Diagnosing Endometriosis: Beyond Pain—What Tests Are Truly Effective for Fertility Patients?

Q: Can blood tests alone definitively diagnose endometriosis?

No. At a cut-off of 35 U/ml, CA-125 has a **sensitivity of only 0.40**, meaning about **6 in 10 women who have endometriosis fall inside the normal range** (PMID: 27132058). It therefore **cannot be used to rule the condition out.** The Cochrane review of 122 biomarkers concluded that none has enough accuracy for clinical use outside a research setting. CA-125 may be referred to as an adjunct or for following a course over time, but it cannot be asked to carry more weight than that.

Endometriosis is a condition that can cause not only painful periods (dysmenorrhea) and chronic pelvic pain but also contribute to infertility. Diagnosing it can sometimes be complex, and for those hoping to conceive (TTC), deciding on the best tests can be a confusing journey. This article will break down diagnostic methods for endometriosis in fertility treatment, based on the latest evidence.

What is Endometriosis and How Does It Affect Fertility?

Endometriosis occurs when tissue similar to the lining inside the uterus (endometrium) grows outside of it, such as on the ovaries, fallopian tubes, or pelvic peritoneum. This misplaced tissue responds to hormonal changes during the menstrual cycle, leading to inflammation, scar tissue formation, and adhesions. This can manifest as severe period pain, chronic pelvic pain, and pain during intercourse. In more severe cases, it can block fallopian tubes, impair ovarian function, or affect egg quality, potentially contributing to infertility.

Current Diagnostic Landscape: The Gold Standard

Definitive diagnosis of endometriosis has traditionally required laparoscopy: a small camera is inserted into the abdomen to inspect for lesions and take tissue samples. It allows accurate assessment of extent and severity, but as surgery it carries physical and emotional burden and a risk of complications.

That position has been shifting. The ACOG clinical practice guideline published in March 2026 addresses the diagnosis of endometriosis, setting out recommendations on clinical, imaging and surgical evaluation (PMID: 41712950).

Let me separate what we were able to verify about this document from what we were not.

What we could verify

It covers diagnosis only; recommendations on how to treat fall outside its scope
It was developed using a modified GRADE framework
The NICE evidence review on endometriosis served as the evidence base for many of its clinical considerations
★It states explicitly that "Ungraded Good Practice Points are included to provide guidance when a formal recommendation cannot be made because of inadequate or nonexistent evidence." So not every recommendation rests on evidence; some reflect expert consensus
Unless otherwise specified, the recommendations also apply to adolescents

What we could not verify

★The full text is paywalled, and the content of the individual recommendations — where laparoscopy sits, which imaging in what order — cannot be read from the abstract. This article will not state, as that document's recommendations, anything we have not read.

For what is actually recommended in your situation, please ask your doctor.

Which tests are used, in what order, and whether laparoscopy is reached depends on current guidance and on your own situation, as judged by your doctor. You do not need to assume that treatment cannot begin until a definitive diagnosis is made — nor that testing is unnecessary. This is a point to confirm with your own clinician.

Non-Invasive Tests: Potential and Limitations

To avoid the invasiveness of laparoscopy, non-invasive tests such as ultrasound, MRI, and blood tests (e.g., CA-125) are often utilized. These can be helpful in diagnosing larger lesions, particularly ovarian endometriomas (chocolate cysts).

However, smaller lesions or peritoneal endometriosis can often be missed by these imaging techniques.

CA-125's real weakness is sensitivity, not specificity

This needs stating precisely. This article previously said that CA-125 has low specificity. The Cochrane numbers do not say that, and we are correcting it.

In the Cochrane review that evaluated 122 blood biomarkers across 141 studies and 15,141 participants (Nisenblat V, et al. 2016. PMID: 27132058), CA-125 at a cut-off of 35 to 36 U/ml performed as follows:

Sensitivity 0.40 (95% CI 0.32 to 0.49)
Specificity 0.91 (95% CI 0.88 to 0.94)

So specificity is actually high; what is low is sensitivity. In practice that means roughly 6 in 10 women who do have endometriosis will have a CA-125 inside the normal range, so "my CA-125 was normal, so I don't have endometriosis" does not follow. Lowering the cut-off to 10 to 14.7 U/ml raises sensitivity to 0.70, but specificity falls to 0.64, picking up women who do not have the disease. There is no setting at which both are acceptable.

The overall verdict on non-invasive testing: not usable yet

The review's conclusion is unambiguous: of the biomarkers that could be meta-analysed, none met the criteria for either a replacement or a triage test, and none displayed enough accuracy to be used clinically outside a research setting. The review also states that all 141 included studies were of poor methodological quality. On top of that, 97 biomarkers assessed across 82 studies did not distinguish women with endometriosis from disease-free controls at all.

