IMPLICATIONS OF SERUM VITAMIN D LEVELS IN FEMALE INFERTILITY: A REVIEW

Abstract

Vitamin D is a fat-soluble vitamin with several physiological functions and has been related as a possible factor of influence on the reproductive process and, especially, on the female reproductive physiology. However, despite the increasing number of studies in the area, its influence on reproductive health has not been clarified, with conflicting results in responding if there is an association between low serum vitamin D levels and female infertility. The aim of this review is to elucidate the effect of vitamin D on female infertility, presenting current evidence of the association of serum levels of vitamin D in the face of several causes of infertility. A bibliographic search was performed in the MEDLINE (Pubmed), Google Academics, Scielo, Cochrane Central, Research Gate and Public Domain databases, using the word combinations: "vitamin D intertility", "vitamina D infertilidade", "vitamin d infertility polycystic ovary syndrome". The selected articles were from January 2018 to April 2019. Selected studies show that low vitamin D levels are associated with impaired fertility in women diagnosed with endometriosis and polycystic ovarian syndrome, as well as an association with successful in vitro fertilization. However, although there are suggestions and physiological evidence to support a relation of vitamin D deficiency and infertility, randomized controlled trials are still required in different populations to confirm that variations ins serum vitamin D concentrations compromises the health and fertility of women. Determination of serum vitamin D concentration in the reproductive period and the vitamin D supplementation would have important implications for the public health of different communities.

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International Journal of Health Science ISSN 2764-0159 DOI 10.22533/at.ed.1592322223069
International
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v. 2, n. 32, 2022
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IMPLICATIONS OF
SERUM VITAMIN D
LEVELS IN FEMALE
INFERTILITY: A REVIEW
Leonardo Marin Batista
Faculdade IPEMED de Ciências Médicas, Rio
de Janeiro, Brasil
https://www.medicosbrasil.com/prossional/
leonardo-marin-batista
João Victor Roza Cruz
Instituto de Ciências Biomédicas,
Universidade Federal do Rio de Janeiro,
Brasil
http://lattes.cnpq.br/1172382822972509
Daniela da Maia Fernandes
Faculdade IPEMED de Ciências Médicas, Rio
de Janeiro, Brasil
https://www.escavador.com/sobre/2215685/
daniela-da-maia-fernandes
Carolina Batista
Instituto de Ciências Biomédicas,
Universidade Federal do Rio de Janeiro,
Brasil
http://lattes.cnpq.br/3520657480211367

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International Journal of Health Science ISSN 2764-0159 DOI 10.22533/at.ed.1592322223069
Abstract: Vitamin D is a fat-soluble vitamin
with several physiological functions and has
been related as a possible factor of inuence
on the reproductive process and, especially,
on the female reproductive physiology.
However, despite the increasing number
of studies in the area, its inuence on
reproductive health has not been claried,
with conicting results in responding if
there is an association between low serum
vitamin D levels and female infertility. e
aim of this review is to elucidate the eect
of vitamin D on female infertility, presenting
current evidence of the association of serum
levels of vitamin D in the face of several
causes of infertility. A bibliographic search
was performed in the MEDLINE (Pubmed),
Google Academics, Scielo, Cochrane
Central, Research Gate and Public Domain
databases, using the word combinations:
“vitamin D intertility”, “vitamina D
infertilidade”, “vitamin d infertility
polycystic ovary syndrome”. e selected
articles were from January 2018 to April
2019. Selected studies show that low vitamin
D levels are associated with impaired fertility
in women diagnosed with endometriosis
and polycystic ovarian syndrome, as well
as an association with successful in vitro
fertilization. However, although there are
suggestions and physiological evidence to
support a relation of vitamin D deciency
and infertility, randomized controlled trials
are still required in dierent populations to
conrm that variations ins serum vitamin D
concentrations compromises the health and
fertility of women. Determination of serum
vitamin D concentration in the reproductive
period and the vitamin D supplementation
would have important implications for the
public health of dierent communities.
Keywords: Vitamin D, Infertility, Vitamin D
deciency.
