Caffeine, alcohol, smoking, and reproductive outcomes among couples undergoing assisted reproductive technology treatments
2018; Elsevier BV; Volume: 110; Issue: 4 Linguagem: Inglês
10.1016/j.fertnstert.2018.05.026
ISSN1556-5653
AutoresLidia Mínguez‐Alarcón, Jorge E. Chavarro, Audrey J. Gaskins,
Tópico(s)Assisted Reproductive Technology and Twin Pregnancy
ResumoDuring the past decade, as the use of assisted reproductive technologies (ART) has continued to increase worldwide, research investigating whether modifiable lifestyle factors, such as alcohol, caffeine, and smoking, may affect ART outcomes has grown. Despite the vast literature, there is still uncertainty regarding the effects of some of these exposures on ART outcomes. The objective of this review is to summarize the epidemiologic literature on intakes of caffeine and alcohol, smoking, and reproductive outcomes among women undergoing ART. Of the five epidemiologic studies on caffeine intake and ART outcomes, only one found a significant negative effect of caffeine intake on live birth following ART. There have been six epidemiologic studies exploring whether alcohol intake is associated with fertility outcomes among women undergoing ART. Three studies assessed current alcohol consumption and observed a negative effect on outcomes such as fertilization, embryo quality, and implantation. When alcohol intake in the year before treatment was assessed, no relationships were observed with clinical outcomes following ART. Finally, numerous epidemiologic studies and a handful of meta-analyses have confirmed that female current smokers have worse ART outcomes compared with nonsmokers. Although former smokers tend to have better ART outcomes than current smokers, very few individual studies have investigated the influence of smoking cessation on ART outcomes. Literature on male smoking, drinking, and caffeine habits in relation to ART outcomes is even sparser and inconsistent, making it difficult to draw strong conclusions on that topic. In summary, there is little evidence supporting a detrimental effect of moderate caffeine intake on ART outcomes. Current consumption of alcohol may have a negative effect on ART outcomes, but at present the evidence is limited. Women who currently smoke cigarettes have been consistently found to have poorer ART outcomes, including reduced live birth rates, but a quantification of the benefits of smoking cessation is lacking. During the past decade, as the use of assisted reproductive technologies (ART) has continued to increase worldwide, research investigating whether modifiable lifestyle factors, such as alcohol, caffeine, and smoking, may affect ART outcomes has grown. Despite the vast literature, there is still uncertainty regarding the effects of some of these exposures on ART outcomes. The objective of this review is to summarize the epidemiologic literature on intakes of caffeine and alcohol, smoking, and reproductive outcomes among women undergoing ART. Of the five epidemiologic studies on caffeine intake and ART outcomes, only one found a significant negative effect of caffeine intake on live birth following ART. There have been six epidemiologic studies exploring whether alcohol intake is associated with fertility outcomes among women undergoing ART. Three studies assessed current alcohol consumption and observed a negative effect on outcomes such as fertilization, embryo quality, and implantation. When alcohol intake in the year before treatment was assessed, no relationships were observed with clinical outcomes following ART. Finally, numerous epidemiologic studies and a handful of meta-analyses have confirmed that female current smokers have worse ART outcomes compared with nonsmokers. Although former smokers tend to have better ART outcomes than current smokers, very few individual studies have investigated the influence of smoking cessation on ART outcomes. Literature on male smoking, drinking, and caffeine habits in relation to ART outcomes is even sparser and inconsistent, making it difficult to draw strong conclusions on that topic. In summary, there is little evidence