Case 1 – Adolescent with Pain:
Endometriosis Diagnosis & Management

Case 1 — Adolescent with Pain

What Are Your Differential Diagnoses?

• Primary Dysmenorrhea
• Endometriosis
• Adenomyosis
• Ovarian Cysts
• Pelvic Inflammatory Disease (PID)
• Ovarian Torsion
• Irritable Bowel Syndrome (IBS)
• Interstitial Cystitis

Pain — Classical Features of Endometriosis

The 7 D's — Endometriosis Symptoms

Endometriosis can be suspected in women (including young women aged ≤17 years) presenting with one or more of the following:

1. Dysmenorrhea
2. Dyspareunia — deep dyspareunia due to stretching of involved tissue
3. Dysuria
4. Dyschezia — in extragenital endometriosis
5. Dysfunctional (abnormal) uterine bleeding
6. Difficulty in conception
7. Diffuse abdominal pain

Additional signs include fixed retroverted uterus or involvement of uterosacral ligaments and rectovaginal septum.

History Taking

Initial evaluation includes a thorough history and a pain diary documenting severity of pain, relation to bowel and bladder, and degree of interference with daily activities (missing school/social activities) — all indicators of the need for intervention.

Clinical Examination

• Abdominal examination may not reveal anything significant
• Most adolescent girls will cooperate for rectal examination
• 5–11% of adolescent endometriotic patients will have associated Müllerian anomalies
• Q-tip test must be performed to rule out transverse vaginal septum
• Adnexal pathologies should be ruled out by rectal examination
• In sexually active adolescent girls, bimanual pelvic examination is feasible
• 32% of adolescent girls will have uterosacral nodularity, endometrioma, or deeply infiltrating endometriosis

Risk Factors for Adolescent Endometriosis

(Christine et al., 2012) — Symptoms and markers in adolescence predicting the risk of endometriosis:

• Chronic pelvic pain (CPP), cyclic and/or non-cyclic
• Severe dysmenorrhea
• Non-contraceptive use of oral contraceptives for dysmenorrhea
• Dysmenorrhea resistant to NSAIDs and/or oral contraceptives
• Interference with daily living during menstruation — e.g. absenteeism from school >18 days/year
• Dyspareunia and/or pain on defecation during menstruation
• History of benign ovarian cysts
• Early age of menarche (≤12 years) but not after 14 years
• Low BMI
• Family history of endometriosis

Imaging Modalities

Modality	Role in Endometriosis	Notes
Transabdominal Sonography (TAS)	Less effective for small or superficial implants; can identify larger endometriomas	First-line in adolescents (non-invasive)
Transvaginal Sonography (TVS)	First-line imaging; excellent for ovarian endometriomas and DIE in rectovaginal septum and uterosacral ligaments	Not always feasible in non-sexually active adolescents
Transrectal Sonography	Limited — only in cases with focused rectal symptoms	Not routinely indicated
MRI	Valuable second-line; identifies DIE, bowel/bladder involvement, adhesions; sensitive for endometriomas	Higher cost; preferred for surgical planning; used if strong clinical suspicion without USG findings
CA-125	No role in diagnosis — markers in blood, endometrial tissue, menstrual or uterine fluids are not diagnostic	Do not rely on CA-125 for diagnosis

Management Goals

The primary goals of therapy include:

• Symptom relief — reduction in pain scores
• Improve quality of life — return to school, daily activities
• Suppression of disease progression
• Protection of future fertility

Medical Management — NSAIDs

NSAIDs interrupt cyclooxygenase-mediated prostaglandin production. They are a first-line treatment option, with studies proving significantly better pain relief from primary dysmenorrhea compared to placebo.

Drug	Initial Dose	Maintenance Dose
Ibuprofen	800 mg	400–800 mg every 8 hours as needed
Naproxen Sodium	440–550 mg	220–550 mg every 12 hours as needed
Mefenamic Acid	500 mg	250 mg every 6 hours as needed
Celecoxib*	400 mg	200 mg every 12 hours as needed

*For females older than 18 years. COX-2 specific inhibitor. Source: Hazel Z. Expert Opin Pharmacother.

Hormonal Therapy — Overview

When NSAIDs provide no pain relief and the patient has visited multiple physicians without improvement, hormonal therapy is initiated empirically.