INTRODUCTION
Infertility has a global rate of around 48.5
million (Voulgaris et al., 2017; Nandi, 2018).
In the United States, it is estimated that 15.5%
of women in reproductive age are aected by
infertility (Chiu et al., 2018). In Brazil it is
estimated that 8 million people are aected by
infertility (Fertility Medical Group). e main
causes of female infertility are anovulation,
polycystic ovary syndrome (PCOS), tubal
problems, endometriosis and unexplained
cases (Vanni et al., 2014; Voulgaris et al., 2017;
Chen et al., 2018).
Vitamin D deciency has been increasingly
recognized as a worldwide epidemic (Holick,
2007). Its deciency in children may result in
rickets incurring an increased risk of fracture
and deformity and in adults it may result in
osteomalacia with the same risk of fracture
and deformity (Are et al., 2018). In addition,
vitamin D deciency appears to be involved
in the pathogenesis of many chronic diseases,
such as autoimmune diseases, infections,
immune deciency, cardiovascular disease,
cancer, and neurocognitive disorders (Gröber
et al., 2013).
ere is a growing interest in the
physiological role of vitamin D at various stages
of reproductive function (Rudick et al., 2014),
highlighting the expression of the vitamin D
receptor (VDR) by the organs of the system
(Johnson and Deluca, 2001; Avila et al., 2004;
Parikh et al., 2010; Aleyasin et al., 2011; Arabian
and Raoo, 2018). e prevalence of vitamin
D deciency is high in women of reproductive
age (Lerchbaum and Rabe, 2014) and its
absence can provide a series of complications
for both fertility and pregnancy (Arabian
and Raoo, 2018). Its deciency in pregnant
women has been associated with gestational
diabetes mellitus and preeclampsia (Burris et
al., 2012; Aghajafari et al., 2013; Barrett and
Mceldu, 2010), and its low concentration is
related to infertility factors, such as: chronic

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International Journal of Health Science ISSN 2764-0159 DOI 10.22533/at.ed.1592322223069
anovulation (PCOS), endometriosis, uterine
myomatosis (broids), spontaneous abortion,
preeclampsia, gestational diabetes, poor egg
quality and implantation of the embryo by
changing the results of in vitro fertilization
(IVF) treatment (Chan et al., 2015).
Vitamin D is a secosteroid prohormone,
mainly produced by the skin aer exposure
to sunlight or through diet and vitamin
supplements (Holick and Chen, 2008; Holick,
2008; Voulgaris et al., 2017; Weinert and
Silveiro, 2015). In the human body, vitamin D
levels are measured through circulating levels
of 25(OH)D because it is a longer half-life
biomarker, and higher serum concentration
compared to 1,25(OH)2D (Holick, 2007;
Weinert and Silveiro, 2015). Calcitriol acts in
two ways: through its binding to the specic
nuclear receptor, VDR, initiating multiple
genomic eects (Voulgaris et al., 2017) or
by binding to its receptor on the plasma
membrane, mediating various non-genomic
eects (Haussler et al., 2011).
Adequate plasma vitamin D levels and
the recommended daily allowance is subject
of debate, essentially because of the wide
variety of health functions associated with
it. According to the “Institute of Medicine”
and the “Brazilian Society of Clinical
Pathology/Laboratory Medicine”, the cuto
value for diagnosis of vitamin D deciency
should be set at 20 ng/mL (50 nmol/L),
but in the literature there is a range of 20
to 30 ng/mL (Holick, 2007; Holick et al.,
2011; Muscogiuri et al., 2017). 20 to 52%
of women of reproductive age are decient
in vitamin D (Lerchbaum and Rabe, 2014;
Chu et al., 2018) and its absence can provide
a number of complications for fertility and
pregnancy (Arabian and Raoo, 2018).
During pregnancy, the role of vitamin D
are still under evaluation, but the literature
indicates that it is essential for fetal skeletal
development and the health of pregnant
women (Chan et al., 2015; Weinert and
Silveiro, 2015).
e purpose of this review is to gather
literature data on the eect of vitamin D on
female infertility, specifying articles from the
year 2018 and 2019, presenting as a cause
of female infertility the polycystic ovary
syndrome and endometriosis, as well as
those presenting cohort data of women who
underwent in vitro fertilization (IVF) (Chan
et al., 2015).
