The Role of Ovarian Microbiota in the Diagnosis and Treatment of Empty Follicle Syndrome in Women

Abstract

Aim. To evaluate the role of ovarian microbiota in the diagnosis and treatment of Empty Follicle Syndrome (EFS) and to develop methods to improve IVF outcomes. Materials and methods. The study included 110 women with a history of Empty Follicle Syndrome: Group I consisted of 40 women of early reproductive age (18-35 years), Group II included 40 women of late reproductive age (36-41 years). The control group consisted of 30 healthy women without reproductive disorders. All patients underwent clinical, laboratory, and instrumental examinations. Illumina MiSeq sequencers were used to analyze the composition of the ovarian follicle microbiota. Polymerase chain reaction (PCR) was used for the identification and quantification of microorganisms, and metagenomic sequencing was used for microbiota analysis. Results. Analysis of the ovarian follicle microbiota composition revealed significant differences between the groups. Women with EFS (Groups I and II) showed a significant decrease in microbiota diversity compared to the control group (p<0.05). In the control group, the microbiota was predominantly composed of Lactobacillus species, indicating a healthy microbiome. Group I predominantly had Lactobacillus species: Lactobacillus crispatus (45%), Lactobacillus gasseri (25%), and Lactobacillus jensenii (20%). Additionally, Bifidobacterium spp. (5%), Streptococcus spp. (3%), and Enterococcus spp. (2%) were present. Group II showed a higher concentration of pathogenic bacteria, such as Gardnerella (20%), Atopobium (15%), Prevotella (5%), Mobiluncus (10%), Megasphaera (5%), Sneathia (5%), Dialister (5%), and Mycoplasma (5%). These microorganisms are often associated with bacterial vaginosis and inflammatory conditions, which can negatively impact reproductive function and contribute to the development of EFS. Conclusion. Our study confirms the significant impact of ovarian microbiota on the success of in vitro fertilization (IVF) programs in women with Empty Follicle Syndrome. We identified pronounced differences in the follicle microbiota composition between women with EFS and healthy women. Dysbiosis of the ovarian microbiota in women with EFS negatively affects IVF success rates, as evidenced by reduced microbiota diversity and the predominance of pathogenic bacteria such as Gardnerella (20%), Atopobium (15%), Prevotella (5%), Mobiluncus (10%), Megasphaera (5%), Sneathia (5%), Dialister (5%), and Mycoplasma (5%). The use of eubiotic therapy aimed at correcting microbiota showed improved reproductive outcomes in women with EFS. Treatment with Saccharomyces boulardii CNCM I-745 lyophilizate increased IVF success rates to 75% in the early reproductive age group and to 73% in the late reproductive age group, compared to 35% and 20% respectively before treatment.