Endometriosis
What is it?
Endometriosis is a benign estrogen-dependent disease characterized by the presence of ectopic endometrial tissue. Endometriosis is a common gynecological condition that effects 10-15% of women of reproductive age. The cells of the endometrium (inner lining of the uterus) “migrate” outside the uterus, to the adjacent organs, and continue to follow the hormonal alterations of the endometrium during the normal menstrual cycle. They may be located in the ovaries, fallopian tubes, intestine or bladder and more rarely in the vagina or cervix, irritating organs and causing chronic pelvic pain.
Pathogenesis
The pathogenesis of endometriosis is still unknown, but there are some dominant theories that support the reason for its occurrence. Menstrual reflux through the fallopian tubes, immunological disorders, the differentiation of peritoneal cells into endometrial cells are just some of them. Recent research has implicated stem cells and genetic predisposition. We already know that women with a family history of endometriosis are 6 times more likely to develop the disease than the general population.
What are the symptoms of endometriosis?
The symptoms of endometriosis vary, but they may not be present. The main symptoms of endometriosis are:
• pelvic pain that usually worsens during the menstrual cycle
• menstrual pain that limits daily activities
• pain during or after sexual intercourse
• pain when urinating
• discomfort, constipation
• infertility
Endometriosis and infertility
Endometriosis occurs in 25-50% of infertile women and in 30-50% of women with endometriosis are presented with primary or secondary infertility.
The chances of infertility in any woman with endometriosis are directly related to the severity of endometriosis. The main mechanisms that affect fertility are inflammation from the ectopic endometrial tissue in the various organs of the pelvis and the formation of abnormal connective tissue (adhesions). The adhesions and the inflammatory reaction caused by the foci of endometriosis, disrupt the anatomy of the pelvis by attaching neighboring organs, mechanically obstructing the release of the egg during ovulation, affecting the motility of sperm, causing abnormal uterine contractions and it has an adverse impact in the fertilization and the implantation of the created embryo.
1. Effect on gametes and the fetus
In women with endometriosis the physiology of the ovulation and the quality of the oocyte released can be compromised. This is due to the presence of inflammatory cells in the free intraperitoneal fluid or the presence of endometriomas, which are cysts that result from the presence of endometrial cells in the ovarian tissue.
Sperm quality and functionality are affected by the inflammatory and toxic effects of the intraperitoneal fluid and the increased macrophage expression as the result of the body’s immune response to the existing inflammation. The same toxic effects seem to affect the implantation of the fetus.
2. Effect on the fallopian tubes and fetal transport
The transport of gametes (sperm and egg) through the fallopian tubes is affected by the production of cytokines, due to inflammation, as well as by the creation of scar tissue which disrupts the motility and proper functioning of the fallopian tubes. Abnormal contractions of the myometrium, which occur in the case of endometriosis, also disrupt gamete transfer and embryo implantation.
3. Effect on endometrial receptivity
Many genes and micromolecular substances that are responsible for the endometrial receptivity are not normally expressed in women with endometriosis. However, the mechanism by which the expression of these genes changes is not fully understood. For example, aromatase, the enzyme that converts androstenedione and testosterone to estrone and estradiol (estrogen), is found in the endometrium of women with endometriosis, which under normal conditions is absent, resulting in increased estrogen production. Increased estrogen production in the endometrium can affect both its development and its receptivity during implantation of the fetus.
Progesterone resistance and disruption of its receptors in the endometrium of women with endometriosis also seem to play an important role in fetal implantation failure. Progesterone is produced during the 2nd phase (luteal) of the menstrual cycle by promoting the growth of blood vessels and enhancing changes that prepare the endometrium for the implantation of the fetus. It seems that progesterone receptors in women with endometriosis are not suppressed in time before implantation, as it should be, while at the same time the endometrium seems to resist to progesterone creating an environment of hyperestrogenemia, which negatively affects the implantation process.
Treatment options in case of infertility
The choice of treatment in the case of endometriosis combined with infertility is an individualized choice based on the special characteristics of each case.
The decision is made by evaluating many factors and mainly by taking into account the preservation of the pelvic anatomy, the maintenance of the ovarian reserve, the partner’s sperm sample, the presence of endometriomas and the duration of infertility. In addition, it depends on the medical history and the age of the woman, the symptoms and the degree of endometriosis. It can be managed conservatively by monitoring or more invasively by removing laparoscopically the endometriosis foci and using artificial reproductive technology (IVF) in order to achieve the desired pregnancy. The suspicion of mild or moderate endometriosis with asymptomatic onset does not appear to require surgery, especially in women under 35 years of age, while, in most cases, these women conceive without IVF. In fact, recent studies have shown that the effect of IVF in women who have been treated conservatively is no different from those who underwent surgery for the removal of endometriosis foci before undergoing IVF treatment. In the case of severe endometriosis and infertility with persistent pelvic pain that does not respond to the use of regular analgesia, surgical removal of endometriosis foci and in vitro fertilization are often unavoidable options for the gynecologist and the infertile couple.
