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Alcohol and Fertility: How Much Is Too Much? Kristin Van Heertum* and Brooke Rossi

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Alcohol and Fertility: How Much Is Too Much? Kristin Van Heertum* and Brooke Rossi Van Heertum and Rossi Fertility Research and Practice (2017) 3:10 DOI 10.1186/s40738-017-0037-x REVIEW Open Access Alcohol and fertility: how much is too much? Kristin Van Heertum* and Brooke Rossi Abstract: Alcohol use is prevalent in the United States. Given that a substantial portion of the drinking population is of reproductive age, it is not uncommon for couples who are attempting conception, or for women who are already pregnant, to be regularly consuming alcohol. Alcohol use is associated with multiple reproductive risks, including having a child with a Fetal Alcohol Spectrum Disorder, increased risk of fetal loss, and decreased chance of live birth. This review serves to examine the risks of alcohol in the context of reproductive health. Keywords: Alcohol, Infertility, Fertility, Lifestyle, Fecundability Background performed using data from the Behavioral Risk Factor Approximately 12% of couples in the U.S. experience Surveillance System (BRFSS), a telephone based survey difficulty conceiving or impaired fecundity, defined as implemented by U.S. state health departments, found the ability to achieve a live birth in a single menstrual that while the overall prevalence of alcohol consumption cycle [1]. As alcohol is the most widely used recreational is not increasing, it appears that the rate of binge drinking substance, it is important to understand any deleterious is rising across the country [5]. effects it has on human reproduction [2]. In this review, The rates of alcohol use in pregnancy in the U.S. we will discuss the prevalence of alcohol use in the U.S.; remain surprisingly high. According to a report from the the health risks and benefits associated with alcohol Substance Abuse and Mental Health Services Adminis- consumption outside of reproduction; the risks of tration, 8.5% of pregnant women in 2011-2012 reported alcohol use in pregnancy including congenital anomalies current alcohol use, 2.7% reported binge drinking, and and pregnancy loss; the effects of alcohol on fertility in 0.3% reported heavy drinking, defined as 5 more both women and men, such as alcohol’s impact on episodes of binge drinking in the past month [6, 7]. A ovarian reserve, steroid hormone production, sperm recent cohort study of over 5000 pregnant women found quality and fecundability; and finally the impact of that women with an intended pregnancy were 31% less alcohol consumption on fertility treatments. likely to consume alcohol in pregnancy than those with unintended pregnancies [8]. This study also found Prevalence of alcohol use and abuse several surprising characteristics associated with drink- Alcohol use is common in the United States. The 2015 ing in pregnancy, including college-education, white National Survey on Drug Use and Health (NSDUH) race, older age (particularly over 35 years), higher found that 86.4% of people age 18 or older reported income, and nulliparity. Factors associated with binge alcohol consumption at some point in their lives, and drinking during pregnancy in this study were smoking 56% reported drinking in the past month [3]. The survey (past or current), illicit drug use, younger age and being reported a prevalence of binge drinking, defined as unmarried. Other risk factors for continuation of alcohol drinking a quantity of alcohol to raise the blood alcohol use during pregnancy include stressful life events prior concentration (BAC) to 0.08 g/dL (typically 4 drinks for to conception and a high level of pre-pregnancy alcohol women and 5 drinks for men in 2 h), of 26.9% (see Table 1 consumption [9, 10]. Women may be less likely to drink for alcohol consumption definitions) [4]. Another study during pregnancy if they have experienced any difficulty conceiving [10]. * Correspondence: [email protected] Rates of alcohol use in women undergoing fertility Department of Reproductive Biology - Case Western Reserve University treatment vary across different studies, but appear to be School of Medicine, University Hospitals MacDonald Women’s Hospital, 11100 Euclid Avenue, Cleveland, OH 44106, USA somewhere between 26 and 41% [11, 12]. However, © The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Van Heertum and Rossi Fertility Research and Practice (2017) 3:10 Page 2 of 7 Table 1 Definitions of Levels of Alcohol Consumption Fetal Alcohol Spectrum Disorders (FASD), which are (compiled from [7]) caused by alcohol exposure in utero, include fetal Level of consumption Definition alcohol syndrome (FAS), partial fetal alcohol syndrome Current use ≥ 1 drink in the past 30 days (PFAS), alcohol-related neurodevelopmental disorder Moderate use Up to 1 drink per day for women, (ARND) and alcohol-related birth defects (see Table 2 up to 2 drinks per day for men for