supporting a detrimental effect of moderate caffeine intake on ART outcomes. Current consumption of alcohol may have a negative effect on ART outcomes, but at present the evidence is limited. Women who currently smoke cigarettes have been consistently found to have poorer ART outcomes, including reduced live birth rates, but a quantification of the benefits of smoking cessation is lacking. Discuss: You can discuss this article with its authors and other readers at https://www.fertstertdialog.com/users/16110-fertility-and-sterility/posts/33448-26261 Discuss: You can discuss this article with its authors and other readers at https://www.fertstertdialog.com/users/16110-fertility-and-sterility/posts/33448-26261 According to data from the Centers for Disease Control and Prevention, around 230,000 assisted reproductive technology (ART) treatments were performed in the United States in 2016 (1Society for Assisted Reproductive Technologies. Preliminary SART clinic summary report. Available at: https://www.sartcorsonline.com/rptCSR_PublicMultYear.aspx?reportingYear=2016.Google Scholar) compared with about 60,000 in 1995 (2Assisted reproductive technology in the United States and Canada: 1995 results generated from the American Society for Reproductive Medicine/Society for Assisted Reproductive Technology Registry.Fertil Steril. 1998; 69: 389-398Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar). This upward trend in the use of ART has been observed in other developed countries as well (3Dyer S. Chambers G.M. de Mouzon J. Nygren K.G. Zegers-Hochschild F. Mansour R. et al.International Committee for Monitoring Assisted Reproductive Technologies world report: assisted reproductive technology 2008, 2009 and 2010.Hum Reprod. 2016; 31: 1588-1609Crossref PubMed Scopus (301) Google Scholar, 4Kushnir V.A. Barad D.H. Albertini D.F. Darmon S.K. Gleicher N. Systematic review of worldwide trends in assisted reproductive technology 2004–2013.Reprod Biol Endocrinol. 2017; 15: 6Crossref PubMed Scopus (179) Google Scholar). Despite the increasing use of these treatments among couples, the live birth rate per initiated cycle has remained relatively stable, at ∼30% per cycle started, since the early 2000s (5Sunderam S. Kissin D.M. Crawford S.B. Folger S.G. Jamieson D.J. Warner L. et al.Assisted reproductive technology surveillance—United States, 2014.MMWR CDC Surveill Summ. 2017; 66: 1-24Crossref PubMed Scopus (91) Google Scholar, 6Wright V.C. Chang J. Jeng G. Macaluso M. Assisted reproductive technology surveillance—United States, 2003.MMWR CDC Surveill Summ. 2006; 55: 1-22PubMed Google Scholar). Therefore, identifying modifiable lifestyle factors that can predict human fertility and increase a couple's chances of success with the use of ART has become a major clinical and public health matter. Among infertility patients, smoking, alcohol, and caffeine are the top three modifiable factors perceived by women as being potentially detrimental to IVF cycle success (7Rossi B.V. Bressler L.H. Correia K.F. Lipskind S. Hornstein M.D. Missmer S.A. Lifestyle and in vitro fertilization: what do patients believe?.Fertil Res Pract. 2016; 2: 11Crossref PubMed Google Scholar). Cigarette smoking is in fact one of the best-characterized modifiable risk factors for female infertility, so much so that many insurance companies now require urine or serum cotinine levels to be obtained within the month of a requested infertility service for women (and their partners) who have acknowledged smoking within the past year. On the other hand, caffeine and alcohol have historically been two of the most studied dietary factors in relation to spontaneous fertility, and mixed findings in the existing literature have resulted in a less well defined understanding of their influence on ART success. The purpose of this review is to summarize the available epidemiologic evidence on the effect of smoking, caffeine, and alcohol intake on ART outcomes with the hope of providing insights to clinicians who are advising patients on these exposures and to identify gaps in the literature where future research should be focused. One