Endometriosis: Symptoms, Diagnosis, Treatment and Fertility
Key Takeaways
Endometriosis is a chronic, estrogen-dependent inflammatory disease that affects about 10% of women of reproductive age. The ESHRE 2022 guideline has reshaped management: diagnosis now starts with imaging (IDEA-protocol ultrasound and MRI), and laparoscopy is no longer the systematic first step. Routine endometrioma cystectomy and prolonged GnRH-agonist pretreatment before IVF are no longer recommended. Pain management relies primarily on combined hormonal contraceptives and progestogens such as dienogest.
Endometriosis: what the 2022 guidelines say
Endometriosis is a chronic, estrogen-dependent, inflammatory and fibrotic disease. It is defined by the presence of endometrial-like tissue outside the uterine cavity — on the peritoneum, ovaries, uterosacral ligaments, recto-vaginal septum, bladder, bowel, and occasionally at remote sites (diaphragm, umbilicus). It affects roughly 10% of women of reproductive age worldwide — close to 190 million people according to the WHO 2023 fact sheet.
The European reference guideline — ESHRE 2022 (Becker et al., Human Reproduction Open) — has profoundly changed management. Three shifts to know:
- Diagnosis starts with imaging (transvaginal ultrasound using the IDEA protocol, then MRI when needed). Laparoscopy is no longer the “gold standard” and is reserved for cases where imaging is negative despite persistent symptoms, or where empirical therapy has failed.
- Routine surgery for ovarian endometriomas before IVF is not recommended: it does not improve live-birth rate and can reduce ovarian reserve.
- Prolonged GnRH-agonist pretreatment (3–6 months) before IVF is no longer recommended: recent data (Cochrane 2019) show no clear benefit.
These changes aim to reduce unnecessary surgery and medical treatment, shorten the diagnostic delay (often 7 to 10 years depending on country), and preserve fertility.
Endometriosis in numbers
- General prevalence: about 4.4% of women (95% CI 3.6–5.2), and up to 10% in clinical series (WHO).
- In infertile women: 23.8% in surgical series (95% CI 16.1–31.5).
- In women with chronic pelvic pain: 50–80%.
- Heritability: about 50%. A large genetics study (Rahmioglu et al., Nature Genetics 2023) identified 42 risk loci and confirmed shared genetic architecture with migraine, multisite chronic pain, asthma and osteoarthritis.
The diagnostic delay remains a major problem in care: a recent review (De Corte et al., BJOG 2025) reports average delays ranging from a few months to more than 12 years depending on the country.
Pathophysiology: why endometriosis develops
No single theory explains every form. The current model is multifactorial:
- Retrograde menstruation (Sampson) — menstrual blood flows back through the tubes into the pelvis. This reflux occurs in over 90% of women, yet only about 10% develop endometriosis — so retrograde menstruation is necessary but not sufficient.
- Coelomic metaplasia (Meyer) — transformation of peritoneal cells into endometrial-like tissue. This explains pre-pubertal endometriosis and some rare forms.
- Embryonic Müllerian rests (Batt) — congenital misplacement of Müllerian tissue, particularly in the recto-vaginal septum.
- Stem cells — hematogenous or lymphatic dissemination of endometrial progenitor cells.
- Immune dysregulation — peritoneal macrophages fail to clear menstrual debris; pro-inflammatory cytokines (IL-6, IL-8, TNF-α) are elevated; cyclooxygenase-2 (COX-2) is stimulated by estrogens, creating self-amplifying loops.
- Genetics — 50% heritability, 42 risk loci identified in 2023.
- Microbiome — a promising but preliminary line of research. No current clinical indication to modify gut or vaginal microbiota routinely.
- Endometrial abnormalities — progesterone resistance in the eutopic endometrium, aberrant aromatase expression in lesions, abnormal HOXA10/11 expression — all of which may impair embryo implantation.
Classifications: understanding the stages
Three systems coexist and complement each other.
r-ASRM (1996/1997 revision)
This is the most widely used system. It assigns a score to lesions and adhesions observed surgically, and classifies the disease in four stages:
- Stage I (minimal) — a few isolated superficial lesions.
- Stage II (mild) — more numerous superficial lesions.
- Stage III (moderate) — deeper lesions, endometriomas, moderate adhesions.
- Stage IV (severe) — extensive lesions, large endometriomas, deep infiltration, dense adhesions.
