Uterine factor infertility is a relatively uncommon cause of female infertility occurring in <5% of women. Many uterine causes for infertility, both acquired and congenital, have been learned. Although uterine factors may be diagnosed during investigation of infertility. A thorough investigation and management of all other causes of infertility should be undertaken at the same time.
Knowledge of the anatomy, physiology, and function of the uterus is paramount to the understanding of the development of congenital anomalies of uterus and their potential impact on fertility. In brief, the uterus is a thick-walled muscular structure, with its sole function being to allow implantation of the developed embryo, and subsequently serving as the incubation chamber for the growing fetus during gestation.
Hence, the development of a normal uterus is a key element in optimizing one’s reproductive potential. The uterus is comprised of three main parts: the uterine corpus, isthmus, and cervix. The uterine corpus, or body of the uterus, consists of three main layers. The first layer and most internal layer, the endometrium, form the inner layer of the triangle-shaped uterine cavity. This layer consists of mucus secreting columnar epithelium.
The endometrium is under hormonal control in the reproductively active female and is divided into two phases of menses. During the proliferative phase, estrogen produced by the ovary promotes growth in the columnar epithelium, angiogenesis, and glandular development. The secretory phase, under the control of progesterone produced by the corpus luteum of the ovary post ovulation, is characterized by secretion of substances from the endometrial glands, to allow for an optimal implantation site for an embryo. If an embryo is not implanted, progesterone levels decrease and ultimately result in the breakdown of endometrium, resulting in menses.
The second layer of the uterine corpus is the myometrium. The myometrium contains smooth muscle that is responsible for the contractile activity of the uterus during labor and delivery. The third layer, and most outer layer of the uterine corpus, is the serosa and is equivalent to the peritoneum.
The isthmus is the most inferior part of the uterine corpus and is adjacent to the cervix, directly above the internal cervical. The cervix is the lowest part of the uterus, is approximately 4 cm. long, and connects the uterus to the vagina. The cervix allows transport of sperm into the uterus, passage of menstrual blood out of the uterus, and dilates and thins during labor to allow passage of the fetus. The uterus is highly vascularized to support the implanted embryo and growing fetus, and its main blood supply is the uterine artery. The uterine artery arises from the anterior division of the interior iliac artery.
A sequence of purposeful events occurs during the embryological development of the uterus, cervix, and vagina, both structurally and ultra-structurally, resulting in a normal-sized uterus, cervix, and vagina that is able to support implantation of the embryo and serve as the carrying vessel for the remainder of gestation until term. Any disruption prenatally along this programmed sequence of events can lead to an alteration in the structure and/or ultrastructure of the uterus, resulting in an array of congenital anomalies of uterus that may impact the ability to conceive and/or ability to carry a pregnancy to term. Post-natal, the uterus is also susceptible to a variety of acquired uterine lesions that may impair fertility and/or reproductive outcomes.
Congenital Anomalies of Uterus
In order to fully appreciate the anatomy of Müllerian disorders, also known as congenital anomalies of uterus, it is important to understand the embryological development of the uterus. There are a number of classification systems to describe the array of simple and complex congenital anomalies of uterus in existence. The most commonly used and widely accepted classification is the American Fertility Society (AFS) classification scheme. The AFS scheme characterizes its classifications of uterine anomalies based on the embryological development of the uterus.
The female reproductive tract is completely developed by approximately the 22nd week of pregnancy. It arises from the urogenital ridge and begins to develop at six weeks of gestation, giving rise to the paired para-mesonephric (Müllerian) ducts that eventually give rise to the fallopian tubes, uterus, cervix, and upper vagina. The development occurs in a particular scheduled series of events that include Müllerian duct elongation, fusion, canalization, and septal resorption. Any disruption in these events leads to what is known as congenital anomalies of uterus.
The AFS classification describes seven classes of congenital anomalies of uterus, Class I to Class VII, based on the stage at which the arrest of the embryological development of the Müllerian system occurred. These classes can be further grouped into three major categories: anomalies with underdevelopment of the Müllerian ducts, Classes I and II. Non-fusion anomalies of the Müllerian ducts, Classes III and IV; and non-resorption anomalies of the Müllerian ducts, Classes V and VI.
