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Micronutrients and Human Fertility

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A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Micronutrients and Human Health".

Deadline for manuscript submissions: closed (30 April 2020) | Viewed by 71067

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Prof. Dr. Fabio Parazzini

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Guest Editor

Department of Clinical Science and Community Medicine, University of Milan, 20122 Milan, Italy
Interests: reproduction; gynecological disease; diet; epidemiology; risk factors
Special Issues, Collections and Topics in MDPI journals

Assoc. Prof. Edgardo Somigliana

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Guest Editor

Infertility Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via M. Fanti, 6, 20122, Milan, Italy; Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy

Special Issue Information

Dear Colleagues,

Human fecundity is low and reasons remain obscure. It is plausible, yet poorly explored, that diet and micronutrients may play a role in modulating both natural and ART-mediated fertility. The definite demonstration of a beneficial effect of micronutrients supplementation for improving human fecundity would represent a significant step forward. Both natural and ART-mediated chance of pregnancy could be improved in a simple, economic, and safe way.

Nutritional status during pregnancy is also a key factor in modulating the characteristics of the environment within which the fetus originates and develops. Women’s nutritional status just before conception and during early pregnancy may influence pregnancy outcomes by affecting critical developmental processes that begin early in pregnancy.

In this Special Issue, we focus on the effects of the most-studied micronutrients, i.e., Vitamin D, folates, and polyunsaturated fatty acids (PUFA) on male and female fertility. The contributions will present biological insights and possible rationale for efficacy and will systematically review available epidemiological and, if available, interventional studies on both natural and ART-mediated infertility and the role of nutritional status in the early phase of pregnancy

Prof. Fabio Parazzini
Assoc. Prof. Edgardo Somigliana
Guest Editors

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Keywords

Fertility
Diet
Vitamin D
Folic acid
Micronutrients
Mediterranean diet
Assisted reproductive techniques
Early pregnancy

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Published Papers (7 papers)

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17 pages, 1058 KiB

Open AccessArticle

The Association between Seafood Intake and Fecundability: Analysis from Two Prospective Studies

by Lauren A. Wise, Sydney K. Willis, Ellen M. Mikkelsen, Amelia K. Wesselink, Henrik Toft Sørensen, Kenneth J. Rothman, Katherine L. Tucker, Ellen Trolle, Marco Vinceti and Elizabeth E. Hatch

Nutrients 2020, 12(8), 2276; https://doi.org/10.3390/nu12082276 - 29 Jul 2020

Cited by 9 | Viewed by 3829

Abstract

Background: Seafood is an important source of omega-3 fatty acids, which have been associated with improved oocyte quality and embryo morphology in some studies. However, seafood is also a source of persistent organic pollutants and heavy metals, which may adversely affect fecundity. Previous studies of seafood intake and fecundity have generated inconsistent results. Methods: In two prospective cohort studies of 7836 female pregnancy planners from Denmark (Snart Foraeldre, n = 2709) and North America (PRESTO, n = 5127), we evaluated the association of dietary intake of total seafood and marine-sourced long-chain omega-3 fatty acids (eicosapentaenoic acid, docosahexaenoic acid, and docosapentaenoic acid) with fecundability. Participants completed a baseline questionnaire on sociodemographics, behavioral factors, anthropometrics, and medical history, and a food frequency questionnaire. Pregnancy status was updated bimonthly for up to 12 months or until reported conception. We estimated fecundability ratios (FRs) and 95% confidence intervals (CIs) using proportional probabilities regression models, adjusted for energy intake and other potential confounders. We restricted analyses to women with ≤6 menstrual cycles of attempt time at enrollment. Results: Intake of total seafood or marine-sourced long-chain omega-3 fatty acids was not appreciably associated with fecundability in either cohort (≥200 vs. <50 g/week total seafood: FR = 0.94, 95% CI: 0.79–1.10 in Snart Foraeldre; FR = 1.00, 95% CI: 0.90–1.13 in PRESTO; marine fatty acids: ≥90th vs. <25th percentile: FR = 1.00, 95% CI: 0.85–1.18 in Snart Foraeldre; FR = 0.97, 95% CI: 0.86–1.09 in PRESTO). In PRESTO, where we collected additional data on seafood preparation, we observed an inverse association between fecundability and fried shellfish (≥10 g/week vs. none: FR = 0.77, 95% CI: 0.61–0.98), but not unfried shellfish (≥20 g/week vs. none: FR = 0.98, 95% CI: 0.89–1.07); in Snart Foraeldre, there was no association with total shellfish intake. Conclusions: We found little association between seafood intake and fecundability overall, but greater intake of fried shellfish was associated with reduced fecundability among North American participants. Full article

