the urogenital sinus. Around 18–20 weeks of pregnancy, the process comes to a close with the resorption of the septum towards the end of the first trimester.
Studies on women with genetic abnormalities, such as Mullerian anomalies and knockout mice models, have led to the discovery of a number of genes that are involved in the development of the female reproductive system and the pathogenesis of uterine malformations. A change in Bcl-2 gene expression in the uterine septum could inhibit apoptosis and uterine septum regression. Mikkila et al. reported an X-linked laterality sequence with uterine septum and hypertelorism in obligate carrier females. Ergun et al. described an unusual familial aggregation in three sisters who each had a septate uterus to varying degrees.
The exact pathophysiology of the septate uterus remains unknown, despite improvements in molecular biology and genetics. The bulk of the scientists believes that polygenic/multifactorial pathogenesis is responsible for nearly all uterine abnormalities.
Uterine Septum Symptoms
Many women may never be aware that they have a septate uterus. They could even have a history of healthy pregnancies. Some of the ladies may have a history of heavy menstrual bleeding.
However, it has the potential to cause infertility and the loss of a pregnancy. In a septate uterus, the septum, or curtain, receives less blood than the uterine walls. If the embryo implants on the septum, it may not survive owing to a lack of blood supply, resulting in implantation failure. Infertility may arise as a result of implantation failure.
In certain situations, the embryo will implant onto the septum, thrive to some degree, but because of a lack of blood supply, the abortion will be spontaneous (women may begin bleeding soon after the missing period) or missed (fetal heart activity may not be detectable).
Abortion may also occur when the uterine cavity is not large enough for the embryo to mature due to the septum. The congenital uterine malformation is commonly coupled with a fragile, therefore pregnancy losses between 3 and 6 months are common (mouth of the uterus).
However, if a USG is performed to check the cervix, this can be avoided. If the USG reveals a fragile cervix or the lady has a history of pregnancy loss after three months, a cervical suture can be used to prevent complications.
Uterine Septum Diagnosis
The majority of congenital uterine defects are asymptomatic; however, they might cause delayed menarche, primary infertility, or repeated multiple miscarriages. Although reproductive abnormalities can be diagnosed during a gynecological exam if there are evident defects of the vaginal and cervix, uterine malformations are primarily identified by imaging findings. Furthermore, only in the case of a septate uterus does surgical therapy yield clear improvements in terms of reproductive results; thus, it is critical to distinguish this disease from other uterine defects. The form of the uterine cavity (including the location of the tubal ostium) and the outer uterine contour should be assessed by an optimum diagnostic tool. Gubbini et al. proposed a simple, systematic, and reproducible subclassification system for uterine anomalies previously classified by the American Fertility Society as classes V and VI, to achieve a precise definition of each uterine anomaly and determine the precise surgical management.
Hysterosalpingography (HSG)
Hysterosalpingography has been the primary diagnostic tool used to detect uterine cavity malformations and is still currently indicated in the early stages of evaluation of the infertile couple. Despite being able to supply important information regarding tubal patency, it does not provide any information on the uterine wall or external uterine contour. Moreover, this technique is not reproducible and is not free from risks arising from radiating exposure and/or upper reproductive tract infection.
Tow-Dimensional Ultrasound
The uterine cavity, inner uterine walls, and outer uterine outline can all be seen clearly using two-dimensional ultrasonography (2D US), which is usually done through an endovaginal route. Its use is popular because of its low cost and reproducibility, but accuracy is mostly dependent on the clinician's experience. 2D US has a sensitivity of 89 to 93 percent and a specificity of 95 to 99 percent, with a positive predictive value of 52–55 percent and a negative predictive value of 89 to 100 percent. Furthermore, sonohysterography, which involves expanding the uterine cavity with a transonic method, improves ultrasound accuracy in the detection of uterine anomalies by providing more precise information on the uterine cavity contour.