Combining tests does not solve it either. The Cochrane review of combination testing (Nisenblat V, et al. 2016. PMID: 27405583; 11 studies, 1,339 participants, again all of poor methodological quality) assessed 15 different combinations, but each was examined by a single study so nothing could be pooled. The authors' bottom line: laparoscopy remains the gold standard for diagnosis, and non-invasive tests should only be undertaken in a research setting.

A 2020 review (Hudson QJ, et al. 2020. PMID: 32019326) likewise states that no clinically accepted biomarker exists, attributing this to variability in study design, cohort selection and analysis that has prevented independent validation. It goes no further than anticipating that a panel of several biomarkers will probably be needed; it recommends no particular test.

One caveat matters here. The populations in these reviews were women suspected strongly enough that surgery was indicated, with endometriosis prevalence of 10% to 85%. Pre-test probability in a general outpatient setting is lower, and the same tests perform worse there.

It's important to understand that while these non-invasive tests can provide clues or help monitor treatment effectiveness, they have limitations in achieving a definitive diagnosis.

Approaching Endometriosis Diagnosis in Fertility Care

When someone trying to conceive (TTC) is suspected of having endometriosis, your doctor will comprehensively evaluate your symptoms, internal examination findings, and imaging results to propose the optimal diagnostic and treatment strategy. Laparoscopy isn't immediately necessary in all cases. The decision considers factors like symptom severity, duration of infertility, age, and presence of other infertility factors, always taking the patient's preferences into account. For instance, prioritizing IVF as an initial treatment option may be discussed. Learn more about fertility treatment options on our homepage.

Even with an endometriosis diagnosis, pregnancy is not impossible. With appropriate diagnosis, treatment, and emotional support, many individuals move forward toward their goal of pregnancy. For more in-depth information on your fertility journey, you can also visit this resource.

Navigating Your Emotions Through the Process

Receiving an endometriosis diagnosis or grappling with infertility can be a significant emotional and physical burden. It's natural to experience a range of emotions, including pain, anxiety, and vague worries about the future. These feelings are never wrong. Don't carry this burden alone; reach out to your partner, trusted friends, family, and your medical team. Acknowledging and validating your emotions, and seeking support, are crucial for navigating this journey.

Frequently Asked Questions (FAQ)

Q1: Does endometriosis always cause infertility?

A1: No, not necessarily. Many individuals with endometriosis conceive naturally. However, the severity of endometriosis is known to increase the risk of infertility.

Q2: What symptoms might indicate endometriosis?

A2: Key symptoms include severe period pain (dysmenorrhea, often worsening over time), chronic pelvic pain, pain during intercourse (dyspareunia), painful bowel movements, fatigue, and infertility. If you experience these symptoms, it's advisable to consult a gynecologist.

Q3: Can blood tests alone definitively diagnose endometriosis?

A3: No. At a cut-off of 35 U/ml, CA-125 has a sensitivity of only 0.40, meaning about 6 in 10 women who have endometriosis fall inside the normal range (PMID: 27132058). It therefore cannot be used to rule the condition out. The Cochrane review of 122 biomarkers concluded that none has enough accuracy for clinical use outside a research setting. CA-125 may be referred to as an adjunct or for following a course over time, but it cannot be asked to carry more weight than that.

Summary

Diagnosing endometriosis is a crucial step in the fertility journey. Laparoscopy allows lesions to be seen directly, but recent guidance has reorganised the place of imaging in diagnosis, and laparoscopy is no longer the only answer. Understanding the pros and cons of each test and having thorough discussions with your healthcare provider are essential to finding the best diagnostic and treatment plan for you. Embrace your feelings, seek appropriate support, and continue on your path forward.

References

Nisenblat V, et al. "Blood biomarkers for the non-invasive diagnosis of endometriosis." Cochrane Database Syst Rev. 2016. PMID: 27132058
Hudson QJ, et al. "Challenges in uncovering non-invasive biomarkers of endometriosis." Exp Biol Med (Maywood). 2020. PMID: 32019326
Nisenblat V, et al. "Combination of the non-invasive tests for the diagnosis of endometriosis." Cochrane Database Syst Rev. 2016. PMID: 27405583
Japanese Society of Obstetrics and Gynecology, "Guidelines for Obstetric and Gynecologic Practice: Gynecologic Outpatient Care 2023"
Diagnosis of Endometriosis. Obstet Gynecol. 2026. PMID: 41712950 (an ACOG clinical practice guideline covering diagnosis; treatment recommendations are outside its scope. ★The full text is paywalled; the content of individual recommendations could not be verified from the abstract. The guideline notes that ungraded Good Practice Points are used where evidence is inadequate or nonexistent)

Written by the same author — a general guide to preconception care and fertility planning: "The Preconception Care Handbook"