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• W2890165404 abstract "This Views and Reviews explores existing data regarding the impact of nutrition, supplements, and lifestyle changes as they relate to weight on the fertility of both men and women. Challenges and shortcomings in developing and performing well-designed studies of nutrition and fertility are reviewed in these five papers, and the best evidence is presented. Recommendations are made based on the data, such as they are. It appears that folic acid supplementation above the level used by women to reduce the risk of neural tube defects may be of value in producing favorable pregnancy outcomes. Certain polyunsaturated fatty acids may have a beneficial effect on fertility, and a Mediterranean diet may prove advantageous in both men and women. Data do not consistently support a beneficial effect of vitamin D on reproduction, and caffeine use has not been shown to have a deleterious effect. Alcohol use may negatively impact reproductive success, and smoking appears to have a clearly negative impact in both men and women. Present data consistently show that obesity is associated with reduced reproductive efficiency in both women and men, but the data do not confirm that weight loss proximate to attempts at conception will reverse this effect. We would do well to appreciate that the ongoing state of being obese appears to be more relevant to reproduction than changing the obese state. This Views and Reviews explores existing data regarding the impact of nutrition, supplements, and lifestyle changes as they relate to weight on the fertility of both men and women. Challenges and shortcomings in developing and performing well-designed studies of nutrition and fertility are reviewed in these five papers, and the best evidence is presented. Recommendations are made based on the data, such as they are. It appears that folic acid supplementation above the level used by women to reduce the risk of neural tube defects may be of value in producing favorable pregnancy outcomes. Certain polyunsaturated fatty acids may have a beneficial effect on fertility, and a Mediterranean diet may prove advantageous in both men and women. Data do not consistently support a beneficial effect of vitamin D on reproduction, and caffeine use has not been shown to have a deleterious effect. Alcohol use may negatively impact reproductive success, and smoking appears to have a clearly negative impact in both men and women. Present data consistently show that obesity is associated with reduced reproductive efficiency in both women and men, but the data do not confirm that weight loss proximate to attempts at conception will reverse this effect. We would do well to appreciate that the ongoing state of being obese appears to be more relevant to reproduction than changing the obese state. Discuss: You can discuss this article with its authors and other readers at https://www.fertstertdialog.com/users/16110-fertility-and-sterility/posts/37082-26718 Discuss: You can discuss this article with its authors and other readers at https://www.fertstertdialog.com/users/16110-fertility-and-sterility/posts/37082-26718 The impact of diet, dietary supplements, and lifestyle is the subject of tremendous interest, and often angst, among those who are planning conception or experiencing difficulty in becoming pregnant. As is so often the case, over-the-top hype, unsubstantiated claims, and personal testimony are widespread while evidence-based recommendations derived from well-designed and valid clinical studies are rarely available to or seen by the concerned lay public. While this regrettable imbalance is due in part to an often-distressing focus on the simple and superficial story rather than a more thoughtful and in-depth analysis, it is also true that the types of well-designed studies that can provide the foundation for firm clinical guidelines are modest in number. Indeed, this is understandable given the challenges investigators face in directly assessing human fecundity. As is widely appreciated, these include studying heterogeneous populations, generalized difficulty in assessing and controlling for dietary intake in cohort studies (retrospective and prospective), and incomplete data regarding clinical outcomes. These challenges are often exacerbated by the tendency to admix studies of general populations with those of infertile patients. Similarly, there are obvious limitations in extrapolating observations made in animal studies to humans. While it is particularly attractive to accept that cellular or mechanistic findings in such studies may be translatable from one animal species to another, the only truly valid approach to confirming such effects is through the types of well-designed clinical studies that are still relatively uncommon. Thus, the practitioner is left to provide comprehensive, valid recommendations to information-hungry patients who often come to our offices with preexisting notions based on confused and fuzzy analyses. The goal of this Views and Reviews is to summarize the most well-established, updated findings regarding diet, supplements, and lifestyle management as they relate to nutrition to help clinicians provide valuable and accurate information so important to our patients. The first paper in this Views and Reviews, by Chiu and colleagues, summarizes our present understanding of the impact of a number of different dietary factors on female fertility. They present data describing effects of micronutrients such as folic acid and vitamin D, as well as macronutrients including whole grains, fatty acids, and various types of proteins (e.g., dairy, animal, fish) on fertility/fecundity, assisted reproduction technology (ART), and overall reproductive outcomes. The authors also address the impact of non-nutritive constituents in our diet on reproductive outcome. These in particular, including mercury, pesticides, polychlorinated biphenyls, and various hormones seem to generate particular concern among our patients. This discussion is most effective in reinforcing both the value and the limitations of existing data, and affords clinicians balanced recommendations that they can provide to their patients. For example, according to existing