The Mediterranean diet for improved outcomes with assisted reproductive technologies

 

When it comes to specific diets linked to positive fertility outcomes, there is substantial evidence showing the benefits of the Mediterranean diet, such as reduced mortality, decreasing cancer rates and diabetes (1). The body of research surrounding adherence to the diet and its influence on female fertility is growing, albeit at times with conflicting study results.

In this post, we will go into more detail about what exactly the Mediterranean diet is, and the evidence thus far on its influence on fertility outcomes, specifically for those using assisted reproductive technologies (ART). ART includes fertility treatment methods such as in vitro fertilisation (IVF) and intra-cytoplasmic sperm injection (ICSI).

What do you mean by fertility outcomes?

Fertility outcomes can be different things, and you’ll see in the evidence presented that depending on the study, different measures are used. But common outcomes that are considered are things like probability of pregnancy, live births (number of pregnancies resulting in a baby being born), reduction in miscarriages, improved ovarian reserve (egg quality) and/or sperm quality/quantity, and improvement in the endometrial environment (making it more hospitable for implantation).

What is the Mediterranean diet?

The definition of the Mediterranean Diet as we know it today, only began to emerge in the 1950s and 1960s from Greece and Southern Italy (2). It is generally agreed that the Mediterranean Diet is a predominantly plant-based diet, focusing on whole grains, fruits, vegetables, pulses, nuts, seeds, herbs, and spices, and favours plant-based protein sources over animal. Fish, seafood, eggs, and (low-fat) dairy products are moderately consumed. Olive oil is the main source of fat in the Mediterranean Diet. Consumption of poultry, red meat, and ultra processed foods is limited. There may be a moderate consumption of red wine (2,3,4).

The Mediterranean Diet pyramid was developed by the Spanish non-profit organisation, Fundación Dieta Mediterránea (5), summarising the staple foods of the diet alongside lifestyle factors such as frugality, physical activity, rest, and conviviality.

In terms of nutrients, the Mediterranean Diet is high in mono- and polyunsaturated fats, low in saturated and trans fats, high in complex carbohydrates and fibre giving it a low glycaemic load, and is high in micronutrients, including vitamins (specifically B-vitamins such as folate), minerals, and antioxidants. Added sugar and sodium consumption are low (2,3). These dietary components can contribute to female fertility by reducing inflammation, protecting against the damage of oxidative stress, and improving insulin sensitivity (6).

The Science: the Mediterranean diet and female fertility outcomes

Most of the evidence regarding the Mediterranean Diet and assisted reproductive technologies outcomes is coming from observational studies which use food frequency questionnaires to assess the degree in which participants follow the diet (6). In the NHS-II study, women with the highest adherence to a Mediterranean-style diet had a 66% lower risk of ovulatory disorder infertility and a 27% lower risk of infertility from other causes compared to those with the lowest diet adherence (7). Similarly, a study from the University of Navarra in Spain found that women with the highest Mediterranean Diet adherence had a 44% lower chance of seeking ART assistance (7), while another study from the United States saw a (non-significant) improvement in ART outcomes from the lowest levels of adherence to the higher levels of adherence (8).

In terms of assisted reproductive technologies outcomes, adherence to the Mediterranean Diet has been correlated to number of fertilized oocytes and embryo yield (1). It may contribute to improved implantation conditions, such as a more favourable endometrial environment as well as better oocyte and embryo quality and maturation, namely due to the high level of micronutrients and antioxidants included the diet (6).

When looking at pregnancy outcomes (clinical or biochemical), a study done in the Netherlands reported a 40% increase in probability of pregnancy in couples adhering to a Mediterranean-style diet (9). Other studies also found a positive correlation, ranging from the 40% increase in probability of pregnancy mentioned previously up to 170% (9,10).

In a meta-analysis of two studies that used the same method of evaluating Mediterranean Diet adherence, a significant association was found between the diet and live births, but not with the probability of achieving clinical pregnancy (3). However, some studies have found no significant association between the Mediterranean Diet and probability of pregnancy or live births (1,11).

What is important to note, is the heterogeneity between the studies that have been conducted in terms of the Mediterranean Diet application and evaluation. In more simplistic terms, different studies have unfortunately not consistently applied the same framework for the Mediterranean Diet, making it challenging to compare or pool results of the studies conducted to come to one overarching conclusion.

