# Embryo Culture Duration Is an Independent Risk Factor for Gestational Diabetes in Frozen Embryo Transfer Pregnancies

**Authors:** Huijun Chen, Shujuan Ma, Yvonne Liu, Yifan Gu, Fei Gong, Philipp Kalk, Carl-Friedrich Hocher, Ge Lin, Berthold Hocher

PMC · DOI: 10.1210/jendso/bvaf161 · 2025-10-17

## TL;DR

Leaving embryos in culture longer before freezing increases the risk of gestational diabetes in pregnancies.

## Contribution

This study identifies prolonged embryo culture as an independent risk factor for gestational diabetes in frozen embryo transfer pregnancies.

## Key findings

- Blastocyst-stage transfers had higher gestational diabetes rates than cleavage-stage transfers.
- Prolonged embryo culture remained a significant risk factor after adjusting for maternal factors.
- Combining blastocyst transfer with maternal metabolic risk factors further increased gestational diabetes incidence.

## Abstract

To investigate whether prolonged embryo culture increases the risk of gestational diabetes mellitus (GDM) in pregnancies conceived via frozen embryo transfer (FET).

In this retrospective cohort study, 26 100 FET pregnancies from 2018 to 2022 were analyzed. GDM was diagnosed by a 75-g oral glucose tolerance test. Embryo culture duration (day 3 vs day 5 vs day 6) and morphology were evaluated. Multivariable logistic regression adjusted for maternal age, body mass index, and fasting glucose. Interaction analyses assessed the combined effect of blastocyst transfer and maternal metabolic risk factors.

GDM occurred in 14.0% of pregnancies. Blastocyst-stage transfers were associated with a significantly higher GDM risk than cleavage-stage transfers (day 3: 15.1%; day 5: 17.4%; day 6: 18.2%; P = .01). Prolonged embryo culture remained an independent risk factor in adjusted models (odds ratio, 1.045; 95% CI, 1.019-1.071; P < .01). Embryo morphology showed no significant association with GDM. The combination of blastocyst transfer and maternal metabolic risk factors further increased GDM incidence.

Prolonged embryo culture is an independent risk factor for GDM after FET. These findings suggest embryo development stage influences maternal glucose metabolism and should be considered in assisted reproductive technology protocols, particularly for women with existing metabolic vulnerabilities.

## Linked entities

- **Diseases:** gestational diabetes mellitus (MONDO:0005406), gestational diabetes (MONDO:0005406)

## Full-text entities

- **Diseases:** GDM (MESH:D016640)
- **Chemicals:** glucose (MESH:D005947)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12860052/full.md

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Source: https://tomesphere.com/paper/PMC12860052