Journal of Obstetrics and Gynaecology

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Association between nutrient intake and female

infertility: a study based on NHANES database

Xiaowei Ji, Yao Ye, Lin Wang, Suying Liu & Xi Dong

To cite this article: Xiaowei Ji, Yao Ye, Lin Wang, Suying Liu & Xi Dong (2023) Association
between nutrient intake and female infertility: a study based on NHANES database, Journal of
Obstetrics and Gynaecology, 43:2, 2285025, DOI: 10.1080/01443615.2023.2285025

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JOURNAL OF OBSTETRICS AND GYNAECOLOGY
2023, VOL. 43, NO. 2, 2285025
https://doi.org/10.1080/01443615.2023.2285025

RESEARCH ARTICLE

Association between nutrient intake and female infertility: a study based

on NHANES database
Xiaowei Ji&, Yao Ye&, Lin Wang, Suying Liu and Xi Dong
Reproductive Medicine Center, Zhongshan Hospital, Fudan University, Shanghai, PR China

ABSTRACT ARTICLE HISTORY

Background: This study was designed to investigate the association between nutrients and female Received 17 July 2023
infertility. Accepted 5 November 2023
Methods: A cross-sectional study on 18–45 years of age reproductive-age women was conducted using
KEYWORDS
the data from the National Health and Nutrition Examination Surveys (NHANES) for the periods 2013–
Nutrients; female infertility;
2014 and 2015–2016. Multivariate logistic regression analysis was performed to evaluate the association NHANES database
between nutrients and female infertility. Subgroup analysis was applied to the body mass index (BMI).
Results were summarised using an odds ratio (OR) with a 95% confidence interval (CI).
Results: Of the total 1713 women, 204 women (11.91%) were infertile. The result demonstrated that
higher intake of carbohydrate (OR: 0.46, 95% CI: 0.24–0.86, p ¼ 0.018), vitamin A (OR: 0.44, 95% CI:
0.24–0.80, p ¼ 0.009), vitamin C (OR: 0.48, 95% CI: 0.26–0.88, p ¼ 0.020), magnesium (OR: 0.36, 95% CI:
0.17–0.76, p ¼ 0.009), iron (OR: 0.43, 95% CI: 0.23–0.82, p ¼ 0.012), lycopene (OR: 0.55, 95% CI: 0.33–
0.91, p ¼ 0.022), and total folate (OR: 0.38, 95% CI: 0.20–0.70, p ¼ 0.003) were associated with a lower
risk of female infertility. The subgroup analysis also reported that intakes of vitamin A, vitamin C, and
lycopene were related to a lower risk of female infertility among women with a BMI being 18.5–
24.9 kg/m2. Among women with BMI > 24.9 kg/m2, high intakes of magnesium, iron and total folate
were associated with a decreased risk of female infertility.
Conclusions: The intake of several nutrients is associated with a decreased risk of female infertility.
These findings provide insight into potentially modifiable lifestyle factors associated with female infer­
tility.

PLAIN LANGUAGE SUMMARY

Infertility is becoming a global challenge in both medical and social aspects. There is growing evidence
of the importance of nutrition in reproduction in animal and human studies, suggesting a correlation
between nutrition and female fertility. We observed that higher intakes of carbohydrates, vitamin A,
vitamin C, magnesium, iron, lycopene and total folate were associated with a lower risk of female infer­
tility. This study helped increase awareness among health professionals and patients about the impor­
tant link between nutrients and infertility, and educate women about the significance of a healthy
lifestyle and diet.

Introduction to more than half of all cases of global childlessness, the

Infertility is defined as the inability to conceive after
12 months of unprotected intercourse or six months for
women aged 35 years or older (Vander Borght and Wyns
2018). Infertility is a global health problem affecting 20–30%
of the female population of reproductive age (Silvestris et al.
2019). Infertility is more than a quality-of-life issue, with con­
siderable public health consequences including psychological
distress, social stigmatisation, economic strain, marital dis­
cord, negative pregnancy outcomes and later-onset adult dis­
eases (Sun et al. 2019). Although male infertility contributes
major psychological and social burdens primarily affect
women (Westerman and Kuhnt 2022). Therefore, it is neces­
sary to explore the factors that may affect female infertility.
A plethora of systemic and gynecological conditions can
affect the female reproductive system and potentially lead to
infertility, including polycystic ovarian syndrome (PCOS),
endometriosis, premature ovarian failure and pelvic inflam­
matory disease (Deshpande and Gupta 2019, Afrin et al.
2021). Besides organic diseases, lifestyle factors such as
unbalanced nutrition and an unhealthy diet may interfere
with the physiological reproductive functions (Afrin