Individual nutrients and fertility outcomes

While results may be inconclusive when looking at the diet as a whole, there is more robust evidence around specific nutrients that tend to be rich in the Mediterranean diet and their impact on fertility outcomes with ART.

Specific nutrients you can focus on include:

  • Unsaturated fatty acids such as olive oil, omega-3 fatty acids (commonly found in fatty fish), and omega-6 fatty acids (commonly found in vegetable oils) (7,9,12)

  • Vitamin B6 commonly found in fortified grain products, fish, poultry, beef, starchy vegetables, non-citrus fruit, and chickpeas (9,13)

  • Folate is found naturally in a variety of foods, such as leafy green vegetables, fruit, nuts, pulses, seafood, eggs, dairy, meat, poultry, and grains. Many countries have begun fortifying grain products with folate (1,7,14)

  • Antioxidants: there are many nutrients that can be considered antioxidants, with vitamin A (beta-carotene), vitamin C, vitamin E, zinc, selenium, and magnesium being the most commonly considered and well documented (3,15)

  • A diet high in whole grains and fibre while being low in glycaemic load (3,16,17,18)

What should be your takeaways regarding the Mediterranean Diet and fertility outcomes with ART?

Your head might be spinning after going through the science, so what should you takeaway from this when it comes to using the Mediterranean diet as a tool to improve fertility?

  • Results are cautiously optimistic that the diet as a whole can improve fertility outcomes with ART although effectiveness may be reduced for populations living geographically further away from this region (3,6).

  • Most of the results are from observational studies - more well structured intervention studies would help provide more concrete evidence.

  • The specific nutrients mentioned above do have evidence showing their benefits towards fertility and are generally abundant in a Mediterranean-style diet.

  • Considering the high financial, emotional, and time costs associated with pursuing ART, dietary changes, while they can be challenging, are a relatively low-cost, accessible, and non-invasive manner of increasing the probability of ART success.

References

(1) Sun, H., Lin, Y., Lin, D., Zou, C., Zou, X., Fu, L., Meng, F., & Qian, W. (2019). Mediterranean diet improves embryo yield in IVF: A prospective cohort study. Reproductive Biology and Endocrinology, 17(1). https://doi.org/10.1186/s12958-019-0520-9

(2) Salas-Salvadó, J., & Papandreou, C. (2020). The Mediterranean diet: History, concepts and elements. In The Mediterranean Diet: An Evidence-Based Approach (pp. 3–11). Elsevier. https://doi.org/10.1016/B978-0-12-818649-7.00001-1

(3) Kellow, N. J., le Cerf, J., Horta, F., Dordevic, A. L., & Bennett, C. J. (2022). The Effect of Dietary Patterns on Clinical Pregnancy and Live Birth Outcomes in Men and Women Receiving Assisted Reproductive Technologies: A Systematic Review and Meta-Analysis. Advances in Nutrition, 13(3), 857–874. https://doi.org/10.1093/advances/nmac023

(4) Winter, H. G., Rolnik, D. L., Mol, B. W. J., Torkel, S., Alesi, S., Mousa, A., Habibi, N., Silva, T. R., Oi Cheung, T., Thien Tay, C., Quinteros, A., Grieger, J. A., & Moran, L. J. (2023). Can Dietary Patterns Impact Fertility Outcomes? A Systematic Review and Meta-Analysis. Nutrients, 15(11). https://doi.org/10.3390/nu15112589

(5) Fundación Dieta Mediterránea. (2010). Mediterranean Diet Pyramid: a lifestyle for today. Fundación Dieta Mediterránea. https://dietamediterranea.com/en/nutrition/

(6) Baroutis, D., Kalampokas, T., Katsianou, E., Psarris, A., Daskalakis, G., Panoulis, K., & Eleftheriades, M. (2024). The Role of the Mediterranean Diet in Assisted Reproduction: A Literature Review. Nutrients, 16(16). https://doi.org/10.3390/nu16162807

(7) Gaskins, A. J., & Chavarro, J. E. (2018). Diet and fertility: a review. American Journal of Obstetrics and Gynecology, 218(4), 379–389. https://doi.org/10.1016/j.ajog.2017.08.010

