The role of herpesviruses in endometrial pathology: frequency of herpesvirus DNA detection in the endometrium, cervix and vagina in patients with chronic endometritis and endometrial hyperplasia

Introduction. Chronic endometritis (CE) is reported in 12% of patients with primary infertility. Herpesviruses are considered as one of the causes of CE.

The aim of the study. To evaluate the frequency of herpesviruses DNA detection in endometrium, cervix and vagina in patients with chronic endometritis and endometrial hyperplasia.

Materials and methods. 167 women of reproductive age were included in the study. Samples from the posterolateral wall of the vagina, cervix and endometrium were taken from each patient. The obtained samples were analyzed by real-time PCR for the presence of Herpes simplex viruses type 1 and 2 (HPV 1,2), Epstein-Barr virus (EBV), Cytomegalovirus (CMV) and Human herpesvirus type 6 (HHV6). Endometrial tissue was subjected to morphologic examination.

Results. Depending on the morphology of endometrial biopsy, all patients were divided into three groups: with CE (N=53), with endometrial hyperplasia (EH, N=63), with normal endometrium (N=51). There were no statistically significant differences in the frequency of herpesvirus detection in endometrial, cervical, and vaginal samples. In endometrial samples, EBV was detected in 1 (1.9%) patient with CE (1.9%) and 1 (1.6%) patient with EH, HPV1,2 — in 1 (2%) woman with normal endometrial histology; DNA of other herpesviruses was not detected.

Conclusions. The relationship between herpesvirus type, positive locus and the presence of endometrial pathology has not been established. The frequency of herpesvirus DNA detection in endometrial, cervical, and vaginal samples was not significantly different between the groups of women with CE, EH, and normal endometrial histology. Only 2 (1.7%) of endometrial samples with pathologic morphology were positive for DNA of herpesviruses, in both cases it was EBV.

1. Zegers-Hochschild F., Adamson G.D., Dyer S., Racowsky C., De Mouzon J., Sokol R., Rienzi L., Rienzi A., Schmidt L., Cooke D.I., Simpson J.L., Van Der Poel S. The international glossary on infertility and fertility care, 2017. Human reproduction. 2017; 32 (9); 1786-1801. https://doi.org/10.1093/humrep/dex234

2. Cox C.M., Thoma M.E., Tchangalova N., Mburu G., Bornstein M.J, Johnson C.L., Kiarie J. Infertility prevalence and the methods of estimation from 1990 to 2021: a systematic review and meta-analysis. Human Reproduction Open. 2022; 2022 (4); hoac051. https://doi.org/10.1093/hropen/hoac051

3. Federal State Statistics Service (Rosstat). Health care in Russia. 2023: Stat.sb./Rosstat; M., Z-46 2023; 179 [ (In Russ.)]

4. Park H.J., Kim Y.S., Yoon T.K., Lee W.S. Chronic endometritis and infertility. Clin Exp Reprod Med. 2016; 43(4); 185-192. https://doi.org/10.5653%2Fcerm.2016.43.4.185

5. Kumnova A., Shahini L., Tabaku B., Arberore K., Valon C., Klodete K. Chronic Endometritis in Patients with Failure of IVF. International Journal of Biomedicine. 2023; 13(2); 273-276. http://dx.doi.org/10.21103/Article13(2)_OA13

6. Polisseni F., Bambirra E. A., Camargos A. F. Detection of chronic endometritis by diagnostic hysteroscopy in asymptomatic infertile patients. Gynecologic and obstetric investigation. 2003; 55 (4); 205-210. https://doi.org/10.1159/000072075

7. Kubyshkin A.V., Aliev L.L., Fomochkina I.I., Kovalenko Y.P., Litvinova S. V., Filonenko T.G., Lomakin N.V., Kubyshkin V.A., Karapetian O.V. Endometrial hyperplasia-related infl ammation: its role in the development and progression of endometrial hyperplasia. Infl ammation research. 2016; 65; 785-794. https://doi.org/10.1007/s00011-016-0960-z

8. Vaduva C. C., Constantinescu C., Serbanescu M., Dara L., Oancea M. D., Carp-Veliscu A. The association between endometrial polyps, chronic endometritis, and IVF outcomes. European Review for Medical & Pharmacological Sciences. 2023; 27 (18); 8895-8904. https://doi.org/10.26355/eurrev_202309_33810

9. Swidsinski A., Verstraelen H., Loening-Baucke V., Swidsinski S., Mendling W., Halwani Z.. Presence of a polymicrobial endometrial biofi lm in patients with bacterial vaginosis. PloS one. 2013; 8 (1); e53997. https://doi.org/10.1371/journal.pone.0053997

10. Blazheva S. Study of the incidence of herpes viruses in the endometrium of women with evidence of chronic endometritis and reproductive problems. Human reproduction. 2022; 37; I387-I388. https://doi.org/10.1093/humrep/deac107.392

11. Voroshilina E. S., Zornikov D.L., Koposova O.V., Islamidi D.K., Ignatova K.Y., Abakumova E.I., Kurbatova N.V., Plotko E.E. Possibilities of uterine cavity microbiota assessment using real-time PCR. Bulletin of the Russian State Medical University. 2020; 1; 14-21. (In Russ.)] https://doi.org/10.24075/vrgmu.2020.012

12. Karahalis L.Y., Kononenko T.S. Taxonomic profi le of endometrial microbiome in chronic endometritis. Obstetrics and Gynecology: News. Opinions. Educ. 2022; 10; 23-30. (In Russ.)] https://doi.org/10.33029/2303-9698-2022-10-4-23-30

13. Maltseva L.I., Sharipova R.I., Tsyplakov D.E., Zhelezova M.E. Morphofunctional state of endometrium in women with bacterial-viral endometritis. Practical Medicine. 2017; 7; 87-91. (In Russ.)]

14. Dicke G.B., Sukhanov A.A., Kukarskaya I.I., Ostromensky V.V.. Cytokine profi le of patients with chronic endometritis and reproductive dysfunction. Voprosy gynecologii, obstetrics and perinatologii. 2021; 20; 82-91. (In Russ.)] https://doi.org/10.20953/1726-1678-2021-6-82-91

15. Marci R., Gentili V., Bortolotti D., Lo Monte G., Caselli E., Bolzani S., Rotola A., Di Luca D., Rizzo R. Presence of HHV-6A in endometrial epithelial cells from women with primary unexplained infertility. PloS one. 2016; 1 (7); e0158304. https://doi.org/10.1371/journal.pone.0158304

16. Coulam C. B., Mahmood B., Maria D.S.G., Dimantha K., Haidy E., Emilio F.F., Joanne K., Kenneth B., Dambaeva S.V. Prevalence of HHV‐6 in endometrium from women with recurrent implantation failure. American Journal of Reproductive Immunology. 2018; 80 (1); e12862. https://doi.org/10.1111/aji.12862