of the main strengths of including only ART studies in this review is the unique opportunity to study many early developmental outcomes, ranging from oocyte production, maturation, and fertilization to preimplantation embryo development and implantation, that are almost impossible to be observed in couples conceiving naturally. Moreover, because all of the women undergoing ART are planning pregnancy, these studies tend to suffer less from the biases relating to the intention of pregnancy that are inherent in studies relating smoking, alcohol, and caffeine to fertility in spontaneously conceived pregnancies. Caffeine is a well known stimulant of the central nervous system, and several studies have linked its consumption to lower estrogen levels in the luteal phase in premenopausal women (8Kotsopoulos J. Eliassen A.H. Missmer S.A. Hankinson S.E. Tworoger S.S. Relationship between caffeine intake and plasma sex hormone concentrations in premenopausal and postmenopausal women.Cancer. 2009; 115: 2765-2774Crossref PubMed Scopus (103) Google Scholar, 9Sisti J.S. Hankinson S.E. Caporaso N.E. Gu F. Tamimi R.M. Rosner B. et al.Caffeine, coffee, and tea intake and urinary estrogens and estrogen metabolites in premenopausal women.Cancer Epidemiol Biomarkers Prev. 2015; 24: 1174-1183Crossref PubMed Scopus (36) Google Scholar, 10Schliep K.C. Schisterman E.F. Mumford S.L. Pollack A.Z. Zhang C. Ye A. et al.Caffeinated beverage intake and reproductive hormones among premenopausal women in the BioCycle Study.Am J Clin Nutr. 2012; 95: 488-497Crossref PubMed Scopus (41) Google Scholar, 11Curtis K.M. Savitz D.A. Arbuckle T.E. Effects of cigarette smoking, caffeine consumption, and alcohol intake on fecundability.Am J Epidemiol. 1997; 146: 32-41Crossref PubMed Scopus (201) Google Scholar). However, findings of whether caffeine intake alters fecundability among women trying to conceive without medical assistance have been equivocal (12Jensen T.K. Henriksen T.B. Hjollund N.H. Scheike T. Kolstad H. Giwercman A. et al.Caffeine intake and fecundability: a follow-up study among 430 Danish couples planning their first pregnancy.Reprod Toxicol. 1998; 12: 289-295Crossref PubMed Scopus (80) Google Scholar, 13Alderete E. Eskenazi B. Sholtz R. Effect of cigarette smoking and coffee drinking on time to conception.Epidemiology. 1995; 6: 403-408Crossref PubMed Scopus (65) Google Scholar, 14Florack E.I.M. Zielhuis G.A. Rolland R. Cigarette smoking, alcohol consumption, and caffeine intake and fecundability.Prev Med. 1994; 23: 175-180Crossref PubMed Scopus (85) Google Scholar, 15Joesoef M.R. Beral V. Rolfs R.T. Aral S.O. Cramer D.W. Are caffeinated beverages risk factors for delayed conception?.Lancet. 1990; 335: 136-137Abstract PubMed Scopus (84) Google Scholar, 16Wilcox A. Weinberg C. Baird D. Caffeinated beverages and decreased fertility.Lancet. 1988; 332: 1453-1456Abstract Scopus (173) Google Scholar, 17Williams M. Monson R. Goldman M. Mittendorf R. Ryan K. Coffee and delayed conception.Lancet. 1990; 335: 1603Abstract PubMed Scopus (42) Google Scholar, 18Grodstein F. Goldman M.B. Ryan L. Cramer D.W. Relation of female infertility to consumption of caffeinated beverages.Am J Epidemiol. 1993; 137: 1353-1360Crossref PubMed Scopus (77) Google Scholar, 19Christianson R. Oechsli F. van den Berg B. Caffeinated beverages and decreased fertility.Lancet. 1989; 333: 378Abstract Scopus (42) Google Scholar). To date, five studies have investigated the effect of caffeine consumption on fertility outcomes among women undergoing ART, and the evidence is mixed (20Klonoff-Cohen H. Bleha J. Lam-Kruglick P. A prospective study of the effects of female and male caffeine consumption on the reproductive end points of IVF and gamete intra-fallopian transfer.Hum Reprod. 2002; 17: 1746-1754Crossref PubMed Scopus (81) Google Scholar, 21Machtinger R. Gaskins A.J. Mansur A. Adir M. Racowsky C. Baccarelli A.A. et al.Association between preconception maternal beverage intake and in vitro fertilization outcomes.Fertil Steril. 