MATERIALS AND METHODS
INCLUSION AND EXCLUSION
CRITERIA
e studies of interest were original
articles and reviews on the topic of vitamin
D and infertility published between 2018 and
2019. Additional studies were considered
when relevant data were cited by any
reviewed article.
Animal model studies and those focusing
on male infertility were excluded.
LITERATURE SEARCH
Data searches were performed through
access to MEDLINE (Pubmed), Google
Academics, Scielo, Cochrane Central,
Research Gate and Public Domain. We
selected articles in English and Portuguese.
e keywords employed were: vitamin
D intertility, “vitamina D infertilidade”.
Literature searches were conducted to identify
studies published between January 2018 to
May 2019.
e study research was performed by two
authors (L.M.B and C.B.). Study selection,
quality assessment via data collection sheets
(designed according to the standards of the
Cochrane Collaboration Book) and data
extraction were performed dependently and
blindly by two authors (L.M.B. and C.B.). Only
studies with ethical approval were included in
the systematic review.

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For each study, the following information
was extracted: rst author’s last name, year
of publication, country of origin, number
of subjects, design of the study, statistical
analysis, outcomes assessed, confounding
factors considered, results.
RESULTS
e PRISMA ow diagram of the review
process is presented in Figure 1. ere were
140 articles identied, 18 duplicates. Of the
122 articles, 70 were selected for reading and
55 were not considered relevant. 15 articles,
dated 2018 and 2019, were analyzed.
STUDY CHARACTERISTICS
e characteristics of the 15 included
studies are presented in Table 1. None of
the included studies declared any conicts
of interest. e included studies were cross-
sectional, randomized, observational, cohort
and case control studies. Sample sizes varied
from 40 to 1254 women. e selected studies
analyzed vitamin D in dierent ways, as there
were studies that analyzed serum 25(OH)D
levels, studies that performed DNA extraction
to analyze polymorphisms in the VDR gene,
studies that analyzed the embryos ultrasound
images, as well as mature oocyte counts
and hormone levels to associate them with
25(OH)D. ere were 6 studies with women
with PCOS, 8 with infertile women, 1 with
infertile women with PCOS, 1 with a cohort
of women with endometriosis. One Study was
performed with women with PCOS candidates
for IVF and another with controlled ovarian
stimulation. In 4 studies women had ovarian
stimulation. 2 studies administered doses
of vitamin D. In one study, serum vitamin
D concentrations were analyzed in infertile
women who had been assisted by dierent
assisted reproduction technologies. In one
study, besides ovarian stimulation, there was
cytoplasmic injection and embryo transfer.
VITAMIN D DEFICIENCY
Literature data indicate that vitamin
D metabolism may vary by race (Sohn et
al., 2018). e prevalence of this vitamin
deciency in the general South Asian
population is between 67-82%, in the
Caucasian population is below 28.4%
compared to 77% in Asians (Mogili et
al., 2018). In addition, Chu et al. (2018)
concluded by meta-analysis that clinical
pregnancy is more likely in women with a
high serum 25(OH)D concentration.
For Gaskins and Chavarro (2018), despite
promising results in animal models, vitamin
D does not appear to play an important role
in human fertility, contradicting Chu et al.
(2018), who concluded by meta-analysis that
clinical pregnancy is more likely in women
with high serum 25(OH)D concentrations.
POLYCYSTIC OVARY SYNDROME
PCOS
ere are a limited number of studies
indicating the use of vitamin D supplementation
to heal symptoms of PCOS such as menstrual
cycle, follicular development, androgen
levels and insulin resistance (Arslan and
Akdevelioğlu, 2018). Vitamin D is believed to
inuence the development of PCOS through
gene transcription, and this hormonal
modulation inuences insulin metabolism
and fertility regulation (omson et al., 2012).
However, Chen and colleagues (2018) found
no correlation between vitamin D and PCOS,
but they found a correlation between 25(OH)
D levels and infertility due to tubal problems
in Chinese women.
