# Caffeine Supplementation Enhances Aged Human Oocyte Quality and Embryo Development in In Vitro Fertilization: A Retrospective Paired Study

## TL;DR

Caffeine added during IVF improves embryo quality and pregnancy chances in older women, with no harm to babies.

## Contribution

Shows caffeine supplementation in IVF improves oocyte spindle integrity and embryo quality in older women.

## Key findings

- Caffeine cycles had higher normal spindle positioning (80.2% vs. 61.2%) and better embryo quality.
- Euploidy rates doubled with caffeine (22.9% vs. 10.9%) and clinical pregnancy rates were 39.1%.
- Neonatal outcomes were reassuring with no adverse effects noted.

## Abstract

To evaluate whether in vitro caffeine supplementation can improve spindle integrity, embryo development, and clinical outcomes in IVF.

This retrospective paired‐cohort study included 704 women aged ≥ 35 years who underwent two ICSI cycles (one caffeine‐supplemented and one non‐caffeine) within 12 months. Oocytes in caffeine cycles were exposed to 1.25 mM caffeine for 4 h before fertilization. Outcomes included spindle positioning, embryo quality, blastocyst development and euploidy rates, and neonatal outcomes from 20 women (24 neonates). Paired comparisons were performed using the Wilcoxon signed‐rank and McNemar's tests.

Caffeine cycles showed higher rates of normal spindle positioning (80.2% vs. 61.2%, p < 0.001), high‐quality cleavage embryos (63.2% vs. 53.6%, p < 0.001), high‐quality blastocysts (39.2% vs. 26.1%, p < 0.001), and euploid embryos (22.9% vs. 10.9%, p = 0.002) than non‐caffeine cycles. The fertilization rates were similar between the groups (81.4% vs. 80.8%, p = 0.628). Clinical pregnancy rate was 39.1%, and neonatal outcomes were reassuring.

Short‐term in vitro caffeine exposure may enhance oocyte and embryo competence in older women undergoing IVF, especially those with prior IVF failures. These findings support caffeine as a simple, practical laboratory intervention. Prospective multicenter studies are warranted to confirm efficacy and safety.

Caffeine supplementation before fertilization is associated with improved spindle integrity, euploidy rates, and embryo quality in oocytes from aged women, with favorable clinical and neonatal outcomes, suggesting a simple and low‐cost strategy that may support IVF outcomes, particularly in older patients or those with repeated IVF failures.