(This article belongs to the Special Issue Micronutrients and Human Fertility)

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11 pages, 2121 KiB

Open AccessArticle

Zinc Oxide Exerts Anti-Inflammatory Properties on Human Placental Cells

by Andrea Balduit, Alessandro Mangogna, Chiara Agostinis, Gabriella Zito, Federico Romano, Giuseppe Ricci and Roberta Bulla

Nutrients 2020, 12(6), 1822; https://doi.org/10.3390/nu12061822 - 18 Jun 2020

Cited by 11 | Viewed by 4351

Abstract

Background: An aberrant and persistent inflammatory state at the fetal-maternal interface is considered as a key contributor in compromised pregnancies. Decidual endothelial cells (DECs) play a pivotal role in the control of the local decidual inflammation. The aim of the current study was to determine whether dietary supplement with zinc oxide (ZnO), due to its very low adverse effects, may be useful for modulating the inflammatory response in the first trimester of pregnancy. Methods: The anti-inflammatory properties of ZnO in pregnancy were evaluated by in vitro tests on endothelial cells isolated from normal deciduas and on a trophoblast cell line (HTR8/Svneo). The effects of this treatment were analyzed in terms of adhesion molecule expression and inflammatory cytokine secretion, by real time-quantitative PCR (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA). Results: Our data showed that ZnO was able to reduce the inflammatory response of DECs, in terms of vascular cell adhesion molecule-1 (VCAM-1), interleukin (IL)-8, IL-6, tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1) expression induced by TNF-α stimulation. This compound exerted no effect on intracellular adhesion molecule-1 (ICAM-1) exocytosis induced by TNF-α on stimulated trophoblast cells, but significantly reduced their IL-6 expression. Conclusion: According to these results, it can be suggested that the ZnO supplement, through its modulation of the pro-inflammatory response of DECs, can be used in pregnancy for the prevention of local decidual inflammation. Full article

(This article belongs to the Special Issue Micronutrients and Human Fertility)

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13 pages, 267 KiB

Open AccessArticle

Dietary Carbohydrate Intake, Dietary Glycemic Load and Outcomes of In Vitro Fertilization: Findings from an Observational Italian Cohort Study

by Stefania Antonia Noli, Elena Ricci, Sonia Cipriani, Stefania Ferrari, Marta Castiglioni, Irene La Vecchia, Edgardo Somigliana and Fabio Parazzini

Nutrients 2020, 12(6), 1568; https://doi.org/10.3390/nu12061568 - 28 May 2020

Cited by 14 | Viewed by 3255

Abstract

In recent decades, increasing attention has been paid to the influence of diet on reproductive health. Carbohydrates in diet affect glucose metabolism and multiple evidences showed the key role of insulin sensitivity in regulating female fertility. We designed a prospective cohort study to investigate the relation between dietary carbohydrate intake, glycemic load (GL) and the outcomes of assisted reproduction. A population of 494 female partners of couples referring to an Italian Fertility Center and eligible for in vitro fertilization (IVF) were enrolled in the study. On the day of the oocyte retrieval, information on their diet was obtained using a validated food frequency questionnaire (FFQ). We calculated the relative risk and 95% confidence interval of embryo transfer, clinical pregnancy and live birth according to the following dietary exposures: GL, glycemic index (GI) as well as the daily carbohydrate and fiber intake. A multiple regression model was used to account for the confounders. After adjusting for age, college degree, body mass index (BMI), leisure physical activity and previous assisted reproduction techniques (ART) cycles, no significant association was observed between the considered dietary exposures and the IVF outcomes. The roles of GL, carbohydrate intake and GI were assessed in strata of the cause of infertility and body mass index and no relation emerged in this further analysis. We found no clear association between the dietary carbohydrate quantity and quality and IVF outcomes in a cohort of infertile Italian women. Full article