CONTACT Xi Dong Dongxi_12345@163.com Reproductive Medicine Center, Zhongshan Hospital, Fudan University, No 250 Xiaomuqiao Road, Shanghai
200032, PR China
&
Co-author
Supplemental data for this article can be accessed online at https://doi.org/10.1080/01443615.2023.2285025.
� 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted
Manuscript in a repository by the author(s) or with their consent.
2 X. JI ET AL.
et al. 2021, Silvestris et al. 2019). Mounting evidence suggests
a correlation between nutrition and female fertility (Silvestris
et al. 2019, Aoun et al. 2021), however, conflicting results
exist. In a Danish and North American preconception cohort
study (Wise et al. 2018), high trans fatty acids intake and low
omega-3 fatty acid intake were associated with reduced
fecundity. A study (Li et al. 2019) performed in Massachusetts
reported that total consumption of vitamins A, C and E
before starting infertility treatment with assisted reproductive
technologies was not associated with live birth rates. A
review demonstrated an association between higher folate
intake with increased fecundability (Gaskins and Chavarro
2018). Nevertheless, another study found that high doses of
folic acid do not increase the odds of pregnancy in infertile
women (Murto et al. 2014). Given the contradictory studies
and there are only a few studies devoted to studying the
association between nutrient intakes and female infertility,
this study was conducted.
Herein, this study was to evaluate the relationship between
multiple nutrients and female infertility, which may be helpful
for guiding the search for appropriate dietary patterns.
Methods
Study design and participants
A cross-sectional study was conducted using data from the
National Health and Nutrition Examination Survey (NHANES)
database between 2013 and 2014 and 2015 to 2016 (https://
www.cdc.gov/nchs/nhanes/about_nhanes.htm). The NHANES
is a program of studies conducted to understand the health
and nutritional status of the United States population since
the 1960s. The survey includes interviews and physical exami­
nations in a nationwide representative sample of about 5000
participants each year. The NHANES gathers demographic,
socioeconomic, dietary and health-related information. The
physical examination section involves medical, dental and
physiological measurements, as well as laboratory tests
directed by qualified medical professionals (Anon 2020). Data
from women of 18–45 years of age who were sexually experi­
enced were analysed. Women who did not answer the ques­
tion ‘history of infertility’, had a history of ovariectomy and
hysterectomy, with missing data on total polyunsaturated
fatty acids (PUFA), with missing data on sex hormone binding
globulin (SHBG), and with missing data on ever use female
hormones were excluded from the study. Pregnant women
were also excluded. The flow chart of data selection is shown
in Figure 1. As the data sets included in the study were
downloaded from public databases, the study did not need
the approval of an ethics committee from our hospital. We
followed the Strengthening the Reporting of Observational
Studies in Epidemiology (STROBE) statement according to the
Enhancing the Quality and Transparency of Health Research
(EQUATOR) guidelines (von Elm et al. 2008).
Variables
The estimated daily intakes of nutrients included caffeine
(mg), carbohydrates (g), protein (g), total fat (g), omega-3
PUFA (g), omega-6 PUFA (g), vitamin A (mcg), vitamin E (mg),
vitamin C (mg), vitamin D (mcg), selenium (mcg), zinc (mg),
magnesium (mg), iron (mg), lycopene (mcg), total folate
(mcg), beta-carotene (mcg) and lutein þ zeaxanthin (mcg). All
nutrient intakes were divided into four groups according to
the interquartile range.
Covariate
Covariate variables included energy (kcal), age (years), ethni­
city (Mexican American, other Hispanic, non-Hispanic white,
non-Hispanic black or other ethnicities), marital status
(divorced, living with a partner, married, never married, sepa­
rated, and widowed), the education level [9–11th grade, col­
lege graduate, high school graduate, less than 9th grade,
some college or Associate of Arts (AA) degree], annual family
income (less than $20,000 or $20,000 or more), body mass
index (BMI, kg/m2), smoking at least 100 cigarettes in life (yes
or no), had at least 12 alcohol drinks/1 year (yes or no), age
when first menstrual period occurred (years), ever treated for
a pelvic infection (yes or no), ever taken birth control pills
(yes or no), ever use female hormones (yes or no), oestradiol
(pg/mL), testosterone (ng/dL) and SHBG (nmol/L).
Self-reported infertility
Infertility is defined as the absence of pregnancy with unpro­
tected intercourse for one year (Anon 2015). The presence of
infertility was assessed using a self-reported questionnaire.
Statistical analysis
The measurement data of the normal distribution were
described with the mean ± standard error [mean (S.E.)], and
a t-test was used for comparison between groups. Counting
data were expressed as numbers and percentages were com­
pared between the two groups using the chi-square test. The
missing values were filled by multiple interpolations. The
missing values before and after interpolation were compared
by performing a sensitivity analysis. Multivariate logistic
regression analysis was used to evaluate the association
between nutrients and female infertility. Model 1 was created
by not adjusting for variates, and Model 2 adjusted for age,
BMI, marital status, pelvic infection, SHBG and energy. The
association between recommended intakes of nutrients and
female infertility was also performed. The subgroup analysis
was performed based on BMI. Statistical significance was
defined as a p value of < 0.05. The data were analysed using
SAS version 9.4 (SAS Institute, Cary, NC).
Results
Basic characteristics of included participants
In total, 1713 women were included, comparing 204 women
being infertile. The mean age of included women was 32.28
(0.26) years. The majority of the participants (46.16%)
included were married. The BMI of 1114 (62.38%) participants