Bakeer et al. (2018) showed that serum
25(OH)D levels were signicantly lower
in the PCOS group compared to controls,
corroborating previous studies (Hahn et
al., 2006). In this study, the authors did
not observe statistical correlation between
antimullerian hormones (HAM) and 25(OH)

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D levels, a result that was consistent with
previous literature data (Cappy et al., 2016),
despite the indication that HAM can be used
as a PCOS biomarker. Other data show that
vitamin D supplementation for eight weeks
in patients with PCOS, candidates for IVF,
was ecient under insulin and cholesterol
metabolism (Dastorani et al., 2018), in
addition to decreasing the levels of HAM.
In a 2019 cohort study, Butts et al. show
that the association between vitamin D and
ovarian stimulation treatment dier according
to the patient’s diagnosis of infertility.
Data show that vitamin D deciency in
women with PCOS who underwent ovarian
stimulation was signicantly associated with
low ovulation levels, low pregnancy rate, and
a reduced chance of live birth. In contrast, the
rate of live births in women with unexplained
infertility who had ovarian stimulation did
not decrease in association with vitamin D
deciency, which supports the hypothesis
that vitamin D deciency negatively aects
specic pathways of PCOS.
Are et al. (2018) presented results
that clearly demonstrate the correlation (p
<0.001) between vitamin D deciency and a
reduced ovarian reserve in the Iranian female
population, while Shapiro et al. (2018) found
no relationship between vitamin D levels and
ovarian reserve markers in a female population
in the United States. Among the reasons that
may explain these inconsistencies in the data
would be the experimental design, the sample
size, which seems to play an important role in
this type of analysis, and the population to be
studied.
Several genetic polymorphisms have
already been correlated with PCOS. e
VDR gene has more than 25 described
polymorphisms, with alterations associated
with several diseases, but still inconsistent
with PCOS. e association of three
polymorphisms with PCOS, namely BsmI,
ApaI and Taq I, conrming in the South
Indian population data already found in
other populations (Siddamalla et al., 2018).
Reginatto et al. (2018) identied an association
between VDR TaqI gene polymorphism and
the reduced number of follicles in infertile
women undergoing ovarian stimulation,
suggesting that VDR signaling aects the
ovarian response to stimulation via unknown
mechanisms.
ENDOMETRIOSIS
Endometriosis is a benign estrogen-related
inammation characterized by the presence
of endometrial tissue outside the cavity. It
aects 5 to 10% of women in reproductive age
(Voulgaris et al., 2017).
Buggio et al. (2019) found no dierences
in serum 25(OH)D levels in women with
and without endometriosis, corroborating
previous literature data (Agic et al., 2007), but
also going against previous data (Somigliana
et al., 2007).
Other studies have identied that women
with endometriosis have more VDR receptors
than control group (Arslan and Akdevelioğlu,
2018). In addition, immunomodulatory,
antiinammatory and antiproliferative
properties of vitamin D indicate a possible
role of this hormone in the pathogenesis of
endometriosis (Buggio et al., 2019).
IN VITRO FERTILIZATION IVF
It is consistent in the literature that in cases
of IVF, women with vitamin D deciency
have decreased their chance of conception
compared with women where vitamin D
levels are normal (Butts et al., 2019).
Ciepiela et al. (2018) observed that
successfully fertilized oocytes contained
signicantly lower levels of 25(OH)D
compared to those not fertilized; clinical
pregnancy and live birth rate were obtained
from oocyte-derived embryos with

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signicantly lower levels of 25(OH)D, but
women’s low serum vitamin D concentrations
increase the abortion rate, as observed by
Raque et al. (2018). e reviews by Zhao et
al. (2018) and Turan (2018) reinforce these
data, where they point out that vitamin D
deciency has a negative eect on pregnancy
aer IVF, but because sample sizes and
characteristics were dierent, cohort studies
are necessary to observe the eect of vitamin
D supplementation and to explore possible
mechanisms.
