Endometriosis And Fertility

Introduction

Gynaecological conditions may be quite perplexing, manifesting with troublesome symptoms and lacking a specific treatment option. One such example is endometriosis, a pathological condition that can affect women and people assigned female at birth (AFAB) of reproductive age. Endometriosis is described as a chronic inflammatory disease, where tissue, similar to the inner lining of the uterus (endometrium), grows outside the uterus, mostly developing on the peritoneum of the pelvis or the ovaries. Typical symptoms of endometriosis include pain and discomfort in the pelvic region, discomfort during menstruation, and pain during penetration. Unfortunately, endometriosis is frequently associated with infertility and high-risk pregnancy, although a precise explanation of this connection is still lacking, particularly in cases of minor endometriosis.¹

The global trend of endometriosis impacts approximately 10%, or around 190 million, people AFAB of reproductive age.² Additionally, online data suggests that 30%-50% of the affected individuals experience infertility, while 25%-50% of infertile individuals AFAB have endometriosis.³ 

With a better understanding, striking down taboos and myths surrounding this condition, and access to appropriate medical aid, e.g., in vitro fertilisation (IVF), symptoms can be alleviated and pregnancy can be rendered achievable.⁴ 

Understanding  endometriosis

Types and stages

Different types of endometriosis have been identified according to their location, characterised by specific pathophysiological features. These types include:⁵

• Superficial peritoneal endometriosis: lesions are mainly found on the peritoneum and can appear red, black, and white, indicating the grade of the disease. Red lesions are presented initially, followed by black lesions, found in advanced cases. White lesions are typically present after healed endometriosis
• Ovarian endometrioma: in this type of endometriosis, fluid-filled cysts are present, which are surrounded by endometrial epithelium and are located within the ovaries
• Deep filtrating endometriosis: lesions of this type of endometriosis involve distinct cell types, which allow the endometriosis to infiltrate deeply into tissues or organs, such as the vagina, bowel, intestines, and urinary bladder

Diverse classification systems have been proposed for categorising endometriosis according to its location, symptom severity, and association with infertility. The American Society for Reproductive Medicine has proposed one system, with a scoring method for lesion sizes in the peritoneum and ovaries. According to it, endometriosis can be categorised in:⁶

• Stage I: minimal endometriosis
• Stage II: mild endometriosis
• Stage III: moderate endometriosis
• Stage IV: severe endometriosis

Causes and development

Several assumptions have been stated, implicating genetic, environmental, and immunological factors, contributing to the development of endometriosis. However, the exact causes of this disorder remain enigmatic.¹

One theory involves retrograde menstruation, the backward flow of menstrual blood through the fallopian tubes into the pelvis, resulting in the attachment and growth of endometrial-like tissue outside the uterus. Moreover, genetic factors, including endometrial stem cells found in patients with endometriosis, may be responsible for ectopic lesions and contribute to anatomical changes in the peritoneal region.^1,7

Another theory for  endometriosis origin  revolves around cellular metaplasia, where cells deriving from the coelomic epithelium, which is present during embryonic development, are transformed into endometrial tissue in the peritoneal cavity. Furthermore, cells of Müllerian origin in the peritoneal cavity also seem to play a crucial role, as they can be stimulated to form endometrial tissue.⁸

Ultimately, it has been suggested that endometriosis can eventually spread to different sites in the body through the lymphatic and blood systems.⁸

Risk factors and symptoms

Several factors have been linked to increased risk of endometriosis, including:^1,9

• Early first period
• Short menstrual cycles
• High menstrual flow
• Family history of endometriosis
• Taller height with a low body mass index

Some symptoms of endometriosis include:¹⁰

• Pelvic pain
• Painful sex
• Infertility
• Constipation and/or diarrhoea
• Pain during defecation
• Severe period pain
• Heavy menstruation
• Fatigue
• Depression
• Pain during urination

Endometriosis and fertility concerns

The multidimensional character of endometriosis with its ambiguous aetiologies , along with delayed diagnosis, has been associated with lower fertility rates compared to individuals AFAB without the disease. The diagnosis of endometriosis may be delayed because of the  absence of typical lesions that may later require surgical intervention. Only half of the people AFAB with endometriosis and infertility exhibit evident lesions. While the relationship remains uncertain as to how endometriosis affects fertility outcomes, early diagnosis is pivotal for increasing the chances of pregnancy.