Limitation: stage correlates poorly with pain and fertility, and underestimates deep disease.
#Enzian (2021 update)
The revised #Enzian system (Keckstein et al., 2021) is a classification by anatomical compartments. It can be applied to imaging (ultrasound, MRI) as well as surgery, and complements r-ASRM by standardising the description of deep endometriosis.
Endometriosis Fertility Index (EFI)
The EFI score (Adamson & Pasta 2010) combines historical factors (age, duration of infertility, prior pregnancies) with surgical findings (tubal and ovarian function, r-ASRM score). It predicts the chance of spontaneous pregnancy after surgery.
For stages III/IV with an EFI above 7, the unassisted live-birth rate reaches about 60% at 3 years and 75% at 5 years. This can justify a waiting period before turning to IVF in eligible patients.
Symptoms
Manifestations vary and are often cycle-dependent. Endometriosis can also be entirely asymptomatic (discovered incidentally on imaging or at surgery).
- Progressive dysmenorrhea — period pain that intensifies year by year and resists usual painkillers.
- Chronic pelvic pain unrelated to menstruation.
- Deep dyspareunia (pain during intercourse), suggesting involvement of the uterosacral ligaments or the recto-vaginal septum.
- Dyschezia (painful defecation), especially perimenstrual — suggesting bowel involvement.
- Dysuria (painful urination), especially perimenstrual — suggesting bladder involvement.
- Infertility (30–50% of infertile women have endometriosis).
- Chronic fatigue, cyclical bowel symptoms, bloating.
- Atypical bleeding — cyclic rectal bleeding, cyclic hematuria.
Clinical examination may reveal tender uterosacral ligaments, nodules in the posterior cul-de-sac, a fixed retroverted uterus, or an adnexal mass. A normal examination does not exclude endometriosis.
Diagnosis: imaging first
This is the major shift in the ESHRE 2022 guideline.
Transvaginal ultrasound (IDEA, 2016)
The IDEA transvaginal ultrasound protocol (Guerriero et al., 2016) systematically explores four steps:
- Uterus and adnexa — assessment for adenomyosis, ovarian cysts, endometrioma;
- “Soft” markers — ovarian tenderness, ovarian fixation;
- Sliding sign in the pouch of Douglas — a “stuck” cul-de-sac indicates deep involvement;
- Anterior and posterior compartments — search for deep nodules in the bladder wall or recto-vaginal septum.
Performed by an experienced operator, IDEA ultrasound has sensitivity and specificity comparable to surgical diagnosis for endometrioma and deep disease.
Pelvic MRI
MRI is requested when ultrasound is inconclusive, when deep endometriosis is suspected, or for surgical mapping. Its accuracy matches expert ultrasound for recto-sigmoid, uterosacral and recto-vaginal involvement.
CA-125: not to be used for screening
CA-125 has a sensitivity of only 20–50% for stages I–II and is useful neither for screening nor to rule out the diagnosis. ESHRE 2022 explicitly advises against its use in this setting.
Laparoscopy: confirmatory, not systematic
ESHRE 2022 (translated): “Laparoscopy is no longer the diagnostic standard and is only recommended in patients with negative imaging and/or where empirical treatment has failed or is not appropriate.”
This does not mean laparoscopy is obsolete: it remains indicated for surgical treatment, for selected infertility work-ups, and to confirm superficial forms not visible on imaging. It is simply no longer the first step.
Ovarian endometrioma: operate or not?
The endometrioma (endometriosis ovarian cyst, sometimes called “chocolate cyst”) is a common situation that raises difficult decisions.
Surveillance or surgery?
- Unilateral, asymptomatic endometrioma smaller than 4 cm in a woman with a fertility project: surveillance, no surgery.
- Surgical indications: refractory pain, suspicion of malignancy (atypical sonographic features, rapid growth), cyst larger than 4 cm impeding follicular access for IVF retrieval, recurrent infection.
Impact of cystectomy on ovarian reserve
Laparoscopic cystectomy reduces ovarian reserve. The evidence is robust:
- Raffi et al. meta-analysis, 2012 — weighted mean AMH decrease of −1.13 ng/mL (95% CI −1.88 to −0.37), with about a 30% drop after unilateral and 44% after bilateral cystectomy.
- Somigliana et al., 2012 — 9 of 11 studies confirm this decline.
- Risk of premature ovarian insufficiency of 2.4–13% after bilateral cystectomy.