data, folic acid supplements at higher doses than those recommended for the prevention of neural tube defects before and during pregnancy may also increase the likelihood of successful pregnancy. Further, there is considerable evidence suggesting that greater intake of omega-3 polyunsaturated fatty acids and lower intake of trans fats are associated with a shorter time-to-pregnancy and better ART outcomes, while the effects of other fatty acids such as omega-6 polyunsaturated fatty acids, saturated, and monounsaturated fatty acids on female fecundity is less clear. On the contrary, despite encouraging data in animal studies, little evidence supports beneficial effects of vitamin D on human fertility, particularly in the absence of frank deficiency. The authors present a convincing argument that current evidence does indeed support diet as a modifiable factor affecting female fecundity and recommend greater adherence to dietary patterns favoring whole grains, fish, fruits, vegetables and olive oils consistent with the 2015 Dietary Guidelines for Americans (1Millen B.E. Abrams S. Adams-Campbell L. Anderson C.A. Brenna J.T. Campbell W.W. et al.The 2015 Dietary Guidelines Advisory Committee scientific report: development and major conclusions.Adv Nutr. 2016; 7: 438-444Crossref PubMed Scopus (178) Google Scholar). Nassan and colleagues present a parallel survey of the best evidence exploring the impact of nutrition on male fertility in our second paper. The authors share the somewhat alarming observation that three meta-analyses have documented a consistently downward trend in sperm parameters over the past eight decades. Indeed, sperm concentration has been shown to have decreased by 50% to 60% in industrialized countries between 1973 and 2011 alone (2Levine H. Jørgensen N. Martino-Andrade A. Mendiola J. Weksler-Derri D. Mindlis I. et al.Temporal trends in sperm count: a systematic review and meta-regression analysis.Hum Reprod Update. 2017; 23: 1-14Crossref Scopus (648) Google Scholar). They cite speculation that these observations may be due, at least in part, to worsening diet quality (3United States Department of Agriculture Profiling food consumption in America.in: Agriculture fact book 2001-2002. United States Government Printing Office, Washington, DC2003: 13-21Google Scholar), and confirm the strong and consistent evidence showing that obesity adversely affects semen quality and fertility (4Sermondade N. Faure C. Fezeu L. Shayeb A.G. Bonde J.P. Jensen T.K. et al.BMI in relation to sperm count: an updated systematic review and collaborative meta-analysis.Hum Reprod Update. 2013; 19: 221-231Crossref PubMed Scopus (379) Google Scholar, 5Sundaram R. Mumford S.L. Buck Louis G.M. Couples' body composition and time-to-pregnancy.Hum Reprod. 2017; 32: 662-668Crossref PubMed Scopus (48) Google Scholar). These authors describe the molecular mechanisms by which sperm production and function might be either promoted or adversely affected by dietary intake of fatty acids, folate, and particularly antioxidants, observations that may be relevant to other basic mechanisms in human reproduction. They similarly note the limitations of existing research as it relates to diet and male reproductive function and acknowledge that there are no clear guidelines to date for male patients seeking fertility treatment. At the same time, they appreciate that our patients are seeking the best available evidence which leads them to suggest that dietary patterns favoring the consumption of seafood, poultry, nuts, whole grains, fruits and vegetables should be encouraged for men who are pursuing pregnancy with their partners. They further note that evidence is strongest for recommending the use of antioxidant supplements to men in couples undergoing infertility treatment, although the specific antioxidants and doses remain unclear, and increasing consumption of omega-3 fatty acids from fish and nuts. The role of antioxidants in fertility in both males and females is addressed in greater depth by Smits and colleagues in our third paper. An additional important gap identified in this latter review is the need to disentangle the apparent benefit of antioxidant supplements to identify specific relevant factors in their use. For example, the preliminary results of the Males, Antioxidants, and Infertility trial presented at the European Society of Human Reproduction and Embryology meeting earlier this year suggest that off-the-shelf products are probably not the answer (6Steiner A. Hansen K. Diamond M.P. Coutifaris C. Cedars M. Legro R. et al.Antioxidants in the treatment of male factor infertility: Results from the double blind, multi-center, randomized controlled Males, Antioxidants, and Infertility (MOXI) trial.Hum Reprod. 2018; 33 ([Abstract]): i30Google Scholar). Instead, a systematic approach to identifying beneficial and non-beneficial components tested in previous antioxidant trials, including those that are clearly not antioxidants, lies ahead of us. In our fourth paper, Norman and Mol focus more directly on the impact of obesity, almost certainly the most common example of nutritional challenge to reproduction. They acknowledge that most expert opinion and guidelines suggest the necessity for weight loss prior to in vitro fertilization (IVF) in women who are overweight or obese based on the documented impact of obesity on pregnancy rates, pregnancy complications, and long-term impact on the child in natural conceptions. The authors summarize a large body of conflicting studies which attempt to characterize the relationship between obesity and decreased fecundity, and specifically explore data assessing the value of weight loss in obese women attempting to conceive. They cite two recently published clinical trials which compared the results of a lifestyle intervention in obese women prior to IVF treatment to outcomes seen in women who were merely given advice and allowed to proceed directly to other fertility treatments or IVF (7Mutsaerts M.A. van Oers A.M. Groen H. Burggraaff J.M. Kuchenbecker W.K. Perquin D.A. et al.Randomized trial of a lifestyle program in obese infertile women.N Engl J Med. 2016; 374: 1942-1953Crossref PubMed Scopus (160) Google Scholar, 8Einarsson S. Bergh C. Friberg B. Pinborg A. Klajnbard A. Karlstrom P.O. et al.Weight reduction intervention for obese infertile women prior to IVF: a randomized controlled trial.Hum Reprod. 