Unpacking the Link Between Cannabis Use and Female Fertility: A Closer Look at the Human Egg

IVF.net Newsdesk

06 October 2025

| | | |

Cannabis is one of the most widely used recreational drugs among people of reproductive age globally. Driven by rising legalization and easier access, cannabis use is increasing worldwide, often at higher strengths, with THC (tetrahydrocannabinol) potency rising from approximately 3% in the 1980s to around 15% or even 30% today.

While the effects of THC—the primary psychoactive compound—on male fertility (sperm count, motility, and DNA) and pregnancy outcomes are relatively well-documented, the impact on the female gamete, the oocyte (egg), has remained a significant knowledge gap. Oocytes are finite in number and highly sensitive to environmental factors, meaning any disruptions in their development could profoundly affect fertility and the health of future embryos.

Recent groundbreaking research, combining clinical analysis with controlled laboratory experiments, sheds light on this critical issue, revealing a complex, two-sided impact of THC on human egg quality.

The Dual Impact: Accelerated Maturation at a Genetic Cost

Researchers at the CReATe Fertility Centre in Toronto investigated how THC exposure influences human oocytes. The study used a dual approach: a retrospective analysis of patients undergoing in vitro fertilization (IVF) and controlled in vitro lab experiments.

1. The Retrospective Clinical Analysis

The team analyzed 1,059 follicular fluid samples from IVF patients, finding that approximately 6% (62 samples) tested positive for THC metabolites. Notably, 73% of those patients who tested positive had not reported cannabis use on their intake questionnaires, highlighting the potential issue of under-reporting in clinical settings.

The analysis revealed a key paradox:

Increased Maturation: Concentrations of THC and its metabolites in the follicular fluid were positively correlated with a higher rate of oocyte maturation.
Reduced Quality: However, the embryos that developed from these oocytes were significantly less likely to have the correct number of chromosomes (meaning a lower rate of euploid embryos) compared to matched controls.

This suggests that THC exposure may push oocytes to mature faster, but this comes "at the cost of genetic stability". A higher maturation rate may appear positive, but developing too quickly can disrupt the essential time chromosomes need to align perfectly for reproduction.

2. The In Vitro Mechanisms

To understand the biological basis for these clinical findings, researchers exposed immature oocytes donated by 24 patients to two concentrations of THC—a physiologically relevant dose (THC1) and a higher, supraphysiological dose (THC2).

Exposure to THC induced several harmful cellular and genetic changes:

Chromosome Errors (Aneuploidy): Both THC concentrations led to a 9% increase in aneuploidy rates (embryos with an incorrect number of chromosomes) in the oocytes tested, along with a higher proportion of complex aneuploidies.
Spindle Disruption: THC exposure resulted in a dose-dependent decrease in the proportion of oocytes with normal spindle morphology. Spindle structures are cellular machinery made of microtubules crucial for separating chromosomes during cell division, and abnormal spindles can lead to errors in chromosome number.
Gene Expression Changes: THC altered gene activity within the oocytes. Many of the affected genes are critical for egg quality and embryo development, playing roles in inflammation, the extracellular matrix, and chromosome segregation. For instance, genes involved in GPCR signaling (RGS5 and RGS18) and inflammation (IFNG and IL33) were dysregulated. Furthermore, the downregulation of MMP9—a gene crucial for the breakdown of the extracellular matrix—may negatively affect key reproductive processes like ovulation, embryo development, and implantation.

The prevailing scientific hypothesis suggests that THC binds to cannabinoid receptors (CB1/CB2) present on the oocyte surface. This binding may activate the receptors, leading to the inhibition of adenylate cyclase, which, in turn, reduces ooplasm cAMP levels. Since high cAMP levels are critical to prevent premature meiotic resumption, its reduction caused by THC could result in the untimely, premature resumption of meiosis. This process increases the likelihood of chromosome misalignment and subsequent aneuploidy.

Implications for Fertility Counseling

These findings underscore the importance of increased awareness and caution among individuals with ovaries, especially those undergoing fertility treatments.

For patients undergoing IVF, exposure to THC could mean fewer euploid embryos available for transfer, which might prolong the time required to achieve a successful pregnancy. THC positivity was found to significantly decrease the odds of achieving a blastulation rate above 50% and a euploidy rate above 60%. Since embryo euploidy is strongly linked to successful implantation and healthy pregnancy, cannabis use may compromise reproductive outcomes by increasing the risk of IVF failure and miscarriage.

Fertility specialists are urged to routinely counsel patients on the potential risks of cannabis use. Experts advise patients attempting conception or undergoing IVF to avoid cannabis use, given that even occasional exposure may introduce THC into the follicular niche. Given the rising potency of cannabis products (some strains reach 30% THC), exposure to higher THC levels poses an increased risk of reproductive complications.

It is important to note that the study focused on oocytes collected during IVF, which may not perfectly reflect eggs maturing naturally, and it did not address the association of cannabis use with live birth outcomes. Further research is needed to determine how THC disrupts egg biology at the molecular level and to track pregnancy and live birth outcomes in larger studies. Ultimately, this research provides a strong basis for regulatory bodies, medical professional societies, and public health organizations to establish clear guidelines regarding cannabis consumption during fertility treatment.

Sources

9 September 2025. Nature Communications