The study presented in this paper is a retrospective cohort study that assessed multiple male and female reproductive outcome measures among all couples completing oocyte retrieval in one IVF center. As the data was collected during years in which the recreational use of cannabis was considered both legally and socially acceptable, patients faced fewer barriers to voluntarily disclose using cannabis. The prevalence of cannabis users in our study (9.4%), male users (7.3%), and female users (4%) was lower than previously reported among couples trying to conceive (Kasman et al. 2018); however, this study included only infertile patients that may be less likely to engage in a potentially unhealthy lifestyle. This rate of cannabis use is similar to the rate reported by a recent Canadian survey (Keethakumar et al. 2021).

All the reproductive outcomes of cannabis users and non-users in our study were comparable. These parameters included measures of ovarian response, sperm quality, efficiency of fertilization, early embryonic development, and implantation. In fact, the ongoing pregnancy rate per cycle start trended higher for the group of cannabis users (35.2% vs. 29.1%). This could partially relate to the female participants in the user group being younger than the non-user counterparts.

The use of cannabis is growing rapidly and gaining widespread legal and social acceptance, while the consumption of tobacco is on a continuous decline because of health concerns, legislation, and social trends (Gagne 2017). According to the Canadian Alcohol and Drug Use Monitoring Survey sponsored by Health Canada, 41.5% of Canadians aged 15 years and older have used cannabis in their lifetime and 10.2% have used cannabis in the past year alone (Porath et al., 2019). In Canada, the use of cannabis for both medicinal and recreational uses was legalized in October 2018. The legalization of cannabis is leading to an inevitable increase in its popularity especially among men and women of reproductive age. A similar trend was also evidenced among couples trying to conceive and pregnant women (Volkow et al. 2019). A recent study compared the preconception, prenatal, and post-natal prevalence use of cannabis in states that legalized recreational cannabis use versus states that did not (Skelton, Hecht, and Benjamin-Neelon 2020). The survey showed women residing in states that legalized recreational cannabis were significantly more likely to use it before and during pregnancy.

Furthermore, the widespread consumption of cannabis among males in the reproductive age raised health concerns.

The increase in the use of cannabis took place despite concerning reports from both animal and human studies associating chronic exposure to inhaled or injected cannabis with sperm abnormalities as well as the development of testicular lesions. Injection of the cannabis-derived tetra-hydro-cannabinol (THC)—the active component of cannabis—to mice was associated with the arrest of spermatogenesis (Dalterio et al. 1982; Nahas et al. 2002).

These reports followed earlier publications reporting that either in vitro or in vivo acute exposure of spermatozoa in a number of species, including humans, to several types of cannabinoids led to a reduced fertilization rate. This finding was attributed to the inhibition of the acrosome reaction as well as decreased sperm motility (Schuel et al. 1994; Amoako et al. 2013; Schuel et al. 1987; Hong et al. 1982; Whan et al. 2006; Chang et al. 1993; Rossato et al. 2005).

A large human cohort study found that a routine use of cannabis at a rate of twice a week or more was associated with a 30% reduction in sperm concentration (Gundersen et al. 2015). This rate was similar to the rate of cannabis use reported by most of the cannabis users in our study.

A recently published systematic review summarized all the in vivo and in vitro studies that assessed the effect of cannabis exposure on male infertility. The authors concluded that the use of cannabis may be associated with a reduction in sperm quality, erectile dysfunction, and testicular cancer (Rajanahally et al. 2019).

In contrast, Kasman et al. who surveyed the association between male and female cannabis use and time to pregnancy among 758 males and 1076 females that were actively trying to conceive between the years 2002 and 2015 were not able to detect any difference in the length of the time to pregnancy between either male or female cannabis users and non-users regardless of the frequency of use (Kasman et al. 2018).

In our study, we were not able to detect any differences in sperm quality parameters between cannabis users and non-users. Interestingly, sperm in the groups of male cannabis users showed the highest semen volume and the best sperm quality. A similar finding was reported by Nassan et al., in a recent report (Nassan et al., 2019a, b).

The effects of cannabis exposure on in vitro fertilization outcomes were assessed in several studies. These studies demonstrated that cannabis use is associated with a lower yield of harvested oocytes during in vitro fertilization. Furthermore, the addition of synthetic (CP 55940, WIN 55212–2), natural (THC), or endogenous (AEA and 2-AG) cannabinoids to embryo culture media resulted in arrested development of two-cell embryos as well as reduction of the number of trophectoderm cells in those blastocysts that were able to escape the developmental arrest. (Wang, Dey, and Maccarrone 2006).

A more recent study that examined the chronic exposure of male mice to THC via intraperitoneal (IP) injections that began at puberty and continued for 1 month found that despite a remarkably high testicular THC concentration, there was no significant difference in testicular size, rate of spermatogenesis, apoptosis, sperm concentration, and motility. They also compared the outcome of IVF using sperm from mice treated with THC vs. control and found no difference in the rate of fertilization and blastocyst formation (Lopez-Cardona et al. 2018). A recent study by Nassan et al. reported that couples undergoing IVF treatment in which the male partner was a current cannabis user had a significantly higher adjusted probability for a live birth (Nassan et al., 2019a, b).

The results of this study are in line with the newer studies suggesting that the use of cannabis is not associated with a compromised outcome for couples undergoing IVF. There may be several explanations for the discrepancy between the results of the newer studies on the effects of cannabis consumption on reproductive health, including this study, and the older ones. Studies that were done before the legalization of cannabis involved consumers of an illegal substance produced in a non-regulated process. Moreover, it was shown that individuals that consume illicit drugs are more likely to engage in other unhealthy behaviors (Keethakumar et al. 2021).