summary of characteristics) [18]. FASD represents a Binge drinking Drinking a quantity of alcohol to continuum of disease characterized by behavioral and raise the BAC to 0.08 g/dL - typically cognitive deficits, craniofacial anomalies, and growth 4 drinks for women and 5 drinks for retardation. Prevalence of FASD has been estimated at men in 2 h 2-5% in the general U.S. population, with rates of FAS Heavy alcohol use Binge drinking on ≥5 days in the past month estimated to be 0.2 to 7 per 1,000 children [19]. While studies have shown that the degree of deficits/defects worsens with increasing dose and exposure time, there studying alcohol consumption in a group of women who has been no definitive identification of a safe exposure are attempting conception or are already pregnant dose or duration in pregnancy [20, 21]. A recent presents significant challenges. While recall bias can prospective cohort of 992 women found a strong associ- occur in any population, these women may be less likely ation between consumption of alcohol in the late first to accurately report their level of alcohol consumption trimester and some characteristic facial anomalies, as they may be embarrassed by, or feel guilty about, their microcephaly, low birth weight and reduced length [22]. alcohol use. However, alcohol use in the second trimester was also associated with low birth weight and length, while use in the third trimester only effected birth length. Other Non-reproductive sequelae of alcohol use studies have confirmed that growth deficiency, neurobe- Excessive alcohol intake can lead to multiple chronic dis- havioral issues and microcephaly can occur following eases including hypertension, heart disease, liver disease, alcohol exposure in any trimester, but the characteristic gastrointestinal bleeds, cancer (breast, mouth, throat, facial features are likely due to first trimester exposure esophagus, liver, colon), dementia and other cognitive def- [23]. In many studies, it is often difficult to determine if icits, anxiety/depression, and social and economic losses, alcohol was consumed in an isolated trimester or such as damage to relationships and loss of employment throughout the pregnancy. Therefore, it is not possible, [13]. Conversely, moderate alcohol intake, defined as up currently, to make a determination regarding the fetal to 1 drink per day for women and up to 2 drinks per day effects of alcohol in women who abstain from use in the for men, may offer some health benefits [14, 15]. These first and/or second trimesters and subsequently use benefits include decreased risk of stroke and diabetes, as alcohol in the third trimester. well as decreased risk of heart disease or mortality from There is conflicting data regarding the effects of alcohol heart disease. In 2005, it was estimated that 26,000 deaths exposure in utero when there is no evidence for FASD. were prevented in the U.S. due to reductions in ischemic Several studies from the Danish National Birth Cohort did heart disease, diabetes and ischemic stroke because of not identify any effect on general intelligence, attention or benefits attributed to moderate alcohol consumption [6]. executive function in 5 year old children whose mothers However, care providers must still balance the overall risks reported low-consumption, moderate-consumption, or and benefits of alcohol use when counseling their patients binge drinking compared with children whose mothers on their level of alcohol intake. Table 2 Fetal Alcohol Spectrum Disorders – all diagnoses require Alcohol use during pregnancy documented prenatal alcohol exposure (compiled from [19]) The teratogenic effects of alcohol use during pregnancy Disorder Features are well documented [16]. Alcohol readily crosses the Fetal alcohol syndrome Facial dysmorphia, growth deficits, placenta to the amniotic fluid and fetus [17]. The fetus and CNS abnormality will typically be exposed to higher concentrations of al- Partial fetal alcohol syndrome Facial dysmorphia with growth cohol than the mother due to accumulation of alcohol deficits or CNS abnormality and its metabolites in the amniotic fluid, and compara- Alcohol related CNS abnormality and/or intellectual tively reduced fetal metabolic enzyme activity [17]. Some neurodevelopmental disorder disabilities without growth deficits proposed mechanisms of teratogenicity include impaired or facial dysmorphia anti-oxidant capability, increased free radicals and react- Alcohol related birth defects Facial dysmorphia plus additional ive oxygen species with resultant increased apoptosis in birth defect(s) without growth deficits or CNS abnormality fetal cranial/brain tissue [17]. Van Heertum and Rossi Fertility Research and Practice (2017) 3:10 Page 3 of 7 reported no alcohol use in pregnancy [24, 25]. How- drinks per week being more than double the risk of ever, there are weaknesses to these studies, as they those who abstained (HR 2.82, 95% CI 2.27-3.49) [28].
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