Hysteroscopy
The cervical canal and uterine cavity can be examined directly using hysteroscopy. Miniaturization combined with adequate image quality has made modern mini-hysteroscopy a popular screening method. It cannot, however, provide information about the uterine wall or the outer uterine contour. Because both the inner and outer aspects of the uterus may be examined, the combined hysteroscopic–laparoscopic method is regarded as the optimum strategy in the evaluation of women with congenital reproductive abnormalities. In addition, endometriosis, peritoneal adhesion, and coexisting tubal and ovarian malformations can all be detected and treated. Nonetheless, this combined technique, like diagnostic instruments, cannot provide objective measurable data because diagnosis is based on the examiner's subjective perception. It should also not be utilized as a main diagnostic tool because of its intrusive nature. The techniques discussed thus far are frequently utilized in the research of Müllerian malformations, but none of them can provide acceptable data on both the uterine cavity and the outer contour of the uterus when viewed independently. The only procedures that can measure both aspects simultaneously are magnetic resonance imaging and three-dimensional ultrasound.
Magnetic Resonance Imaging
Because MRI accuracy in the identification of uterine abnormalities has been proven in multiple studies, 3D US represents a promising new alternative because it gives image quality comparable to MRI while being more patient-friendly and less expensive. The 3D fast recovery fast spin-echo (FRFSE) cube, a newly added MR method, can be utilized to create high-resolution volumetric picture sets. Using the 2D FRFSE technique, image data can be reformatted in any plane, removing the danger of improper plane prescription regardless of the prescribed plane during picture collection. This is useful because, in the incidence of a Müllerian abnormality, changing uterine architecture can make it difficult to choose the right cross-sectional planes in 2D imaging. Furthermore, capturing a single picture volumetric series rather than numerous sequences on different planes reduces MR exam acquisition time, improving patient comfort.
Three-Dimensional Ultrasound
By analyzing the external profile of the uterus in coronal plane scans, Ghi et al. proved the efficiency of 3D US in discriminating arcuate, subseptate, septate, and bicornuate uterus. A bicornuate uterus is identified by a fundal outer indentation greater than or equal to 10 mm that separates two uterine cornua; septate, subseptate, and arcuate uteri, on the other hand, have a convex fundal outline or a fundal indentation less than 10 mm. While the septum entirely divides the cavity from the fundus to the cervix in the septate uterus, the septum bulges inside the uterine cavity in the subseptate and arcuate uteri, respectively, creating an acute or obtuse angle at its central point.
Bermejo et al. discovered that 3D US and MRI had a high level of correlation in the diagnosis and classification of uterine abnormalities. They used a formula proposed by Troiano and McCarthy to analyze coronal plane scans to distinguish bicornuate from septate uteri using 3D US: if a line passing through tubal ostia crosses the fundus or its distance from the fundus is less than or equal to 5 mm, it is a bicornuate uterus; if the distance is greater than 5 mm, it is a septate uterus, regardless of fundus shape. The clinical diagnosis proposed by the American Fertility Society (AFS) and previously utilized by Woefler et al. were employed by Faivre et al.
As a result, 3D ultrasound should be used to screen women with suspected Müllerian abnormalities, especially before surgery. The high expenses of MRI, combined with the necessity for uterine malformation knowledgeable specialists, limit its utilization to situations that are uncertain or difficult.
Uterine Septum Treatment
A metroplasty procedure can be used to correct a septate uterus. A hysteroscopy is currently used to do the surgery. The hysteroscopic surgery allows for therapy within the uterus without requiring an exterior abdominal incision.
A lighted tool is passed into the vagina, via the cervix, and into the uterus during a hysteroscopic metroplasty. Another device is introduced to cut the septum away and remove it.
This procedure is minimally invasive and takes around one hour to complete. The majority of women who choose to have a hysteroscopic metroplasty come back home the same day.
Between sixty and eighty percent of women who have had recurrent miscarriages will have a healthy future pregnancy after the operation. Up to 25% of women who were previously unable to conceive may be able to do so after undergoing this surgery.
Uterine Septum Complications
Obstetric Complication
Obstetric difficulties affect 22-25 percent of women with a septate uterus, the most prevalent of which are recurrent miscarriage and preterm labor.