(This article belongs to the Special Issue Micronutrients and Human Fertility)

8 pages, 251 KiB

Open AccessArticle

The Relationship between Vitamin D Metabolites and Androgens in Women with Polycystic Ovary Syndrome

by Jakub Mesinovic, Helena J. Teede, Soulmaz Shorakae, Gavin W. Lambert, Elisabeth A. Lambert, Negar Naderpoor and Barbora de Courten

Nutrients 2020, 12(5), 1219; https://doi.org/10.3390/nu12051219 - 26 Apr 2020

Cited by 13 | Viewed by 4567

Abstract

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of reproductive age, with hyperandrogenism present in up to 90% of affected women. Some evidence suggests a link between vitamin D deficiency and PCOS features via insulin resistance and inflammation. Our aim was to explore the relationship between biochemical markers of vitamin D status and androgens in women with PCOS. This cross-sectional study used bio-banked samples from 46 pre-menopausal women with PCOS (mean ± SD: age 30 ± 6 years; BMI 29 ± 6 kg/m²). We measured 25-hydroxyvitamin D (25[OH]D), vitamin D-binding protein (DBP), total testosterone, sex hormone-binding globulin (SHBG), and calculated the free androgen index (FAI) and bioavailable and free 25(OH)D. Fasting glucose and insulin were used to calculate the homeostatic model assessment of insulin resistance (HOMA-IR) and body fat percentage was determined via dual energy x-ray absorptiometry. High-sensitivity C-reactive protein (hs-CRP) was measured as a marker of inflammation. DBP was positively associated with total 25(OH)D and expectedly, negatively associated with free 25(OH)D. There were no associations between vitamin D metabolites and total testosterone, SHBG or FAI, even after adjusting for age, body fat percentage, HOMA-IR and hs-CRP. We found no associations between vitamin D metabolites and androgens in women with PCOS. Studies that have identified a vitamin D–androgen link have largely relied on methodology with numerous pitfalls; future studies should exclusively use gold-standard measures to confirm these findings in this population. Full article

(This article belongs to the Special Issue Micronutrients and Human Fertility)

12 pages, 1002 KiB

Open AccessArticle

Maternal Selenium, Copper and Zinc Concentrations in Early Pregnancy, and the Association with Fertility

by Jessica A. Grieger, Luke E. Grzeskowiak, Rebecca L. Wilson, Tina Bianco-Miotto, Shalem Y. Leemaqz, Tanja Jankovic-Karasoulos, Anthony V. Perkins, Robert J. Norman, Gus A. Dekker and Claire T. Roberts

Nutrients 2019, 11(7), 1609; https://doi.org/10.3390/nu11071609 - 16 Jul 2019

Cited by 43 | Viewed by 7713

Abstract

Trace elements such as zinc, copper, and selenium are essential for reproductive health, but there is limited work examining how circulating trace elements may associate with fertility in humans. The aim of this study was to determine the association between maternal plasma concentrations of zinc, copper, and selenium, and time to pregnancy and subfertility. Australian women (n = 1060) who participated in the multi-centre prospective Screening for Pregnancy Endpoints study were included. Maternal plasma concentrations of copper, zinc and selenium were assessed at 15 ± 1 weeks’ gestation. Estimates of retrospectively reported time to pregnancy were documented as number of months to conceive; subfertility was defined as taking more than 12 months to conceive. A range of maternal and paternal adjustments were included. Women who had lower zinc (time ratio, 1.20 (0.99–1.44)) or who had lower selenium concentrations (1.19 (1.01–1.40)) had a longer time to pregnancy, equivalent to a median difference in time to pregnancy of around 0.6 months. Women with low selenium concentrations were also at a 1.46 (1.06–2.03) greater relative risk for subfertility compared to women with higher selenium concentrations. There were no associations between copper and time to pregnancy or subfertility. Lower selenium and zinc trace element concentrations, which likely reflect lower dietary intakes, associate with a longer time to pregnancy. Further research supporting our work is required, which may inform recommendations to increase maternal trace element intake in women planning a pregnancy. Full article

(This article belongs to the Special Issue Micronutrients and Human Fertility)