2017; 108: 1026-1033Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar, 22Abadia L. Chiu Y.H. Williams P.L. Toth T.L. Souter I. Hauser R. et al.The association between pre-treatment maternal alcohol and caffeine intake and outcomes of assisted reproduction in a prospectively followed cohort.Hum Reprod. 2017; 32: 1846-1854Crossref PubMed Scopus (19) Google Scholar, 23Al-Saleh I. El-Doush I. Grisellhi B. Coskun S. The effect of caffeine consumption on the success rate of pregnancy as well various performance parameters of in-vitro fertilization treatment.Med Sci Monit. 2010; 16: 598-605Google Scholar, 24Choi J.H. Ryan L.M. Cramer D.W. Hornstein M.D. Missmer S.A. Effects of caffeine consumption by women and men on the outcome of in vitro fertilization.J Caffeine Res. 2011; 1: 29-34Crossref PubMed Google Scholar). The first study to address this question in an ART setting was published in 2002 by Klonoff-Cohen et al., who conducted a cohort study among 221 women attending seven fertility clinics in southern California. The authors found no effect of caffeine intake in the year before the cycle start on oocyte retrieval, fertilization, embryo transfer, or implantation after in vitro fertilization (IVF) or gamete intrafallopian transfer (GIFT) (20Klonoff-Cohen H. Bleha J. Lam-Kruglick P. A prospective study of the effects of female and male caffeine consumption on the reproductive end points of IVF and gamete intra-fallopian transfer.Hum Reprod. 2002; 17: 1746-1754Crossref PubMed Scopus (81) Google Scholar). However, they found that women with usual caffeine intakes of 2–50 and >50 mg/d had adjusted odds ratios (95% confidence interval [CI]) of not achieving a live birth of 3.1 (1.1–9.7) and 3.9 (1.3–11.6), respectively, compared with women consuming <2 mg/d. These findings raised concern, and the authors suggested that caffeine intake, which is common among reproductive-age women, should be minimized (essentially to zero) before and while undergoing IVF/GIFT. Subsequent to that initial study, Choi et al. studied the relationship between current caffeine intake among 2,474 women with no history of IVF treatment who underwent 4,716 IVF treatment cycles at three clinics in the greater Boston area from 1994 to 2003 (24Choi J.H. Ryan L.M. Cramer D.W. Hornstein M.D. Missmer S.A. Effects of caffeine consumption by women and men on the outcome of in vitro fertilization.J Caffeine Res. 2011; 1: 29-34Crossref PubMed Google Scholar). Of all the IVF outcomes examined, only peak E2 levels were negatively associated with caffeine intake. Notably, no associations were observed with implantation and live birth rates, despite having a population of women with a wide range of caffeine intake. Consistent with the latter study, a follow-up study by Al-Saleh et al. among 619 Saudi Arabian women undergoing ART for the first time reported no relationship between current caffeine consumption and pregnancy rate, despite having a median caffeine intake of 456 mg/d (23Al-Saleh I. El-Doush I. Grisellhi B. Coskun S. The effect of caffeine consumption on the success rate of pregnancy as well various performance parameters of in-vitro fertilization treatment.Med Sci Monit. 2010; 16: 598-605Google Scholar). Abadia et al. also found no association between usual caffeine intake over the previous year (median 125 mg/d) and clinical ART outcomes among a cohort of 300 women (493 ART cycles) attending a fertility center in Boston from 2006 to 2016 (22Abadia L. Chiu Y.H. Williams P.L. Toth T.L. Souter I. Hauser R. et al.The association between pre-treatment maternal alcohol and caffeine intake and outcomes of assisted reproduction in a prospectively followed cohort.Hum Reprod. 2017; 32: 1846-1854Crossref PubMed Scopus (19) Google Scholar). Finally, in the most recent study, including 340 women undergoing IVF at a university-affiliated center in Israel (2014–2016), Matchinger et al. failed to find an association between preconception caffeine intake (median 142 mg/d) and number of total, mature, and fertilized oocytes, embryo quality measures, implantation, clinical pregnancy, or live birth (21Machtinger R. Gaskins A.J. Mansur A. Adir M. Racowsky C. Baccarelli A.A. et al.Association between preconception maternal beverage intake and in vitro fertilization outcomes.Fertil Steril. 