A retrospective study conducted in the 2000s on 198 women with septate uteri and 498 pregnancies found a 44 percent miscarriage rate, a 22 percent preterm labor rate, and a 32 percent term birth rate. Other authors have reported similar findings in recent years, confirming that the existence of a uterine septum is linked to a poor pregnancy outcome. As a result, the reproductive outcome in women with a septate uterus serves as a benchmark for evaluating the efficacy of hysteroscopic metroplasty. Several studies have already shown that women treated with hysteroscopic metroplasty have a lower rate of abortion and preterm labor. Only 60 incidences of recurrent abortion and 25 cases of premature labor were recorded in a series of 367 pregnancies following hysteroscopic septum excision. When compared to preoperative rates of 86.4 percent for miscarriage and 9.9 percent for preterm labor, these results were much better.
Metroplasty's preventive efficacy in asymptomatic or nulliparous women is still debatable. Only symptomatic women would have their septum surgically removed due to the higher risk of uterine rupture in future pregnancies and the requirement for cesarean delivery. Scientific research, on the other hand, shows a definite link between a septate uterus and poor pregnancy outcomes, as well as a considerable improvement in reproductive outcomes after resection.
Infertility
In the last two decades, researchers have reported conflicting findings of the impact of uterine abnormalities on fertility. Although uterine deformities can interfere with fetal implantation and placentation, Grimbizis et al. observed that infertile women and the general population have equal rates of uterine malformations. Other researchers corroborated these findings. As a result, a direct link between uterine abnormalities and infertility must be ruled out. Arcuate uterus, on the other hand, is the most frequent uterine deformity in the fertile population, while the septate uterus is twice as prevalent in infertile women as it is in the general population. These findings point to a link between a septate uterus and female infertility, particularly in secondary cases.
When metroplasty is utilized to increase pregnancy rates in situations of unexplained female infertility, the mismatch of data available in the literature is reflected in clinical practice. Even yet, the data available is inconclusive, as it is largely based on retrospective research involving small numbers of individuals who were typically chosen based on varied criteria.
Homer et al. did a systematic review and discovered a pregnancy rate of 49 percent following resection in women with primary infertility, indicating that hysteroscopic metroplasty can be used in these instances. Pabuccu et al. presented the first prospective study on the use of metroplasty in infertile women in 2004, revealing a 42% postoperative spontaneous conception rate in women with infertility of unclear etiology. The writers found a significantly higher pregnancy rate and live birth rate in the metroplasty group than in the control group in a prospective controlled trial conducted by Mollo et al. on 45 women with septate uterus and otherwise unexplained infertility and 133 women with unexplained infertility as a control group. Research by Shokeir et al. in 2012 found a 42 percent postoperative pregnancy rate with 80 percent spontaneous pregnancies. Despite the lack of randomized controlled studies, published data on hysteroscopic metroplasty in patients with primary infertility from 1986 to 2011 revealed a pregnancy rate of around 41%.
In terms of the benefits of hysteroscopic resection of endometrial polyps, submucous fibroids, and uterine septum in terms of the reproductive outcome before a program for assisted reproduction, most authors agree with the benefits of hysteroscopic removal of endometrial polyps, mucosal fibroids, and uterine septum in terms of reproductive outcome. About 2,500 patients with a septate uterus who were undergoing assisted reproduction were investigated by Tomazevic et al. They discovered that hysteroscopic metroplasty before IVF or intracytoplasmic sperm injection enhanced pregnancy and live birth rates considerably. As a result, they reach the same conclusion as Homer: hysteroscopic correction of uterine anomalies is a practical, safe procedure that improves reproductive outcomes not just in women with recurrent pregnancy loss and preterm labor, but also in infertile women, particularly when IVF is used.
Conclusion
Mullerian duct fusion is either incomplete or wholly unsuccessful, resulting in a septate uterus. About 25–30 percent of women with a septate uterus have obstetric difficulties that necessitate hysteroscopic surgery. Although obstetric difficulties are the most common reason for metroplasty, the uterine sputum's unfavorable effect in otherwise unexplained infertility cannot be ruled out. The scientific evidence does not support a direct etiological relationship, although it is inconclusive and requires further investigation. According to the most recent statistics, given the ease and safety of hysteroscopic metroplasty, it appears safe to recommend it for infertile women, particularly those who are nulliparous and over 35 years old or who plan to undergo a PMA program.