The pathophysiological mechanisms of endometriosis give rise to further concerns with fertility, however, more research is required to validate these findings. These processes include:¹¹

• Pelvic pain, discomfort, and pain during intercourse

These are some of the most obvious variables affecting fertility in individuals with endometriosis, which are often overlooked. It is only natural for the intensity of pain to negatively impact the sexual life of an affected individual, thus influencing not only fertility but also personal well-being

• Structural factors

Anatomically speaking, a pelvis with endometriosis may be characterised by abnormalities, adhesions, scar tissue, and general inflammation, which can influence the process of conception. These elements can interfere with the ability of the ovaries to function normally, affecting the maturation of follicles, sperm function and motility, and contact between the sperm and oocyte

• Ovarian reserve

Endometriosis, particularly when located in the ovaries, can have a negative impact in the ovarian reserve, meaning the capacity of the ovaries to provide egg cells suitable for fertilisation. The mechanisms underlying endometriosis-induced decline in ovarian function remain unclear. However, oxidative stress and inflammation caused by endometrioma are believed to directly alter ovarian function. The presence of scar tissue and its expansion may also lower the number of follicles, playing an important role in endometriosis infertility

• Impaired ovulation:

Hormonal irregularities, such as excess levels of prolactin, detected in individuals AFAB with endometriosis, as well as changes in oestrogen and progesterone levels, may lead to disturbances in the normal ovulation process

• Endometrial receptivity:

Embryo attachment is greatly dependent on endometrial receptivity, which can be undermined by endometriosis through deficient processes in the essential changes of the endometrium during pregnancy. This action may be responsible for decreasing implantation rates. Additionally, the extended inflammation of the endometrium and the hormonal and molecular dysregulation spotted in endometriosis may cause defects in embryo implantation

Treatment options for infertility in endometriosis

Individuals with endometriosis have been reported to have a fecundity rate (the total number of potential offspring) of 2% to 10%, with lower rates being observed in more severe cases of the disease. When no medical treatment is incorporated, the ability to conceive has been registered as 50% for individuals with mild endometriosis, while this score drops to 25% for moderate endometriosis. The availability of potential treatment plans for individuals AFAB who desire to get pregnant is crucial for improving outcomes of successful births. Each treatment plan should be individualised after careful consideration of factors such as age, ovarian reserve, infertility duration, stage, and previous surgical treatments. Some examples of current treatment approaches include:^3,11

• Surgical interventions

Operative laparoscopy may be performed to remove endometrial lesions, promoting in this way spontaneous pregnancy and life birth rates in stages I and II of endometriosis. However, the risk of ovarian damage and a decrease in ovarian reserve have been associated with this technique. Laparoscopy is primarily used before assisted reproduction, taking into consideration the endometriosis fertility index, a predictive tool used to estimate pregnancy outcomes

• Assisted reproductive techniques (ART)

Various methods, including intrauterine insemination, typically for minimal to mild cases of endometriosis, and IVF, for moderate to severe cases, may be used to positively affect fertility rates, although results are still debated

• Fertility preservation 

Individuals with endometriosis should seek reproductive counselling to analyse methods of fertility preservation, such as embryo or egg freezing

Summary

Endometriosis is an inflammatory condition affecting individuals AFAB of reproductive age. It is characterised by the presence of tissue resembling the endometrium, growing outside the uterus, resulting in severe pain. This tissue can grow in various locations, where it is not normally found, including the peritoneum, ovaries, bladder, intestines, and rectum. The location and the type of lesions give rise to the different types of endometriosis. A grading system ranging from stages I to IV has been proposed after identifying the severity of symptoms and lesions.

The location and type of lesions, and the severity of endometriosis, can strongly influence fertility outcomes. The ovarian reserve, ovulation, and endometrial receptivity can be affected by endometriosis, also causing anatomical changes in the reproductive organs and processes, resulting in endometriosis-related infertility. Specific treatment options, such as laparoscopy and ART seem to have positive outcomes in pregnancy and fecundity rates, with tailored approaches recommended for each case. 

If you are dealing with endometriosis and want to get pregnant, consult an experienced medical team to go through your options. Counselling with experts and exploring together the risks and fertility preservation options will aid in managing pregnancy with endometriosis.