2017; 108: 1026-1033Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar). The only significant association that was observed in this study was a detrimental effect of sugared soda on total and mature oocytes retrieved, number of fertilized oocytes, number of top-quality embryos, and live birth rates. At present, little evidence supports a detrimental effect of caffeine consumption on reproductive outcomes among women undergoing ART treatments. In fact, only the Klonoff-Cohen et al. study found evidence that caffeine intake may be detrimental to live birth following ART. It is important to note, however, that 36% of the women in that study underwent GIFT, a procedure that has been largely phased out in the US (use was <1% in 2015), and the study was performed during a time when many more embryos were transferred, on average, than today (median in their study was four embryos vs. an average of less than two in the U.S. in 2015). Nevertheless, given the limited studies on this topic, it is difficult to completely rule out caffeine as a potential reproductive toxicant. For example, two recent meta-analyses conducted among all studies, regardless of infertility treatment use, reported that preconception caffeine was associated with a small but significant increased risk of spontaneous abortion (SAB) (25Lyngso J. Ramlau-Hansen C.H. Bay B. Ingerslev H.J. Hulman A. Kesmodel U.S. Association between coffee or caffeine consumption and fecundity and fertility: a systematic review and dose-response meta-analysis.Clin Epidemiol. 2017; 9: 699-719Crossref PubMed Scopus (31) Google Scholar, 26Greenwood D.C. Thatcher N.J. Ye J. Garrard L. Keogh G. King L.G. et al.Caffeine intake during pregnancy and adverse birth outcomes: a systematic review and dose-response meta-analysis.Eur J Epidemiol. 2014; 29: 725-734Crossref PubMed Scopus (82) Google Scholar). It was noted, however, that the studies had significant heterogeneity and risk of bias detected, including considerable risk of publication bias (e.g., smaller studies finding no association between caffeine and SAB were less likely to be published) (25Lyngso J. Ramlau-Hansen C.H. Bay B. Ingerslev H.J. Hulman A. Kesmodel U.S. Association between coffee or caffeine consumption and fecundity and fertility: a systematic review and dose-response meta-analysis.Clin Epidemiol. 2017; 9: 699-719Crossref PubMed Scopus (31) Google Scholar). Therefore, the current guideline from the American Congress of Obstetricians and Gynecologists that suggests women who are pregnant and capable of pregnancy limit their caffeine intake to A polymorphism in intron 1 of the cytochrome P450 CYP1A2 gene tested with caffeine.Br J Clin Pharmacol. 1999; 47: 445-449Crossref PubMed Scopus (628) Google Scholar), future studies are needed that evaluate circulating caffeine levels and its metabolites (e.g., serum paraxanthine) in combination with targeted genotyping. Research into the role of sugar-sweetened beverages, specifically soda, on outcomes of ART also is warranted, given the recent findings that higher sugared soda intake was associated with decreased live birth in a prospective cohort of ART patients (21Machtinger R. Gaskins A.J. Mansur A. Adir M. Racowsky C. Baccarelli A.A. et al.Association between preconception maternal beverage intake and in vitro fertilization outcomes.Fertil Steril. 2017; 108: 1026-1033Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar) and lower fecundability in a time-to-pregnancy study (29Hatch E.E. Wesselink A.K. Hahn K.A. Michiel J.J. Mikkelsen E.M. Sorensen H.T. et al.Intake of sugar-sweetened beverages and fecundability in a North American preconception cohort.Epidemiology. 2018; 29: 369-378Crossref PubMed Scopus (32) Google Scholar). Excessive alcohol consumption has long been known for its detrimental effect on human health, including increased risk of many cancers, stroke, heart failure, and death (30Wood A.M. Kaptoge S. Butterworth A.S. Willeit P. Warnakula S. Bolton T. et al.Risk thresholds for alcohol consumption: combined analysis of individual-participant data for 599 912 current drinkers in 83 prospective studies.Lancet. 