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Adenomyosis and Infertility

Anatomy of the uterus

To understand adenomyosis, it is necessary to understand that the uterus has different layers. The innermost layer, which lines the uterine cavity, is called the endometrium. An embryo implants in the cells of the endometrium. The endometrium is what is shed each month when a woman has a period. Moving outward, the next layer is composed of mostly muscle and is called the myometrium. The myometrium can be further divided into an inner layer which is also called the junctional zone (JZ) and an outer layer. The outermost layer of the uterus is a very thin covering called the serosa.
In normal women, the “dividing line” between the endometrium and the junctional zone (JZ) is clear and distinct. The JZ is thin.

Normal uterine layers

Adenomyosis

Adenomyosis is a poorly understood condition. Scientists and physicians are not certain what causes it to develop or the best way to treat it. Women with adenomyosis will sometimes have symptoms such as pelvic pain, pain with periods, irregular bleeding or heavy periods but sometimes they do not. It is uncertain whether women with adenomyosis are more likely to have infertility . More on that below.
Even describing adenomyosis is difficult. In milder cases, the only abnormality may be a thickened junctional zone. This thickening can be spread out all over the uterus (diffuse) or located in one spot (focal). In more advanced cases, there are areas where the endometrium has crossed the dividing line which normally separates it from the junctional zone. In the most severe cases, there are “islands of endometrial tissue in the muscle layer which form cysts in the uterus.
Previously, adenomyosis was only diagnosed after a woman had her uterus removed (hysterectomy) and inspected under a microscope. Today, there are two techniques that be used to help identify women with adenomyosis: transvaginal ultrasound  and magnetic resonance imaging (MRI). Even with these excellent new tools, the diagnosis of adenomyosis remains difficult.
Criteria used to make a diagnosis of adenomyosis on transvaginal ultrasound are as follows:
1) a globular or bulky uterus
2) poor definition of the dividing line between the  endometrium and the muscle portion of the uterus (myometrium)
3) thickening of the muscle portion of the uterus (myometrium)especially if
a) it is thicker on one side compared to another (asymmetry)
b) the junctional zone can be measured and is thicker than 10 or 12 mm
4) Cysts in the muscle portion of the uterus (myometrium)
5) Different appearance of the texture of the muscle portion of the uterus (myometrium)
6) Increased blood flow in the junctional zone

Ultrasound features of adenomyosisAdenomyosis on ultrasoundMyometrial cyst in adenomyosis

Image credits: Michelle L. Stalnaker, MD, and Andrew M. Kaunitz, MD OBG Manag. 2014;26(6)

Adenomyosis and infertility

It is uncertain whether adenomyosis is a cause for infertility in women. There are few studies on the topic and even fewer good studies. One of the reasons why it has been difficult to determine whether adenomyosis is a cause for infertility is due to the fact that many women with adenomyosis also have another problem called endometriosis which is well known to cause infertility. Studies have estimated that of women with endometriosis, anywhere from 27% to 70% of those women may also have adenomyosis. The large range is due to differences in how adenomyosis is diagnosed (ultrasound vs MRI versus surgical removal of the uterus) and the criteria used to make the diagnosis.
There are several reasons to suspect that adenomyosis could be a cause for infertility. The first has to do with uterine contractions. Some uterine contractions are good. There are uterus and fallopian tube contractions that help sperm to reach the egg in the fallopian tube. It seems that adenomyosis disrupts these good contraction. Later, at the time of embryo implantation, too many uterine contractions are bad. Adenomyosis may actually increase these bad contractions. The final reason is very complex. Whatever factors are responsible for the development of adenomyosis may simply make the uterus less able to allow embryos to implant.
In vitro fertilization is one of the best treatments for infertility that we have. Several studies have been performed to try to determine whether adenomyosis affects in vitro fertilization pregnancy rates. In 2013, an analysis in which all of these studies were combined suggested that adenomyosis reduces the chance for pregnancy and increases the risk for miscarriage. Of particular interest was a study that looked at women using egg donation  instead of their own eggs. Using donated eggs ensures that all the women had good egg quality. Any difference in the pregnancy rate is more likely to be due to problems with the uterus. This study found that women with adenomyosis had double the risk of miscarriage. Remember, that the quality of these studies and their ability to rule out other causes of infertility (like endometriosis) are poor.

Treatment of adenomyosis to improve fertility

If we are not even sure that adenomyosis causes infertility then how can we be sure that treatment of adenomyosis will improve fertility. The answer is – we aren’t sure. Until better studies are performed, the treatment of adenomyosis to treat infertility should be considered experimental.

Surgery for adenomyosis and infertility

 This is certainly the most invasive and the riskiest option. Some cases in which portions of the uterus with focal or nodular adenomyosis are removed and then resulted in pregnancy have been reported. These are difficult surgeries to perform because adenomyosis does not have distinct borders that distinguish normal uterus from the adenomyosis some precise removal is challenging. This is obviously not an option for diffuse adenomyosis.

Medications for adenomyosis and infertility

GnRH agonists (Lupron) which are commonly used to treatment endometriosis by lowering estrogen levels have been used to treat adenomyosis as well with some reported pregnancies. Aromatase inhibitors such as Letrozole also lower estrogen levels and have also been reported in the treatment of adenomyosis.
Some scientists have identified that the junctional zone in women with adenomyosis may grow blood vessels more readily that other women. This is called angiogenesis. Angiogenesis is complex but one factor which drives the growth of new blood vessels is a hormone called VEGF. Therefore, a possible treatment to improve fertility in adenomyosis could be to reduce the action of VEGF in the uterus. One medication that does this is called cabergoline.  Fertility doctors are very familiar with the use of cabergoline since it is more commonly used to treat women with high prolactin levels. Another medication that may block the action of VEGF is called pentoxiphylline which is commonly used to improve blood flow in in patients with circulation problems. Pentoxiphylline has been studied as a treatment for endometriosis but so far has failed to be of proven benefit.