UMIN-ICDS Clinical Trial

Public title

Multicenter prospective cohort study on the impact of prior probiotic use on endometrial microbiota (EMMA/ALICE) and chronic endometritis (CD138) diagnosis

Acronym

Probiotic Use and EMMA/ALICE-CD138 Concordance Study

Scientific Title

Multicenter prospective cohort study on the impact of prior probiotic use on endometrial microbiota (EMMA/ALICE) and chronic endometritis (CD138) diagnosis

Scientific Title:Acronym

Probiotic Use and EMMA/ALICE-CD138 Concordance Study

Region

Japan

Condition

Repeated implantation failure (after 1-2 failed FET cycles); suspected chronic endometritis

Classification by specialty

Obstetrics and Gynecology

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

To examine the impact of prior probiotic (Lactosupli) use on the diagnosis of chronic endometritis (CE) by EMMA/ALICE (endometrial microbiota qPCR) and CD138 immunohistochemistry, through simultaneous evaluation of the same biopsy specimen.
Primary hypothesis: prior probiotic use lowers the pathogen positivity rate by EMMA/ALICE.
Secondary hypothesis: to examine whether prior probiotic use affects the CD138-positive CE rate.

Basic objectives2

Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

Composite EMMA/ALICE positivity rate (positive for any of the 26-species panel, EMMA2 qPCR, sampled during the luteal phase P+5-12 or LH+7-12)

Key secondary outcomes

CD138-positive CE rate (5 or more stromal plasma cells/10HPF); distribution across the EMMA/ALICE x CD138 2x2 matrix (groups A-D) by probiotic use; L. crispatus positivity rate and detection rates of major pathogenic species (Bifidobacterium, Gardnerella, Atopobium); pathogen clearance rate on retesting after treatment in EMMA/ALICE-abnormal cases; clinical and ongoing pregnancy rates at the next FET after treatment based on the EMMA/ALICE report; exploratory: frequency and FET outcomes of the discordant group (EMMA/ALICE-negative, CD138-positive), and effect-size estimation for a future interventional RCT

Study type

Observational

Basic design

Randomization

Randomization unit

Blinding

Control

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

Purpose of intervention

Type of intervention

Interventions/Control_1

Interventions/Control_2

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

18

years-old

<=

Age-upper limit

Not applicable

Gender

Female

Key inclusion criteria

Patients at Kamiya Ladies Clinic or Kameda IVF Clinic Makuhari who did not achieve clinical pregnancy after 1-2 FET cycles (regardless of Layer 1 enrollment); willing and consenting to undergo EMMA/ALICE testing; consenting to CD138 immunohistochemistry on the same biopsy specimen; age 18 years or older; written informed consent obtained

Key exclusion criteria

Patients who have already undergone EMMA/ALICE testing with results available (since the relevant oocyte retrieval cycle); systemic antibiotic treatment within 2 weeks before endometrial biopsy; known recurrent pregnancy loss (antiphospholipid syndrome, uterine anomaly, parental chromosomal abnormality, etc.); refusal of study participation

Target sample size

496

Name of lead principal investigator

1st name	HIrobumi
Middle name
Last name	Kamiya

Organization

Iryo Hojin Shadan Kamiya Ladies Clinic

Division name

Reproductive Medicine

Zip code

0600003

Address

NX Sapporo Bldg 2F, 2-1, Nishi2, Kita3, Chuo-ku, Sapporo, Hokkaido, 0600003, Japan

TEL

0112312722

Email

kamiya@fine.ocn.ne.jp

Name of contact person

1st name	Nanako
Middle name
Last name	Iwami

Organization

Iryo Hojin Shadan Kamiya Ladies Clinic

Division name

Reproductive Medicine

Zip code

0600003

Address

NX Sapporo Bldg 2F, 2-1, Nishi2, Kita3, Chuo-ku, Sapporo, Hokkaido, 0600003, Japan

TEL

0112312722

Homepage URL

Email

nanakoiwami@gmail.com

Institute

Iryo Hojin Shadan Kamiya Ladies Clinic

Institute

Department

Personal name

Organization

Iryo Hojin Shadan Kamiya Ladies Clinic

Organization

Division

Category of Funding Organization

Self funding

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Iryo Hojin Shadan Kamiya Ladies Clinic

Address

NX Sapporo Bldg 2F, 2-1, Nishi2, Kita3, Chuo-ku, Sapporo, Hokkaido, 0600003, Japan

Tel

0112312722

Email

tozawa@kamiyaclinic.com

Secondary IDs

YES

Study ID_1

UMIN000063413

Org. issuing International ID_1

University hospital Medical Information Network (UMIN) Center

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2026

Year

10

Month

27

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Preinitiation

Date of protocol fixation

2026

Year

03

Month

10

Day

Date of IRB

2026

Year

03

Month

14

Day

Anticipated trial start date

2026

Year

10

Month

27

Day

Last follow-up date

2028

Year

03

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Prospective, multicenter (2 sites: Kamiya Ladies Clinic [Sapporo] and Kameda IVF Clinic Makuhari [Chiba]), independent cohort study.
Exposure and outcome: In patients undergoing EMMA/ALICE testing after 1-2 unsuccessful frozen-thawed embryo transfer (FET) cycles, the primary evaluation is the association between prior probiotic (Lactosupli 2) use (use or non-use for 10 days or more before EMMA/ALICE testing) and the pathogen positivity rate by EMMA/ALICE (endometrial microbiota qPCR, EMMA2). We will also examine the concordance with the diagnosis of chronic endometritis (CE) by CD138 immunohistochemistry on the same biopsy specimen (2x2 matrix evaluation).
Sampling: Consecutive enrollment. No case-control type selection will be performed.
Grouping is based on the patient's clinical decision on probiotic use. No randomization by investigators will be performed. Patients are recruited independently regardless of Layer 1 enrollment.
Analysis: Groups will be compared by the chi-square test and multivariable logistic regression, as a superiority design (an analytic framework independent of the propensity score matching in Layer 1).
This study is related to UMIN000063413 (Layer 1: a study of an individualized probiotic administration strategy based on vaginal culture screening and pregnancy outcomes of FET). Both are conducted under the same principal investigator and the same ethics committee approval.

Registered date

2026

Year

10

Month

26

Day

Last modified on

2026

Year

10

Month

26

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000072577