Antichlamydial antibodies, human fertility, and pregnancy wastage

Abstract

Genital infections with Chlamydia trachomatis (C. trachomatis) continue to be a worldwide epidemic. Immune response to chlamydia is important to both clearance of the disease and disease pathogenesis. Interindividual responses and current chlamydial control programs will have enormous effects on this disease and its control strategies. Humoral immune response to C. trachomatis occurs in humans and persistent antibody levels appear to be most directly correlated with more severe and longstanding disease and with reinfection. There is a close correlation between the presence of antichlamydial antibodies in females and tubal factor infertility; the closest associations have been found for antibodies against chlamydial heat shock proteins. The latter antibodies have also been shown to be useful among infertile patients with prior ectopic pregnancy, and their presence has been correlated with poor IVF outcomes, including early pregnancy loss. We review the existing literature on chlamydial antibody testing in infertile patients and present an algorithm for such testing in the infertile couple.

Figure 1

The effects of C. trachomatis infection on human fallopian tubal morphology. Human fallopian tubes in organ culture were left uninfected (a and b) or were infected with C. trachomatis serovar D (c and d). Ultrastructural analysis of the intratubal architecture uses scanning electron microscopy. Uninfected tubes are densely ciliated and contain intact secretory cells. The mucosal surface of C. trachomatis-infected tubes show remarkable deciliation and cellular disruption ([9], and reproduced with permission).

Figure 2

The life cycle of genital serovars of C. trachomatis. The chlamydial growth cycle involves transformation between distinct forms: the elementary body (EB) and the reticulate body (RB). The highly infectious EB attaches to nonciliated columnar or cuboidal epithelial cells and induces ingestion by the host cell. EB are metabolically inactive and represent the extracellular C. trachomatis growth form. Once ingested into a phagosome, fusion of the phagosome with the host lysosome is prevented, a highly unusual occurrence that ensures EB survival. The EB reorganizes within the phagosome into a metabolically active RB. RBs are noninfectious but can replicate and do so by binary fission. Several stimuli, including antibiotic and IFNγ exposure, can drive chlamydia into a persistent state, which lasts in vitro until removal of the exogenous stressor. If persistence is avoided, or if infection is reactivated from persistence, the RB will ultimately reorganize back into EB, which will be released from the host cell to infect surrounding epithelial cells (reproduced with permission [17]).

Figure 3

A proposed algorithm for use of chlamydial antibody screening in infertile couples.