2018; 391: 1513-1523Abstract Full Text Full Text PDF PubMed Scopus (634) Google Scholar, 31Voelker R. Even low, regular alcohol use increases the risk of dying of cancer.JAMA. 2013; 309: 970Crossref PubMed Scopus (3) Google Scholar). Moreover, numerous studies have shown that maternal alcohol consumption during pregnancy can have negative impacts on multiple fetal organ systems, the best studied being the adverse effects on the developing brain. Despite the knowledge of these links, preconception alcohol intake by women is still a very relevant exposure: 10% of pregnant women and 50% of nonpregnant women consume alcohol (32Tan C.H. Denny C.H. Cheal N.E. Sniezek J.E. Kanny D. Alcohol use and binge drinking among women of childbearing age—United States, 2011–2013.MMWR Morb Mortal Wkly Rep. 2015; 64: 1042-1046Crossref PubMed Scopus (191) Google Scholar). Whether intake of alcohol reduces the ability to achieve a pregnancy is uncertain (11Curtis K.M. Savitz D.A. Arbuckle T.E. Effects of cigarette smoking, caffeine consumption, and alcohol intake on fecundability.Am J Epidemiol. 1997; 146: 32-41Crossref PubMed Scopus (201) Google Scholar, 33Greenlee A.R. Arbuckle T.E. Chyou P.H. Risk factors for female infertility in an agricultural region.Epidemiology. 2003; 14: 429-436Crossref PubMed Scopus (127) Google Scholar, 34Grodstein F. Goldman M.B. Cramer D.W. Infertility in women and moderate alcohol consumption.Am J Public Health. 1994; 85: 1021-1022Google Scholar, 35Hakim R.B. Gray R.H. Zacur H. Alcohol and caffeine consumption and decreased fertility.Fertil Steril. 1998; 70: 632-637Abstract Full Text Full Text PDF PubMed Scopus (111) Google Scholar, 36Juhl M. 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Gray R.H. Zacur H. Alcohol and caffeine consumption and decreased fertility.Fertil Steril. 1998; 70: 632-637Abstract Full Text Full Text PDF PubMed Scopus (111) Google Scholar, 39Grodstein F. Goldman M.B. Cramer D.W. Infertility in women and moderate alcohol use.Am J Public Health. 1994; 84: 1429-1432Crossref PubMed Scopus (127) Google Scholar), others have not observed any detrimental effect (11Curtis K.M. Savitz D.A. Arbuckle T.E. Effects of cigarette smoking, caffeine consumption, and alcohol intake on fecundability.Am J Epidemiol. 1997; 146: 32-41Crossref PubMed Scopus (201) Google Scholar, 36Juhl M. Nyboe Andersen A.M. Gronbaek M. Olsen J. Moderate alcohol consumption and waiting time to pregnancy.Hum Reprod. 2001; 16: 2705-2709Crossref PubMed Scopus (60) Google Scholar, 37Mikkelsen E.M. Riis A.H. Wise L.A. Hatch E.E. Rothman K.J. Cueto H.T. et al.Alcohol consumption and fecundability: prospective Danish cohort study.BMJ. 2016; 354: i4262Crossref PubMed Scopus (39) Google Scholar, 38Olsen J. Bolumar F. Boldsen J. Bisanti L. European Study Group on Infertility and SubfecundityDoes moderate alcohol intake reduce fecundability? A European multicenter study on infertility and subfecundity.Alcohol Clin Exp Res. 1997; 21: 206-212Crossref PubMed Scopus (74) Google Scholar). To date, six studies have investigated the potential relationship between alcohol consumption and reproductive outcomes among women undergoing ART, and overall the results are quite conflicting (22Abadia L. Chiu Y.H. Williams P.L. Toth T.L. Souter I. Hauser R. et al.The association between pre-treatment maternal alcohol and caffeine intake and outcomes of assisted reproduction in a prospectively followed cohort.Hum Reprod. 2017; 32: 1846-1854Crossref PubMed Scopus (19) Google Scholar, 40Klonoff-Cohen H. Lam-Kruglick P. Gonzalez C. Effects of maternal and paternal alcohol consumption on the success rates of in vitro fertilization and gamete intrafallopian transfer.Fertil Sterility. 2003; 79: 330-339Abstract Full Text Full Text PDF PubMed Scopus (100) Google Scholar, 41Wdowiak A. Sulima M. Sadowska M. Grzegorz B. Bojar I. Alcohol consumption and quality of embryos obtained in programmes of in vitro fertilization.Ann Agric Environ Med. 2014; 21: 450-453Crossref PubMed Scopus (13) Google Scholar, 42Rossi B.V. Berry K.F. Hornstein M.D. Cramer D.W. Ehrlich S. Missmer S.A. Effect of alcohol consumption on in vitro fertilization.Obstet Gynecol. 