Guidelines recommend hormonal therapy as empirical treatment to reduce endometriosis-associated pain and pelvic pain (EAPP):

Treatment	Evidence Level	Source
Hormonal Contraceptives	A	ESHRE / NICE
Progestogens	A	ESHRE
Anti-progestogens	B	ESHRE
GnRH Agonists	A	ESHRE / NICE

Combined Oral Contraceptives (COCs)

COCs are used off-label for endometriosis and are commonly prescribed as empirical therapy without a confirmed surgical diagnosis. ESHRE classifies as Grade B the COC prescription to reduce dyspareunia, dysmenorrhea, and non-menstrual pain.

Progestins & Dienogest

Progestins must be considered as the first line of therapy at Evidence Level A. Oral or depot MPA, norethisterone acetate, dienogest, or danazol are indicated to reduce EAPP.

Dienogest (DNG) — Key Data

• 74.05% reduction in dysmenorrhea observed
• 42.71% reduction in dyspareunia
• 48.91% reduction in chronic pelvic pain
• Safe for long-term use up to 5 years (Evidence Level A)
• At 2 mg/day — as effective as GnRH agonists with significantly fewer side effects (Evidence Level A)
• Comparable pain reduction in both surgically and clinically diagnosed patients

When NOT to Prescribe Dienogest

• Active thromboembolic disease
• Presence or history of arterial/cardiovascular disease
• Diabetes mellitus with vascular involvement
• Active hepatic disease
• Presence or history of liver tumours
• Undiagnosed vaginal bleeding
• When patient wants to conceive

Common Side Effects of Dienogest

• Headache
• Breast discomfort
• Depression / mood swings
• Acne
• Nausea / vomiting / flatulence
• Weight gain

Norethindrone Acetate (NETA)

NETA has strong progestogenic effects and androgenic side effects (weight gain, acne, seborrhea). Continuous administration of NETA 5 mg/day is FDA approved for endometriosis. Low-dose NETA 2.5 mg/day is considered an effective, tolerable, and inexpensive first choice for symptomatic rectovaginal endometriosis.

GnRH Agonists & Antagonists

GnRH Agonists

GnRH agonists (nafarelin, leuprolide, deslorelin, goserelin, triptorelin) can be used as one of the options for reducing endometriosis-associated pain. Commonly used: Leuprolide and Goserelin (Evidence Level A).

GnRH Antagonists (Oral)

Emerging evidence from RCTs on oral GnRH antagonists (elagolix, relugolix, linzagolix) suggests they are effective in relief of endometriosis-associated pain. ESHRE recommends that in young women and adolescents, GnRH antagonists should be used after careful consideration and discussion in a secondary or tertiary care setting.

Elagolix vs GnRH Agonist vs Dienogest

Feature	GnRH Agonist	Elagolix
Route	Injection (IM/SC)	Oral tablets
Estradiol suppression	Complete suppression	Dose-dependent inhibition — minimal hypoestrogenic effects
Onset	Delayed; initial flare before suppression (2–4 weeks)	Faster onset; no initial flare
Return to baseline	Required weeks to months	Return to normal estradiol within 48 hours

Feature	Dienogest	Elagolix
Breakthrough bleeding	Present	Absent
Return to baseline	Return to normal within 2 months after cessation	Return to normal estradiol levels within 48 hours

Alternative Therapies

Role of Laparoscopy

Indications for Laparoscopy

• Chronic pelvic pain and dysmenorrhea not responding to NSAIDs and OCPs — diagnostic laparoscopy indicated; if early endometriosis found, treat immediately
• USG and MRI evidence of endometriosis (endometrioma and DIE) in symptomatic patients — therapeutic laparoscopy indicated
• Endometriosis associated with Müllerian anomalies
• Emergency situations like ruptured endometrioma
• Recurrent endometrioma with severe pain, size >4 cm, no response to medical management, or suspicion of malignancy

In adolescents, unless there is severe pain indicating DIE or endometrioma >5 cm with severe pain, diagnostic/operative laparoscopy is not indicated. May be done if endometrioma increases in size or there is no response to hormonal therapy.

