Abstract
Endometriosis is an estrogen-dependent inflammatory disease that affects up to 10% of women of reproductive age and accounts for up to 50% of female infertility cases. It has been highly associated with poorer outcomes of assisted reproductive technology (ART), including decreased oocyte retrieval, lower implantation, and pregnancy rates. A better understanding of the pathogenesis of endometriosis-associated infertility is crucial for improving infertility treatment outcomes. Current theories regarding how endometriosis reduces fertility include anatomical distortion, ovulatory dysfunction, and niche inflammation-associated peritoneal or implantation defects. This review will survey the latest evidence on the role of inflammatory niche in the peritoneal cavity, ovaries, and uterus of endometriosis patients. Nonhormone treatment strategies that target these inflammation processes are also included. Furthermore, mesenchymal stem cell-based therapies are highlighted for potential endometriosis treatment because of their immunomodulatory effects and tropism toward inflamed lesion foci. Potential applications of stem cell therapy in treatment of endometriosis-associated infertility in particular for safety and efficacy are discussed.
Highlights
Endometriosis is an estrogen-dependent inflammatory disease characterized by the presence of endometrial glands and stroma outside the uterine cavity
Another study by the same authors aimed to identify endometriosis patients among women assessed for infertility, and concluded that a panel of 11 cytokines (IL-5, IL-9, IL-13, IFN-α2, cutaneous T-cell attracting chemokine (CTACK), hepatocyte growth factor (HGF), monocyte chemoattractant protein (MCP)-1, monocyte chemotactic protein 3 (MCP-3), M-CSF, leukemia inhibitory factor (LIF), and SCGF-β) was distinguishable in infertile patients with endometriosis; this profile suggested that dysregulated Th1/Th2 activity could underlie endometriosis-associated infertility [49]
This review focuses on systemic pharmacologic treatments, tubal flushing with oil-based contrast media has been shown to increase short-term pregnancy rate in endometriosis and infertile patients, possibly by increasing the uterine natural killer (NK) cell population and restoring endometrial osteopontin expression [100,101]
Summary
Endometriosis is an estrogen-dependent inflammatory disease characterized by the presence of endometrial glands and stroma outside the uterine cavity. For patients with suspected endometriosis based on presented symptoms and signs, many clinicians begin empirical treatment before making a definitive diagnosis, using medical therapies such as nonsteroidal anti-inflammatory drugs, hormonal contraceptives, progestogens, antiprogestogens, gonadotropin-releasing hormone (GnRH) agonists and antagonists, and aromatase inhibitors [11,12]. These reagents function by inducing hypoestrogenism, amenorrhea, or endometrial atrophy [13]. We first examine the dysregulated niche immune modulation in each anatomical compartment, and discuss novel treatment strategies that target immune pathways to restore fertility in endometriosis patients
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