What does müllerian mean and what causes these anomalies?

What does müllerian mean?
The uterus, fallopian tubes and upper vagina are made up of two partially fused tubes, which, in the embryo, are known as müllerian ducts, named for physiologist Johannes Peter Müller, who first described them in 1830. They are also known as the paramesonephric ducts, and are at first present in embryos of both sexes.

Normally, these ducts run down vertically from flank to pelvic floor in the young embryo and eventually fuse into a double-barreled tube with two loose ends, known as the uterovaginal primordium, or UVP. The double UVP will eventually merge into a single-barreled uterus, cervix and upper vagina, while the loose ends develop into the fallopian tubes. In adulthood, these organs are referred to as the müllerian tract and congenital malformations of this tract are called müllerian anomalies, or MAs.

In the male embryo, in the presence of anti-müllerian hormone (AMH), the müllerian structures disintegrate during early development. They persist in the female because she does not produce AMH.

In the embryo, the müllerian ducts act as scaffolding for the mesonephric ducts, which give rise to the kidneys. Because of this parallel structural relationship, it is common for a kidney or other urinary anomaly to be present with a müllerian anomaly.

What causes müllerian anomalies?
To date, there is no singular cause for müllerian anomalies. Some may be hereditary , others result from an insult to the fetus while in the womb (the T-shaped uterus of fetuses exposed to DES, for example), and still others may be attributed to random mutation. It is important to remember that in our grandmothers and mothers’ generations, many women with this problem were not diagnosed; while up to 4% of women may have a müllerian anomaly, it may be far more common than physicians realize. Only as diagnostic technology improves and women become more aware of their reproductive health will science get a better understanding as to how common these differences really are. In future years, our honest communication with our children will help build a larger base for understanding the causes of this uniqueness.

What are the different types of müllerian anomalies?

a. Agenesis & hypoplasia: Mayer-Rokitansky-Kuster-Hauser syndrome is most common. All or part of the müllerian tract fails to form, or is extremely underdeveloped. For example, a cervix may be a tissue-thin membrane rather than a tough, fibrous "donut" several centimeters thick. Most women suffering from agenesis or extreme hypoplasia have severe fertility problems, simply by lacking sufficient tissue to support a growing pregnancy. A common diagnosis used to be "infantile uterus," but it simply means a smaller-than-average uterus and does not refer to the MA described above. The old "infantile uterus" is typically capable of supporting a pregnancy very well, since a uterus easily grows during pregnancy. The "infantile" term has fallen by the wayside in recent years.

b. Unicornuate uterus (UU): When one müllerian duct is underdeveloped or fails to develop, a banana-shaped half-uterus is formed. It may or may not be accompanied by a rudimentary horn, and that other horn may or may not have an endometrial cavity or communicate with the main uterine cavity. A missing kidney or other kidney problems accompany this asymmetric anomaly more than they do other MAs. Frequently, the ovary on the rudimentary side is found in an odd place, further up by the ribs. Adverse pregnancy outcomes are common with UU. SEE FIGURE BELOW.

Unicornuate uterus

c. Uterus didelphys (UD): The müllerian tract fails to fuse along all or most of its length. There may be complete duplication of the vagina, cervix and uterus, and the two halves may be divided by a ligament of connective tissue. UD is reported to have the best pregnancy outcomes of all the MAs. SEE IMAGE BELOW.

Uterus didelphys

d. Bicornuate uterus (BU): The uterine fundus fails to fuse and a myometrial division extends down to the cervix in a complete bicornuate uterus, or part way to the cervix in a partial bicornuate uterus. The division is visible on the outside of the uterus, evidenced by a groove or cleft in the uterine dome exceeding 1.5 centimeters. Cervix and vagina are usually single but may be septate or duplicate. BU has relatively few pregnancy complications when compared to SU or UU, with breech presentation being one of the most common. SEE IMAGE BELOW.

Bicornuate uterus

e. Septate uterus (SU): The müllerian tract has fused properly and the uterus looks single from the outside, but the inner duct wall (i.e. the median septum) has failed to dissolve around 20 weeks of gestation, and the uterus retains a double cavity. There may or may not be a shallow groove of 1.5 centimeters or less on the outer uterine dome, and sometimes even a whitish triangle of tissue, the septum itself, is visible. The somewhat fibrous inner septum extends to the internal cervical opening or beyond in a complete septate uterus, and extends only part of the way down in a partial septate or subseptate uterus. The inadequate blood supply and progesterone receptors of the median septum may cause problems in pregnancy, giving the SU the worst pregnancy outcomes of all the MAs. SEE IMAGE BELOW.

Septate uterus

f. Arcuate uterus (AU): The fundus of the uterus may be indented slightly both inside and outside. This shape has been variously defined as slightly bicornuate and slightly septate (and may be either one), and is so slight that it is considered a variation of normal. However, a few studies suggest that increased incidence of adverse pregnancy outcomes are associated with an arcuate uterus.

g. DES-related uterus: A T-shaped uterine cavity, dilated horns and malformed cervix and upper vagina may characterize this anomaly. Unlike the other anomalies, a T-shaped uterus is sometimes caused by maternal ingestion of DES, although sometimes the cause is unknown. When caused by DES, there are often other problems, such as incompetent cervix, infertility and abnormal tissue in the cervix and vagina. DES use is associated with high rates of female cancers, including cancer of the vagina.

Diagnostic Methods

First of all, in an infertility work-up, a hysterosalpingogram (HSG) should be done to either rule out or assess the presence of a two-chambered uterus, the depth of the division, as well as tubal patency. But an HSG alone cannot differentiate between septate and bicornuate uterus. Misdiagnoses of BU by HSG are very common.
Other methods have better levels of reliability:

• Transvaginal ultrasound is nearly 100% successful in detecting a bifid uterus, but only 80% successful in differentiating between SU and BU. It can be a helpful tool in the diagnostic process, but should not be relied upon alone.
• Three-dimensional ultrasound (3DUS), is 92% accurate in differentiation of BU from SU, according to one 1997 study, but not widely available at the time of this writing. It should not be relied upon alone, with an 8% margin of error.
• MRI - According to two studies done in 1994 and 1995, MRI can reliably differentiate between BU from SU, with an accuracy of 100% in comparison with laparoscopy/hysteroscopy. More recent studies cast some doubt on this. Proceed with caution after an MRI.
• Concurrent laparoscopy and hysteroscopy are considered the "gold standard” of BU/SU differentiation. This test is invasive, but if needed, corrective hysteroscopic metroplasty can be done at the same time.