The levonorgestrel-releasing intrauterine system is associated with delayed endocervical clearance of Chlamydia trachomatis without alterations in vaginal microbiota

Abstract

Progestin-based contraception may impact women's susceptibility to sexually transmitted infection. We evaluated the effect of the levonorgestrel intrauterine system (LNG-IUS) on cervical persistence of Chlamydia trachomatis (CT) in a baboon model. Female olive baboons (Papio anubis) with or without an LNG-IUS received CT or sham inoculations. CT was detected in cervical epithelium with weekly nucleic acid amplification testing (NAAT) and culture. Presence of the LNG-IUS was associated with prolonged persistence of CT. Median time to post-inoculation clearance of CT as detected by NAAT was 10 weeks (range 7-12) for animals with an LNG-IUS and 3 weeks (range 0-12) for non-LNG-IUS animals (P = 0.06). Similarly, median time to post-inoculation clearance of CT by culture was 9 weeks (range 3-12) for LNG-IUS animals and 1.5 weeks (range 0-10) for non-LNG-IUS animals (P = 0.04). We characterized the community structure of the vaginal microbiota with the presence of the LNG-IUS to determine if alterations in CT colonization dynamics were associated with changes in vaginal commensal bacteria. Vaginal swabs were collected weekly for microbiome analysis. Endocervical CT infection was not correlated with alterations in the vaginal microbiota. Together, these results suggest that LNG-IUS may facilitate CT endocervical persistence through a mechanism distinct from vaginal microbial alterations.

Keywords: contraception; sexually transmitted infection; vaginal microbiome.

Graphical Abstract Figure.

In a baboon model, the levonorgestrel-releasing intrauterine system is associated with prolonged Chlamydia trachomatis infection without changes in the commensal bacteria of the vagina.

Figure 1.

Dynamics of CT endocervical infection as detected by culture or NAAT in baboons with or without an LNG-IUS.

Figure 2.

Relative abundance of bacterial genera over time for a representative animal from the (A) LNG-IUS and (B) non-LNG-IUS groups.

Figure 3.

The impact of the LNG-IUS on the baboon vaginal microbiota. (A) The change in Shannon diversity index from baseline for each individual animal over the course of 16 weeks of LNG-IUS acclimation. (B) PCoA of vaginal microbial community distances before (black) and after (blue) LNG-IUS insertion. (C) A comparison of between and within animal community distances at baseline, immediately following LNG-IUS insertion (weeks 1–4), and at the end of the acclimation phase (weeks 20–24).

Figure 4.

The impact of CT on the baboon vaginal microbiota. (A) The change in Shannon diversity index from baseline for each individual animal over the course of 16 weeks of observation during and following CT inoculation. (B) PCoA of vaginal microbial community distances before (black) and after (red) first CT inoculation. (C) A comparison of between and within animal community distances at baseline, during CT inoculation (weeks 1–4), and at the end of the experimental observation (weeks 12–16).

Figure 5.

The impact of CT on the baboon vaginal microbiota in the presence of the LNG-IUS. (A) The change in Shannon diversity index from baseline for each individual animal over the course of 16 weeks of observation during and following CT inoculation. (B) PCoA of post-LNG-IUS acclimation vaginal microbial community distances before (black) and after (pink) first CT inoculation. (C) A comparison of between and within animal community distances at post-LNG-IUS acclimation baseline, during CT inoculation (weeks 1–4) and at the end of the experimental observation (weeks 12–16).