Endometriosis and its link to fertility

By Katherine Bethell 

Endometriosis is a condition that affects up to 15% of all women and is the most common cause of chronic pelvic pain (Parasar P et al., 2017). It is a condition characterised by oestrogen-dependent inflammation which affects pelvic tissue, commonly occurring in teenagers and young adults as they begin menstruating (Vercellini P et al., 2014). Not only does endometriosis cause chronic pain but it is also often associated with infertility (Bulun S et al., 2019). This review will explore the pathologic mechanisms of endometriosis and how it can result in fertility problems, whilst also investigating potential treatments. 

The definition of endometriosis is the presence of endometrial tissue, an inner epithelial layer, outside of the uterine cavity where it is normally found. There are several different types of endometriosis which are likely to have different pathogenic causes, however the most widely supported is called the retrograde menstruation phenomenon. This occurs when the endometrial tissue is shed, which occurs during menstruation, and fragments of it move through the fallopian tubes and reach the peritoneal cavity. Here, the fragments can implant, establish a blood supply to grow and invade pelvic structures including the bladder, parametria and anterior rectal wall resulting in chronic pain (Vercellini P et al., 2014) (Macer M and Taylor H, 2012). There are several factors which can contribute to endometriosis development including a young age at the beginning of menstruation, short menstrual cycles, increased alcohol intake and a family history. Whilst biologically increased expression of oestrogen receptors (ERβ) also increases the likelihood of developing endometriosis as oestrogen increases growth of endometrial fragments present outside of the uterus (Vercellini P et al., 2014). 

Endometriosis has been shown to adversely impact fertility, with up to 50% of patients infertile (Bulletti C et al., 2010). There are several mechanisms which result in endometriosis reducing fertility. The chronic inflammation caused by endometriosis can increase the number of inflammatory immune cells activated. A high number of activated macrophages, immune cells which digest foreign material, may reduce the number of sperm whilst inflammatory cells in the peritoneal fluid can have toxic effects to both oocytes and embryos. Hence reducing the viability of embryos in women suffering from endometriosis (Macer M and Taylor H, 2012). Inflammation caused by endometriosis also results in impaired fallopian tube function which prevents transport of gametes and implantation of the embryo. In addition, genes which are abnormally expressed in the endometrium of patients with endometriosis may prevent implantation of the embryo and hence contribute to infertility; however, the exact pathway this occurs by remains unknown and more research needs to be undertaken to explore this (Macer M and Taylor H, 2012). 

A diagnosis of endometriosis is often delayed, with women waiting an average of 6.7 years after the onset of symptoms. This is likely due to a lack of non-invasive and consistent biomarkers for endometriosis, making diagnosis difficult; surgery or laparoscopic visualisation is often used to detect endometrial tissue outside the uterus, but these invasive procedures are not used for the majority of women suspected of endometriosis (Parasar P et al., 2017) (Bulun S et al., 2019). Instead, diagnosis is more patient focused with greater importance placed on the symptoms of endometriosis such as painful periods, cycles of chronic pain, uninterrupted episodes of ovulation, heavy periods, and painful sexual intercourse (Bulun S et al., 2019).

The treatments currently available are aimed at relieving symptoms and not correcting the pathological causes. For example, combined oral contraceptives are used to alleviate pain symptoms as they suppress ovarian function but are not curative (Ferrero S and Evangelisti G, 2018). Surgery which involves removing the endometrial lesions found in the pelvic region may help to enhance fertility potential but is also associated with high recurrence rates of endometriosis (Vercellini P et al., 2014). Hence, it may be more efficient to look into assisted reproductive technologies to aid infertility rather than going through surgery to then develop endometriosis again several years later. One of the most promising drugs currently in research are gonadotropin-releasing hormone antagonists which suppress the release of pituitary and ovarian hormones, including oestrogen. (Ferrero S and Barra F, 2018). These hormones are responsible for promoting the growth of endometrial tissue fragments outside of the uterus and causing endometriosis symptoms, hence gonadotropin-releasing hormone antagonists help to prevent the cause of chronic pelvic pain experienced by women.  

To conclude, endometriosis is a chronic inflammatory condition caused when endometrial tissue moves from the uterus to the peritoneal cavity and abnormally grows on pelvic structures. It can cause pain through activation of inflammatory immune cells. This is also the reason why it leads to high levels of infertility as the activated immune system creates a toxic environment for both gametes and embryos, preventing successful fertilisation and implantation. Diagnosis takes a long time as it is reliant on surgery or laparoscopy, however based on symptoms experienced a preliminary diagnosis may be given. Treatment is largely aimed at helping alleviate symptoms and the chronic pain caused by inflammation, this is usually done through medication including combined oral contraceptives, as surgery is largely not successful resulting in recurrence of endometriosis later. 

References: 

Parasar P, Ozcan P, Terry KL. Endometriosis: Epidemiology, Diagnosis and Clinical Management. Curr Obstet Gynecol Rep. 2017;6(1):34-41. Available from: doi:10.1007/s13669-017-0187-1

Vercellini, P., Viganò, P., Somigliana, E. et al. Endometriosis: pathogenesis and treatment. Nat Rev Endocrinol. 2014; 10: 261–275. Available from: doi: 10.1038/nrendo.2013.255

Bulun SE, Yilmaz BD, Sison C, et al. Endometriosis. Endocr Rev. 2019;40(4):1048-1079. Available from: doi:10.1210/er.2018-00242

Macer M, Taylor H. Endometriosis and infertility: a review of the pathogenesis and treatment of endometriosis-associated infertility. Obstet Gynecol Clin North Am. 2012;39(4):535-549. Available from: doi:10.1016/j.ogc.2012.10.002

Bulletti C, Coccia M, Battistoni S, Borini A. Endometriosis and infertility. J Assist Reprod Genet. 2010;27(8):441-447. Available from: doi:10.1007/s10815-010-9436-1

Ferrero S, Evangelisti G. Current and emerging treatment options for endometriosis. Expert Opinion on Pharmacotherapy. 2018; 19(10): 1109-1125. Available from: doi: 10.1080/14656566.2018.1494154 

Ferrero S, Barra F. Current and Emerging Therapeutics for the Management of Endometriosis. Drugs. 2018; 78: 995–1012. Available from: https://doi.org/10.1007/s40265-018-0928-0

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Google photo

You are commenting using your Google account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s