Antunes et al. (2018) investigated whether
25(OH)D intrafollicular concentrations
are related to the type of ovarian response
in patients undergoing IVF, investigating
the relationship between follicular uid
vitamin D concentrations and ovarian
stimulation outcomes. ey observed that
follicular 25(OH)D concentrations remain
unchanged through dierent common
causes of infertility; Women with follicular
uid concentrations below vitamin D had
a better response to ovarian stimulation,
as demonstrated by higher production of
larger follicles and higher serum estradiol
concentration.
Yilmaz et al. (2018) found no relationship
between lack of vitamin D and infertility.
ey did not nd signicant dierences
between pregnant and non-pregnant
women who underwent ovulation induction
with intrauterine insemination treatment
in relation to serum 25(OH)D levels. In
addition, no association was found between
infertility and serum 25(OH)D levels. In
this study conducted in Turkey, the authors
highlight the fact that vitamin D deciency
is a public health problem in the country,
with 200 of 207 patients, who also included
women without fertility problems, who had
vitamin D deciency on initial examination.
Similar results were found by Arabian and
Raoo (2018) in a cohort of 153 Iranian
infertile women, where the authors indicate
that vitamin D deciency is not the main
limitation for fertility.
DISCUSSION
Several functions of vitamin D have
been studied in recent years, associating its
deciency with comorbidities. Despite the
growing number of investigations about the
physiological role of vitamin D in various
stages of reproductive function, the results are
still scarce and controversial. It is well known
that this deciency can negatively aect female
fertility by disrupting ovarian physiology
and deregulating follicular recruitment and
selection (Heyden and Wimalawansa, 2018).
Results presented in the literature showed
that 20 to 52% of women of reproductive
age are vitamin D decient (CHU et al.,
2018). In a study of the Brazilian population,
regardless of women’s ethnicity, Lopes et al.
(2017) reported a high proportion (81.1%)
of Brazilian women with hypovitaminosis D,
but found no dierence between the control
group and infertile women.
e association between vitamin D and
PCOS manifestations is not well established.
Although some studies have shown an
inverse relationship between vitamin D and
androgens, most studies have not conrmed
a direct relationship between vitamin D and
reproductive parameters (Nandi, 2018).
Systematic reviews and meta-analyzes
(Vanni et al., 2014; Voulgaris et al., 2017)
suggest the association of vitamin D with
several metabolic and reproductive processes
characteristic of PCOS and, therefore, vitamin
D would be involved in the pathogenesis
of the syndrome. Women with polycystic
ovary syndrome have lower 25(OH)D levels
compared to healthy women (Voulgaris et al.,
2017); among the population of polycystic
ovary syndrome, obese women had lower
levels of 25(OH)D when compared to

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overweight or thin women (Panidis et al.,
2005; Ngo et al., 2011; Voulgaris et al., 2017).
However, obesity leads to insulin resistance
in these patients, but not necessarily to PCOS
(Sur and Chakravorty, 2015).
Arslan and Akdevelioğlu (2018) point out
that the results on the subject are conicting
because, while some suggest that vitamin D
deciency is more common among women
with PCOS compared to healthy individuals,
others nd no dierences between those
with or without SOP. In addition, the limited
number of intervention studies involving
women with PCOS was not randomized and
were conducted in a small cohort of patients,
which makes it dicult to generalize the
results.
ere are studies examining the
contribution of vitamin D receptor gene
polymorphisms in metabolic and endocrine
disorders of polycystic ovary syndrome
(Mahmoudi, 2009; Mahmoudi et al., 2015;
Jedrzejuk et al., 2015; Dasgupta et al., 2015;
Nandi, 2018). Taq I polymorphism of the VDR
gene, for example, is associated with increased
risk of PCOS (El-Shal et al., 2013).
Data linking vitamin D and endometriosis
emerge mainly from observational studies,
but the results are still conicting. Voulgaris
et al. (2017) reviewed several studies and
pointed out that there is no dierence between
serum 25(OH)D levels in endometriosis
patients and healthy women. However, data
from Harris et al. (2013) indicate an inverse
relationship between vitamin D level and
endometriosis, women with higher 25(OH)
D levels had a 24% lower risk of developing
endometriosis than women with lower
levels. Somigliana et al. (2007) observed that
endometriosis may be associated with higher
serum vitamin D levels, but did not conclude
whether such a high concentration of 25(OH)
D would be the cause or consequence of the
disease.
