Hum. Reprod. Advance Access originally published online on February 27, 2004
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Human Reproduction, Vol. 19, No. 4, 1025-1030,
April 2004
© 2004 European Society of Human Reproduction and Embryology
Maternal C-reactive protein levels are raised at 4 weeks gestation
1 Department of Reproductive Medicine, Hammersmith Hospital, Du Cane Road, London W12 0HS, UK
2 To whom correspondence should be addressed. e-mail: g.sacks{at}imperial.ac.uk
BACKGROUND: The aim of this study was to determine whether there is evidence of a systemic maternal inflammatory response in very early pregnancy. METHODS: Successive women receiving treatment by IVF or ICSI had serum C-reactive protein (CRP) levels measured on the day of their pregnancy blood test at 4 weeks gestation (14 days post-egg collection). Women with positive 
HCG levels had ongoing pregnancies confirmed by serial transvaginal ultrasound scans up to 8 weeks gestation. RESULTS: Pregnant women (n = 40) were significantly younger (mean age 34 years) than women who failed to become pregnant (n = 95, mean age 37 years, P < 0.001), received significantly lower treatment doses of recombinant FSH (2000 versus 2400 IU, P < 0.05) and had significantly more eggs collected (11 versus 8, P < 0.01). There were no significant differences in body mass index, parity, a history of smoking, endometriosis or polycystic ovaries, pre-treatment CRP levels and white cell counts, peak serum estradiol levels and numbers of embryos transferred. Pregnant women had significantly higher CRP levels (median 3.68 mg/l) than those who were not pregnant (median 1.495 mg/l, P < 0.0001), a difference that persisted after excluding potential confounding variables. Six pregnant women with ovarian hyperstimulation syndrome had higher CRP levels than those who did not (P < 0.01). CONCLUSIONS: This well-controlled study is the first to demonstrate that maternal CRP levels are raised as early as 4 weeks gestation and thus that the maternal inflammatory response is established during the earliest phases of implantation. It is hypothesized that an abnormal response (either exaggerated or absent) could cause some cases of miscarriage.
Key words: C-reactive protein/early pregnancy/inflammatory response/IVF/miscarriage
Submitted on August 11, 2003 resubmitted on November 13, 03 ; accepted on December 12, 2003
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