Before IVF: surgery does not improve live-birth rate
ESHRE 2022 issues a strong recommendation: systematic cystectomy of endometriomas before IVF is not recommended. The Hamdan et al. meta-analysis, 2015 finds no gain in clinical pregnancy (OR 0.97; 95% CI 0.78–1.20) or live birth (OR 0.90; 95% CI 0.63–1.28) compared with an expectant approach.
ESHRE 2022 (translated): “Clinicians are not recommended to routinely perform surgery for ovarian endometrioma prior to assisted reproductive treatment to improve live birth rate, given the absence of demonstrated benefit and the likely negative impact on ovarian reserve.”
Surgery may still be discussed case by case to relieve pain, facilitate follicular access, or when malignancy is suspected.
Surgical technique
When surgery is indicated, several principles matter: laparoscopic cystectomy with minimal use of bipolar coagulation (prefer suturing or hemostatic agents), energy-sparing techniques (plasma energy or CO₂ laser for wall ablation, when available).
Endometriosis and infertility
Why does endometriosis reduce fertility?
Several mechanisms coexist:
- Anatomical distortion (adhesions, hydrosalpinx, fixed ovaries) in stages III/IV.
- Toxic peritoneal environment — pro-inflammatory cytokines, reactive oxygen species, which damage gametes and early embryos.
- Reduced oocyte quality (Sanchez et al., Human Reproduction Update) — fewer mature oocytes, more meiotic spindle abnormalities.
- Altered endometrial receptivity — progesterone resistance, abnormal HOXA10/11 expression, integrin β3 abnormalities.
- Ovarian reserve sometimes already reduced before any surgery (Muzii et al., 2018 — meta-analysis).
Decision: wait or IVF?
The choice depends on stage, EFI, age and associated factors:
- Stage I/II + EFI ≥ 5–6 + woman under 35: 6–12 months of expectant management after confirmed surgery, with or without intrauterine insemination (IUI) depending on male and tubal factors.
- Stage III/IV + EFI ≥ 7: a 6–12 month waiting period is reasonable, with an unassisted live-birth rate of about 60% at 3 years. ART is offered to patients who have not conceived.
- EFI ≤ 4, or age ≥ 35, or advanced disease combined with a male or tubal factor: IVF directly.
- Severely diminished ovarian reserve (AMH < 0.5 ng/mL, AFC < 5): IVF without prior surgery, with adapted strategies (random-start, DuoStim, embryo accumulation).
Long GnRH-agonist pretreatment before IVF: not recommended
For a long time, an “ultralong” protocol of 3 to 6 months of GnRH-agonist before IVF was used routinely. The updated Cochrane review (Georgiou et al., 2019) downgraded the quality of the evidence to “very low” and did not confirm a benefit in live birth or clinical pregnancy.
ESHRE 2022 issues a strong recommendation against this practice in routine care. It may be discussed case by case in selected patients with severe pain symptoms, after counselling.
Choice of IVF protocol
ESHRE 2022 (translated): “No specific assisted reproduction protocol can be recommended for women with endometriosis. GnRH-agonist and GnRH-antagonist protocols can both be offered, in line with couple and clinician preference, given the absence of demonstrated differences in pregnancy or live-birth outcomes.”
Frozen embryo transfer (freeze-all) may be considered in selected situations (severe disease, hyperstimulation risk, uncertain endometrial receptivity), but should not be imposed routinely.
Pain management
A stepwise approach is recommended. Your doctor will determine the strategy based on pain intensity, pregnancy plans, comorbidities and tolerability.
First tier — analgesics and combined hormonal contraceptives
- NSAIDs on demand for painful episodes.
- Combined hormonal contraceptives (oral pill, vaginal ring, patch) — preferably continuous or extended-cycle use to suppress menstruation. ESHRE 2022 issues a strong first-line recommendation.
Second tier — progestogens
- Dienogest 2 mg/day — efficacy confirmed in the Strowitzki 2010 trials (PMID 20089522), with an acceptable bleeding profile and limited impact on bone density at 24 months.
- Levonorgestrel-releasing IUD or etonogestrel implant — useful progestogen alternatives depending on the contraceptive context.
Third tier — GnRH agonists
Reserved for refractory cases, with mandatory add-back therapy (norethisterone, or low-dose estrogen plus progestogen) started from the outset to limit hot flushes and bone loss. Duration limited to 6–12 months.
