Lactobacilli Deficiency in Infertile Women Seeking IVF in Arash Hospital: An Imbalance in the Genital Microbiome
Abstract
Objective: It is estimated that infertility affects approximately 9-30% of couples in their reproductive age and microorganisms may play an important role in such genital system dysfunction. The aim of this study was to investigate the presence of lactobacilli, Gardnerella, Enterobacteriaceae, and streptococci in the vagina, cervix and endometrium of women who referred for infertility and the healthy women who referred for oocyte donation.
Materials and methods: The endometrial, cervical and vaginal swab specimens were collected three days after the end of menstruation and cultured to isolate lactobacilli. DNA form these specimens was extracted and subjected to quantitative real-time PCR to determine the frequency of the above bacteria. All uterine biopsy samples were tested for the presence of bacterial DNA by PCR method.
Results: 94% of uterine biopsy samples contained bacterial DNA. The frequency of lactobacilli identified by real-time quantitative PCR in these two groups was 40% (endometrial samples), 70% (cervical samples), and 80% (vaginal samples), which differed from lactobacilli isolated by the culture method. The number of lactobacilli from cervical endometrium of healthy donors was higher than in the diseased group. There was a significant difference in the mean of Gardnerella bacteria in the cervix and endometrium and Streptococcus in the cervix (p<0.05).
Conclusion: Considering the decrease of lactobacilli and the increase of other bacteria, it is suggested to consider the composition and number of bacteria in the genital tract of asymptomatic infertile women as one of the possible causes of infertility.
2. Frąszczak K, Barczyński B, Kondracka A. Does lactobacillus exert a protective effect on the development of cervical and endometrial cancer in women? Cancers. 2022;14(19):4909.
3. Tomaiuolo R, Veneruso I, Cariati F, D'Argenio V. Microbiota and Human Reproduction: The Case of Female Infertility. High Throughput. 2020;9(2):12.
4. Chenoll E, Moreno I, Sánchez M, Garcia-Grau I, Silva Á, González-Monfort M, et al. Selection of New Probiotics for Endometrial Health. Front Cell Infect Microbiol. 2019;9:114.
5. Souza SV, Monteiro PB, Moura GA, Santos NO, Fontanezi CTB, Gomes IA, et al. Vaginal microbioma and the presence of Lactobacillus spp. as interferences in female fertility: A review system. JBRA Assist Reprod. 2023;27(3):496-506.
6. Koedooder R, Singer M, Schoenmakers S, Savelkoul PHM, Morré SA, de Jonge JD, et al. The vaginal microbiome as a predictor for outcome of in vitro fertilization with or without intracytoplasmic sperm injection: a prospective study. Hum Reprod. 2019;34(6):1042-1054.
7. Parolin C, Marangoni A, Laghi L, Foschi C, Ñahui Palomino RA, Calonghi N, et al. Isolation of Vaginal Lactobacilli and Characterization of Anti-Candida Activity. PLoS One. 2015;10(6):e0131220.
8. Delroisse JM, Boulvin AL, Parmentier I, Dauphin RD, Vandenbol M, Portetelle D. Quantification of Bifidobacterium spp. and Lactobacillus spp. in rat fecal samples by real-time PCR. Microbiol Res. 2008;163(6):663-70.
9. Akiyama K, Nishioka K, Khan KN, Tanaka Y, Mori T, Nakaya T, et al. Molecular detection of microbial colonization in cervical mucus of women with and without endometriosis. Am J Reprod Immunol. 2019;82(2):e13147.
10. Fredricks DN, Fiedler TL, Thomas KK, Oakley BB, Marrazzo JM. Targeted PCR for detection of vaginal bacteria associated with bacterial vaginosis. J Clin Microbiol. 2007;45(10):3270-6.
11. Zhang LL, Zhang LF, Xu JG. Chemical composition, antibacterial activity and action mechanism of different extracts from hawthorn (Crataegus pinnatifida Bge.). Sci Rep. 2020;10(1):8876.
12. Ricci S, De Giorgi S, Lazzeri E, Luddi A, Rossi S, Piomboni P, et al. Impact of asymptomatic genital tract infections on in vitro Fertilization (IVF) outcome. PLoS One. 2018;13(11):e0207684.
