Arcuate Uterus associated with Endometriosis Pain and Infertility

Overview

Uterine anomalies play an understated role in the common perception of endometriosis. While they often have been associated with infertility cases, they also can have an effect in the development of endometriosis. In fact, in our own clinical setting, we have found that 38% of our patients who had a mild form of uterine structure abnormality, specifically arcuate uterus upon hysteroscopic evaluation, tested positive for endometriosis. This is significant to note as less than 5% of the females on average have been found to have arcuate uterus upon hysteroscopic evaluation. This means that patients with endometriosis, have a statistically significant higher chance of having an arcuate uterus in comparison to the general population. For these reasons, we think it is highly important to shed some light on uterine malformations and the impact that they can have on endometriosis patients.

What is a uterine anomaly?

Uterine anomalies, also known as uterine malformations, are female genital malformations that often result from abnormal development. They can result in physical mishappening of the uterus or more subtle abnormalities within the uterine cavity. Some of these differences have been found to be associated with such conditions as pelvic pain, infertility, and even endometriosis.

Different forms of uterine anomalies?

Malformations of the uterus can take on a number of different forms, ranging from major uterine cavity physical changes to more subtle abnormalities. In a 2011 observational study conducted by Chan et al [ 1 ], 94 patients with abnormal uteri (5.5% of the total population of patients), were studied in order to determine some of the most common forms of anomalies. The findings included the following:

• Arcuate uterus - This term has been classically difficult to define but represents a mild form of a septal uterus. In it, the myometrium of the fundus (the top portion of the uterus, opposite of the cervix), dips inward into the uterine cavity, possibly causing a small septation. This division is part of the reason why arcuate uterus is so challenging to define, as it can difficult to discern this from the more pronounced septate uterus.Infact in Europe, the term “arcuate uterus” is not even made, as all of these uteri either fall under the category of a normal or septate uterus. However, when defined separately from the septate uterus by having a midline prominence of 1.5cm or less, thearcuate  uterus was found to make up 70% of uterine abnormalities. While, it does not have any obstetrical implications, meaning it has not been found to have an association with infertility or miscarriages, it has shown some correlations with other gynecological diseases, such as endometriosis. For this reason, it can be highly beneficial to separate arcuate uterus as a subcategory of a septate uterus.

  

• Septate uterus - A malformation in which the uterine cavity is divided by a septum protruding from the fundus, but keeps the normal outer shape intact. The debate often arises on where to separate the distinction between arcuate and septate uterus. Recent studies have shown though, that septate uterus is less common in patients without a history of infertility in comparison to the more subtle form that is the arcuate uterus. [ 2 ] In other words, a septate uterus is a common anomaly in women with a history of miscarriages and infertility, which was found in over 15% of women in the study. There are also rare instances in which this septum completely divides the uterine cavity and cervix into two halves, termed uterine didelphis (double uterus).
• Bicornuate Uterus - Bicornuate uterus is a uterine duplication anomaly caused by a partial failure of fusion of the Müllerian ducts (connection between the uterine cavity and fallopian tubes). It accounts for approximately 25% of congenital uterine anomalies. It is characterized by an outer fundal cleft that is greater than 1cm and a wide intercornual (tube) distance that can be appreciated via hysteroscopy, as well as laparoscopy. A bicornuate uterus cannot be treated with simple resection and surgical intervention is not necessarily indicated. Nevertheless, it is associated with a risk of recurrent pregnancy loss, cervical incompetence, and possible cerclage placement. The hysteroscope can be used to explore the two uterine horns and appreciate the depth and angle of the two horns. Surgical correction can be performed in cases of reproductive failure but is best handled by a reproductive specialist.
• Unicornuate uterus - This form of uterine anomaly is also known as a “one-sided uterus.” In it the uterus is blocked from one side, closing of one of the two Müllerian ducts. This abnormality takes up a “banana shape” upon imaging tests and has been shown to significant effects for infertility cases, which includes a greater risk of miscarriage, preterm delivery and in some cases ectopic pregnancy. [ 3 ]
• Müllerian agenesis - Under developments or complete absence of the uterus, this uterine anomaly is known as Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome. While rare, it has tremendous impacts on the reproductive system as patients are usually infertile and lack a menstrual period due to the absence of the uterus.