Figure 1. Flow chart of data selection. NHANES: National Health and Nutrition Examination Surveys; PUFA: polyunsaturated fatty acid; SHBG: sex hormone binding
globulin.
was greater than 24.9 kg/m2. The basic characteristics of the
included participants are presented in Table 1. The mean
estimated daily intake of carbohydrates was 233.51 (3.40) g.
Participants without female infertility had a higher mean esti­
mated daily intake of vitamin A [590.63 (21.78) mcg] com­
pared with participants with female infertility [543.12 (48.53)
mcg]. Participants without female infertility had a higher
mean estimated daily intakes of protein, Vitamin E, Vitamin
C, Vitamin D, selenium, zinc, magnesium, iron, lycopene, total
folate, Beta-carotene and lutein þ zeaxanthin. Characteristics
of nutrients intakes in participants with and without female
infertility are shown in Table 2. There were statistically signifi­
cant differences in age, marital status, BMI, pelvic infection,
SHBG, total fat, vitamin C, zinc and total folate between infer­
tile and non-infertile women (all p < 0.05).
Association between nutrients and female infertility
From Model 1, intakes of vitamin C in group 3 (62.07–
139.6 mg), group 4 (�139.6 mg), zinc in group 2 (6.66–
9.82 mg) and higher intake of total folate were associated
with female infertility. Higher intake of carbohydrates (odds
ratio [OR]: 0.46, 95% confidence interval [CI]: 0.24–0.86,
p ¼ 0.018], vitamin A (OR: 0.44, 95% CI: 0.24–0.80, p ¼ 0.009),
vitamin C in group 3 (OR: 0.48, 95% CI: 0.27–0.87, p ¼ 0.016),
vitamin C in group 4 (OR: 0.48, 95% CI: 0.26–0.88, p ¼ 0.020),
higher intake of magnesium (OR: 0.36, 95% CI: 0.17–0.76,
p ¼ 0.009), iron in group 3 (OR: 0.49, 95% CI: 0.30–0.81,
p ¼ 0.007), group 4 (OR: 0.43, 95% CI: 0.23–0.82, p ¼ 0.012),
lycopene (OR: 0.55, 95% CI: 0.33–0.91, p ¼ 0.022) and total fol­
ate (OR: 0.38, 95% CI: 0.20–0.70, p ¼ 0.003) were found to be
NUTRIENT INTAKE AND FEMALE INFERTILITY 3
associated with a lower risk of female infertility after adjust­
ing for variates in Model 2. Table 3 shows the association
between nutrients and female infertility. Supplementary
Table 1 presents the association between recommended
intakes of nutrients and female infertility. Intakes of vitamin
A, vitamin C, magnesium, iron and total folate that were
higher than the recommended dietary intakes were associ­
ated with a reduced risk of female infertility.
Subgroup analysis of the association between nutrients
and female infertility based on BMI categories
As only 2.74% population weighed <18.5 kg/m2, subgroup ana­
lysis was conducted based on 2 BMI categories (BMI: 18.5–
24.9 kg/m2 and BMI: >24.9 kg/m2). High intakes of vitamin A (OR:
0.22, 95% CI: 0.07–0.71, p ¼ 0.013), vitamin C (OR: 0.17, 95% CI:
0.05–0.60, p ¼ 0.008), and lycopene (OR: 0.37, 95% CI: 0.15–0.87,
p ¼ 0.025) were related to a lower risk of female infertility in
women with a BMI of 18.5–24.9 kg/m2. Among women with a
BMI > 24.9 kg/m2, high intakes of magnesium (OR: 0.39, 95% CI:
0.19–0.81, p ¼ 0.014), iron (OR: 0.37, 95% CI: 0.14–0.96, p ¼ 0.041),
and total folate (OR: 0.31, 95% CI: 0.13–0.69, p ¼ 0.006) were asso­
ciated with a reduced risk of female infertility. Subgroup analysis
of the association between nutrients and female infertility based
on BMI categories is described in Figure 2.
Discussion
Infertility is becoming a global challenge in both medical and
social aspects (Inhorn and Patrizio 2015). There is growing
4 X. JI ET AL.

Table 1. Basic characteristics of included participants.

Female infertility
Variables Total (n ¼ 1713) Yes (n ¼ 204) No (n ¼ 1509) Statistics p
Age in years at screening, years, Mean (S.E) 32.28 (0.26) 35.99 (0.60) 31.73 (0.26) t ¼ 7.16 <0.001
Ethnicity /Hispanic origin, n (%) v2 ¼ 3.658 0.454
Mexican American 327 (12.62) 40 (12.02) 287 (12.72)
Non-Hispanic Black 349 (12.58) 47 (13.11) 302 (12.50)
Non-Hispanic White 576 (57.40) 73 (62.00) 503 (56.71)
Other Hispanic 192 (7.79) 17 (5.46) 175 (8.14)
Other ethnicities 269 (9.61) 27 (7.40) 242 (9.94)
Marital status, n (%) v2 ¼ 39.969 <0.001
Divorced 120 (7.00) 18 (7.53) 102 (6.92)
Living with a partner 236 (13.79) 26 (10.38) 210 (14.30)
Married 752 (46.16) 126 (67.97) 626 (42.91)
Never married 540 (29.84) 29 (10.11) 511 (32.78)
Separated 58 (2.62) 4 (2.57) 54 (2.63)
Widowed 7 (0.59) 1 (1.43) 6 (0.46)
Education level, n (%) v2 ¼ 2.675 0.614
9–11th grade 180 (8.21) 18 (6.08) 162 (8.53)
College graduate 488 (33.39) 58 (37.51) 430 (32.78)
High school graduate 326 (17.63) 41 (17.71) 285 (17.62)
Less than 9th grade 95 (3.56) 9 (2.93) 86 (3.65)
Some college or AA degree 624 (37.21) 78 (35.77) 546 (37.43)
Annual family income, n (%) v2 ¼ 1.370 0.242
$20,000 and over 1370 (83.26) 160 (85.63) 1210 (82.91)
Under $20,000 343 (16.74) 44 (14.37) 299 (17.09)
BMI, kg/m2, Mean (S.E) 29.15 (0.24) 31.82 (1.02) 28.75 (0.26) t ¼ 2.80 0.009
BMI, kg/m2, n (%) v2 ¼ 3.449 0.178
<18.5 52 (2.74) 5 (2.68) 47 (2.75)
18.5–24.9 547 (34.88) 55 (27.40) 492 (35.99)
>24.9 1114 (62.38) 144 (69.92) 970 (61.26)
Smoked at least 100 cigarettes in life, n (%) v2 ¼ 0.917 0.338
No 1235 (68.72) 145 (72.26) 1090 (68.19)
Yes 478 (31.28) 59 (27.74) 419 (31.81)
Had at least 12 alcohol drinks/year, n (%) v2 ¼ 0.369 0.543
No 585 (27.90) 58 (25.99) 527 (28.19)
Yes 1128 (72.10) 146 (74.01) 982 (71.81)
Age when first menstrual period occurred, years, mean (S.E) 12.63 (0.06) 12.61 (0.19) 12.64 (0.05) t ¼ −0.16 0.875
Ever treated for a pelvic infection, n (%) v2 ¼ 13.921 <0.001
No 1640 (95.95) 184 (90.63) 1456 (96.74)
Yes 73 (4.05) 20 (9.37) 53 (3.26)
Ever taken birth control pills, n (%) v2 ¼ 3.714 0.054
No 568 (26.69) 49 (20.46) 519 (27.62)
Yes 1145 (73.31) 155 (79.54) 990 (72.38)
Ever use female hormones, n (%) v2 ¼ 0.096 0.757
No 1671 (97.17) 198 (96.73) 1473 (97.24)
Yes 42 (2.83) 6 (3.27) 36 (2.76)
Oestradiol, pg/mL, mean (S.E) 98.30 (3.47) 115.07 (13.63) 95.80 (3.59) t ¼ 1.33 0.192
Testosterone, total, ng/dL, mean (S.E) 27.24 (0.65) 27.08 (1.28) 27.27 (0.68) t ¼ −0.14 0.887
SHBG, nmol/L, mean (S.E) 82.08 (2.42) 70.88 (5.17) 83.75 (2.74) t ¼−2.14 0.041
Notes: BMI: body mass index; SHBG: sex hormone binding globulin; mean (S.E.): mean ± standard error; t: t-test; v2: chi-square