Aromatase inhibitors
Letrozole or anastrozole for refractory pain, particularly in postmenopausal women with residual endometriosis. Off-label, to be combined with a progestogen or combined contraceptive in premenopausal women.
Integrative approaches
- Pelvic floor physiotherapy — recommended by ESHRE 2022 when a myofascial component is present.
- Cognitive-behavioral therapy for the chronic-pain component.
- Acupuncture — limited but positive evidence in small trials.
- Anti-inflammatory diets and supplements — no robust benefit demonstrated; not to be used as a substitute for validated medical therapy.
Surgery: excision rather than ablation
For superficial lesions
Surgical excision of lesions is preferred to ablation (coagulation or thermal destruction) when expertise allows. The Pundir et al. meta-analysis, 2017 (3 randomized trials, 335 patients) shows significantly greater improvement at 12 months for dyschezia, chronic pelvic pain and the EHP-30 global pain score. The 5-year follow-up by Healey et al., 2014 confirms superiority for dyspareunia and less need for long-term hormonal treatment after excision.
The biological argument also favors excision: complete histology (to rule out atypia), less thermal damage to healthy ovarian tissue, fewer microscopic remnants.
Deep endometriosis (DIE): multidisciplinary team
Deep endometriosis (rectum, sigmoid, bladder, ureters or recto-vaginal septum) should be managed in expert centres with a multidisciplinary team (gynecological, colorectal, urological surgery) and dedicated pre-operative imaging.
Bowel-sparing techniques (shaving, discoid excision) are preferred over segmental resection when anatomically feasible. The Bendifallah et al. meta-analysis, 2020 (60 studies) shows substantially lower complication rates with shaving:
- Rectovaginal fistula: OR 0.19 (95% CI 0.10–0.36) vs disc; OR 0.26 (95% CI 0.15–0.44) vs segmental resection.
- Anastomotic leak: OR 0.22 (95% CI 0.06–0.73) vs disc.
- Persistent bladder dysfunction: OR 0.34 (95% CI 0.18–0.63) vs segmental.
Recurrence
Post-operative recurrence is estimated at about 21.5% at 2 years and 40–50% at 5 years without post-operative medical therapy. Maintenance hormonal therapy (continuous combined contraceptive, dienogest) significantly reduces the risk of endometrioma recurrence.
Endometriosis in adolescents
Endometriosis can begin from the first menstrual cycles. Lesions are often atypical (red, vesicular) rather than the classic “pigmented” lesions. A high index of suspicion is warranted in cases of incapacitating dysmenorrhea, school absenteeism or pain resistant to usual analgesics.
ESHRE 2022 (translated): “In adolescents with severe dysmenorrhea and/or endometriosis-associated pain, clinicians should prescribe hormonal contraceptives or progestogens (systemic or levonorgestrel IUD) as first-line treatment.”
Early hormonal treatment can relieve pain, preserve future fertility and limit disease progression. Surgery is reserved for refractory cases, in expert centres.
Turkish context
Turkish regulation prohibits oocyte donation, sperm donation, embryo donation and surrogacy. This constraint particularly affects patients with advanced endometriosis and severely diminished ovarian reserve: the strategies available in Turkey are limited to own-oocyte cycles (repeated cycles, embryo accumulation, random-start or DuoStim protocols). This information must be communicated clearly during consultation so that patients can make informed decisions. Options abroad are discussed for informational purposes only.
Practical takeaways
Endometriosis is a chronic disease, not a one-off event. Its management has changed substantially since 2022:
- Diagnosis starts with imaging (IDEA ultrasound, then MRI when needed); laparoscopy is reserved for unresolved cases.
- CA-125 is not useful for screening or diagnosis.
- Before IVF: neither routine cystectomy nor prolonged GnRH-agonist pretreatment is recommended.
- Stepwise medical pain management — NSAIDs, combined hormonal contraceptives, dienogest, then GnRH agonists with add-back for refractory cases.
- Excision rather than ablation for surgery; deep endometriosis in expert centres.
- Multidisciplinary approach — gynecologist, ART team, surgeon, pelvic floor physiotherapist, psychological support as needed.
The right decision for you depends on multiple factors: symptoms, pregnancy plans, age, ovarian reserve, extent of disease, surgical history. No single strategy fits every patient.
FAQ
Can endometriosis be cured?