What can uterine anomalies cause?

The effects of uterine anomalies can vary from patient to patient. One common complication that structure anomaly can lead to is painful peristalsis (dysperistalsis) and abnormal outflow of menstrual debris, thereby potentially increasing reflux of retrograde flow that can participate in endometriosis development. While some normal menstrual flow is expelled out of the uterus, retrograde reflux blood and debris can move into the fallopian tubes and pool into the pelvic cavity and peritoneum, leading to endometriosis development.

How can uterine anomalies be observed?

Hysteroscopy: Hysteroscopic evaluation is very important when a patient receives laparoscopic evaluation and surgery. It uses a hysteroscope (camera) to visualize the uterine cavity by inserting the device vaginally. Using this imaging technique, a trained surgeon is able to identify any uterine anomalies, including the arcuate uterus, septal uterus, etc. This procedure is a crucial part of any thorough gynecological surgery performed in the operating room in order to assess whether or not a septum appears within the uterine cavity, and if so the extent of such. Thus a hysteroscopy should be accompanied by any laparoscopic surgery for endometriosis.

MRI: Magnetic resonance imaging (MRI) is a preoperative medical imaging technique used in radiology to form pictures of the inner anatomy and organs. Using magnetic fields and radio waves, an MRI is able to make out abnormal intrauterine structures, which bodes highly useful in presumptively diagnosing a believed form of uterine anomaly. [4]

Endometriosis and Uterine Anomalies

How is endometriosis connected to uterine anomalies?

Both obstructive and nonobstructive uterine anomalies have been associated with endometriosis. One common explanation for this relationship is due to the abnormal menstrual flow associated with these uterine anomalies. Reverse peristalsis occurs so sperm can swim upstream and travel into the fallopian tubes and combine with an egg. This ability is believed to be driven by coordinated contractions of uterine muscular fibers, which could possibly have differential activation. In cases of uterine abnormalities, retrograde menstrual debris can take advantage of this pathway and move backward into the fallopian tubes, ovaries, peritoneum and pelvic cavity. All of these areas are common sites for the endometrial tissue, stem cells and inflammatory enzymes contained within this reflux debris, to latch onto and eventually develop into endometriosis lesions. Therefore, uterine anomalies can pose as another suspected cause of endometriosis, secondary to retrograde menstruation.

Endometriosis connection to arcuate uterus?

While arcuate uterus is often considered a normal anatomical variation with questionable reproductive repercussions, it must be recognized as a pathological finding in endometriosis patients. In fact, our studies have shown abnormal arcuate architecture and its subtle forms are associated with increased prevalence of both peritoneal and advanced endometriosis. Thus what arcuate uterus means for an obstetric patient (infertility case) is different than that for the endometriosis patient. Continued testing and identification of arcuate uterus, is thus important for endometriosis patients, as potential resection of midline prominence may be a significant step for treatment of endometriosis patients.

Our Approach

How do we assess uterine abnormalities?

We at the Seckin Endometriosis Center feel that is crucial to assess the uterine structure and function of each patient that comes in for surgery. Thus we conducted a hysteroscopy on all of our patients that come in for surgery. This is needed to assess if there are any uterine abnormalities, which we have found could be associated with endometriosis. On top of this, we advise our patients to receive an MRI pre-surgery, so that we can get a presumptive understanding of the uterus structure.

How do we define and assess arcuate uterus?

As discussed earlier, an arcuate uterus is the mildest form of a septal uterus. While it is considered a normal variation from an obstetrical standpoint, we have found it to be a much more common anomaly in our endometriosis patients. For these reasons, it is highly important to make the distinction of arcuate versus septal uteruses. As known, sub-distinction between the two abnormalities comes in the differing length of midline protuberance, which we cut off at 1.5cm. However, we believe that these anomalies should also be defined in a more continuous definition, in terms of midline defect or degree of “arcuateness” (ranging from mild to severe).