Correcting vitamin D deciency in
women with PCOS signicantly improves
the growth of ovarian follicles, the formation
of dominant follicles and the regularity of
menstrual cycles (Fang et al., 2017), which
makes the recent evidence that the vitamin
D may have a direct eect on folliculogenesis
and oocyte maturation (Xu et al., 2016). e
results of Antunes et al. (2018) are in line with
data already described in the literature, as in
part those observed by Ozkan et al. (2010),
who observed in their cohort that women
with higher levels of vitamin D in serum and
uid follicular are more likely to develop a
pregnancy aer IVF; pregnancy rates aer
IVF are higher in women who have elevated
25(OH)D levels than in those who are vitamin
D decient.
In a meta-analysis study, Lv et al. (2016)
concluded that a lower serum vitamin D
level is not associated with a lower clinical
pregnancy rate, but is related to a lower live
birth rate. In a study in India, Banker et
al. (2017) found no statistical dierence in
reproductive outcomes in the oocyte recipient
and oocyte donor groups, although the study
suggests that recipients and donors with an
insucient level of vitamin D have a better
reproductive outcome compared to the group
with vitamin D deciency.
In a systematic review, Skowrońska et al.
(2016) conclude that concentrations of several
forms of vitamin D may be associated with
endometriosis, but their possible dependence
on environmental factors, such as time of
year and skin type, should also be taken into
account.
CONCLUSION
Due to the heterogeneity of the ndings,
there are few conclusions drawn from the
results of the relationship between vitamin D
and female fertility. Studies in the literature
indicate that there is a correlation between

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hypovitaminosis D and reproductive
problems, but the true role of vitamin D in
the reproductive system has not yet been
determined (Franasiak et al., 2017).
It is not known whether the eects of
vitamin D are direct on genes generated in
reproduction or whether vitamin D acts
through secondary messengers, such as
calcium, estradiol signaling, insulin pathway
or immune modulation (Nandi, 2018;
Gaskins and Chavarro, 2018). While vitamin
D deciency may possibly be detrimental
to fertility, it is unclear whether higher
vitamin D levels confer additional benet
once suciency has been achieved. Being
a very new topic of scientic focus, data
linking vitamin D with female infertility
still contradict each other. erefore, it is
important to constantly review the literature
so that it is possible to identify the results
that are really relevant and clarify the causes
of such contradiction.
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CHEN, W. et al. Vitamin D deciency and high serum IL-6 concentration as risk factors for tubal factor infertility in Chinese
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Figure 1: PRISMA ow diagram for selecting articles.

12
International Journal of Health Science ISSN 2764-0159 DOI 10.22533/at.ed.1592322223069
Study Time and type Females Intervention Analysis Results Country and
Financing fund
Antunes
et al., 2018
Type: prospective
study;
Time: September
2013 to September
2015.
202 patients, with 2
excluded.
Women undergoing
ovarian stimulation
for IVF.
Follicular uid 25(OH)D
concentrations were assessed
in the rst follicle aspirate
on oocyte retrieval day;
oestradiol and progesterone
concentrations were assessed
on the
trigger day.
Lower follicular 25(OH)D
concentrations predicted a
better response to ovarian
stimulation shown by a
greater production of larger
follicles
and higher serum oestradiol
concentrations.
Country: Brazil;
Fund: FAPERJ,
CNPq, CAPES.
Arabian;
Raoo, 2018
Type: cross-sectional
study;
Time: from 2014 to
2016.
153 infertile
women undergoing
induction of
ovulation.
Induction of
ovulation.
Serum vitamin D level was
measured and the rate of
clinical pregnancy and
patient and cycle parameters
were determined.
ere was no correlation
between the serum level of
vitamin D and pregnancy
rate.
Country: Iran;
Fund: Uninformed.
Bakeer et al.,
2018
Type: cross-sectional
study;
Time: uninformed.
53 PCOS females
aged from 17
to 39;
17 control group
females, aged from
19 to 35.