2011; 117: 136-142Crossref PubMed Scopus (58) Google Scholar, 43Dodge L.E. Missmer S.A. Thornton K.L. Hacker M.R. Women's alcohol consumption and cumulative incidence of live birth following in vitro fertilization.J Assist Reprod Genet. 2017; 34: 877-883Crossref PubMed Scopus (7) Google Scholar, 44Firns S. Cruzat V.F. Keane K.N. Joesbury K.A. Lee A.H. Newsholme P. et al.The effect of cigarette smoking, alcohol consumption and fruit and vegetable consumption on IVF outcomes: a review and presentation of original data.Reprod Biol Endocrinol. 2015; 13: 134Crossref PubMed Scopus (48) Google Scholar); however, once studies are grouped by the timing of alcohol exposure (e.g., current intake vs. average intake over the past year) more consistent trends emerge. Regarding average intake before the start of ART, the first published study on the topic, by Klonoff-Cohen et al., found that alcohol intake in the year before ART was negatively related to oocyte retrieval but found no associations with other outcomes, including live birth, among 221 women undergoing ART in southern California (1993–1997) (40Klonoff-Cohen H. Lam-Kruglick P. Gonzalez C. Effects of maternal and paternal alcohol consumption on the success rates of in vitro fertilization and gamete intrafallopian transfer.Fertil Sterility. 2003; 79: 330-339Abstract Full Text Full Text PDF PubMed Scopus (100) Google Scholar). Similarly, in a prospective cohort study of women undergoing fertility treatment in Boston (2006–2016), Abadia et al. also concluded that alcohol intake in the year before their first ART cycle (median 5.6 g/d) was not associated with any of the ART outcomes under study, including live birth (22Abadia L. Chiu Y.H. Williams P.L. Toth T.L. Souter I. Hauser R. et al.The association between pre-treatment maternal alcohol and caffeine intake and outcomes of assisted reproduction in a prospectively followed cohort.Hum Reprod. 2017; 32: 1846-1854Crossref PubMed Scopus (19) Google Scholar). Regarding alcohol consumption immediately before the ART cycle, the studies are more numerous and paint a potentially more hazardous picture. For example, although Klonoff-Cohen et al. did not find an association between long-term alcohol intake and ART outcomes, they did find an increased risk of miscarriage and decreased risk of becoming pregnant when participants were asked about their alcohol intake in the month or week before the ART cycle, despite relatively low intakes (mean intakes of 6.1 and 7.1 g/d, respectively). Wdowiak et al. also observed a detrimental effect of current alcohol intake (albeit at relatively high levels, >25 g/d) before the ART cycle on embryo quality among 54 women undergoing ART in Poland (41Wdowiak A. Sulima M. Sadowska M. Grzegorz B. Bojar I. Alcohol consumption and quality of embryos obtained in programmes of in vitro fertilization.Ann Agric Environ Med. 2014; 21: 450-453Crossref PubMed Scopus (13) Google Scholar). Moreover, Rossi et al. reported that women who consumed >50 g of alcohol per week, assessed at the start of the ART cycle, had lower peak E2 levels and greater odds of failed fertilization in a large cohort study (n = 2,545) of U.S. women in the Boston area from 1994 to 2003 (42Rossi B.V. Berry K.F. Hornstein M.D. Cramer D.W. Ehrlich S. Missmer S.A. Effect of alcohol consumption on in vitro fertilization.Obstet Gynecol. 2011; 117: 136-142Crossref PubMed Scopus (58) Google Scholar). They also found that compared with women who consumed fewer than four alcoholic drinks per week, those who consumed higher amounts had lower probabilities of live birth. In a large retrospective cohort study of women undergoing fertility treatment in Boston (2009–2013), Dodge et al. found increased risk of spontaneous abortion and a nonstatistically significant lower risk of live birth in the first ART cycle among daily alcohol drinkers compared with nondrinkers; however, they found no differences in ART outcomes by type of al
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