Chlamydia Trachomatis IgG Seropositivity is Associated With Lower Natural Conception Rates in Ovulatory Subfertile Women Without Visible Tubal Pathology

S.F.P.J. Coppus; J.A. Land; B.C. Opmeer; P. Steures; M.J.C. Eijkemans; P.G.A. Hompes; P.M.M. Bossuyt; F. van der Veen; B.W.J. Mol; J.W. van der Steeg


Hum Reprod. 2011;26(11):3061-3067. 

In This Article

Abstract and Introduction


BACKGROUND The relation between Chlamydia trachomatis infection and subsequent tubal damage is widely recognized. As such, C. trachomatis antibody (CAT) testing can be used to triage women for immediate tubal testing with hysterosalpingography (HSG) or laparoscopy. However, once invasive tubal testing has ruled out tubal pathology, CAT serology status is ignored, as its clinical significance is currently unknown. This study aimed to determine whether positive CAT serology is associated with lower spontaneous pregnancy rates in women in whom HSG and/or diagnostic laparoscopy showed no visible tubal pathology.
METHODS We studied ovulatory women in whom HSG or laparoscopy showed patent tubes. Women were tested for C. trachomatis immunoglobulin G (IgG) antibodies with either micro-immunofluorescence (MIF) or an ELISA. CAT serology was positive if the MIF titre was ≥1:32 or if the ELISA index was >1.1. The proportion of couples pregnant without treatment was estimated at 12 months of follow-up. Time to pregnancy was considered censored at the date of the last contact when the woman was not pregnant or at the start of treatment. The association between CAT positivity and an ongoing pregnancy was evaluated with Cox regression analyses.
RESULTS Of the 1882 included women without visible tubal pathology, 338 (18%) had a treatment-independent pregnancy within 1 year [estimated cumulative pregnancy rate 31%; 95% confidence interval (CI): 27–35%]. Because of differential censoring after 9 months of follow-up, regression analyses were limited to the first 9 months after tubal testing. Positive C. trachomatis IgG serology was associated with a statistically significant 33% lower probability of an ongoing pregnancy [adjusted fecundity rate ratio 0.66 (95% CI 0.49–0.89)].
CONCLUSIONS Even after HSG or laparoscopy has shown no visible tubal pathology, subfertile women with a positive CAT have lower pregnancy chances than CAT negative women. After external validation, this finding could be incorporated into existing prognostic models.


The devastating effect of Chlamydia trachomatis infections on the female reproductive tract is widely recognized (Paavonen and Eggert-Kruse, 1999). The diagnostic value of C. trachomatis immunoglobulin G (IgG) antibody titre (CAT) testing has been studied extensively, showing fairly good screening properties. In the Netherlands, this has resulted in a recommendation to include CAT testing as part of the routine fertility workup of subfertile couples (NVOG, 2004).

CAT is mainly used to identify women at high risk of tubal pathology and to triage them for further tubal testing (Coppus et al., 2007a). CAT serology status is ignored however, once invasive testing has ruled out tubal pathology, as its clinical significance is currently unknown. The causal relationship between Chlamydia infections and tubal factor subfertility has been well established, but the question whether positive CAT serology is associated with lower pregnancy rates has been studied less often. It has been postulated that Chlamydia infections have a detrimental effect on the endometrium resulting in impaired implantation and lower pregnancy rates (Witkin, 1999; Neuer et al., 2000). Yet studies examining the association between elevated C. trachomatis IgG antibody levels and pregnancy rates in an IVF population were not uniformly conclusive. Whereas some studies suggested a lower implantation and a lower ongoing pregnancy rate (Rowland et al., 1985; Lunenfeld et al., 1989; Witkin et al., 1994; Pacchiarotti et al., 2009), other work suggested that IVF outcome was not associated with CAT status (Osser et al., 1990; Tasdemir et al., 1994; Claman et al., 1996; Sharara et al., 1997; Spandorfer et al., 1999).

The prognostic value of C. trachomatis antibodies on spontaneous pregnancy rates in subfertile women is equally uncertain. To the best of our knowledge, four previous studies have examined this relation, with conflicting results (Idahl et al., 2004; Keltz et al., 2006; Perquin et al., 2007; El Hakim et al., 2009). As a consequence, it is still unclear whether positive CAT serology is associated with lower spontaneous pregnancy rates once invasive tubal testing has ruled out tubal pathology. The objective of this study was to assess in a prospective consecutive series of subfertile couples, whether evidence of a past Chlamydia infection affects the probability of spontaneous pregnancy in women without visible tubal pathology.


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