Review Highlights Need for Further Research, Individualized Treatments for Endometriosis-Associated Infertility

Endometriosis is known to be associated with infertility, but the mechanisms behind the association are not fully understood. A review published in Frontiers in Endocrinology summarizes current knowledge and treatments relevant to endometriosis-related infertility, which requires a multidisciplinary and personalized approach for the best possible outcomes.

The main underlying drivers of endometriosis are chronic inflammation and hormonal dependence, the combination of which makes the natural history of endometriosis unique. The condition’s multifactorial and systemic nature causes both direct and indirect effects on reproduction in affected women, although the entire pathogenesis of the disease and its varied clinical presentations are still not fully understood.

Establishing the cause of infertility related to endometriosis has proven difficult, as the population of infertile women with endometriosis is heterogenous. The diverse phenotypes seen in clinical settings also make differentiation of a single mechanism challenging.

Even so, there is a clinically recognized association between endometriosis and infertility. Up to half of infertile women are diagnosed with endometriosis, and infertility rates are nearly twice as high in women with endometriosis compared with women who do not have it.

There are various theories surrounding the pathogenesis of endometriosis, although none sufficiently explain the disease history or its heterogenous clinical presentations. The only common aspects between theories are currently a proinflammatory microenvironment coupled with dysregulated hormonal signaling.

“A complex interaction between endometriosis subtype, pain, inflammation, altered pelvic anatomy, adhesions, disrupted ovarian reserve/function, and compromised endometrial receptivity as well as systemic effects of the disease define endometriosis-associated infertility,” the authors wrote.

Pain is one factor with a potential impact on fertility, as sexual intercourse is an important aspect of natural conception that can be significantly affected by pain associated with endometriosis. Previous reviews have found that about two-thirds of women with endometriosis show sexual dysfunction in some capacity.

The process of natural conception could also be impacted by mechanical factors such as pelvic adhesions and anatomical distortion. Ovarian reserves, a main prognostic factor in fertility, are also affected by endometriosis, which most often occurs in the ovary. However, the pathophysiologic mechanism behind depleted ovarian reserves in endometriosis is not well defined. Data are also inconclusive on the effects of surgery on residual ovarian function in endometriosis.

Impaired ovulation is another theoretical factor in endometriosis, but comprehensive data are lacking. Data are also conflicting regarding potential effects on endometrial receptivity on implantation rates.

Delayed diagnoses are also common in endometriosis, which is often only found once surgical intervention is needed. This is another important factor for women with endometriosis-associated infertility, whose disease compounded with the effects of age on ovarian reserves can further impact fertility.

Novel, noninvasive diagnostic methods capable of predicting the risk of infertility could significantly improve diagnostic efficiency for women with endometriosis, who currently face a diagnostic delay of 4 to 11 years. Identifying effective and noninvasive diagnostic tools is a major priority in ongoing research, but no biomarkers have shown sufficient sensitivity and specificity to translate to clinical settings yet.

Similar to diagnostic tools, treatment methods and guidelines for endometriosis-associated infertility are lacking, making treatment challenging. Currently, surgical intervention and assisted reproductive therapy are the standards for treating infertility in these patients.

“From the patient perspective, a shared and informed decision is mandatory because different treatment options may involve both clinical and personal aspects,” the authors wrote.

Another challenge lies in the current therapy options approved for endometriosis, all of which can adversely impact fertility or prevent it altogether. Nonhormonal therapies that could interfere with different disease pathways and potentially improve fertility are needed to overcome this issue. Emerging strategies include noncoding RNAs, selective inhibition of prostaglandin receptors, and stem cell therapies.

Overall, patients with endometriosis-associated infertility require individualized treatment, because the clinical manifestations are heterogenous and the etiology is still not entirely understood. The patient’s individual characteristics, phenotype of endometriosis, and severity of their disease should all be considered as treatment strategies are outlined.

Reference

Bonavina G, Taylor HS. Endometriosis-associated infertility: from pathophysiology to tailored treatment. Front Endocrinol (Lausanne). Published online October 26, 2022. doi:10.3389/fendo.2022.1020827