It cannot be definitively cured, but it can be controlled. Medical treatment manages pain and slows progression; surgery relieves lesions and may improve fertility; pregnancy and menopause often attenuate the disease. The goal is an acceptable quality of life and, when desired, a pregnancy carried to term.
Should every endometriosis be operated?
No. The decision depends on pain, pregnancy plans, age, lesion size and location. ESHRE 2022 has clearly narrowed the routine indications for surgery, particularly before IVF.
Why isn’t laparoscopy used systematically for diagnosis anymore?
Because transvaginal ultrasound and MRI, performed by experienced operators, have accuracy comparable to surgical diagnosis for endometriomas and deep lesions. Laparoscopy is reserved for cases that imaging cannot resolve, or when surgical treatment is needed at the same time.
Why not operate my endometrioma before IVF?
Because studies do not show improved live-birth rates after pre-IVF cystectomy, and surgery can reduce ovarian reserve (average AMH drop of about 30% after unilateral cystectomy, up to 44% after bilateral). Surgery remains an option if you have severe pain, suspected malignancy, or a cyst impeding follicular access.
Which pain treatment for which situation?
In general: NSAIDs and continuous combined contraceptives first; dienogest second; GnRH agonists with add-back third for refractory cases. Your doctor will choose based on your symptoms, your pregnancy plans, and the tolerability of each option.
How long after endometriosis surgery before considering IVF?
It depends on stage and EFI (Endometriosis Fertility Index). For stages III/IV with EFI above 7, a 6–12 month wait is reasonable, since about 60% of patients conceive naturally within 3 years. For lower EFI, advanced age or an associated male factor, IVF is offered sooner.
Can endometriosis worsen during IVF?
Ovarian stimulation produces high estrogen levels that could theoretically worsen lesions. Clinical data do not confirm a significant impact on the disease itself. The benefit of IVF almost always outweighs this theoretical risk in the infertile patient.
What if I have endometriosis with severely diminished ovarian reserve?
This is a difficult situation. Since oocyte donation is prohibited in Turkey, management is limited to own-oocyte cycles: random-start protocols, DuoStim, embryo accumulation over multiple cycles. Your ART team will also discuss fertility preservation as early as possible if surgery is planned.
What should I bring to my consultation?
Bring your pelvic ultrasound and MRI reports, hormonal tests (AMH, FSH, estradiol, prolactin), any operative reports, current medications, a cycle and pain diary (visual analogue scale if possible), and your partner’s semen analysis if available.
Sources
- Becker CM, Bokor A, Heikinheimo O, et al. ESHRE guideline: endometriosis. Human Reproduction Open 2022;2022(2):hoac009.
- WHO. Endometriosis Fact Sheet, March 2023.
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- Rahmioglu N, Mortlock S, Ghiasi M, et al. The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions. Nat Genet 2023;55:423–436.
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- Somigliana E, Berlanda N, Benaglia L, et al. Surgical excision of endometriomas and ovarian reserve: a systematic review on serum antimüllerian hormone level modifications. Fertil Steril 2012;98(6):1531–1538.
- Georgiou EX, Melo P, Baker PE, et al. Long-term GnRH agonist therapy before in vitro fertilisation (IVF) for improving fertility outcomes in women with endometriosis. Cochrane Database Syst Rev 2019;CD013240.
- Pundir J, Omanwa K, Kovoor E, et al. Laparoscopic Excision Versus Ablation for Endometriosis-associated Pain: An Updated Systematic Review and Meta-analysis. J Minim Invasive Gynecol 2017;24(5):747–756.
- Healey M, Cheng C, Kaur H. To excise or ablate endometriosis? A prospective randomized double-blinded trial after 5-year follow-up. J Minim Invasive Gynecol 2014;21(6):999–1004.
- Bendifallah S, Vesale E, Daraï E, et al. Bowel-sparing techniques versus segmental resection for deep infiltrating colorectal endometriosis: systematic review and meta-analysis. J Minim Invasive Gynecol 2020.
- Strowitzki T, Marr J, Gerlinger C, et al. Dienogest is as effective as leuprolide acetate in treating the painful symptoms of endometriosis. Hum Reprod 2010;25(3):633–641.
- Sanchez AM, Vanni VS, Bartiromo L, et al. Is the oocyte quality affected by endometriosis? A review of the literature. Hum Reprod Update 2017;23(5):600–622.
The content has been created by Dr. Senai Aksoy and medically approved.