evidence of the importance of nutrition in reproduction in
animal and human studies, suggesting a correlation between
nutrition and female fertility (Bosdou et al. 2019, Vitagliano
et al. 2021). A review assessed the evidence for the effective­
ness of different antioxidants in female subfertility. However,
in this review, there was low- to very low-quality evidence to
show that there was low- to very low-quality evidence to
show that taking an antioxidant may benefit subfertile
women (Showell et al. 2020). The association of various types
of nutrients with female infertility still needs evaluation. This
study was conducted to evaluate the association between
multiple nutrients and female infertility and indicated that
higher intakes of carbohydrates, vitamin A, vitamin C, magne­
sium, iron, lycopene and total folate were associated with a
lower risk of female infertility. In addition, intakes of vitamin
A, vitamin C, and lycopene were related to a lower risk of
female infertility among women with a BMI being 18.5–
24.9 kg/m2. Among women with BMI > 24.9 kg/m2, high
intakes of magnesium, iron and total folate were associated
with a reduced risk of female infertility.
The ability to sense nutrients and to adapt physiological
responses to nutrient availability and characteristics allowed
organisms to increase their opportunities to survive and to
expand their progenies (Della Torre et al. 2014). This study
did not observe the association between PUFAs and female
infertility. A cross-sectional study conducted among women
aged 20–44 years found that PUFA intake is only slightly
associated with infertility (Wang et al. 2022). No statistical
association between vitamin D and female infertility was
observed in our study. However, a recent study demon­
strated that vitamin D status appears to be relevant to repro­
ductive physiology, and to physiological processes underlying
common gynecological disorders as well as for reproductive
success (Simpson and Pal 2023). The relationships between
PUFAs/vitamin D and female infertility need further elucida­
tion. In an Italian study of women undergoing in vitro
 NUTRIENT INTAKE AND FEMALE INFERTILITY 5