Replacing Diagnostic Laparoscopy with 'See and Treat' Approach

To minimize exposure to multiple surgeries, surgery can be reserved for diagnostic confirmation and simultaneous treatment. Challenges of routine diagnostic laparoscopy include failure to recognise atypical lesions, inability to always perform excision of lesions at time of diagnostic procedure, and risk of complications.

Fertility Preservation in Adolescent Endometriosis

Case 3 — Infertility with Bilateral Endometriomas

Incidence & Prevalence of Endometriosis in Infertility

How Does Endometriosis Lead to Infertility?

• Adhesions: Pelvic adhesions disrupt anatomy and block sperm passage
• Chronic Inflammation: Inflammatory mediators impair sperm motility, DNA integrity, and fertilization
• Disturbed Folliculogenesis: Hormonal dysfunction leads to poor oocyte quality
• LUF Syndrome: Follicles fail to release eggs, reducing ovulation success
• Tubal Dysfunction: Abnormal motility hampers gamete and embryo transport
• Sperm Damage: Cytokines and oxidative stress hinder sperm function
• Altered LH surge, steroidogenesis, and uterine receptivity
• Increased oxidative stress (ROS): DNA damage to oocyte, sperm, and endometrial cells

Role of HSG in Endometriosis

HSG is not a definitive diagnostic tool for endometriosis. It helps visualize the fallopian tubes and uterine cavity, may reveal indirect signs (hydrosalpinx, tubal occlusion, peritubal adhesions), and can rule out other causes of infertility. If endometriosis is suspected on HSG, further investigation (MRI or laparoscopy) is needed to confirm diagnosis.

Probable Diagnosis: Primary Infertility with Bilateral Endometriomas

Factors to consider:

• Women's age
• Duration of infertility
• Ability to undergo IVF-ET
• Family history
• Pelvic pain

Endometriosis Fertility Index (EFI)

The EFI is based on:

• Patient Characteristics: Age, duration of infertility, and pregnancy history
• Intra-operative Lesion Description: ASRM/AFS Endometriosis Score
• Functional Post-operative Score: Least Function (LF) Score

EFI Score	Cumulative Non-ART Pregnancy Rate at 36 Months
0–2	~10%
9–10	~69%

ESHRE Guidelines — Surgical Management of Endometrioma

Preventing Recurrence

Timing of surgery: Surgeries in the follicular phase had a 2-fold decreased recurrence compared to luteal phase surgeries.

Why NOT Hormonal Treatment for Endometriosis-Associated Infertility?

Minimal/Mild Endometriosis — Surgery Outcomes

• Clinical pregnancy rate improved: Risk Ratio 1.44 (95% CI: 1.24–1.68)
• Live birth odds improved: Odds Ratio 1.94 (95% CI: 1.20–3.16)
• Monthly fecundity rate increased from 2.4% to 4.7%
• 36-week cumulative pregnancy probability rose from 17.7% to 30.7%

ART & Post-Surgical Management

Post-Surgery Fertility Options

ESHRE guidelines suggest IUI with gonadotrophin stimulation works better post-surgery. Results improve from 8% to 26%. RCOG recommends IUI to improve pregnancy in minimal and mild endometriosis.

Ideally, fertility treatment must be started soon after endometriosis surgery in a woman desiring pregnancy — without resorting to medical management first.

AMH After Surgery

Role of Ovarian Suppressant Prior to ART Stimulation

• Not recommended to increase live birth rate
• Can consider in segmental cycle if planning FET (COCs, progestins, danazol, GnRH analogs)

Role of Surgery in Moderate to Severe Endometriosis (rASRM Stage III or IV)

Decision to perform surgery should be guided by:

• Presence or absence of pain symptoms
• Patient age and preferences
• History of previous surgery
• Presence of other infertility factors
• Ovarian reserve
• Estimated EFI score

Conditions Where Surgery Can Be Considered Before ART

• Large endometrioma
• Inaccessible ovaries
• Severe pain impairing quality of life
• Suspicion of malignancy

Conclusion

• In minimal and mild endometriosis — surgical excision or ablation is first line with doubling of pregnancy rate
• In moderate and severe endometriosis — surgical excision also recommended as first line
• In patients who failed to conceive spontaneously after surgery — assisted reproduction is more effective than repeat surgery
• In women who have failed assisted reproduction — further management remains controversial