You are on page 1of 11

Reproductive Sciences

https://doi.org/10.1007/s43032-022-01040-8

REVIEW

The Association Between Lipid Serum and Semen Parameters:


a Systematic Review
Cennikon Pakpahan1,2   · Andri Rezano1,3   · Ria Margiana1,4   · Bella Amanda1,2 · Agustinus Agustinus1,2   ·
Darmadi Darmadi5 

Received: 21 April 2022 / Accepted: 12 July 2022


© The Author(s), under exclusive licence to Society for Reproductive Investigation 2022

Abstract
Increased lipid levels sometimes not only affect sexual function but also are considered to harm semen quality. It is often a
suspicion that elevated lipids are a factor in infertility. We conduct a systematic review. Articles that met the criteria were
identified according to The Preferred Reporting Items for Systematic Review and Meta-analysis of recommendations in the
PubMed, ProQuest, EBSCO, Web of Science Wiley Online, Springer Link, Scopus, and Science Direct databases with no
time restriction for publication. Seven studies are eligible for qualitative analysis from nine studies that have the potential to
be assessed. These studies measure the correlation of serum lipids (VLDL, HDL, LDL, triglycerides, total cholesterol, free
cholesterol, phospholipids, free fatty acids) with semen parameters (concentration, motility, morphology, DNA fragmentation
index). Although not all studies consistently report that lipids impact semen quality, this review suspects that lipids have a
significant impact on sperm quality. This study implies that it is necessary to maintain lipid levels to maintain sperm quality
and quality of life. However, further investigation with an observational cohort study design needs to be carried out to assess
the effect of lipids on semen quality more precisely for the promotion of reproductive health care.

Keywords  Lipid serum · Sperm motility · Sperm morphology · Sperm concentration · Reproductive health care · Male
infertility

Introduction of infertility becomes aware of other underlying diseases


after getting a fertility examination. Therefore, infertility,
Infertility affects about 15% of all couples and around 50% defined as a disease, can be a marker of general health,
of cases have a male factor [1]. Previous studies revealed that especially in males. The exact etiology is still unknown,
fertility might be disturbed by several diseases such as such but likely involves some genetic, epigenetic, developmen-
as cancer, obesity, and diabetes [2–7]. Furthermore, in some tal, and health/lifestyle factors [8]. Recent linkage studies
conditions, the male who comes with the chief complaint report various associations between male factor infertility
and overall survival [9–11].
The data regarding male infertility-related illness is still
* Cennikon Pakpahan
cennikon.pakpahan@fk.unair.ac.id inadequate. Several fertilities center more focus more to
the main outcome, pregnancy and limit the male fertility
1
Andrology Study Program, Faculty of Medicine, Universitas evaluation to semen analysis only. In many cases, primary
Airlangga, Surabaya, Indonesia treatment focuses solely on pregnancy outcomes using
2
Department of Biomedical Science, Faculty of Medicine, assisted reproductive technology, with little consideration
Universitas Airlangga, Jl. Mayjen Prof. Dr. Moestopo 47, to men’s general health. In fact, not only male infertility can
Surabaya 60131, Indonesia
be caused by a variety of etiologies and semen parameter
3
Department of Biomedical Science, Faculty of Medicine, merely represents the endpoint of different pathophysiologi-
Universitas Padjadjaran, Sumedang, Indonesia
cal mechanism [12].
4
Department of Anatomy, Faculty of Medicine, Universitas Interestingly, the increase of lipid serum levels, which
Indonesia, Jakarta, Indonesia
is not rarely found in obese males, is often used as a
5
Department of Internal Medicine, Faculty of Medicine, “scapegoat” for infertility. Numerous studies indicated
Universitas Sumatera Utara, Medan, Indonesia

13
Vol.:(0123456789)
Reproductive Sciences

that decreasing semen quality is associated with increased “semen analysis” or “sperm analysis” or “sperm parameters”
obesity. A cohort study performed in France showed that on database such as PubMed, ProQuest, EBSCO, Web of Sci-
increased body mass index was not only associated with ence Wiley Online, Springer, Scopus, and Science Direct.
reduced semen quality, but also affecting volume, concentra-
tion, and motility [13]. Another study in the Asian popula- Criteria for Study
tion indicated increased body fat was associated with lower
sperm concentration and lower normal sperm morphology All studies must meet the following requirements: (1) Obser-
[14]. Higher consumption of saturated fat and processed vational analytic design (case–control, cohort, or cross-sec-
meat was found to be inversely related to semen quality in tional); (2) Written in English; (3) Assessing the association
studies conducted in the USA [15], Spain [16] as well as in between one or more lipid serum and semen parameters; (4)
Asian countries [17]. Presents the value of statistical analysis either odds ratio
The potential role of lipids in human fertility is hypoth- (OR), relative risk (RR) or correlation coefficient (r); (5) the
esized because cholesterol is the main source for sex steroid complete text of the study was available. The studies that met
hormone synthesis [18] and a determinant role in steroido- the following criteria were excluded: (1) The study design
genesis and spermatogenesis [19]. Studies in animal models was not in the form of observational analytic; (2) Duplicate
have shown the association between cholesterol, steroido- studies; (3) Studies that are not available in full text or main
genesis, and male fertility [20–22]. In addition, cholesterol data or data specific about lipid serum and sperm parameters
fed to male rats and rabbits for 120 days reduced spermatid cannot be obtained; (4) non-English language; (5) Study not
cell numbers, reduced seminiferous tubules’ diameters, and in human; (6) Abstract proceedings or literature review.
lower Leydig cell nuclear dimensions [23]. Even in mild
hyperlipidemic rats exhibited significantly reduced sperm Study Selection
motility and density in the cauda epididymis and testis [24].
The relationship between lipids and sperm production is Two people (CP and BA) conducted separate computer-
complex and unclear. In humans, the amount of cholesterol ized searches and retrieved data that matched the terms we
in sperm varies considerably, even among ejaculates; [25] needed. Any issues that arose throughout the search that
meanwhile, the amount of cholesterol present within sperm caused confusion were addressed in a conversation with all
membranes is directly related to the normal sperm mor- authors (AA, AR, and RM). The first author's name, year of
phology [26] and fertility potential [25]. However, studies publication, study design, country origin, sample size, sam-
exploring the detailed associations between lipid profiles and ple criteria, age (mean ± SD or median (IQR)), lipid serum
semen parameters are limited. parameters being assessed (mean ± SD or median (IQR)),
The aim of this study was to analyze available studies semen parameters being assessed (mean ± SD or median
regarding the semen quality and lipid profiles of male fac- (IQR)), statistical analysis or association value (RR, OR, or
tor infertility to elucidate the association between semen correlation coefficient (r)) with p-value between parameter
abnormalities and serum lipid levels. or group. All these data were collected from each study. If
the required information is missing, we will contact the arti-
cle's related author. We do not perform quantitative analysis
Materials and Methods because the statistical analysis between studies is different.

