Shruti Menon

Human and Pathogen Factors Associated with Chlamydia trachomatis-Related Infertility in Women

SUMMARY Chlamydia trachomatis is the most common bacterial sexually transmitted pathogen worldwide. Infection can result in serious reproductive pathologies, including pelvic inflammatory disease, ectopic pregnancy, and infertility, in women. However, the processes that result in these reproductive pathologies have not been well defined. Here we review the evidence for the human disease burden of these chlamydial reproductive pathologies. We then review human-based evidence that links Chlamydia with reproductive pathologies in women. We present data supporting the idea that host, immunological, epidemiological, and pathogen factors may all contribute to the development of infertility. Specifically, we review the existing evidence that host and pathogen genotypes, host hormone status, age of sexual debut, sexual behavior, coinfections, and repeat infections are all likely to be contributory factors in development of infertility. Pathogen factors such as infectious burden, treatment failure, and tissue tropisms or ascension capacity are also potential contributory factors. We present four possible processes of pathology development and how these processes are supported by the published data. We highlight the limitations of the evidence and propose future studies that could improve our understanding of how chlamydial infertility in women occurs and possible future interventions to reduce this disease burden.

Development and evaluation of a multi-antigen peptide ELISA for the diagnosis of Chlamydia trachomatis related infertility in women.

Chlamydia trachomatis results in tubal factor infertility in some women. Diagnosis of this tubal infertility is difficult and typically involves laparoscopy or hysterosalpingography to detect the tubal blockages. Numerous serological tests have been developed; however, they are presently not used for diagnosis without subsequent surgical investigation during the infertility investigation. This study aimed to develop a highly specific serological assay for chlamydial tubal factor infertility in women that could be used to recommend direct progression to invitro fertilization (IVF) treatment for women who are positive. Women were recruited from a variety of settings including women seeking fertility treatment, sexual health and general practitioner (GP) consultations or antenatal care (n=259). The serological assay was developed using sera from a large group of women by using infertile microimmunofluorescence (MIF)-positive women with tubal damage as the positives compared to infertile or acute infection and/or fertile controls (negatives). The new multi-peptide ELISA was highly specific for the detection of tubal factor infertility (P=0.011) compared to another ELISA (P=0.022) and MIF (P=0.099). The sensitivity of the assay should be improved before clinical utility. Potentially, a two-step testing protocol could be used during the initial infertility investigation, where MIF followed by a highly specific ELISA could be used to recommend direct progression to IVF for women who are positive.

CXCL10, CXCL11, HLA-A and IL-1β are induced in peripheral blood mononuclear cells from women with Chlamydia trachomatis related infertility

Chlamydia trachomatis infections can result in the development of serious sequelae such as pelvic inflammatory disease and tubal infertility. In this study, peripheral blood mononuclear cells from women who were undergoing or had recently undergone IVF treatment were cultured ex vivo with C. trachomatis to identify the immune responses associated with women who had serological evidence of a history of Chlamydia infection. Cytokines secreted into the supernatant from the cultures were measured using ELISA, and the level of IL-1β was found to be significantly higher in Chlamydia positive women than Chlamydia negative women. qRT-PCR analysis of the expression of 88 immune-related genes showed trends towards an upregulation of CXCL10, CXCL11 and HLA-A in Chlamydia positive women compared with Chlamydia negative women. These findings support that some women launch a more marked proinflammatory response upon infection with C. trachomatis and this may be associated with why C. trachomatis induces infertility in some infected women.