We always look to assess to assess these anomalies and this distinction in our surgeries through the use of hysteroscopy. During this procedure, we look to surgically identify arcuate uterus through four key criteria points: midline prominence, vertical stria, bilateral cornual funneling and dilation of tubal ostia. The first criteria point is seeing whether or not a septum exists by evaluating midline prominence. We then look to identify any vertical stria, which are stretch marks that can exist when the uterus is misshapen, such as when the fundus concaves inward. The next key component to evaluate is the Müllerian ducts, which is a common site for abnormalities to take place in arcuate uteruses due to abnormal development during embryogenesis (embryo development). Here, we look to examine if there is proper cornual funneling of the uterus into the fallopian tubes on both sides. We also look to make sure there is proper dilation of the tubal ostia, which is the proper widening of the tubes themselves. In cases of an arcuate uterus, sometimes the funneling of these tubes can come earlier and narrower due to the minor septum formed within the uterine cavity. Thus these are all important factors to take into account when assessing the uterus for any structural abnormalities during a hysteroscopy.

Our data on uterine abnormalities

Based on the many hysteroscopies we have performed, our clinical research data has shown that our endometriosis patients are commonly prone to having uterine abnormalities, specifically arcuate uterus. Of the 260 hysteroscopies we performed from 2015-2016, 100 (38%) showed arcuate uterus and minor variations, while the other 160 (62%) patients had a normal uterine cavity. This is a notable similarity of what was found in a study by LaMonica et. All, which showed 37% of endometriosis patients as having arcuate uterus upon laparoscopic and hysteroscopic procedures. While this is, in fact, is not a majority, it is significant to note as an arcuate uterus is reported to be in less than 5% of females according to recent studies. Of these 100 patients that had an arcuate uterus, nearly 60% of their excision specimens came back positive for endometriosis on average. The remaining specimens showed inflammation and fibrosis.

On top of this, 39 cases of endometrioma came back as positive out of the 100 patients (39%) with an arcuate uterus, whereas only 38 out of 160 normal (24%) uterine cases of endometrioma were positive.This is important to note as this means that uterine anomalies brought a 1.76 fold more incidence of ovarian endometrioma than those with a normal uterus. These endometriomas, in turn, can lead to further development of endometriosis to the point of stage 3 or 4 deep infiltrating endometriosis.

Thus it was found that patients with an arcuate uterine cavity have a statistically significant higher number of positive endometriosis and endometrioma specimens per case than the average normal uterus patient. This was shown to be true in cases of endometrioma, and can therefore very well be assumed to have an impact on more severe cases of deep infiltrating uterus. All of this is crucial to note as it shows that what arcuate uterus means for the obstetric patient, appears to be different than for cases of endometriosis. Therefore, identification of arcuate uterus through hysteroscopy is important for endometriosis patients. It also possesses the thought that potential resection of midline prominence may be a significant step for surgical treatment of endometriosis patients.

At the Seckin Endometriosis Center, we take great care in understanding our patients, both from a surgical perspective and personal. Endometriosis patients are some of the strongest women around, and they, therefore deserve the strongest care. We take great pride in assuring that no stone goes unturned in your case and assessing uterine abnormalities and their possible effects on your case are no exception.

REFERENCES

1. Chan Y, Jayaprakasan K, Zamora J, Thornton J, Raine-Fenning N, Coomarasamy A. “The Prevalence of Congenital Uterine Anomalies in Unselected and High-Risk Populations: A Systematic Review.” Hum Reprod Update. 2011;17(6):761-771
2. Woelfer B, Salim R, Banerjee S, Elson J, Regan L, Jurkovic D. “Reproductive Outcomes in Women with Congenital Uterine Anomalies Detected by Three-Dimensional Ultrasound Screening.” Obstet Gynecol. 2001;98(6): 1099-1103.
3. Reichman, David; Laufer, Marc R.; Robinson, Barrett K. (2009). "Pregnancy outcomes in unicornuate uteri: A review". Fertility and Sterility. 91 (5): 1886–94. doi:10.1016/j.fertnstert.2008.02.163. PMID 18439594.
4. Leyendecker G, Kunz G, Wildt L, Beil D, Deininger H. “Uterine Hyperperistalsis and Dysperistalsis as Dysfunctions of the Mechanism of Rapid Sperm Transport in Women with Endometriosis and Infertility.” Human Reprod. 1996;11(7):1542-1551.
5. LaMonica R, Pinto J, Luciano D, Lyapis A, Luciano A. “Incidence of Septate Uterus in Reproductive-Aged Women with and Without Endometriosis.” J Minim Invasive Gynecol. 2016;23(4):610-613.