Evidence map›Paper›PMID 40373756›Full record

Observational studyGynecologic and obstetric investigation2026

Endometrial Metabolism of 17β-Estradiol during the Window of Implantation in Women with Recurrent Implantation Failure.

Linda B P M Stevens Brentjens, Bert Delvoux, Janneke E den Hartog, Darina Obukhova, Sofia Xanthoulea, Andrea Romano, Ron J T van Golde

Abstract readObservational Study
In one paragraph

Observational study in Gynecologic and obstetric investigation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Review
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

7 authors.

Linda B P M Stevens BrentjensDepartment of Obstetrics and Gynaecology, Maastricht University Medical Centre+, Maastricht, The Netherlands, linda.brentjens@mumc.nl.
Bert DelvouxDepartment of Obstetrics and Gynaecology, Maastricht University Medical Centre+, Maastricht, The Netherlands.
Janneke E den HartogDepartment of Obstetrics and Gynaecology, Maastricht University Medical Centre+, Maastricht, The Netherlands.
Darina ObukhovaGROW Research Institute for Oncology and Reproduction, Maastricht University, Maastricht, The Netherlands.
Sofia XanthouleaDepartment of Obstetrics and Gynaecology, Maastricht University Medical Centre+, Maastricht, The Netherlands.
Andrea RomanoDepartment of Obstetrics and Gynaecology, Maastricht University Medical Centre+, Maastricht, The Netherlands.
Ron J T van GoldeDepartment of Obstetrics and Gynaecology, Maastricht University Medical Centre+, Maastricht, The Netherlands.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

<p>Objectives: Alterations in 17β-estradiol metabolism are known to potentially impair endometrial receptivity. Previous pioneering studies have investigated the role of endometrial steroid metabolism by determining steroid hormone levels and steroid-metabolizing enzyme activity in endometrial biopsies of patients undergoing IVF. The activity of oxidative and reductive 17β-hydroxysteroid dehydrogenases (17β-HSDs), which catalyze the interconversion between estrone and 17β-estradiol, was found to be similar between IVF patients who - after fresh embryo transfer in the cycle following endometrial biopsy - did and did not become pregnant. However, inhibition of the reductive enzyme 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1), the most prominent 17β-HSD type in 17β-estradiol formation, was found to differ between groups. The primary objective of this study was to determine oxidative and reductive 17β-HSD enzyme activity in the endometrium of two well-defined groups: IVF patients with recurrent implantation failure (RIF) and control patients.

designThis is a prospective observational study of IVF patients with RIF (n = 52) and controls (n = 25). Patients undergoing treatment because of pre-implantation genetic testing, a severe male factor, or bilateral tubal pathology were recruited as controls since these conditions did not suggest an endometrial contribution to infertility. PARTICIPANTS/MATERIALS, SETTING,

methodsEndometrial biopsies were obtained 5-8 days after a positive urine ovulation test in a natural cycle using a Pipelle catheter. Activity of oxidative and reductive enzymes, inhibition of 17β-HSD1, 5, 7, and 12, and immunostaining of 17β-HSD7 were performed. The formation of 17β-estradiol by reduction of estrone (reductive enzymes), formation of estrone by oxidation of 17β-estradiol (oxidative enzymes), and inhibition of specific 17β-HSD enzymes were determined using high-performance liquid chromatography. Formalin-fixed paraffin-embedded tissue was used for immunostaining. The Student's t test and Mann-Whitney U test were used for statistical analysis. Multivariate analysis was used to determine the influence of confounders.

resultsNo differences were found in activity of oxidative and reductive 17β-HSD enzymes in RIF patients and controls. Combined inhibition of 17β-HSD5, 7, and 12 was significantly lower in the RIF group compared to controls (p = 0.04). Inhibition of 17β-HSD1 and 17β-HSD7 combined was also significantly lower (more production of 17β-estradiol remained) in the RIF group compared to controls (p < 0.01). However, solely inhibiting 17β-HSD1 or 17β-HSD7 showed no significant difference between groups. Immunostaining revealed the expression of 17β-HSD7 in all endometrial samples. LIMITATIONS: Results should be interpreted carefully due to possible cycle-to-cycle variation, challenges to translate in vitro findings to biological conditions, and the heterogeneous etiology of RIF.

conclusionsDifferences in formation of 17β-estradiol in the presence of two specific inhibitors of 17β-HSD1 and 7 between RIF patients and controls were found. Although 17β-HSD1, expressed at the fetal-maternal interface, has been associated with fertility, the potential role of 17β-HSD7 in human implantation has not been previously described. The observed differences between patients with RIF and controls warrant future research on the role of this main enzyme and its lesser-known 17β-HSD type in endometrial receptivity and implantation. </p>.

Indexed as

17-Hydroxysteroid DehydrogenasesEmbryo ImplantationEndometriumEstradiolAdultEmbryo TransferFemaleFertilization in VitroHumansPregnancyProspective StudiesTreatment Failure17-Hydroxysteroid DehydrogenasesEstradiol17β-EstradiolEndometriumImplantationIntracrinologyIn vitro fertilization

Identifiers

PMID40373756
PMCPMC12215175

What OpenQuestion holds

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Registered trials

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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.