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13 pages, 1096 KiB

Open AccessArticle

Effect of Nut Consumption on Erectile and Sexual Function in Healthy Males: A Secondary Outcome Analysis of the FERTINUTS Randomized Controlled Trial

by Albert Salas-Huetos, Jananee Muralidharan, Serena Galiè, Jordi Salas-Salvadó and Mònica Bulló

Nutrients 2019, 11(6), 1372; https://doi.org/10.3390/nu11061372 - 19 Jun 2019

Cited by 17 | Viewed by 35270

Abstract

Lifestyle risk factors for erectile and sexual function include smoking, excessive alcohol consumption, lack of physical activity, psychological stress, and adherence to unhealthy diets. In the present study, we evaluated the effects of mixed nuts supplementation on erectile and sexual function. Eighty-three healthy male aged 18–35 with erectile function assessment were included in this FERTINUTS study sub-analysis; a 14-week randomized, controlled, parallel feeding trial. Participants were allocated to (1) the usual Western-style diet enriched with 60 g/day of a mixture of nuts (nut group; n = 43), or (2) the usual Western-style diet avoiding nuts (control group; n = 40). At baseline and the end of the intervention, participants answered 15 questions contained in the validated International Index of Erectile Function (IIEF), and peripheral levels of nitric oxide (NO) and E-selectin were measured, as surrogated markers of erectile endothelial function. Anthropometrical characteristics, and seminogram and blood biochemical parameters did not differ between intervention groups at baseline. Compared to the control group, a significant increase in the orgasmic function (p-value = 0.037) and sexual desire (p-value = 0.040) was observed during the nut intervention. No significant differences in changes between groups were shown in peripheral concentrations of NO and E-selectin. Including nuts in a regular diet significantly improved auto-reported orgasmic function and sexual desire. Full article

(This article belongs to the Special Issue Micronutrients and Human Fertility)

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24 pages, 2333 KiB

Open AccessReview

The Association between Vitamin D and Anti-Müllerian Hormone: A Systematic Review and Meta-Analysis

by Irene Moridi, Alice Chen, Oded Tal and Reshef Tal

Nutrients 2020, 12(6), 1567; https://doi.org/10.3390/nu12061567 - 28 May 2020

Cited by 73 | Viewed by 11204

Abstract

Accumulating evidence from animal and human studies indicates a role for vitamin D in female reproductive physiology, and numerous clinical studies have suggested its potential benefit for various aspects of human reproduction. Anti-Müllerian hormone (AMH) is an ovarian biomarker that plays an important role in folliculogenesis. It is the most sensitive ovarian reserve marker and is widely used clinically in reproductive medicine. While initial studies have suggested that vitamin D may be associated with ovarian reserve markers, including AMH, evidence has been conflicting. Currently, there is considerable debate in the field whether vitamin D has the capacity to influence ovarian reserve, as indicated by the AMH level. The current systematic review aims to evaluate and summarize the available evidence regarding the relationship between vitamin D and AMH. In total, 18 observational studies and 6 interventional studies were included in this systematic review. Cross-sectional studies have reported largely discrepant findings regarding an association between serum vitamin D and AMH levels, which are likely due to the heterogeneity in study populations, as well as the apparently complex relationship that may exist between vitamin D and AMH. However, meta-analysis of interventional studies performed herein that examined the effects of vitamin D supplementation on serum AMH levels indicates a cause-effect relationship between vitamin D and AMH, the direction of which appears to depend on a woman’s ovulatory status. Serum AMH was significantly decreased following vitamin D supplementation in polycystic ovarian syndrome (PCOS) women (standardized mean difference (SMD) −0.53, 95% CI −0.91 to −0.15, p < 0.007), while it was significantly increased following vitamin D supplementation in ovulatory women without PCOS (SMD 0.49, 95% CI 0.17 to 0.80, p = 0.003). In conclusion, the results of this systematic review demonstrate that the relationship between vitamin D and AMH is a complex one, and large, randomized trials of vitamin D supplementation focusing on different vitamin D status ranges are necessary to gain more insight into the nature of this relationship and the potential benefit of vitamin D to female reproduction in general. Full article

(This article belongs to the Special Issue Micronutrients and Human Fertility)

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