Fertility Implications of Congenital Anomalies of Uterus
The prevalence of congenital anomalies of uterus has historically been estimated to be approximately 1%. However, advances in diagnostic imaging modalities now estimate the prevalence to be closer to 5.5% in the general population. Further, if we look at women with recurrent pregnancy loss, the prevalence has been reported to be as high as 13%. Congenital anomalies of uterus can often go unrecognized because many of the women with these congenital anomalies of uterus have minimal to no symptoms and are often only detected during pregnancy or as part of an infertility workup.
What remains a conundrum is whether or not congenital anomalies of uterus has a negative impact on the reproductive potential of women and which, if any, treatment may be of benefit. Despite recent systematic reviews and meta-analysis, there remains a lack of sufficiently powered well-designed randomized controlled trials exploring surgical versus expectant management of congenital uterine anomalies with regard to optimizing reproductive potential.
The type of congenital anomalies of uterus dictate whether or not it is associated with a women’s inability to conceive and/or carry a pregnancy to term. Hence, an assessment of the uterine cavity is paramount in women presenting with infertility or recurrent pregnancy loss. Historically, the gold standard for making a diagnosis of any congenital anomalies of uterus is a diagnostic hysteroscopy and laparoscopy as it provides direct visualization of both the exterior and interior contours of the uterus. At present, radiological imaging has taken the lead in the diagnosis of congenital anomalies of uterus. The most commonly used imaging modalities include ultrasonography, sonohysterography or saline infusion sonography (SIS), hysterosalpingography (HSG), and magnetic resonance imaging (MRI).
One imaging modality may be more appropriate than another for a given congenital anomaly of uterus with the goal in mind being to identify surgically correctable from inoperable uterine anomalies. Overall, ultrasound is routinely used as the initial modality for the diagnosis of congenital uterine anomalies with an accuracy approximating 90%. Transvaginal sonography (TVUS) is superior to transabdominal, as it provides higher-resolution images, as the female reproductive organs lay low in the pelvis, and thus the vaginal transducer is closer to the structures to be imaged.
Further, three-dimensional (3D) ultrasound yields a greater degree of accuracy than two-dimensional (2D) ultrasound. However, MRI is overall considered clinically the gold standard imaging modality for the delineation of uterine anomalies as it can differentiate between surgically correctable from inoperable forms of uterine anomalies. The accuracy of MRI in the diagnosis of congenital uterine anomalies approaches 100%. MRI also has the added advantage of identifying renal anomalies commonly associated with certain classes of uterine anomalies that are overall seen in approximately 11-30% of congenital anomalies of uterus.
With MRI, T2-weighted sequences depict the classic inherent contrast for delineating the anatomy of the Müllerian system, and a single-shot, fast spin echo image with a larger field of view can also be obtained and enable visualization of the kidneys. Recent reports note that 3D sonography with saline infusion has a 100% accuracy when compared with laparoscopy and hysteroscopy for the diagnosis of septate, bicornuate, and arcuate uterus.
In addition, saline infusion sonogram with 3D ultrasonography has been shown to diagnose congenital anomalies of uterus with the same sensitivity and specificity and accuracy as a diagnostic hysteroscopy. The 3D technology allows for visualization of the coronal view of the uterus, which assists in accurate assessment of the uterine contour and degree of myometrial/septal indentation, if it is present. Swift advances in 3D/4D sonographic technology will soon be the new clinical imaging gold standard, if it is not already, for the diagnosis of congenital anomalies of uterus.
With any imaging modality, there are three key anatomical elements that need to be ascertained in order to assist in the accurate diagnosis of the class of congenital anomalies of uterus present:
Is the uterus present or absent, and if present, is it normal or smaller?
If the uterus is present, is the outer contour of the uterine fundus normal in configuration (convex)?
If the uterus displays an abnormal fundal contour, is the degree of myometrial/septal indentation into the uterine cavity less than or greater than 1 cm.?