Without intervation. Serum AMH and 25(OH)D
were measured.
AMH were signicantly
higher in PCOS females in
comparison to control group.
Country: Egypt;
Fund: Uninformed.
Buggio et al.,
2019
Type: case–control
study;
Time: October 2014
to January 2017.
217 endometriosis
women. Without intervation.
25(OH)D serum levels in
women with and without
endometriosis.
e results do not support an
association between serum
vitamin D levels and dierent
phenotypes of endometriosis.
Country: Italy;
Fund: Italian scal
contribution 2012.
Butts et al.,
2019
Type: retrospective
cohort study;
Time: uninformed.
607 participants
from the Pregnancy
in Polycystic Ovary
Syndrome II RCT;
647 participants from
the Assessment of
Multiple Intrauterine
Gestations from
Ovarian Stimulation
RCT of unexplained
infertility.
Serum 25(OH)D
levels measured.
Primary: live birth;
secondary: ovulation
(PPCOS II), pregnancy, and
early
pregnancy loss.
e association between
vitamin D deciency and
diminished live birth relied
on carrying the diagnosis of
PCOS and was
not observed in unexplained
infertility.
Country: USA;
Fund: National
Institutes of Health.

13
International Journal of Health Science ISSN 2764-0159 DOI 10.22533/at.ed.1592322223069
Chen et al.,
2018
Type: case–control;
Time: from 2013 to
2015.
377 women
who were diagnosed
with infertility.
Without intervation.
Serum concentrations of
25(OH)D, IL-6, IL-1 β, and
interferon-α were measured.
ere was an interaction
between IL-6 and 25(OH)D
for the risk for tubal factor
infertility.
Country: China;
Fund: Uninformed.
Ciepiela et
al., 2018
Type: perspective
cohort study;
Time: February 2014
to October 2015.
198 infertile women.
Intracytoplasmic
sperm injection and
a single embryo
transfer provided
serum samples
and follicular uid
specimens.
Serum sample from infertile
women scheduled for
intracytoplasmic
sperm injection and a single
embryo transfer and 322
follicular uid specimens,
each
from a single follicle on the
day of oocyte retrieval.
e level of 25(OH)D in
follicular uid correlates
negatively with the oocytes’
ability to undergo
fertilization and subsequent
preimplantation embryo
development. Oocytes
matured in follicular
uid with low 25(OH)D
concentration
are more likely to produce
top quality embryos and
are associated with higher
pregnancy and delivery
rates. Low serum vitamin D
concentration is associated
with higher miscarriage rates.
Country: Poland;
Fund: National
Science Centre of
Poland.
Dastorani
et al., 2018
Type: randomized,
double-blinded,
placebo-controlled
trial;
Time: from
December 2017
through
March 2018.
40 infertile women,
aged
18 to 40 years old,
with PCOS, who
were candidate for in
vitro fertilization.
2 intervention groups
for receiving either
50,000 IU vitamin D
or placebo (n = 20
each group) every
other
week for 8 weeks.
Gene expression for insulin
and lipid metabolism was
conducted using peripheral
blood
mononuclear cells (PBMCs)
of women with PCOS, via
RT-PCR method.
50,000 IU vitamin D
supplementation every other
week for 8 weeks had
benecial eects on insulin
metabolism, and lipid prole
of infertile women with
PCOS
who are candidate for IVF.
Country: Iran;
Fund: Vice-
chancellor for
Research, Kashan
University of Medical
Sciences, Kashan,
Iran.

14
International Journal of Health Science ISSN 2764-0159 DOI 10.22533/at.ed.1592322223069
Jafari-
Sdvajani et
al., 2018
Type: randomized
controlled clinical
trial;
Time: March 2016 to
February 2017.
60 PCOS women
with vitamin D
insuciency.
Participants
randomly recruited
to a 12-week
intervention
arm consisting of
50,000 IU/week of
vitamin D3
pearl + low-calorie
diet (n = 30) or to a
control arm of a
weekly placebo pearl
+ low-calorie diet (n
= 30).
