Clarification on preconception metformin exposure timing and the heterogeneity across included studies (reply to letter to the editor)
Cheshire, James Garg, Akanksha Smith, Paul Devall, Adam J Coomarasamy, Arri Dhillon-Smith, Rima K
Cheshire, James
Garg, Akanksha
Smith, Paul
Devall, Adam J
Coomarasamy, Arri
Dhillon-Smith, Rima K
Abstract
We are responding to the letter regarding our recent publication.1,2 The author rightly observes that the included trials in our article differ regarding both the initiation of preconception metformin and the duration of treatment. Some studies began preconception metformin up to 12 weeks before either ovulation induction (OI) or controlled ovarian stimulation (COS), whereas other studies initiated metformin concurrently with the start of OI/COS. We acknowledge this heterogeneity and recognize the time-dependent metabolic and endocrine mechanisms by which metformin has been proposed to reduce insulin resistance. However, because of several factors, including the nature of anovulation associated with polycystic ovary syndrome (PCOS), variation in individual participants’ response and their required duration of OI treatment, the duration of COS protocols, and uncertainty surrounding individual participant’s time to conception, it is impossible to know the precise duration of preconception metformin for each participant. Given the above, adjusting for preconception metformin exposure length in our analyses was not possible, and a pragmatic approach was adopted.
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Date
2025-12-22
Type
Article
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Citation
Cheshire J, Garg A, Smith P, Devall AJ, Coomarasamy A, Dhillon-Smith RK. Clarification on preconception metformin exposure timing and the heterogeneity across included studies (reply to letter to the editor). Am J Obstet Gynecol. 2026 May;234(5):e187-e188. doi: 10.1016/j.ajog.2025.12.051. Epub 2025 Dec 22.