Endometriosis Reduces Ovarian Reserve via Inflammation and Surgery

Endometriosis significantly depletes ovarian reserve through chronic pelvic inflammation, oxidative stress, and the surgical interventions used to manage it, according to a systematic review published in the International Journal of Women's Health.¹ The results showed that anti-Müllerian hormone (AMH) levels and antral follicle count (AFC) are depleted in patients with endometriosis compared with healthy individuals.

The review compiled information from 10 studies published between 2015 and 2024 and found that ovarian reserve depletion was documented in 70% to 85% of patients across included studies, reinforcing the condition's status as a serious threat to female fertility.

How Endometriosis Depletes Ovarian Reserve

The review identifies 3 overlapping biological pathways through which endometriosis erodes ovarian function. First, endometriotic tissue generates pro-inflammatory cytokines including IL-1β, IL-6, and tumor necrosis factor-alpha (TNF-α). These cytokines then recruit macrophages and T cells to the pelvic environment, triggering oxidative stress that damages granulosa cells and accelerates oocyte apoptosis. IL-6, in particular, upregulates pro-apoptotic genes including Bax and caspase-3.

Second, hormonal dysregulation compounds the damage. Estrogen promotes the proliferation of ectopic endometrial tissue and enhances reactive oxygen species (ROS) production, while progesterone resistance, which is a hallmark of the condition, strips the body of its natural anti-inflammatory counter-mechanism. Disruption of the estrogen-progesterone balance impairs normal ovarian cycling, reduces endometrial receptivity, and limits fertilization prospects.

Third, vascular endothelial growth factor (VEGF)–driven angiogenesis, while supporting lesion survival, reduces follicular blood flow and creates localized hypoxia that impairs oocyte maturation and folliculogenesis.

Ovarian endometriomas amplify all 3 mechanisms. The cyst fluid contains iron and oxidized hemoglobin that generate hydroxyl radicals, inducing DNA, protein, and lipid damage in surrounding ovarian cells. Mechanical compression by the cyst further depletes the follicular pool by damaging antral follicles and reducing oocytes available for maturation.

The Surgery Paradox: Treatment That Further Reduces Reserve

Surgical management of endometriomas presents a clinical dilemma where the same intervention that relieves symptoms and may improve spontaneous conception rates can permanently lower ovarian reserve by removing healthy ovarian tissue. The review found that cystectomy is associated with lasting AMH reductions, with the magnitude of decline greater following bilateral vs unilateral procedures and with more invasive approaches compared with conservative techniques such as ablation, which minimize tissue damage.

Even ablative methods carry risk, as thermal energy generated during cyst ablation can induce coagulative necrosis in surrounding healthy ovarian tissue, and any surgical trauma risks fibrosis that impairs long-term ovarian function. The review authors note that no consensus has been reached on the optimal surgical technique for preserving ovarian reserve over time, which remains a persistent gap in the evidence base.

Infertility is a well-recognized complication of endometriosis, though clinicians continue to grapple with how best to sequence surgical and medical management for patients who wish to conceive.² A 2022 review in Frontiers in Endocrinology similarly underscored that endometriosis-related infertility requires multidisciplinary, personalized management, given the complexity of overlapping inflammatory and hormonal drivers.³

Diagnostic Delay Worsens the Fertility Outlook

The review highlights a compounding problem: The average time from symptom onset to confirmed endometriosis diagnosis is 7 to 10 years. Each year of delay represents additional inflammatory and structural damage to the ovarian environment that may be partially irreversible by the time treatment begins. Endometriomas are frequently misdiagnosed as functional ovarian cysts on imaging—a distinction that matters directly for ovarian reserve, because untreated endometriomas progressively damage ovarian tissue.⁴

What Clinicians and Payers Should Watch For

The review's clinical implications point toward earlier monitoring and intervention. Regular tracking of AMH levels and AFC is recommended for women with known or suspected endometriosis to establish trajectories before reserve is critically compromised. The authors also highlight potential for pharmacological strategies targeting oxidative stress and inflammation to complement or defer surgical management in fertility-prioritizing patients.¹

For managed care stakeholders, the implications are also structural. Diagnostic delays of a decade mean that by the time many patients receive confirmed diagnoses and seek specialty fertility care, they are entering assisted reproductive technology (ART) pathways with a materially diminished ovarian reserve driving utilization and cost. Interventions that shorten the diagnostic window, standardize AMH monitoring, and expand access to fertility-preservation counseling for younger patients could reduce downstream ART burden.

Future research priorities identified by the authors include longitudinal molecular studies, long-term surgical comparison trials with comprehensive risk-benefit analyses, genetic and epigenetic profiling, and pharmacological trials assessing reserve preservation during medical endometriosis management.

References:

1. Christina NLL, Tjahyadi D, Anwar R, Rachmawati A, Rafi MA. The impact of endometriosis on ovarian reserve: a systematic review. Int J Womens Health. 2026;18:604715. doi:10.2147/IJWH.S604715
2. AJMC Staff. Multiple barriers inhibit optimal treatment of endometriosis: Dr Robin Kroll. AJMC®. April 18, 2026. Accessed June 4, 2026. https://www.ajmc.com/view/multiple-barriers-inhibit-optimal-treatment-of-endometriosis-dr-robin-kroll
3. McNulty R. Review highlights need for further research, individualized treatments for endometriosis-associated infertility. AJMC. November 22, 2022. Accessed June 4, 2026. https://www.ajmc.com/view/review-highlights-need-for-further-research-individualized-treatments-for-endometriosis-associated-infertility
4. Hohmann E. 5 conditions endometriosis is commonly mistaken for—and why getting it right matters. AJMC. May 22, 2026. Accessed June 4, 2026. https://www.ajmc.com/view/5-conditions-endometriosis-is-commonly-mistaken-for-and-why-getting-it-right-matters