P-307 Evaluation of pregnancy rates post-probiotic treatment in patients with varied Lactobacillus species in pre-transfer endometrial microbiome analysis
Authors: García de Miguel L , Beltrán J , Díaz-López C , Campos D , Díez-Tercero L , Horcajadas Almansa J  A , Llaneza A 
Published: July 2024

Abstract

Study question
Are there differences in clinical outcomes based on the predominant species of Lactobacillus in the endometrium of patients treated with probiotics?

Summary answer
No discernible variations in clinical outcomes were noted based on the Lactobacillus species identified in the pre-transfer microbiome analysis after personalized probiotic treatment.

What is known already
Lactobacillus is the genus with the greatest presence in the female reproductive tract. They are responsible for acidifying the environment and play an important role in the prevention of excessive proliferation of pathogens through different mechanisms (competitive inhibition or production of antimicrobial compounds). Among the species of Lactobacillus, crispatus, iners, jensenii and gasseri are the most frequent in the endometrium. Lactobacillus species share some genus-specific characteristics. However, there are differences in the production of antimicrobial compounds among the species: L. iners has a lower production of hydrogen peroxide and lower anti-inflammatory capacity and therefore has lower protective capacity against pathogens.

Study design, size, duration
A retrospective study analyzed with 209 endometrial samples from 164 patients with previous implantation failure or miscarriage (average age= 41.47-/+4.66 years). Patients underwent endometrial microbiota testing between May 2021 and December 2022. Following analysis, patients received personalized probiotic treatment based on results, particularly tailored for L. iners overgrowth. One hundred and thirty-five patients underwent an embryo transfer after completing the treatment.

Participants/materials, setting, methods
DNA from endometrial biopsies was analyzed to detect bacteria, fungi and viruses. To evaluate the potential impact of L. iners presence, clinical outcomes were calculated across patient groups with varying percentages of this Lactobacillus species. These rates were compared to those of L. crispatus, known as the most favourable species. Furthermore, the analysis subdivided the detected percentages of each species into differente ranges to discern potential variations in clinical outcomes based on the percentage levels.

Main results and the role of chance
The overall implantation rate following probiotic and antibiotic treatment (as needed) was 52.59%, with a clinical pregnancy rate of 46.67%. Notably, no statistically significant differences were observed in between patients with a dominant Lactobacillus microbiome (&gt;90%) and those without prior to the treatments. These findings were anticipated, given the probiotic treatment’s inclusion of Lactobacillus strains, which foster an acidic environment conducive to the establishment of endometrial Lactobacillus species. Interestingly, regardless of the percentage of L. crispatus detected in the endometrial biopsy prior to probiotic treatment, implantation rates remained consistently above 50%, with no statistically significant differences observed. Conversely, patients with a high percentage of L. iners (&gt;75%) exhibited a lower implantation rate of 38%, though this disparity was not statistically significant compared to patients with a high percentage of L. crispatus. No statistically significant differences were observed in the clinical outcomes comparing L. crispatus and L. iners. However, high % of L. crispatus was associated with a lower miscarriage rate compared to high % of L. iners (13%vs22%, respectively). This may be attributed to the treatment administered prior transfer, which aims to rebalance Lactobacillus composition, especially in cases of L. iners dominance.

Limitations, reasons for caution
All patients included in this study underwent personalized probiotic treatment before embryo transfer, limiting the ability to directly assess the impact of L. iners on pregnancy outcomes. Additionally, increasing the number of patients would strengthen the study’s findings and confirm the observed findings.

Wider implications of the findings
Microbiota studies can effectively identify various species within the same genus (Lactobacillus spp). Personalized probiotic treatment appeared to balance endometrial microbiota, not only increasing the percentage of Lactobacillus in patients with a non- dominant Lactobacillus environment, but also modify the type of Lactobacillus species that are present in the endometrium.

Trial registration number
not applicable