A pilot study and case reports on endometrial microbiota and pregnancy outcome: An analysis using 16S rRNA gene sequencing among IVF patients, and trial therapeutic intervention for dysbiotic endometrium

Abstract

Purpose: The present study aimed to analyze the pregnancy outcomes of IVF patients presenting Lactobacillus-dominated microbiota (LDM) or non-Lactobacillus-dominated microbiota (NLDM) of their endometrium and to report cases who were treated for NLDM concurrently with antibiotics and prebiotic/probiotic supplements in a Japanese infertile population.

Methods: Ninety-two IVF patients were recruited from August 2017 to March 2018. Endometrial fluid samples for sequencing were collected using an IUI catheter. The bacterial status of the endometrium and the pregnancy outcomes were analyzed. For cases with NLDM, antibiotics and prebiotics/probiotics were administered according to their individual microbial conditions.

Results: Forty-seven cases (51.1%) presented LDM and 45 cases (48.9%) presented NLDM at initial analysis. Nine Patients with NLDM were treated by antibiotics and prebiotics/probiotics, and successfully became Lactobacillus-dominant. Pregnancy rates by single vitrified-warmed blastocyst transfers were higher in the LDM group (58.9% per patient and 36.3% per FBT) than in the NLDM group (47.2% per patient and 34.7% per FBT) but not significantly different.

Conclusion: The results of this study could not necessarily prove the clear benefit of establishing Lactobacillus-dominated endometrium in terms of pregnancy outcome, but there is significance in searching for endometrial microbial status of infertile patients and recovering Lactobacillus-dominated endometrium might benefit implantation.

Keywords: dysbiosis; endometrium; infertility; prebiotics; probiotics.

Figure 1

Details of patients included in this study. A total of 117 IVF patients were analyzed from August 2017 to March 2018. Ninety‐two patients who eventually underwent frozen‐thawed blastocyst transfers were eligible for this study. LDM, Lactobacillus‐dominated microbiota; NLDM, non‐Lactobacillus‐dominated microbiota; FBT, frozen‐thawed blastocyst transfer

Figure 2

A, The endometrial microbiomes of the NLDM patients before treatment. Those patients became LDM after therapeutic interventions. B, The endometrial microbiomes of the LDM patients who presented NLDM before treatment. ^*Patients achieved pregnancy in the following FBT. The letters below the graph show each participant. The same letter belongs to the same patient

Figure 3

The endometrial microbiomes of the NLDM patients who had no interventions before FBT. ^*Patients achieved pregnancy in the following FBT. ^**Patients achieved pregnancy but ended up in early miscarriages in the following FBT. The letters below the graph show each participant

Figure 4

The endometrial microbiomes of the NLDM patients who had therapeutic interventions before FBT. ^*Patients achieved pregnancy in the following FBT. ^**Patients achieved pregnancy but ended up in early miscarriages in the following FBT. The letters below the graph show each participant. NLD‐L is identical to NT‐G in Figure 3; this patient underwent two FBTs during the study period, first FBT was after the initial endometrial microbiome analysis (without treatment), and second FBT was after the reanalysis (with treatment intervention). NLD‐J1 is identical to NLD‐J2

Figure 5

Course of treatment in Case 1 (identical to Case B in Figure 2). AMPC, amoxicillin

Figure 6

Course of treatment in Case 2 (identical to Case A in Figure 2). FBT, frozen‐thawed blastocyst transfer; LVFX, levofloxacin

Figure 7

Course of treatment in Case 3 (identical to Case D in Figure 2). CFDN, cefdinir; DOXY, doxycycline; FBT, frozen‐thawed blastocyst transfer; LVFX, levofloxacin; OPU, oocyte pickup