Table 2. Characteristics of nutrients intakes in participants with and without female infertility.
Female infertility
Variables Total (n ¼ 1713) Yes (n ¼ 204) Yes (n ¼ 204) Statistics p
Energy, kcal, mean (S.E) 1962.93 (23.46) 2001.49 (53.61) 1957.19 (24.24) t ¼ 0.81 0.425
Caffeine, mg, mean (S.E) 121.80 (6.47) 137.82 (15.09) 119.42 (6.49) t ¼ 1.26 0.218
Carbohydrate, g, mean (S.E) 233.51 (3.40) 229.50 (5.54) 234.11 (3.77) t ¼ −0.71 0.483
Carbohydrate, g, n (%) – – – v2 ¼ 1.934 0.586
Group 1: <158.64 419 (24.99) 46 (24.83) 373 (25.01) – –
Group 2: 158.64–219.62 420 (24.93) 49 (25.06) 371 (24.92) – –
Group 3: 219.62–287.09 426 (25.07) 53 (28.87) 373 (24.50) – –
Group 4: �287.09 448 (25.01) 56 (21.25) 392 (25.57) – –
Protein, g, mean (S.E) 73.88 (0.94) 73.49 (2.00) 73.94 (1.03) t ¼ −0.20 0.843
2
Protein g, n (%) – – – v ¼ 4.468 0.215
Group 1: <51.33 448 (24.87) 49 (20.41) 399 (25.53) – –
Group 2: 51.33–68.83 416 (25.12) 45 (26.46) 371 (24.92) – –
Group 3: 68.83–92.1 411 (24.99) 54 (30.14) 357 (24.22) – –
Group 4: �92.1 438 (25.02) 56 (22.98) 382 (25.33) – –
Total fat, g, mean (S.E) 76.79 (1.08) 82.13 (3.09) 75.99 (0.99) t ¼ 2.12 0.043
Total fat, g, n (%) – – – v2 ¼ 4.851 0.183
Group 1: <50.86 463 (24.99) 50 (24.76) 413 (25.02) – –
Group 2: 50.86–71.68 420 (24.97) 47 (19.65) 373 (25.77) – –
Group 3: 71.68–97.53 410 (25.01) 41 (24.33) 369 (25.11) – –
Group 4: �97.53 420 (25.03) 66 (31.26) 354 (24.10) – –
Omega-3 PUFA, g, mean (S.E) 1.81 (0.04) 1.99 (0.11) 1.78 (0.04) t ¼ 1.79 0.083
2
Omega n-3 PUFA, gm, n (%) – – – v ¼ 3.537 0.316
Group 1: <0.97 445 (24.97) 49 (22.36) 396 (25.36) – –
Group 2: 0.97–1.5 416 (24.96) 48 (25.00) 368 (24.96) – –
Group 3: 1.5–2.3 418 (25.03) 45 (22.09) 373 (25.47) – –
Group 4: �2.3 434 (25.03) 62 (30.56) 372 (24.21) – –
Omega-6 PUFA, g, mean (S.E) 16.23 (0.30) 17.68 (0.86) 16.01 (0.29) t ¼ 1.97 0.059
Omega −6 PUFA, g, n (%) – – – v2 ¼ 5.506 0.138
Group 1: <9.17 444 (24.95) 50 (23.13) 394 (25.22) – –
Group 2: 9.17–14.64 439 (24.90) 52 (27.21) 387 (24.55) – –
Group 3: 14.64–21.03 403 (25.11) 39 (19.01) 364 (26.02) – –
Group 4: �21.03 427 (25.04) 63 (30.65) 364 (24.20) – –
Vitamin A, mcg, mean (S.E) 584.47 (20.51) 543.12 (48.53) 590.63 (21.78) t ¼ −0.93 0.359
2
Vitamin A, mcg, n (%) – – – v ¼ 4.042 0.257
Group 1: <255.36 465 (24.92) 56 (28.01) 409 (24.46) – –
Group 2: 255.36–457.03 453 (25.07) 61 (27.49) 392 (24.71) – –
Group 3: 457.03–739.04 407 (25.00) 51 (26.46) 356 (24.78) – –
Group 4: �739.04 388 (25.01) 36 (18.05) 352 (26.04) – –
Vitamin E, mg, mean (S.E) 9.96 (0.33) 9.22 (0.62) 10.07 (0.33) t ¼ −1.41 0.168
Vitamin E, mg, n (%) – – – v2 ¼ 0.692 0.875
Group 1: <4.76 448 (24.96) 54 (27.09) 394 (24.64) – –
Group 2: 4.76–7.38 451 (25.03) 53 (22.33) 398 (25.43) – –
Group 3: 7.38–11.74 422 (24.99) 47 (25.04) 375 (24.98) – –
Group 4: �11.74 392 (25.02) 50 (25.53) 342 (24.95) – –
Vitamin C, mg, mean (S.E) 118.28 (8.63) 100.86 (17.04) 120.88 (8.95) t ¼ −1.16 0.256
2
Vitamin C, mg, n (%) – – – v ¼ 8.321 0.04
Group 1: <23.97 454 (24.97) 67 (33.84) 387 (23.65) – –
Group 2: 23.97–62.07 418 (25.00) 50 (27.26) 368 (24.67) – –
Group 3: 62.07–139.6 417 (25.10) 40 (19.71) 377 (25.90) – –
Group 4: �139.6 424 (24.93) 47 (19.20) 377 (25.78) – –
Vitamin D mcg, mean (S.E) 4.09 (0.13) 3.78 (0.32) 4.14 (0.16) t ¼ −0.92 0.367
Vitamin D, mcg, n (%) – – – v2 ¼ 1.478 0.687
Group 1: <1.1 433 (23.42) 51 (24.90) 382 (23.20) – –
Group 2: 1.1–2.8 440 (26.38) 53 (25.16) 387 (26.57) – –
Group 3: 2.8–5.4 416 (24.81) 53 (27.63) 363 (24.39) – –
Group 4: �5.4 424 (25.38) 47 (22.31) 377 (25.84) – –
Selenium, mcg, mean (S.E) 109.21 (1.60) 104.78 (3.43) 109.88 (1.81) t ¼ −1.25 0.22
2
Selenium, mcg, n (%) – – – v ¼ 0.836 0.841
Group 1: <71.5 441 (24.79) 51 (25.37) 390 (24.70) – –
Group 2: 71.5–97.64 399 (25.19) 44 (26.18) 355 (25.04) – –
Group 3: 97.64–135.7 420 (25.03) 52 (26.45) 368 (24.81) – –
Group 4: �135.7 453 (25.00) 57 (22.00) 396 (25.45) – –
Zinc, mg, mean (S.E) 12.11 (0.31) 11.61 (0.72) 12.19 (0.32) t ¼ −0.78 0.439
Zinc, mg, n (%) – – – v2 ¼ 8.030 0.045
Group 1: <6.66 459 (24.93) 47 (21.57) 412 (25.43) – –
Group 2: 6.66–9.82 422 (25.01) 53 (33.37) 369 (23.76) – –
Group 3: 9.82–14.89 425 (24.94) 57 (26.18) 368 (24.75) – –
Group 4: �14.89 407 (25.12) 47 (18.89) 360 (26.05) – –
Magnesium, mg, mean (S.E) 292.22 (5.31) 281.00 (13.52) 293.89 (5.65) t ¼ –0.90 0.374
2
Magnesium, mg, n (%) – – – v ¼ 2.905 0.407
Group 1: <192.33 464 (24.82) 56 (27.75) 408 (24.38) – –
Group 2: 192.33–263.59 424 (24.86) 53 (25.91) 371 (24.71) – –
(continued)
6 X. JI ET AL.

