Marijuana Smoking and Outcomes of Infertility Treatment With Assisted Reproductive Technologies

Feiby L. Nassan; Mariel Arvizu; Lidia Mínguez-Alarcón; Audrey J. Gaskins; Paige L. Williams; John C. Petrozza; Russ Hauser; Jorge E. Chavarro; EARTH Study Team

Disclosures

Hum Reprod. 2019;34(9):1818-1829. 

In This Article

Abstract and Introduction

Abstract

Study Question: What is the association of female and male partner marijuana smoking with infertility treatment outcomes with ART?

Summary Answer: Women who were marijuana smokers at enrollment had a significantly higher adjusted probability of pregnancy loss during infertility treatment with ART whereas, unexpectedly, there was a suggestion of more favorable treatment outcomes in couples where the man was a marijuana smoker at enrollment.

What is Known Already: Data on the relation of female and male partner marijuana use with outcomes of infertility treatment is scarce despite increased use and legalization worldwide.

Study Design, Size, Duration: We followed 421 women who underwent 730 ART cycles while participating in a prospective cohort (the Environment and Reproductive Health Study) at a fertility center between 2004 and 2017. Among them, 200 women (368 cycles) were part of a couple in which their male partner also enrolled in the study.

Participants/Materials, Setting, Methods: Participants self-reported marijuana smoking at baseline. Clinical endpoints were abstracted from electronic medical records. We used generalized linear mixed models with empirical standard errors to evaluate the association of baseline marijuana smoking with ART outcomes adjusting for participants' age, race, BMI, tobacco smoking, coffee and alcohol consumption, and cocaine use. We estimated the adjusted probability of implantation, clinical pregnancy, and live birth per ART cycle, as well as the probability of pregnancy loss among those with a positive B-hCG.

Main Results and the Role of Chance: The 44% of the women and 61% of the men had ever smoked marijuana; 3% and 12% were marijuana smokers at enrollment, respectively. Among 317 women (395 cycles) with a positive B-hCG, those who were marijuana smokers at enrollment (N = 9, cycles = 16) had more than double the adjusted probability of pregnancy loss than those who were past marijuana smokers or had never smoked marijuana (N = 308, 379 cycles) (54% vs 26%; P = 0.0003). This estimate was based on sparse data. However, couples in which the male partner was a marijuana smoker at enrollment (N = 23, 41 cycles) had a significantly higher adjusted probability of live birth than couples in which the male partner was a past marijuana smoker or had never smoked marijuana (N= 177, 327 cycles) (48% vs 29%; P = 0.04), independently of the women's marijuana smoking status. Treatment outcomes of past marijuana smokers, male and female, did not differ significantly from those who had never smoked marijuana.

Limitations, Reasons for Caution: Marijuana smoking was self-reported with possible exposure misclassification. Chance findings cannot be excluded due to the small number of exposed cases. The results may not be generalizable to couples from the general population.

Wider Implications of the Findings: Even though marijuana smoking has not been found in past studies to impact the ability to become pregnant among pregnancy planners in the general population, it may increase the risk of pregnancy loss among couples undergoing infertility treatment. Marijuana smoking by females and males may have opposing effects on outcomes of infertility treatment with ART.

Study Funding/Competing Interest(s): The project was financed by grants R01ES009718, P30ES000002, and K99ES026648 from the National Institute of Environmental Health Sciences (NIEHS). None of the authors has any conflicts of interest to declare.

Introduction

One in six couples trying to conceive experience infertility (Louis et al., 2013; Thoma, et al., 2013) and many seek treatment with ART. In the last decade, multiple studies linked fertility to environmental factors and lifestyle choices including exposure to environmental chemicals (Dodge et al., 2015; Minguez-Alarcon et al., 2016), air pollution (Gaskins et al., 2018; Nassan et al., 2018a), diet (Gaskins and Chavarro, 2018; Nassan et al., 2018b), tobacco smoking (Budani et al., 2018), and drug use (Joesoef et al., 1990; Joesoef et al., 1993; du Plessis et al., 2015; Samplaski et al., 2015).

Marijuana is the most widely used illicit drug in the world (UNODC, 2017). In 2016, more than 24 million Americans reported using marijuana (SAMHSA, 2016). Prevalent marijuana use by women and men of reproductive age is of concern given data scarcity on its potential reproductive effects. To date, only three (Klonoff-Cohen et al., 2006; Kasman et al., 2018; Wise et al., 2018) studies have evaluated the relation of marijuana smoking in both partners on fertility. Two studies among pregnancy planners found no evidence that either partner's marijuana use was related to time to pregnancy (Kasman et al., 2018; Wise et al., 2018). Another study (Klonoff-Cohen et al., 2006) among couples undergoing ART, reported that marijuana smoking from both partners was related to lower oocyte yield and fertilization rate but unrelated to pregnancy or live birth rates. These last findings, however, may not be applicable to current practice as more than half of participants underwent gamete or zygote intrafallopian transfer (GIFT/ZIFT) cycles, which currently represent <1% of ART (CDC, 2015). The dearth of literature on the effects on reproduction has been acknowledged by the American College of Obstetricians and Gynecologists (ACOG) (ACOG, 2017). To further study this question using more recent data, we evaluated the relation of marijuana smoking with outcomes of infertility treatment among couples attending the Massachusetts General Hospital (MGH) fertility center. We hypothesized that marijuana smoking in couples would be unrelated to outcomes of infertility treatment.

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