Research eyes chlamydia, ectopic pregnancy link
A ruptured ectopic pregnancy is the leading cause of maternal mortality in the first trimester and accounts for 10 to 15% of all maternal deaths.1-3
A history of diagnosed chlamydial infection is associated with a two-fold increased risk for ectopic pregnancy.4 However, the extent to which such infection accounts for the adhesions, tubal alteration, and damage that predispose women to the condition remains largely unknown. The link between chlamydia and ectopic pregnancy is of concern for family planning clinicians, as chlamydia is the most frequently reported bacterial sexually transmitted disease in the United States. In 2008, more than 1.2 million chlamydial infections were reported to the Centers for Disease Control and Prevention from 50 states and the District of Columbia.5
Results from a new study indicate how chlamydia can increase the risk of an ectopic pregnancy.6 Researchers at the University of Edinburgh in Scotland have found that women who had had the sexually transmitted infection were more likely to produce a particular protein in their Fallopian tubes. Increased production of the protein, known as PROKR2, makes a pregnancy more likely to implant in the Fallopian tube, the scientists state.6 The current study follows previous research by the University of Edinburgh team, which showed that production of a similar protein increased the likelihood of smokers having an ectopic pregnancy.7
"We know that chlamydia is a major risk factor for ectopic pregnancy, but until now we were unsure how the infection led to implantation of a pregnancy in the Fallopian tube," said Andrew Horne, PhD, MRCOG, clinician scientist and honorary consultant in obstetrics and gynecology at the University of Edinburgh, in a statement accompanying the publication. "We hope that this new information allows health care providers to give women accurate information about risks following chlamydial infection and to support public health messages about the importance of safer sex and chlamydia testing."
Blood test in wings?
Could a blood test indicate the presence of an ectopic pregnancy? Current diagnosis relies on the use of ultrasound.
Researchers at the Wistar Institute and the University of Pennsylvania School of Medicine, both in Philadelphia, identified protein markers that might serve as the first reliable blood test to predict ectopic pregnancies. Their research is available online in the Journal of Proteome Research.8
A related small-scale study of clinical samples indicates that one of the proteins identified in the online publication, ADAM12, showed a nearly 97% correlation with ectopic pregnancy.9
In the online publication, scientists compared the proteomic signature of blood samples taken from known cases of ectopic pregnancy with blood samples taken from women who experienced a normal pregnancy. About 70 candidate biomarkers were identified that could signal ectopic pregnancy. Statistical analysis narrowed the field to the 12 most promising biomarkers. While some of the proteins previously had known associations with ectopic pregnancies, the researchers found at least two, including ADAM12, which previously had never been associated with ectopic pregnancy.
The scientists now plan to further confirm and validate the usefulness of the identified panel of biomarkers. By using additional patient samples, they hope to create a practical, reliable blood test for ectopic pregnancy. Among their goals is to identify particular isoforms (variations of a given protein) that are most relevant to identifying ectopic pregnancy. "The great power of biomarkers is to detect clinical disorders such as ectopic pregnancy or diseases, such as cancer, early when it is often easiest to treat the patient," said David Speicher, PhD, professor and co-leader of Wistar's Molecular and Cellular Oncogenesis Program and director of Wistar's Center for Systems and Computational Biology. "Here we can envision a useful blood test that could, as part of routine early prenatal care, save the lives of many women."
References
- Ectopic pregnancy United States, 1990-1992. MMWR 1995;44:46-48.
- Phillips RS, Tuomala RE, Feldblum PJ, et al. The effect of cigarette smoking, Chlamydia trachomatis infection, and vaginal douching on ectopic pregnancy. Obstet Gynecol 1992; 79:85-90.
- Abbott J, Emmans LS, Lowenstein SR. Ectopic pregnancy: ten common pitfalls in diagnosis. Am J Emerg Med 1990;8:515-522.
- Bakken IJ, Skjeldestad FE, Nordbø SA. Chlamydia trachomatis infections increase the risk for ectopic pregnancy: a population-based, nested case-control study. Sex Transm Dis 2007;34:166-169.
- Centers for Disease Control and Prevention. Chlamydia. CDC fact sheet. Accessed at http://www.cdc.gov/std/chlamydia/stdfact-chlamydia.htm.
- Shaw JL, Wills GS, Lee KF, et al. Chlamydia trachomatis infection increases fallopian tube PROKR2 via TLR2 and NFkB activation resulting in a microenvironment predisposed to ectopic pregnancy. Am J Pathol 2011;178:253-260.
- Shaw JL, Oliver E, Lee KF, et al. Cotinine exposure increases Fallopian tube PROKR1 expression via nicotinic AChRalpha-7: a potential mechanism explaining the link between smoking and tubal ectopic pregnancy. Am J Pathol 2010;177:2509-2515.
- Beer LA, Tang HY, Sriswasdi S, et al. Systematic discovery of ectopic pregnancy serum biomarkers using 3-d protein profiling coupled with label-free quantitation. J Proteome Res 2011;10:1126-1138. Accessed at http://pubs.acs.org/toc/jprobs/10/3.
- Rausch ME, Beer L, Sammel MD, et al. A disintegrin and metalloprotease protein 12 as a novel marker for the diagnosis of ectopic pregnancy. Fertil Steril 2011. Doi:10.1016/j.fertnstert.2010.12.040.
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