Semaglutide may interfere with ovarian function and fertility through insulin-AMPK-mTOR signaling pathways | Research

The takeaway

Semaglutide affects insulin, AMPK, IGF-1, mTOR, and sirtuin pathways that converge on ovarian function and oocyte development, raising concerns about off-label use before IVF and potential starvation/sarcopenia effects on fertility.

No reproductive safety data
Semaglutide affects multiple pathways critical for ovarian function, yet no preclinical data exist on its reproductive implications

What the researchers found

SG affects insulin/AMPK/IGF-1/mTOR/sirtuin pathways that regulate oocyte development, ovarian aging, and embryo implantation. Off-label use could cause starvation/sarcopenia with fertility consequences. No preclinical data exist on ovarian implications of SG.

Why it matters

Millions of reproductive-age women are taking semaglutide, often off-label for cosmetic weight loss. The lack of any reproductive safety data is a critical gap, especially for women planning pregnancy or IVF.

How the study worked

Narrative review examining GLP-1 signaling pathway intersections with reproductive biology, focusing on energy balance, ovarian function, and follicular development.

What this study cannot tell us

Review based on pathway analysis, not direct reproductive studies. No clinical or preclinical data specific to SG and fertility. Theoretical concerns may not translate to actual risks.

How to read the evidence

Narrative review of pathway biology. Raises important theoretical concerns but lacks direct evidence of reproductive harm.

When this study was published

Published in 2025; addresses an urgent and growing concern.

The bigger picture

As semaglutide becomes one of the most prescribed drugs globally, its effects on fertility represent a massive blind spot in our safety knowledge. The growing number of reproductive-age users makes this an urgent research priority.

Questions still open

Does semaglutide affect oocyte quality or quantity?
Should women stop semaglutide before IVF, and how far in advance?
Could semaglutide-induced weight loss improve or worsen IVF outcomes?

Common questions

Could semaglutide affect fertility?

This review raises theoretical concerns that semaglutide's effects on insulin, energy-sensing, and growth factor pathways could interfere with egg development, ovarian function, and embryo implantation. However, no direct studies have been done—the concern is based on biological pathway analysis, not proven harm.

Should I stop semaglutide before trying to get pregnant?

The manufacturer already recommends stopping semaglutide at least 2 months before conception. This review adds urgency to that recommendation, noting that semaglutide's effects on metabolic pathways critical for reproduction are completely unstudied. Women planning pregnancy or IVF should discuss timing with their doctor.

Read the original research

Semaglutide and human reproduction: caution at the intersection of energy balance, ovarian function, and follicular development.

Reproductive biology and endocrinology : RB&E, 23(1), 116

View on PubMed ↗Publisher’s paper ↗

Citation

Sills, E Scott; Harrity, Conor; Chu, Howard I; Wang, Jing-Wen; Yang, Fan; Wood, Samuel H. (2025). Semaglutide and human reproduction: caution at the intersection of energy balance, ovarian function, and follicular development.. Reproductive biology and endocrinology : RB&E, 23(1), 116. https://doi.org/10.1186/s12958-025-01435-7