Table 2. Continued.
Female infertility
Variables Total (n ¼ 1713) Yes (n ¼ 204) Yes (n ¼ 204) Statistics p
Group 3: 263.59–350.57 417 (25.20) 48 (26.85) 369 (24.95) – –
Group 4: �350.57 408 (25.12) 47 (19.50) 361 (25.95) – –
Iron, mg, mean (S.E) 16.63 (0.46) 15.77 (1.49) 16.75 (0.43) t ¼ –0.67 0.508
Iron, mg, n (%) – – – v2 ¼ 4.302 0.231
Group 1: <8.49 439 (24.95) 55 (27.63) 384 (24.55) – –
Group 2: 8.49–12.23 415 (24.83) 52 (29.89) 363 (24.08) – –
Group 3: 12.23–19.04 450 (25.13) 50 (22.25) 400 (25.56) – –
Group 4: �19.04 409 (25.08) 47 (20.24) 362 (25.81) – –
Lycopene, mcg, mean (S.E) 4429.51 (210.21) 3439.92 (390.37) 4577.02 (226.68) t ¼ −2.65 0.013
Lycopene, mcg, n (%) – – – v2 ¼ 6.373 0.095
Group 1: <12.54 419 (24.83) 53 (31.31) 366 (23.87) – –
Group 2: 12.54–1691.33 435 (25.10) 57 (27.55) 378 (24.74) – –
Group 3: 1691.33–5017.56 436 (25.03) 43 (20.85) 393 (25.65) – –
Group 4: �5017.56 423 (25.03) 51 (20.29) 372 (25.74) – –
Total folate, mcg, mean (S.E) 367.43 (7.90) 329.15 (14.71) 373.14 (8.75) t ¼ −2.68 0.012
Total folate, mcg, n (%) – – – v2 ¼ 6.118 0.106
Group 1: <211.77 443 (24.89) 58 (29.40) 385 (24.22) – –
Group 2: 211.77–320.53 426 (25.01) 48 (24.19) 378 (25.14) – –
Group 3: 320.53–461.3 426 (25.08) 55 (28.45) 371 (24.58) – –
Group 4: �461.3 418 (25.01) 43 (17.96) 375 (26.06) – –
Beta-carotene, mcg, mean (S.E) 2337.85 (175.71) 2264.58 (473.90) 2348.78 (188.85) t ¼ −0.17 0.87
Beta-carotene, mcg, n (%) – – – v2 ¼ 3.219 0.359
Group 1: <264.64 433 (24.86) 56 (27.15) 377 (24.52) – –
Group 2: 264.64–691.69 435 (25.04) 53 (27.07) 382 (24.73) – –
Group 3: 691.69–2239.54 424 (25.09) 50 (25.98) 374 (24.95) – –
Group 4: �2239.54 421 (25.02) 45 (19.80) 376 (25.79) – –
Lutein þ zeaxanthin, mcg, mean (S.E) 1846.05 (127.81) 1441.22 (204.20) 1906.40 (139.16) t ¼ −2.04 0.05
Lutein þ zeaxanthin, mcg, n (%) – – – v2 ¼ 4.550 0.208
Group 1: <329.43 442 (24.92) 54 (28.64) 388 (24.36) – –
Group 2: 329.43–735.05 450 (25.07) 60 (28.86) 390 (24.51) – –
Group 3: 735.05–1666.51 437 (24.94) 50 (19.89) 387 (25.70) – –
Group 4: �1666.51 384 (25.07) 40 (22.62) 344 (25.43) – –
Notes: PUFA: polyunsaturated fatty acids; mean (S.E.): mean ± standard error; t: t-test; v2: chi-square All nutrients intakes concentrations were divided into four
groups according to the interquartile range.

fertilisation, the author found no association between carbo­
hydrate consumption and in vitro fertilisation (Noli et al.
2020). However, the Nurses’ Health Study II reported that a
high-carbohydrate diet with a high glycemic index was asso­
ciated with an increased risk of infertility due to ovulation
disorders in apparently healthy women (Chavarro et al. 2009).
This finding demonstrated no association between carbohy­
drate intake and female infertility when the carbohydrate
intake was less than 287.09 g. However, we found that a
higher intake of carbohydrates was associated with a lower
risk of female infertility. We speculate that the difference may
be caused by the difference in population or intake dose.
The relationship between carbohydrate intake and female
infertility needs to be further elucidated through research.
Folate and folic acid are water-soluble B vitamins, also
known as vitamin B9 (Scaglione and Panzavolta 2014). The
two terms are often used interchangeably, but the first refers
to the form naturally present in some foods, including green
and leafy vegetables, sprouts, some fruits, legumes, seeds
and offal, while the second is synthetic molecule introduced
in supplements or fortified foods (Ferrazzi et al. 2020). In this
study, total folate intake was associated with a lower risk of
female infertility. Previous studies agree that the intake of fol­
ate is recommended for the prevention of neural tube
defects and is related to a lower frequency of infertility
(Gaskins and Chavarro 2018, Czeizel et al. 2011). In a recent
study, Kadir et al. reported a significant increase in the
number of antral follicles in women who took folic acid daily
(Kadir et al. 2022). WHO strongly recommends all women of
reproductive age daily use 400 mg of folic acid, in addition to
consuming food with folate from a varied diet (Gomes et al.
2016). The possible reason was that folate has been reported
to be possibly capable of improving ovarian response and
oocyte quality (Thaler 2014).
In this study, greater intakes of vitamin A and vitamin C
were associated with decreased risk of female infertility.
Vitamin A represents a group of fat-soluble retinoids includ­
ing retinol and retinoic acid, which can be obtained from
vegetables, dairy products, eggs and fruits (Olza et al. 2017).
A previous study (Baleato et al. 2005) reflects a direct require­
ment for retinoids by germ cells for the resumption of
spermatogenesis in vitamin A deficient animals via mecha­
nisms that involve the suppression of BMP4 expression.
Vitamin C could notably compensate undesirable effects of
ovarian ageing in a mouse model (Abdollahifar et al. 2019).
The evaluation of the effects of vitamin A and vitamin C on
female infertility needs more studies.
In this study, a higher intake of lycopene seemed to
decrease female infertility. Antioxidation may be the mechan­
ism for the correlation between lycopene and decreased risk
of female infertility. Lycopene is rich in antioxidants, more
consumption of which was reported to be associated with
easier conception in a shorter time in patients with unex­
plained infertility (Ruder et al. 2014). Reactive oxygen species
 NUTRIENT INTAKE AND FEMALE INFERTILITY 7

Table 3. Association between nutrients and female infertility. Table 3. Continued.

