Endometriosis is a disease that affects approximately 10% of all reproductive-aged women and the prevalence rises to 20–50% in infertile women. Endometriosis is notorious for causing such problems as severe pelvic pain, menstrual cramps and pain with intercourse. It is also associated with irritable bowel syndrome, hormonal dysfunctions and an increased risk of a variety of cancers.
In endometriosis the tissue that normally covers the inside of the womb grows outside of it, usually on neighbouring organs in the lower abdomen. The tissue continues to thicken and shed outside the uterus and causes local irritation eventually causing the development of scar tissue where internal organs and tissues stick together as adhesions develop. Endometriosis may proliferate and invade other tissues due to a loss of control of growth and proliferation.
Endometriosis could affect fertility in patients at multiple levels:
- anatomic distortion with scar tissue, adhesion
- alteration of oocyte quality due to high levels of inflammatory factors and ROS
- poor embryo development due to altered mitochondrial function and disrupted meiosis process
- peritoneal inflammation that can disrupt the endometrial receptivity and lead to miscarriage
- diminished ovarian reserve
A host of cells and their products, ranging from cytokines to growth factors, all contribute to the progression of endometriosis and associated infertility. High levels of inflammatory factors and poor regulation of oxidative stress and the resulting reactive oxidative species seen in endometriosis exert dramatic effects on oocyte/ embryo quality and cause immune changes in the uterine environment that in many cases leads to implantation failure.
The problem is most women do not even discover they have endometriosis until they undergo diagnostic laparoscopy to determine the cause of their infertility.
In cases of severe endometriosis and distorted pelvic anatomy, the mechanism of infertility is easily explained and the risk of infertility is high. In mild endometriosis with infertility, the altered intrafollicular and endometrial cytokine milieu may explain the poor quality oocytes and the lower capacity of resulting embryos to implant in the uterus. In the case of ‘silent’ endometriosis getting a diagnosis is difficult and unexplained infertility is likely. IVF outcome is poor with endometriosis.
A recent review article summarizes the potential causative factors of endometriosis in the following three categories:
- dysregulation of immune cells in the peritoneal fluid and endometriotic lesions
- alteration of apoptotic signalling in retrograde menstrual tissue and cytotoxic T cells involved in endometriosis progression and
- dysregulation of oxidative stress.
Endometriosis is an inflammatory and immune disease in nature and is possibly a systemic condition, not just a reproductive disorder. As can be seen, immune dysfunction is prominent and recently there has been a debate concerning whether it is an autoimmune disease. Endometriosis creates a noxious environment in the whole peritoneal cavity with pro-inflammatory cytokines being increased in the serum. Recent research demonstrates the microflora changes and their influences on endometrial proliferation.
Traditionally endometriosis is treated either surgically or medically.
Hormonal treatments have been offered as the front-line treatment of endometriosis. These act as artificial suppressants of the reproductive system, which gives symptomatic relief along with a long litany of side effects. Current systemic oestrogen blocking therapy using gonadotropin-releasing hormone agonists, oral contraceptives, synthetic progestins and/or aromatase inhibitors which block the production of oestrogen either put the woman into an artificial menopausal state or an artificial pregnancy state. Thus there are many unresolved side effects of treatment, including adverse consequences for normal reproductive function.
The surgical approach, if expertly done, is generally more effective in providing relief from pain and for future fertility purposes. However, surgical procedures always have innate risks and scarring and adhesions can be caused as a result of the surgical procedure itself and even with treatments, there is some rate of recurrence with the disease.
Alternative treatment strategies with higher efficacy and fewer side effects and with positive pregnancy outcomes are more desirable.