How Endometriosis Contributes to Infertility

Endometriosis and Fertility: Essential Insights

Endometriosis is a complex and often misunderstood condition that can substantially affect fertility. Gaining clarity on how it develops, why it occurs, and the ways it can influence conception is important for identifying effective treatment strategies.

What Is Endometriosis?

Endometriosis is a benign, estrogen-dependent disorder that affects approximately one in ten cisgender women during their reproductive years. It may also affect transgender men, where the condition may be present at a higher percentage. Although cases have been reported in cisgender men, they are exceedingly rare. The discussion of fertility here focuses on impacts involving the uterus, Fallopian tubes, and ovaries.

The condition is defined by the presence of endometrial-like tissue outside the uterus. These implants are often located within the pelvis—on the ovaries, fallopian tubes, and the outer surface of the uterus—though in some instances they extend beyond the pelvic region. While an estimated 10–15% of cisgender women of reproductive age are affected, endometriosis is even more prevalent among those facing infertility, occurring in up to 25%–50% of this group. The underlying cause remains under investigation, and its impact on fertility is multifactorial and complex.

How Endometriosis Develops: Leading Theories

Multiple theories aim to explain the pathogenesis of endometriosis, reflecting the complexity of the condition and its varied presentation.

Retrograde Menstruation

The oldest and most widely known theory suggests that menstrual blood containing endometrial cells flows backward through the fallopian tubes into the pelvic cavity. These cells then attach to peritoneal surfaces, proliferate, and form endometriosis implants.

Coelomic Metaplasia and Metastatic Spread

Another perspective posits that cells in the peritoneum can transform into endometrial cells, a process called coelomic metaplasia. A separate but related hypothesis proposes that endometrial tissue spreads via the bloodstream or lymphatic system to distant sites, accounting for implants found outside the pelvis.

Altered Immunity

A further theory proposes that individuals with endometriosis may have immune system alterations that fail to clear endometrial cells from the peritoneal cavity. This immune dysfunction may also facilitate disease progression by promoting the survival and growth of implants.

Stem Cells and Genetics

Emerging research points to the involvement of stem cells and genetic predisposition. Bone marrow–derived stem cells may differentiate into endometriosis cells, contributing to ectopic endometrial-like tissue. Genetics also appear to play a substantial role, with a first-degree relative affected by the disease increasing a person’s risk by sevenfold.

Learn more: Current Knowledge on Endometriosis Etiology: A Systematic Review (https://www.gynecologiconcologyinstitute.org/news/endometriosis/endometriosis-news/endometriosis-causes-a-review/)

How Endometriosis Can Cause Infertility

Endometriosis can impair fertility through several mechanisms that affect gametes, embryo transport, and implantation.

Effect on Gametes and Embryo

Endometriosis may influence the production and quality of oocytes and can also affect sperm function and embryo health. Endometriomas and the inflammatory environment they create can negatively affect oocyte production and ovulation.

Effect on Fallopian Tubes and Embryo Transport

Inflammation associated with endometriosis can disrupt fallopian tube function and normal uterine contractions. These changes can impair tubal motility and hinder the transport of eggs, sperm, and embryos.

Effect on the Endometrium

Endometriosis can alter the uterine lining, potentially leading to implantation failure. Research indicates that changes in gene expression within the endometrium may reduce its receptivity to embryo implantation.

Treatment Options for Endometriosis-Associated Infertility

Approaches to managing infertility related to endometriosis include expectant management, medical therapy, surgical intervention, and assisted reproductive technologies, with the goal of improving reproductive outcomes based on disease severity and individual circumstances.

Expectant Management

Some individuals with mild to moderate endometriosis may conceive without intervention, particularly younger patients without additional fertility problems. Despite the overall reduction in fertility rates associated with endometriosis, careful observation can be an appropriate option in selected cases.

Surgical Treatment

Surgery can serve both diagnostic and therapeutic purposes. The primary aims are to remove or reduce endometriosis implants, restore normal pelvic anatomy, and lessen inflammatory effects. These outcomes may improve fertility, especially in those with more severe disease.

Assisted Reproductive Technology

In vitro fertilization (IVF) is currently the most effective treatment for infertility associated with endometriosis. It is particularly beneficial for individuals with severe endometriosis or for those who have not achieved pregnancy with other treatments.

Medical Treatment

Hormonal medications—including combined oral contraceptives, progestins, danazol, and gonadotropin-releasing hormone agonists or antagonists (GnRH analogs)—are commonly used to reduce disease severity and alleviate symptoms. However, these therapies have not demonstrated significant benefit in treating endometriosis-associated infertility itself.

The Road Ahead: Potential Future Treatments

As research advances, novel therapies targeting abnormal gene expression and inflammatory pathways are being explored. Stem cell–based approaches and genetic interventions also hold promise for addressing endometriosis-associated infertility. Continued scientific progress offers hope for more effective strategies to manage this condition and improve fertility outcomes.