2017; 32: 1621-1630Crossref PubMed Scopus (83) Google Scholar). No compelling evidence of the value of lifestyle intervention for weight loss on live birth rates was shown in these well-conducted studies. These and similar observations presented by the authors provide important information about the impact of obesity on reproduction, but also provide a more updated context of how we might approach the clinical care of obese infertile women, and what new approaches deserve more intense study. In the final paper, Mínguez-Alarcón and colleagues provide an updated discussion of the effects of caffeine, alcohol and cigarette smoking on reproductive outcomes. While perhaps not directly related to nutrition in the same manner as was described in our first four papers, there is a great deal of interest if not frank anxiety over the use of caffeine, alcohol, and tobacco among our patients, many of whom are exposed to one or more of these substances. The authors acknowledge the potential long-term impacts on reproductive outcomes of women who use alcohol and tobacco in particular, though primarily focus on the impact of their use during active treatment by ART. They present a comprehensive view of the existing data which generally show little if any effect of caffeine on reproductive outcome with increasingly more worrisome effects in consumers of alcohol and tobacco. The authors also summarize the present data relating to these exposures in men attempting to produce a pregnancy. They confirm the relative dearth of good studies to help direct our recommendations but do observe a consistent observation that caffeine and alcohol have no impact on semen quality (or at most very modest impact in the case of alcohol) while smoking has a very clear deleterious impact on semen quality (9Li Y. Lin H. Li Y. Cao J. Association between socio-psycho-behavioral factors and male semen quality: systematic review and meta-analyses.Fertil Steril. 2011; 95: 116-123Abstract Full Text Full Text PDF PubMed Scopus (208) Google Scholar). However, it is not clear that this documentable decrease in semen quality is manifest by reduced fertility, particularly with ART. Randomizing couples seeking pregnancy to continuing or stopping alcohol, caffeine, smoking and other behaviors such as marijuana smoking, will likely remain ethically indefensible. Hence, increasing the evidence base from adequately designed observational studies, and studies addressing the effects of short-term change in behavior, will be critical. The authors stress that using alcohol and especially smoking cigarettes constitute an important modifiable exposure to substances that either clearly or likely have a deleterious impact on reproductive success, and a decision to attempt conception may represent an ideal opportunity to motivate patients to reduce alcohol intake or stop smoking. It is also important to ask ourselves where we should go from here. If weight loss immediately before infertility treatment is not particularly useful but body mass index (BMI) is still related to lower success rates, should we shift our efforts to preventing weight gain earlier in life? Should, for example, preventing weight gain for the purposes of protecting future fertility become part of the conversation with young women seeking contraception or routine gynecological care? Alternatively, would longer interventions with a slower rate of weight loss yield better results and will they offset the effect of concurrent ovarian aging? Also, does the failure of weight loss trials to prove a benefit mean that we also need to reevaluate the evidence on the other end of the weight spectrum? Do we need trials to test the effect of weight gain among underweight women presenting for infertility treatment? More generally, this apparent disconnect begs the question of whether the BMI and ART outcomes data have been adequately interpreted all along. While scant, epidemiologic data already suggested, before the trials were completed, that short term weight loss immediately before treatment would not improve live birth rates even though baseline BMI was related to this outcome (10Chavarro J.E. Ehrlich S. Colaci D.S. Wright D.L. Toth T.L. Petrozza J.C. et al.Body mass index and short-term weight change in relation to treatment outcomes in women undergoing assisted reproduction.Fertil Steril. 2012; 98: 109-116Abstract Full Text Full Text PDF PubMed Scopus (96) Google Scholar). If there is a lesson to be learned from this story it is that being obese, or lean is not the same as becoming one or the other. More explicitly, we now know that the difference in treatment outcomes between the state of being lean and the state of being overweight is not the same as the effect of gaining or losing weight. This distinction between difference in status and change may also be true for other nutritional and lifestyle factors and should be kept in mind as the field moves forward. By and large, the most promising evidence on diet influencing fertility falls within the being, or current status category (i.e., the relation between current intake, current serum biomarker levels, etc.). Data on change over time, including observational data and randomized trials, are still limited. The articles in this series make a compelling argument for testing the effects of increasing adherence to specific dietary patterns and intake of specific nutrients (e.g., high dose folic acid/B12 in women, omega 3 fatty acids) in both women and men. Norman and Mol point out in their review that reproductive medicine relied for far too long on the assumption that the association between BMI and ART outcomes implied that weight loss would improve treatment outcomes. Ideally, we will leverage the data presented in this Views and Reviews to more assertively develop valuable randomized trials evaluating the effect of nutritional and lifestyle interventions that will produce evidence that will more rapidly improve patient outcomes." @default.
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• W2890165404 title "Introduction" @default.
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