(8) Gaskins, A. J., Nassan, F. L., Chiu, Y. H., Arvizu, M., Williams, P. L., Keller, M. G., Souter, I., Hauser, R., & Chavarro, J. E. (2019). Dietary patterns and outcomes of assisted reproduction. American Journal of Obstetrics and Gynecology, 220(6), 567.e1-567.e18. https://doi.org/10.1016/j.ajog.2019.02.004

(9) Vujkovic, M., de Vries, J. H., Lindemans, J., MacKlon, N. S., van der Spek, P. J., Steegers, E. A. P., & Steegers-Theunissen, R. P. M. (2010). The preconception Mediterranean dietary pattern in couples undergoing in vitro fertilization/intracytoplasmic sperm injection treatment increases the chance of pregnancy. Fertility and Sterility, 94(6), 2096–2101. https://doi.org/10.1016/j.fertnstert.2009.12.079

(10) Karayiannis, D., Kontogianni, M. D., Mendorou, C., Mastrominas, M., & Yiannakouris, N. (2018). Adherence to the Mediterranean diet and IVF success rate among non-obese women attempting fertility. Human Reproduction, 33(3), 494–502. https://doi.org/10.1093/humrep/dey003

(11) Ricci, E., Bravi, F., Noli, S., Somigliana, E., Cipriani, S., Castiglioni, M., Chiaffarino, F., Vignali, M., Gallotti, B., & Parazzini, F. (2019). Mediterranean diet and outcomes of assisted reproduction: an Italian cohort study. American Journal of Obstetrics and Gynecology, 221(6), 627.e1-627.e14. https://doi.org/10.1016/j.ajog.2019.07.011

(12) Urata, Y., Harada, M., Komiya, S., Akiyama, I., Tuchida, C., Nakaoka, Y., Fukuda, A., Morimoto, Y., Kawahara, T., Ishikawa, Y., & Osuga, Y. (2024). Lifestyle and fertility-specific quality of life affect reproductive outcomes in couples undergoing in vitro fertilization. Frontiers in Endocrinology, 15. https://doi.org/10.3389/fendo.2024.1346084

(13) Vitamin B6 - Fact sheet for health professionals. (2023, June 16). National Institutes of Health. Retrieved December 16, 2024, from https://ods.od.nih.gov/factsheets/VitaminB6-HealthProfessional/

(14) Folate - Fact sheet for health professionals. (2022, November 30). National Institutes of Health. Retrieved December 16, 2024, from https://ods.od.nih.gov/factsheets/Folate-HealthProfessional/

(15) Kabodmehri, R., Javaheri, F. S. H., Alami, F., Mahmoudi, Z., Amjadi, A., Saeedirad, Z., Omidi, S., Sadeghi, S., Hoseini, M. S. M., Mohamadiyan, Z., Salimi, Z., Shafaei, H., Rasekhmagham, R., Sharami, S. H., Karimian, M., Karimi, H., & Doaei, S. (2023). Female infertility and dietary antioxidant index (DAI); a case-control study. BMC Women’s Health, 23(1). https://doi.org/10.1186/s12905-023-02747-9

(16) Gaskins, A. J., Chiu, Y. H., Williams, P. L., Keller, M. G., Toth, T. L., Hauser, R., & Chavarro, J. E. (2016). Maternal whole grain intake and outcomes of in vitro fertilization. Fertility and Sterility, 105(6), 1503-1510.e4. https://doi.org/10.1016/j.fertnstert.2016.02.015

(17) Chavarro, J.E., Rich-Edwards, J.W., Rosner, B.A., Willett, W.C. (2009). A prospective study of dietary carbohydrate quantity and quality in relation to risk of ovulatory infertility. Eur. J. Clin. Nutr., 63(1): 78–86. https://doi-org.ezproxy.library.wur.nl/10.1038/sj.ejcn.1602904

(18) Noli, S. A., Ferrari, S., Ricci, E., Reschini, M., Cipriani, S., Dallagiovanna, C., Parazzini, F., & Somigliana, E. (2020). The role of diet in unexpected poor response to ovarian stimulation: a cross-sectional study. Reproductive BioMedicine Online, 41(5), 874–883. https://doi.org/10.1016/j.rbmo.2020.07.011

 
Heather GorhamEnglish, Diet, Fertility - General