The effect of iodine supplementation on oocyte apoptosis and proliferation in women with diminished ovarian reserve: a pilot study

Masoumi M, Bagheri M, Hantoushzadeh S, Jafarabadi M, Tarazjani MD, Haghollahi F, Hedayati M, Naseri F, Nazeri P

Published October 3, 2025 Scientific reports, 15(1), 34501
DOI 10.1038/s41598-025-16545-w PMID 41044113 PMC PMC12494958

RRM Academy Synopsis

Mature eggs rose after iodine in 10 women with low ovarian reserve

Mature egg counts rose after two months of iodine supplements in 10 women with diminished ovarian reserve, a small before-and-after pilot. Cells around the eggs showed less cell death in these women. Total eggs retrieved did not change significantly.

Key Findings

  • Mature (metaphase II) eggs per woman rose from 1.9 ± 1.4 before supplementation to 3.2 ± 2.2 after (P = 0.021).
  • Total eggs retrieved went from 2.8 ± 2.3 to 4.1 ± 2.8 (P = 0.093), a difference that was not statistically significant.
  • Live cumulus cells rose from 26.4% ± 2.8 to 67.9% ± 6.5, and total apoptosis (cell death) fell from 64.0% ± 2.0 to 22.7% ± 5.1 (both P < 0.001).
  • Expression of PCNA, a cell-growth marker, showed a mean fold change of 3.38 ± 1.10 after supplementation (P < 0.001).
  • Urinary iodine moved from borderline sufficiency to optimal levels (P = 0.001).

Interpretation

The study is a before-and-after pilot with no control group. Each woman's second stimulation cycle, after iodine, was compared with her first. The authors name natural variation over time and repeated stimulation cycles as possible confounders. The authors call for a double-blind randomized trial. The 10 women were aged 25 to 42 and had no endometriosis or thyroid disorder. Cell measures are surrogate markers that may not translate into pregnancy or live birth. The paper reports no pregnancy outcomes and calls its findings hypothesis-generating.

RRM Context

Restorative reproductive medicine treats low ovarian reserve as a finding to investigate. Nutrient status belongs among the questions. A US cohort study cited by the paper (Mills 2018) associated moderate-to-severe iodine deficiency with a 46% decrease in the monthly chance of conceiving. The pilot followed no couple to conception.

Abstract

Iodine, an essential trace element, may play a role in reproductive health through its extrathyroidal actions. This study aimed to investigate the effects of iodine supplementation on oocyte apoptosis and proliferation in women with diminished ovarian reserve. A quasi-experimental study was conducted on ten women undergoing two cycles of ovarian stimulation. In the first cycle, they followed the standard protocol, while in the second, they received a daily 150 µg iodine supplement for two months. Urinary iodine levels, cumulus cell apoptosis and necrosis, and PCNA expression were evaluated before and after supplementation. We found that iodine supplementation significantly improved women's iodine status, increasing it from borderline sufficiency to optimal levels. This improvement was accompanied by a significant increase in the number of metaphase II oocytes. Following iodine supplementation, we observed a marked increase in cumulus cell viability and a reduction in both early and late apoptosis. Additionally, the expression of PCNA was upregulated, showing a positive association with the percentage of live cells and a reduction in total apoptosis. These findings suggest that iodine supplementation could be a promising therapeutic strategy for improving oocyte quality and enhancing fertility outcomes, particularly in women with diminished ovarian reserve.

By this author

Related research

Masoumeh Masoumi, Maryam Bagheri, Sedighe Hantoushzadeh, Mina Jafarabadi, Masoumeh Dehghan Tarazjani, Fedyeh Haghollahi, Mehdi Hedayati, Farnush Naseri, Pantea Nazeri
M Masoumi, M Bagheri, S Hantoushzadeh, M Jafarabadi, M Tarazjani, F Haghollahi, M Hedayati, F Naseri, P Nazeri
PMID 41044113 41044113 DOI 10.1038/s41598-025-16545-w 10.1038/s41598-025-16545-w Masoumi et al. 2025, Masoumi 2025