Model 1 Model 2 Model 1 Model 2

Variables OR (95% CI) p OR (95% CI) p Variables OR (95% CI) p OR (95% CI) p
Carbohydrate (g) Group 2: 211.77–320.53 0.79 (0.51–1.24) 0.294 0.74 (0.44–1.25) 0.247
Group 1: < 158.64 Ref Ref Group 3: 320.53–461.3 0.95 (0.62–1.47) 0.824 0.75 (0.43–1.33) 0.318
Group 2: 158.64–219.62 1.01 (0.64–1.60) 0.954 0.84 (0.50–1.43) 0.514 Group 4: � 461.3 0.57 (0.35–0.93) 0.025 0.38 (0.20–0.70) 0.003
Group 3: 219.62–287.09 1.19 (0.71–1.99) 0.503 0.86 (0.51–1.44) 0.547 Beta-carotene (mcg)
Group 4: � 287.09 0.84 (0.56–1.25) 0.368 0.46 (0.24–0.86) 0.018 Group 1: < 264.64 Ref Ref
Protein (g) Group 2: 264.64–691.69 0.99 (0.62–1.56) 0.958 0.94 (0.58–1.54) 0.803
Group 1: < 51.33 Ref Ref Group 3: 691.69–2239.54 0.94 (0.62–1.42) 0.765 0.73 (0.44–1.21) 0.215
Group 2: 51.33–68.83 1.33 (0.91–1.93) 0.131 1.30 (0.79–2.14) 0.289 Group 4: � 2239.54 0.69 (0.42–1.14) 0.14 0.61 (0.36–1.03) 0.063
Group 3: 68.83–92.1 1.56 (0.95–2.54) 0.074 1.29 (0.73–2.26) 0.371 Lutein þ zeaxanthin (mcg)
Group 4: � 92.1 1.13 (0.70–1.83) 0.595 0.86 (0.44–1.67) 0.635 Group 1: < 329.43 Ref Ref
Total fat (g) Group 2: 329.43–735.05 1.00 (0.63–1.59) 0.994 0.84 (0.52–1.38) 0.484
Group 1: < 50.86 Ref Ref Group 3: 735.05–1666.51 0.66 (0.37–1.16) 0.141 0.53 (0.28–1.02) 0.057
Group 2: 50.86–71.68 0.77 (0.49–1.22) 0.255 0.87 (0.52–1.45) 0.578 Group 4: � 1666.51 0.76 (0.45–1.27) 0.283 0.61 (0.33–1.12) 0.106
Group 3: 71.68–97.53 0.98 (0.60–1.60) 0.931 1.04 (0.63–1.72) 0.862 Notes: OR: odds ratio; CI: confidence interval; PUFA: polyunsaturated fatty
Group 4: � 97.53 1.31 (0.93–1.86) 0.123 1.61 (0.89–2.93) 0.114 acids
Omega-3 PUFA (g) All nutrients intakes concentrations were divided into four groups according
Group 1: < 0.97 Ref Ref to the interquartile range; Model 1 was created by not adjusting for any
Group 2: 0.97–1.5 1.14 (0.69–1.87) 0.606 1.17 (0.67–2.05) 0.562 variable, and Model 2 adjusted for age, BMI, marital status, pelvic infection,
Group 3: 1.5–2.3 0.98 (0.60–1.61) 0.945 0.93 (0.52–1.65) 0.788 SHBG and energy.
Group 4: �2.3 1.43 (0.94–2.17) 0.089 1.38 (0.79–2.43) 0.247
Omega-6 PUFA (g)
Group 1: < 9.17 Ref Ref
Group 2: 9.17–14.64 1.21 (0.75–1.95) 0.426 1.20 (0.74–1.97) 0.448 are known as an important cause of female infertility and
Group 3: 14.64–21.03 0.80 (0.48–1.32) 0.362 0.77 (0.46–1.29) 0.316
Group 4: � 21.03 1.38 (0.90–2.11) 0.13 1.30 (0.78–2.17) 0.297 abundant antioxidants from the lycopene pattern may allevi­
Vitamin A (mg) ate the oxidative damage to fertility (Agarwal et al. 2012).
Group 1: < 255.36 Ref Ref The study found that higher intakes of magnesium and
Group 2: 255.36–457.03 0.97 (0.57–1.64) 0.912 0.89 (0.51–1.57) 0.69
Group 3: 457.03–739.04 0.93 (0.52–1.66) 0.807 0.74 (0.40–1.39) 0.341 iron were associated with a lower risk of female infertility.
Group 4: � 739.04 0.61 (0.36–1.01) 0.053 0.44 (0.24–0.80) 0.009 Magnesium is one of the cations found in the human body
Vitamin E (mg) that takes part in energy transformations and determines the
Group 1: < 4.76 Ref Ref
Group 2: 4.76–7.38 0.80 (0.44–1.45) 0.445 0.74 (0.39–1.39) 0.33 proper course of hormonal reactions and insulin secretion
Group 3: 7.38–11.74 0.91 (0.55–1.51) 0.713 0.76 (0.43–1.36) 0.345 (Pokorska-Niewiada et al. 2021). Mhaibes et al. observed sig­
Group 4: � 11.74 0.93 (0.54–1.61) 0.791 0.67 (0.35–1.27) 0.206 nificantly lower concentrations of magnesium in the serum of
Vitamin C (mg)
Group 1: < 23.97 Ref Ref PCOS patients compared with the control group (Mhaibes
Group 2: 23.97–62.07 0.77 (0.46–1.31) 0.325 0.75 (0.44–1.26) 0.264 et al. 2017). As the most abundant trace element in the
Group 3: 62.07–139.6 0.53 (0.31–0.92) 0.025 0.48 (0.27–0.87) 0.016 human body, iron plays a key role in the synthesis of DNA
Group 4: � 139.6 0.52 (0.29–0.92) 0.026 0.48 (0.26–0.88) 0.020
Vitamin D (mcg) and proteins, the production of erythrocytes, electron trans­
Group 1: < 1.1 Ref Ref port, cellular respiration, cell proliferation and the regulation
Group 2: 1.1–2.8 0.88 (0.53–1.46) 0.616 0.77 (0.47–1.25) 0.28 of gene expression. This study demonstrated an association
Group 3: 2.8–5.4 1.06 (0.61–1.81) 0.839 0.89 (0.52–1.53) 0.674
Group 4: � 5.4 0.80 (0.52–1.25) 0.324 0.62 (0.38–1.03) 0.065 between the intake of iron and female infertility. High con­
Selenium (mcg) sumption of iron exacerbated hyperlipidaemia and hypergly­
Group 1: < 71.5 Ref Ref caemia as well as induced fatty liver changes and sterility
Group 2: 71.5–97.64 1.02 (0.65–1.60) 0.935 0.81 (0.49–1.32) 0.382
Group 3: 97.64–135.7 1.04 (0.64–1.67) 0.874 0.76 (0.44–1.34) 0.334 along with a reduction of female fertility (Kim et al. 2017).
Group 4: � 135.7 0.84 (0.49–1.44) 0.517 0.54 (0.29–1.02) 0.056 Chavarro et al., analysing the relationship between the con­
Zinc (mg) sumption of various forms of iron and ovulatory infertility,
Group 1: < 6.66 Ref Ref
Group 2: 6.66–9.82 1.66 (1.02–2.68) 0.041 1.47 (0.84–2.58) 0.17 found that the use of iron supplements with high iron con­
Group 3: 9.82–14.89 1.25 (0.79–1.97) 0.332 0.88 (0.52–1.49) 0.624 tent was associated with a reduced risk of ovulatory infertility
Group 4: � 14.89 0.85 (0.46–1.60) 0.612 0.59 (0.30–1.18) 0.134 (Gu€nalan et al. 2018). The optimal dose for magnesium and
Magnesium (mg)
Group 1: <192.33 Ref Ref iron intake needs to be further clarified.
Group 2: 192.33–263.59 0.92 (0.59–1.44) 0.712 0.72 (0.40–1.29) 0.256 Based on our subgroup analyses, high intakes of magne­
Group 3: 263.59–350.57 0.95 (0.53–1.68) 0.843 0.65 (0.34–1.24) 0.183 sium, iron, and total folate were associated with a reduced
Group 4: � 350.57 0.66 (0.40–1.08) 0.097 0.36 (0.17–0.76) 0.009
Iron (mg) risk of female infertility among women with BMI > 24.9 kg/
Group 1: < 8.49 Ref Ref m2. The possible reason for this finding is that obese and
Group 2: 8.49–12.23 1.10 (0.69–1.78) 0.677 1.01 (0.60–1.71) 0.962 overweight people themselves are deficient in magnesium,
Group 3: 12.23–19.04 0.77 (0.52–1.16) 0.207 0.49 (0.30–0.81) 0.007
Group 4: � 19.04 0.70 (0.40–1.21) 0.194 0.43 (0.23–0.82) 0.012 iron, and total folate. Magnesium deficiency is frequent in
Lycopene (mcg) obese patients (Piuri et al. 2021). Magnesium deficiency is
Group 1: < 12.54 Ref Ref often associated with negative health outcomes, including
Group 2: 12.54–1691.33 0.85 (0.51–1.41) 0.513 0.84 (0.54–1.29) 0.407
Group 3: 1691.33–5017.56 0.62 (0.34–1.13) 0.114 0.59 (0.32–1.09) 0.091 low-grade inflammation (Pelczynska et al. 2022). Furthermore,
Group 4: � 5017.56 0.60 (0.36–1.01) 0.054 0.55 (0.33–0.91) 0.022 low-grade chronic inflammation is often associated with sev­
Total folate (mcg) eral gynaecologic disorders associated with female infertility
Group 1: < 211.77 Ref Ref
(continued) (Di Renzo et al. 2022). Similarly, one of the pathologic condi­
tions observed in obesity is systemic iron deficiency and
8 X. JI ET AL.
Figure 2. Subgroup analysis of the association between nutrients and female infertility based on BMI categories. BMI: body mass index; OR: odds ratio; CI: confi­
dence interval; Ref.: reference.
hypoferremia (Nikonorov et al. 2015). A case-control study
reported that ferritin levels <30 mg/L were associated with
unexplained infertility (Holzer et al. 2023). Overweight and
obese individuals have lower serum folate concentrations
when compared with individuals with normal weight (Kose
et al. 2020). Intake of supplemental folic acid, particularly at
doses higher than those recommended for the prevention of
neural tube defects, has been consistently related to a lower
frequency of infertility (Gaskins and Chavarro 2018).
This study helped increase awareness among health pro­
fessionals and patients about the important link between
nutrients and infertility, and educate women about the sig­
nificance of a healthy lifestyle and diet. During the daily work
of physicians in the department of reproductive medicine,
counselling about dietary suggestions is usually required.
Testing nutritional status prior to pregnancy may help to
highlight micronutrient deficiencies and plan an appropriate
nutrient-rich diet. However, several limitations should not be