At the beginning and end of
the study, the anthropometric
indices, body composition,
25-hydroxyvitamin
D, total testosterone,
dehydroepiandrosterone
sulfate, sex hormone-binding
globulin and free androgen
index were measured and
regularity of menses was
compared among the two
groups.
In women with PCOS,
androgen prole did
not change with vitamin
D supplementation when
combined
with low-calorie diet,
but menstrual frequency
signicantly
improved.
Country: Iran;
Fund: Faculty of
Health,
ShahidSadoughi
University of Medical
Sciences, Yazd, Iran.
Mogili et al.,
2018
Type: observational
study;
Time: from March
2016 to March 2017.
256 infertile women
with PCOS, in the
age group of 20–40
years.
Without intervation.
e primary outcome was
estimation of the prevalence
of vitamin D deciency
in infertile PCOS women.
Secondary outcomes were
to study the association of
hypovitaminosis D with
metabolic syndrome, obesity
and hypercholesterolemia in
PCOS patients.
Vitamin D deciency is
highly prevalent in infertile
PCOS women and there
seems to be no association
between hypovitaminosis D
and the metabolic syndrome
in the same population.
Country: India;
Fund: No funding.
Raque et al.,
2018
Type: retrospective
cohort study;
Time: January 2012
to January 2016
192 infertile women.
Analysis of the
outcome aer the
intervention done
in the
form of dierent
assisted reproduction
treatment options.
Association
between vitamin D decient
(less than 50nmol/l) and
insucient group
(50-75nmol/l) through the
application of chi-square test
for evaluate to see
the 25(OH)D and major
outcome measure (successful
pregnancy).
Vitamin D deciency,
as well as insuciency,
adversely aect the outcome
of assisted reproduction
treatment contributing to
lower pregnancy rates among
Arabian women in the
reproductive age group.
Country: Saudi
Arabia;
Fund: Research
center at KFMC.

15
International Journal of Health Science ISSN 2764-0159 DOI 10.22533/at.ed.1592322223069
Reginatto
et al., 2018
Type: case–control
study;
Time: uninformed.
121 control group;
70 women
undergoing
controlled ovarian
stimulation.
Controlled ovarian
stimulation.
Evaluate the association
between the TaqI, BsmI, and
FokI VDR polymorphisms
and ovarian responses in
women undergoing
controlled ovarian
stimulation.
Association between the
VDR TaqI polymorphism
and reduced follicle number
in women undergoing
controlled ovarian
stimulation.
Country: Brazil;
Fund: FAPERJ,
CNPq, CAPES.
Shapiro et al.,
2018
Type: retrospective
cohort study;
Time: September of
2014 to November of
2017.
457 infertile women
21–50 years of age.
Controlled ovarian
stimulation Hormone measurements.
Vitamin D levels were not
associated with ovarian
reserve in a large group of
infertile women with a high
prevalence of
diminished ovarian reserve.
Country: USA;
Fund: Uninformed.
Sohn et al.,
2018
Type: cross-sectional
study;
Time: uninformed.
233 infertile
women without any
supplementation
of vitamin D.
Serum samples were
obtained on oocytes
retrieval
day and tested
vitamin D level and
divided women into
two groups according
to their vitamin D
levels.
e group analyzed
their relation with
antimullerian hormones,
number of total
oocytes, mature oocytes,
pregnancies, as well as
implantations.
Infertile Korean women who
were not vitamin D
insucient/replete did not
have a decreased ovarian
reserve; antimullerian
hormones levels did not
present any signicance;
vitamin D deciency have no
eect on in vitro fertilization.
Country: South
Korea;
Fund: Uninformed.
Yilmaz et al.,
2018
Type: cross-sectional
study;
Time: March 2014 to
June 2014.
104 infertile women;
103 fertile women.
Clinical assessment;
infertile patients
were evaluated for
clomiphene citrate or
gonadotropins and
intrauterine
insemination use.
Individual characteristics
and 25(OH)D levels were
compared between the
groups.
ere is no association
between female infertility
and serum vitamin D levels.
Country: Turkey;
Fund: Uninformed.
Table 1: Characteristics of articles included in the Systematic Review.