Restoring the Endometrial Microbiota to Overcome the Consequence of Infertility in Women with a History of Gynecologic Infection
Medha Narwankar
Introduction. Pelvic inflammatory disease (PID) is a broad spectrum of reproductive tract infections that can cause inflammation and damage to fallopian tubes1,2. The endometrial microbiome creates a biofilm and dynamic interface that supports interaction between gametes, the embryo, and maternal tissue3. Statistics have shown that 2.5 million reproductive-aged women have reported PID, of which 15% develop infertility4. PID ultimately impairs the endometrial epithelium which leads to poor gamete transport and interaction during fertilization, increasing the risk of infertility1,3. Patients present asymptomatically during the acute stages of PID and diagnosis requires symptomatic proof which is usually confirmed when the disease becomes chronic, causing symptoms of pelvic pain, vaginal discharge, fever, and irregular bleeding4,5. Methods. Comparison of the endometrial microbiome between a normal (control) patient and one diagnosed with PID was used to identify the bacteria responsible for infection6,7. This set of pathogens was used to train a machine learning model to screen endometrial samples collected from patients for PID6,7. Subjects were also screened every 4 months and compared to those screened every 3 years as guidelines suggest in order to analyze development of comorbidities such as infertility8. Vaginal microbiome transplantation was studied in patients with a history of recurrent or antibiotic-resistant bacterial vaginosis as a means for treatment9. Results. Identification of the endometrial microbiome in a patient with PID consists of varying levels of Dialister, Bifidobacterium, Prevotella, Gardnerella, and Anaerococcus taxa when compared to control patients6,7. Studies showed a significant correlation between these pathogens and comorbidities associated with PID such as infertility, which were decreased in patients who were more periodically screened8. Vaginal microbiome transplantation in patients with bacterial vaginosis proved to be successful in clearing inflammatory cells and restoring the microbiome9. Conclusions. Current gaps with PID diagnosis and care involve timely screening, repair of scarred tissue, and restoration of the endometrial microbiome. Damaged tissue that results due to chronic inflammation has to be surgically repaired if the goal is to return the tissue back to a healthy state. Antibiotics simply treat the infection, but relapse may occur due to antibiotic driven clearance of protective microbes necessary for optimal function9. To diagnose PID in its more acute stages preventing chronic comorbidities, annual bacterial screening should be conducted. If a patient tests positive, their endometrial tissue should be assessed for damage and surgical repair utilized as needed. For sustained treatment and restoration of dysfunctional tissue, endometrial microbiome transplantation can be done.
- Vander Borght M, Wyns C. Fertility and infertility: Definition and epidemiology. Clin Biochem. 2018 Dec;62:2-10. doi: 10.1016/j.clinbiochem.2018.03.012. Epub 2018 Mar 16. PMID:
- Rhoton-Vlasak A. Infections and infertility. Prim Care Update Ob Gyns. 2000 Sep 1;7(5):200-206. doi: 10.1016/s1068-607x(00)00047-0. PMID:
- Franasiak JM, Scott RT Jr. Introduction: Microbiome in human reproduction. Fertil Steril. 2015 Dec;104(6):1341-3. doi: 1016/j.fertnstert.2015.10.021. Epub 2015 Oct 26. PMID: 26515381.
- Roberts, MD, Aaron, and Stephen J. Hilgers, MD, JD, CFCMC, Dip. ABOG. “Endometriosis and the Prevalence of Infectious Agents within the Endometrium and Endo-Cervix.” The Journal of Minimally Invasive Gynecology, vol. 26, no. 7, ser. 168-S169, 1 Nov. 2019. 168-S169, doi:https://doi.org/10.1016/j.jmig.2019.09.303.
- Haggerty, L., Totten, P. A., Tang, G., Astete, S. G., Ferris, M. J., Norori, J., Bass, D. C., Martin, D. H., Taylor, B. D., & Ness, R. B. (2016). Identification of novel microbes associated with pelvic inflammatory disease and infertility. Sexually transmitted infections, 92(6), 441–446. https://doi.org/10.1136/sextrans-2015-052285NLM
- Liu Y, Ko EY, Wong KK, et Endometrial microbiota in infertile women with and without chronic endometritis as diagnosed using a quantitative and reference range-based method. Fertil Steril. 2019;112(4):707-717.e1. doi:10.1016/j.fertnstert.2019.05.015
- Tamarelle J, Thiébaut ACM, Sabin B, et al. Early screening for Chlamydia trachomatis in young women for primary prevention of pelvic inflammatory disease (i-Predict): study protocol for a randomised controlled trial. Trials. 2017;18(1):534. Published 2017 Nov 13. doi:10.1186/s13063-017-2211-1
- Lev-Sagie A, Goldman-Wohl D, Cohen Y, et al. Vaginal microbiome transplantation in women with intractable bacterial Nat Med. 2019;25(10):1500-1504. doi:10.1038/s41591-019-0600-6
- Perrotta AR, Borrelli GM, Martins CO, et al. The Vaginal Microbiome as a Tool to Predict rASRM Stage of Disease in Endometriosis: a Pilot Study. Reprod Sci. 2020;27(4):1064-1073. doi:10.1007/s43032- 019-00113-5