ignored before fully understanding this article. First, because
this study is based on a cross-sectional design, it is impos­
sible to establish causal relationships among the findings.
Second, important confounding factors are not available in
the database, such as the frequency of sexual intercourse,
and length of the menstrual cycle, which may affect our
results. Third, ‘infertility’ is a participant’s reported answer,
not an explicit diagnosis of infertility, which may affect the
results. More information regarding the role of nutrients in
female infertility is needed to provide guidelines devoted to
the nutritional management of infertile women.
Conclusions
Higher intakes of carbohydrates, vitamin A, vitamin C, mag­
nesium, iron, lycopene and total folate were associated with
a lower risk of female infertility. These findings provide
insight into potentially modifiable lifestyle factors associated
with female infertility.
Ethics statement
As the data sets included in the study were downloaded from public
databases, the study did not need the approval of an ethics committee
from our hospital.
Disclosure statement
The authors report there are no competing interests to declare.
Authors contribution statement
Xiaowei Ji and Yao Ye designed the study. Xiaowei Ji Wang wrote the
manuscript. Yao Ye, Lin Wang, and Suying Liu collected, analysed and
interpreted the data. Xi Dong critically reviewed, edited and approved
the manuscript. All authors read and approved the final manuscript.
Funding
The author(s) reported there is no funding associated with the work fea­
tured in this article.
Data availability statement
The datasets generated and/or analysed during this study are available
in the NHANES database, https://wwwn.cdc.gov/nchs/nhanes/.
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