CA-125 is Physiologically Elevated During Pregnancy and Should Not Be Interpreted Using Standard Non-Pregnant Reference Ranges
Yes, pregnancy significantly affects CA-125 levels, making this tumor marker less reliable for evaluating adnexal masses or malignancy in pregnant patients compared to non-pregnant women. 1
How Pregnancy Affects CA-125 Levels
First Trimester
- CA-125 elevations are expected beginning in the first trimester with reported mean values ranging from 19 to 85 U/mL 1
- Maximum reported values can reach as high as 550 U/mL in healthy pregnant women 1
- Approximately 9.1% of normal pregnancies show CA-125 levels above the standard 35 U/mL cutoff 2
- The median level at 11-14 weeks is approximately 23.4 U/mL (range 2.2-166.3 U/mL) 3
Second Trimester
- CA-125 levels typically decrease and are usually at or below the normal range cutoff value 1
- Median values around 14-16.76 U/mL 2, 4
- Maximum reported value of 73 U/mL in healthy pregnancies 1
Third Trimester
- CA-125 levels may rise again, with median values around 19.6-21.0 U/mL 5, 4
- Can remain persistently elevated in some healthy patients, with maximum reported values reaching 2420 U/mL 1
- This extreme elevation can occur in completely normal pregnancies
Clinical Implications
For Adnexal Mass Evaluation
Tumor markers are less reliable in pregnant patients than in non-pregnant patients, with studies reporting differing and sometimes contradictory results 1. The standard cutoff of 35 U/mL used in non-pregnant women cannot be applied to pregnant women 3.
When CA-125 May Still Be Useful
- If malignancy is strongly suspected or identified, tumor marker trends may be valuable rather than absolute values 1
- Serial measurements showing progressive elevation may be more informative than single values
- When CA-125 is elevated in pregnancy, other causes such as adnexal lesions should be investigated rather than dismissing it as physiologic 2
Other Tumor Markers in Pregnancy
In contrast to CA-125, the following markers remain within normal limits during pregnancy and are more reliable 1:
- CEA (though may increase slightly in third trimester) 5
- Inhibin B
- Anti-müllerian hormone
- Lactate dehydrogenase (LDH) - except when elevated by preeclampsia
Key Pitfalls to Avoid
- Do not use standard non-pregnant CA-125 reference ranges to evaluate pregnant patients
- Do not rely on CA-125 alone for malignancy assessment in pregnancy - ultrasound characteristics and MRI are more reliable 1
- Do not dismiss all elevated CA-125 values as physiologic - investigate for pathology when levels are markedly elevated or rising 2
- Be aware that pregnancy-associated conditions (not just normal pregnancy) can cause CA-125 derangements
Recommended Approach
When evaluating an adnexal mass in pregnancy:
- Prioritize ultrasound characteristics using validated scoring systems (IOTA Simple Rules, Sassone) 1
- Use MRI for further characterization when ultrasound is inconclusive 1
- Consider CA-125 trends rather than absolute values if malignancy is suspected
- Remember that approximately 70% of incidentally identified adnexal masses in pregnancy spontaneously resolve 1