Evidence map›Paper›PMID 39419175›Full record

ArticleF&S science2025

A positive ReceptivaDx result for BCL6 does not correlate with abnormal ERA results or decreased expression of receptivity-associated markers: two sides of the endometrial receptivity coin in fertility evaluation and treatment.

David Huang, Emily Flynn, Ana Almonte-Loya, Brittany Davidson, Meagan Chan, Amber Casillas, Juan C Irwin, Gabriela K Fragiadakis, Hakan Cakmak, Alexis J Combes and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in F&S science, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Observational
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

David HuangDivision of Reproductive Endocrinology and Infertility, Department of Obstetrics, Gynecology & Reproductive Sciences, University of California San Francisco, San Francisco, California. Electronic address: David.Huang@UCSF.edu.
Emily FlynnCoLabs, University of California San Francisco, San Francisco, California.
Ana Almonte-LoyaBakar Computational Health Sciences Institute, University of California San Francisco, San Francisco, California; Biomedical Informatics Program, University of California San Francisco, San Francisco, California.
Brittany DavidsonCoLabs, University of California San Francisco, San Francisco, California.
Meagan ChanDivision of Reproductive Endocrinology and Infertility, Department of Obstetrics, Gynecology & Reproductive Sciences, University of California San Francisco, San Francisco, California.
Amber CasillasDivision of Reproductive Endocrinology and Infertility, Department of Obstetrics, Gynecology & Reproductive Sciences, University of California San Francisco, San Francisco, California.
Juan C IrwinDivision of Reproductive Endocrinology and Infertility, Department of Obstetrics, Gynecology & Reproductive Sciences, University of California San Francisco, San Francisco, California.
Gabriela K FragiadakisCoLabs, University of California San Francisco, San Francisco, California; Division of Rheumatology, Department of Medicine, University of California San Francisco, San Francisco, California.
Hakan CakmakDivision of Reproductive Endocrinology and Infertility, Department of Obstetrics, Gynecology & Reproductive Sciences, University of California San Francisco, San Francisco, California.
Alexis J CombesCoLabs, University of California San Francisco, San Francisco, California.
Marcelle I CedarsDivision of Reproductive Endocrinology and Infertility, Department of Obstetrics, Gynecology & Reproductive Sciences, University of California San Francisco, San Francisco, California.
Marina SirotaBakar Computational Health Sciences Institute, University of California San Francisco, San Francisco, California.
Linda C GiudiceDivision of Reproductive Endocrinology and Infertility, Department of Obstetrics, Gynecology & Reproductive Sciences, University of California San Francisco, San Francisco, California.

Funding

Project 4: Human Endometrial Programming for Successful ImplantationP50HD055764 · NICHD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FUNG, JENNIFER C · 2014 to 2022
$16.4M
REPRODUCTIVE ENDOCRINOLOGYT32HD007263 · NICHD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MELLON, SYNTHIA H · 1985 to 2023
$4.1M
NICHD NIH HHS P50 HD055764NICHD NIH HHS T32 HD007263
6 · The paper itself

Abstract

objectiveTo investigate if a positive result on ReceptivaDx for evaluation of B-cell lymphoma 6 (BCL6), a proposed marker of progesterone resistance associated with impaired uterine receptivity, correlates with a suboptimal profile of receptivity-associated markers in the window of implantation using the endometrial receptivity array and single-nucleus transcriptomic analysis.

designRetrospective clinical cohort study; pilot study of single-nucleus RNA sequencing of prospectively collected window of implantation endometrium undergoing ReceptivaDx BCL6 evaluation. SUBJECTS: Patients with infertility who underwent endometrial biopsy for concurrent endometrial receptivity array analysis (ERA; Igenomix, Valencia, Spain) and BCL6 immunostaining (ReceptivaDx; Cicero Diagnostics, Inc., Huntington Beach, CA). EXPOSURE: Positive BCL6 result on ReceptivaDx (histologic score >1.4).

main outcome measuresPrereceptive ERA result; relative expression levels of endometrial receptivity-associated epithelial genes by single-nucleus sequencing.

resultsOne hundred and seventy-two patients with concurrent ERA and ReceptivaDx evaluation were included in the analysis: 40 were BCL6-positive and 132 were BCL6-negative. One patient (2.5%) in the BCL6-positive group had a prereceptive ERA result, compared with 29 patients (22.0%) in the BCL6-negative group (P<.01). BCL6 positivity was associated with decreased odds of a prereceptive ERA result (odds ratio, 0.09; 95% confidence interval, 0.01-0.69; P=.02). Single-nucleus transcriptomic analysis of 5,718 epithelial cell nuclei from four individuals showed significant cell type-specific transcriptomic changes associated with a positive ReceptivaDx BCL6 result in both natural cycle (NC) and programmed cycle (PC) endometrium: there were 2,801 significantly differentially expressed genes comparing NC BCL6-positive with -negative, and 1,062 differentially expressed genes comparing PC BCL6-positive with -negative. Of the 34 receptivity-associated epithelial markers evaluated, 16 were significantly upregulated in NC BCL6-positive vs. -negative endometrium epithelial nuclei. In PC epithelial nuclei, 12 of the 34 receptivity-associated genes were significantly upregulated, whereas only one was significantly downregulated in BCL6-positive vs. -negative endometrium.

conclusionsA positive ReceptivaDx BCL6 result does not correlate with a prereceptive ERA. Epithelial cells from BCL6-positive endometrium did not show significantly decreased expression in most of the receptivity markers evaluated. These findings demonstrate discordance between the interpretation of "endometrial receptivity" by ReceptivaDx and ERA, and highlight the need for further validation of endometrial evaluation methods in fertility treatment.

Indexed as

Embryo ImplantationEndometriumInfertility, FemaleProto-Oncogene Proteins c-bcl-6AdultBiomarkersFemaleFertilityHumansPilot ProjectsRetrospective StudiesBCL6 protein, humanBiomarkersProto-Oncogene Proteins c-bcl-6BCL6implantation failureinfertilityreceptivity

Identifiers

PMID39419175
PMCPMC11829826

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.