Academic Research · Case Study

Endometriosis as a Systemic,
Immune-Driven Disease:
A Genetic and Clinical Case Study

Kaitlyn Stewart Stories of Endo Inc.
Abstract
Endometriosis is widely misclassified as a reproductive disorder, but growing evidence supports its systemic, immune-driven nature. This case study presents both genetic analysis and lived experience to illustrate how endometriosis can evolve into a life-threatening, multi-organ disease. Through 16 surgeries, uterine rupture, adrenal insufficiency, systemic complications, and the neonatal course of my son, combined with comprehensive genomic analysis, this thesis demonstrates that endometriosis is a systemic, autoimmune-like condition requiring reclassification and multi-system treatment.
Section 1

Introduction

Endometriosis affects millions worldwide and is often seen as a 'pelvic-only' disease. My history proves otherwise: 16 surgeries, uterine rupture, placenta increta, systemic inflammation, adrenal insufficiency, trigeminal neuralgia, fibromyalgia, and the devastating loss of my son.

This paper combines genetic data and clinical narrative to demonstrate that endometriosis is a systemic, immune-driven disease with life-threatening consequences — and that its current classification fails the women who live with it.

Section 2

Genetic Evidence

Comprehensive genomic analysis reveals a convergence of mutations that create the conditions for systemic inflammatory disease:

MTHFR C677T
Reduced folate and B12 activation, causing methylation dysfunction — impairs the body's ability to regulate inflammation and detoxify estrogen metabolites.
CBS Mutations
Impaired detoxification and sulfur pathway stress — creates a toxic burden that amplifies inflammatory signaling throughout the body.
HLA Variants
Immune hyper-reactivity — the immune system attacks beyond its intended targets, enabling endometrial tissue to establish in locations far outside the pelvis.
NR3C1 · CYP21A2
Steroid pathway dysfunction causing adrenal insufficiency — the body cannot mount a normal stress response, compounding every surgical and inflammatory event.
Section 3

Clinical Case Presentation

By 2012, I had undergone five surgeries for endometriosis and adenomyosis. One procedure involved a uterine suspension and internal wedge resection to remove adenomyosis growing into the uterine muscle. This created a hidden scar — like the seam of jeans — that later became the weak point where my placenta invaded.

2008–2012
Five surgeries for endometriosis and adenomyosis. Uterine suspension and internal wedge resection performed — not labeled as myomectomy, so high-risk pregnancy flag was never set.
2013
Became pregnant with son Kalib at age 22. At 5 months, ultrasounds showed placental lakes — suspicion raised for placenta accreta spectrum. Scar tissue hid the invasion on imaging. MRI scheduled for September 4.
Aug 26, 2013
Uterine rupture before the MRI. The placenta had grown through the wedge scar, into the fallopian tube, and onto the sigmoid colon — placenta increta. 2.5 liters of internal bleeding. Emergency hysterectomy and transfusions. Kalib delivered at 26 weeks + 4 days.
Sep 11, 2013
After 16 days in the NICU with devastating brain injury, we chose compassionate extubation. Kalib passed peacefully in my arms at 18:35. Because one counts.
Neonatal Course — Kalib
Apgar scores 0/1/3/4 at birth — no signs of life initially, minimal recovery despite full resuscitation
Severe hypoxia and metabolic acidosis (pH 6.73)
Grade IV intraventricular hemorrhage, hypoxic-ischemic encephalopathy, and hydrocephalus
EEG: very low voltage, showing severely limited brain activity
Newborn screen showed methionine spike — likely from ingesting maternal blood during rupture, compounded by inherited methylation vulnerability
Multiple PRBC transfusions for anemia — I could not donate despite same blood type due to my own hemorrhagic losses
Medical Bias Note: Before rupture, a physician told me over the phone to abort — based only on my surgical history, not my son's scans. He assumed I would not survive pregnancy due to scarring and uterine weakness. This reflects both systemic bias and the life-threatening dangers endometriosis creates when not properly classified and managed.
Section 4

Discussion: Linking Genetics
and Clinical Course

The cascade is direct and documented:

→
Immune overactivation (HLA variants) — tissues attacked beyond the pelvis, enabling extra-pelvic disease progression
→
Poor methylation/detox (MTHFR, CBS) — accumulation of estrogen, toxins, and inflammatory byproducts with no adequate clearance mechanism
→
Steroid pathway dysfunction (NR3C1, CYP21A2) — adrenal insufficiency and compromised stress response during every surgical event
→
Clinical progression — Endometriosis → wedge resection scar → placenta increta → uterine rupture → catastrophic neonatal outcome

This course demonstrates how maternal endometriosis-related scarring, systemic inflammation, and genetic vulnerabilities can cascade into multi-organ, life-threatening consequences. This is not a reproductive disease. This is a systemic disease.

Section 5

Conclusion &
Call to Action

This case proves that endometriosis is not 'just pelvic pain.' It is a systemic, immune-driven disease capable of causing multi-organ involvement, adrenal dysfunction, neurological pain, catastrophic pregnancy complications, and neonatal death.

Endometriosis must be reclassified as a systemic disease requiring multi-specialty management — not a gynecological footnote. Every year that classification is delayed, women like me are dismissed. Pregnancies are not flagged as high risk. Surgeries create scars that are not documented properly. And women die.

This story is proof. One story. One life. One son. Because one counts.

This research matters.

Help us make sure every woman with endometriosis gets the multi-specialty care this disease demands.

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Kaitlyn Stewart · ORCID: 0009-0004-3339-5034
Stories of Endo Inc. · 501(c)(3) Nonprofit