C-reactive Protein As a Marker of Persistent Infection is Not Associated with Tubal Factor Infertility-an Independent Clinical Validation Study

Study Question: Does C-reactive protein (CRP), as a marker of persisting low-grade inflammation, identify IgG antibody test (CAT)-positive women who are at the highest risk for tubal factor infertility (TFI)?

Summary Answer: No association was found between slightly elevated CRP (seCRP) levels and TFI in our CAT-positive patient population.

What Is Known Already: In the fertility work-up, CAT is used to estimate the risk for TFI and to select high-risk patients for additional invasive diagnostic procedures (e.g. hysterosalpingography and laparoscopy). However, a high number of false positives exist among CAT-positive patients. In a previous study, it has been suggested that women with TFI may be identified more accurately when combining CAT with CRP, a marker for persistent low-grade inflammation.

Study Design Size Duration: Our original retrospective cohort consisted of 887 consecutive female patients who visited the fertility clinic of a tertiary care centre between 2007 and 2015. All CAT-positive women who underwent laparoscopy (as the reference test for evaluation of tubal function) and who had not undergone previous pelvic surgery were included in the study. CRP was determined in spare serum samples, and medical data was obtained by chart review.

Participants/materials Setting Methods: A total of 101 women (11.4%) were CAT-positive, and 64 of these 101 women (7.2%) met all inclusion criteria. CAT was performed with an ELISA. TFI was assessed by laparoscopy and strictly defined as extensive peri-adnexal adhesions and/or distal occlusion of at least one tube. In spare sera, CRP was performed with a high-sensitivity CRP ELISA, and CRP levels between 3 and 10 mg/L were defined as positive. Analyses were corrected for BMI, endometriosis and smoking.

Main Results And The Role Of Chance: There was no statistically significant association between seCRP level and TFI after adjusting for BMI, endometriosis and smoking (odds ratio 1.0; 95% CI 0.3-3.3;  = 64).

Limitations Reasons For Caution: Our retrospective study had a small sample size due to a low CAT-positivity rate and a conservative clinical policy with regard to invasive diagnostic testing. Additionally, CRP levels were only measured once, while they may change throughout the menstrual cycle and in time.

Wider Implications Of The Findings: Contrary to previous findings, our results show CRP is not suitable as a marker of persistent low-grade inflammation in CAT-positive women. Other inflammatory markers and immunogenetic host factors should be studied on their clinical validity and utility to improve non-invasive risk assessment for TFI in the fertility work-up.

Study Funding/competing Interests: This work was partially supported by the European EuroTrans-Bio Grant [Reference number 110012 ETB] and the Eurostars grant (E!9372). S.A.M., a full-time employee of Amsterdam University Medical Centres location VUMC (0.56 fte) and the Maastricht University Medical Center (0.44 fte), is the founder (2011) and CEO of TubaScan Ltd, a spin-off company, Dept. of Medical Microbiology and Infection Prevention, Amsterdam UMC, location VUmc, Amsterdam, the Netherlands. S.O. and E.F.v.E. at the time of conducting this research had a partial appointment at TubaScan Ltd.