1 Nutritional factors and fertilityJorge E. Chavarro, MD, ScD Associate Professor of Nutrition, Epidemiology and Medicine Harvard T. H. Chan School of Public Health Harvard Medical School
2 Why Nutrition? Clinical motivationFew modifiable risk factors for infertility known Predictors of successful treatment outcomes, including modifiable lifestyle factors. Public Health Motivation Magnitude of the infertility burden Dramatic shifts in known risk factors for infertility Conflicts between physiological limits and cultural expectations
3 Prevalence of infertilityThoma et al. Fertil Steril 2013; Thonneau et al Hum Reprod 1991; Hull et al BMJ 1985; Rachootin et al Int J Epidemiol1982; WHO 2004
4 Effectiveness of ART, CDC. Annual ART Success Rate Reports
5 Where could nutrition play a role?Ovulation disorders 27% Male factor % Tubal factor % Unexplained % Endometriosis % Other % Treatment Outcomes Prevention
6 Ovulation disorders Energy balanceInsulin sensitivity/glycemic control Specific micronutrients
7 BMI and risk of infertilityChavarro et al. Obstet Gynecol 2007
8 Diet and anovulatory infertilityIncreased Risk (RR) Trans fats (2.31) Glycemic load (1.92) Low fat dairy (1.85) Animal protein (1.39) Reduced Risk (RR) Folic acid (0.41) Non-heme iron (0.60) High fat dairy (0.73) Vegetable protein (0.78) Chavarro et al. Obstet Gynecol 2006; Eur J Clin Nutr 2007; Am J Clin Nutr 2007; Hum Reprod 2007; Am J Obstet Gynecol 2008
9 Diet composition and infertility08 Diet composition and infertility Ovulation disorders All other causes Chavarro et al. Obstet Gynecol 2007
10 Diet, physical activity and BMIChavarro et al. Obstet Gynecol 2007
11 Do these findings apply to men?Do these findings apply to couples undergoing infertility treatment?
12 Body weight
13 Female BMI and live birth ratesLuke et al. Hum Reprod 2011
14 Female weight change and ARTChavarro et al. Fertil Steril 2012
15 BMI and oligo/azoospermiaSermonade et al. Hum Reprod Update 2012
16 BMI and sperm DNA damageChavarro et al. Fertil Steril 2010
17 Male BMI and ART outcomesColaci et al. Fertil Steril 2012
18 Male BMI and ART outcomesColaci et al. Fertil Steril 2012
19 Male BMI and ART outcomesColaci et al. Fertil Steril 2012
20 Dietary fats
21 Sperm Omega-3 Fatty Acids75th %tile 25th %tile 50th %tile 89 x 106 /mL Chavarro et al. Fertil Steril 2010
22 Fish intake and sperm countsAfeiche et al. J Nutr 2014
23 Sperm trans fatty acids75th %tile 25th %tile 50th %tile 97 x 106 /mL Chavarro et al. Fertil Steril 2010
24 04 Trans fat intake Chavarro et al. Hum Reprod 2014
25 04 Saturated fat intake Attaman et al. Hum Reprod 2012
26 Male fat intake and ART outcomes04 Male fat intake and ART outcomes Fertilization [OR (95%CI)] Implantation Clinical Pregnancy Live Birth Saturated (5%) 1.59 ( ) 1.51 ( ) 0.89 ( ) 1.14 ( ) Monounsaturated (5%) 0.85 ( ) 1.58 ( ) 2.13 ( ) 1.33 ( ) N-6 polyunsaturated (5%) 1.31 ( ) 0.34 ( ) 0.37 ( ) 0.40 ( ) N-3 polyunsaturated (1%) 0.76 ( ) 1.71 ( ) 1.42 ( ) 0.65 ( ) Trans (1%) 0.28 ( ) 0.26 ( ) 0.28 ( ) 0.25 ( ) Arvizu Boy et al. ASRM 2015
27 Female fat intake and oocyte yieldTrans fat – total yield Saturated fat – M2 oocytes Chavarro et al. ESHRE 2014
28 Female fat intake and live birthsP, trend = 0.03 Chavarro et al. ESHRE 2014
29 Soy
30 Soy intake, sperm conentrationChavarro et al Hum Reprod 2008
31 Male soy intake and ART Minguez-Alarcon et al. Andrologia 2015
32 Female soy intake and ARTVanegas et al. Fertil Steril 2015
33 Micronutrients Antioxidants (male) Folate/B12 (female)
34 Antioxidants Showell et al. Chochrane Database Syst Rev 2011
35 Folate Supplementation04 Folate Supplementation Wong et al. Fertil Steril 2002
36 Carotenoids and motilityZareba et al. Fertil Steril 2013
37 Dietary folate and ART Gaskins et al. Obstet Gynecol 2014
38 Serum folate, B12 and ART Gaskins et al. Am J Clin Nutr 2015
39 One Carbon Metabolism in ARTEmbryo development Folicular Fluid Hcy: ↓ day 3 embryo quality Ebisch et al. Hum Reprod 2006 Blood B12: ↑ day 3 embryo quality Boxmeer et al. Hum Reprod 2009
40 Sporadic anovulation Gaskins et al. PLoS One 2012
41 Infertility due to anovulationChavarro et al. Fertil Steril 2008
42 Pregnancy loss Gaskins et al. Obstet Gynecol 2014
43 Interaction with environmental chemicalsFruits and vegetables - pesticides Soy - BPA
44 Fruits, vegetables, pesticides and SQChiu et al. Hum Reprod 2015
45 Bisphenol A (BPA) and ART outcomesMinguez-Alarcon et al. Hum Reprod 2015
46 BPA, soy intake and ART outcomesNo Soy Intake No Soy Intake Chavarro et al. J Cin Endocrinol Metab 2016
47 Conclusions Diet modification may have a role in:Prevention of certain infertility cases Co-adjuvant to fertility treatment Modify the deleterious effects of environmental chemicals (?) Some factors appear to have effects on multiple relevant outcomes Body weight One carbon metabolism Dietary fats (Much) More research is needed
48 Acknowledgements Nurses’ Health Study Trainees Stacey MissmerJanet Rich-Edwards Walter Willett Bernard Rosner EARTH Study/MGH Russ Hauser Thomas Toth Irene Souter John Petrozza Cigdem Tanrikut RYMS/MYMS/CYMS Shanna Swann Jaime Mendiola Niels Jørgensen Trainees Audrey Gaskins Myriam Afeiche Yu-Han Chiu Xia Wei Lidia Minguez-Alarcon Jose Vanegas Mariel Arvizu Boy Daniela Colaci Piotr Zareba Jill Attaman Anatte Karmon
49 Nutritional factors and fertilityJorge E. Chavarro, MD, ScD Associate Professor of Nutrition, Epidemiology and Medicine Harvard T. H. Chan School of Public Health Harvard Medical School