13. Riganelli L, Iebba V, Piccioni M, Illuminati I, Bonfiglio G, Neroni B, et al. Structural Variations of Vaginal and Endometrial Microbiota: Hints on Female Infertility. Front Cell Infect Microbiol. 2020;10:350.
14. Kumar M, Jiang L, Lai H-L, Lee C-L, Ng EHY, Yeung WSB, et al. Impact of microbiota on female fertility and gynecological problems. Reproductive and Developmental Medicine (RDM). 2024;08(04):242-51.
15. Bernabeu A, Lledo B, Díaz MC, Lozano FM, Ruiz V, Fuentes A, et al. Effect of the vaginal microbiome on the pregnancy rate in women receiving assisted reproductive treatment. J Assist Reprod Genet. 2019;36(10):2111-2119.
16. Zhao C, Wei Z, Yang J, Zhang J, Yu C, Yang A, et al. Characterization of the Vaginal Microbiome in Women with Infertility and Its Potential Correlation with Hormone Stimulation during In Vitro Fertilization Surgery. mSystems. 2020;5(4):e00450-20.
17. Moreno I, Codoñer FM, Vilella F, Valbuena D, Martinez-Blanch JF, Jimenez-Almazán J, et al. Evidence that the endometrial microbiota has an effect on implantation success or failure. Am J Obstet
Gynecol. 2016;215(6):684-703.
18. Fu M, Zhang X, Liang Y, Lin S, Qian W, Fan S. Alterations in Vaginal Microbiota and Associated Metabolome in Women with Recurrent Implantation Failure. mBio. 2020;11(3):e03242-19.
19. Karaer A, Doğan B, Günal S, Tuncay G, Arda Düz S, Ünver T, et al. The vaginal microbiota composition of women undergoing assisted reproduction: a prospective cohort study. BJOG. 2021;128(13):2101-2109.
20. Kliman HJ. Comment on "the placenta harbors a unique microbiome". Sci Transl Med. 2014;6(254):254le4.
21. DiGiulio DB, Romero R, Amogan HP, Kusanovic JP, Bik EM, Gotsch F, et al. Microbial prevalence, diversity and abundance in amniotic fluid during preterm labor: a molecular and culture-based investigation. PLoS One. 2008;3(8):e3056.
22. Perez-Muñoz ME, Arrieta MC, Ramer-Tait AE, Walter J. A critical assessment of the "sterile womb" and "in utero colonization" hypotheses: implications for research on the pioneer infant microbiome. Microbiome. 2017;5(1):48.
23. Mitchell CM, Haick A, Nkwopara E, Garcia R, Rendi M, Agnew K, et al. Colonization of the upper genital tract by vaginal bacterial species in nonpregnant women. Am J Obstet Gynecol. 2015;212(5):611.e1-9.
24. Wessels JM, Domínguez MA, Leyland NA, Agarwal SK, Foster WG. Endometrial microbiota is more diverse in people with endometriosis than symptomatic controls. Sci Rep. 2021;11(1):18877.
25. Bhandari P, Rishi P, Prabha V. Positive effect of probiotic Lactobacillus plantarum in reversing LPS-induced infertility in a mouse model. J Med Microbiol. 2016;65(5):345-350.
26. Ravel J, Moreno I, Simón C. Bacterial vaginosis and its association with infertility, endometritis, and pelvic inflammatory disease. Am J Obstet Gynecol. 2021;224(3):251-257.
27. Oghbaei H, Rastgar Rezaei Y, Nikanfar S, Zarezadeh R, Sadegi M, Latifi Z, Nouri M, Fattahi A, Ahmadi Y, Bleisinger N. Effects of bacteria on male fertility: Spermatogenesis and sperm function. Life Sci. 2020;256:117891.
| Files | ||
| Issue | Vol 19, No 2 (June 2025) | |
| Section | Original Articles | |
| DOI | https://doi.org/10.18502/jfrh.v19i2.19300 | |
| Keywords | ||
| Infertility Bacteria Gardnerella Enterobacteriaceae Streptococci Lactobacillus Quantitative Real-Time PCR | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