Database Searching Strategy Quality and Risk of Bias Assessment

To generate an adequate report on this systematic review, The Newcastle–Ottawa quality evaluation scale was used to
we compiled data using the Preferred Reporting Items for assess the quality of the studies that were included (NOQS).
Systematic Reviews and Meta-Analyzes (PRISMA) guide- This scale is designed to evaluate the quality of observa-
line [27]. The research protocol was submitted into the tional studies to produce a decent systematic review result.
PROSPERO database, which is a worldwide prospective The included studies were rated as high (9 stars), medium
register of systematic reviews. The registered number is (7–8 stars), or low (less than 7 stars) in terms of quality [28].
CRD42022306433.
In this systematic review, we will investigate all research
from any year that studied the association between lipid serum Results
and semen parameters. At least one or more lipid and semen
parameters are assessed. Semen parameters were investigated We searched on eight databases, including PubMed,
still using WHO guideline 2010. We used the MeSH terms EBSCO, ProQuest, Wiley Online, Web of Science, Springer
“lipid serum” or “lipid levels” and “semen parameters or Link, Scopus, and Science Direct, using the PRISMA

13
Reproductive Sciences

flowchart (Fig. 1). We found 564 studies that were relevant text and no information of statistical analysis of lipid serum
to the keywords. After then, four studies were found to be and sperm parameters value.
duplicates. We chose nine possibly relevant papers after Finally, seven studies were eligible for qualitative anal-
screening them for written in English, on human studies, ysis by recruiting 14.363 participants. The articles were
obtain lipid serum and semen parameters study, and obser- published from 2014 to 2020. Each study had a sample
vational analytic study. Two of the nine research did not size ranging from 17 to 7601 participants. Of all the stud-
match our criteria. These two papers did not provide in full ies included in this systematic review, three studies from

Records idenfied through database


searching
PubMed = 367, EBSCO = 38, Wiley = 52,
Springer = 76, Scopus = 17, ProQuest = 11,
Idenficaon

Web of Science = 3
n =564

Records aer duplicates removed


(n = 560)

Records excluded
Screening

(n = 551)
Not in English = 24, Not in human =
Records screened 192, Not lipid serum and sperm
(n = 560) study = 294, Literature Review =
28, Abstract preceding = 13

Records excluded (n = 2)
Full-text arcles assessed Non-Full-text arcles excluded = 1,
Eligibility

for eligibility No informaon of stascal lipid


(n = 9) serum value and sperm parameter
value = 1

Studies included in
qualitave synthesis
Included

(n = 7)

Fig. 1  PRISMA flowchart for study search

13
Reproductive Sciences

Europe, one from France, one from Russia, one from Italy. review has compiled the search results for studies investigat-
Three studies were from Asia, one from Japan, one from ing this question.
China, and one from Taiwan. And the rest from USA. The Lipid is a chemicals that have been classified together due
age of the participants included in this study varied from to their lack of interaction with water. Some lipids, such as
young adults to the elderly. steroid hormones, act as chemical messengers between tis-
From seven studies, one cross-sectional study, two sues, cells, and organs, while others signal that a single cell's
case–control, and the rest cohort study (Table 1). The results biochemical systems have a variety of functions and impor-
association of between lipid serum and semen parameters tance in the body; as a result, lipids are one of the blood
are shown in Table 2. We also checked the quality of the parameters linked to fertility and obesity [38]. Increased
studies using NOQS. We found that two studies had high triglycerides and fatty acids in seminal plasma have been
quality, while five studies had medium quality. linked to sperm characteristics alterations. Gamete matura-
tion negatively affects in this lipid-rich environment [38].
Abnormalities in lipid metabolism have been observed in
Outcomes various patients who are obese [39, 40]. According to Fein-
gold, 60 to 70% of individuals with obesity have dyslipi-
We wanted to analyze each serum lipid parameter to the daemia [39]. Male fertility parameters are affected by lipid
semen parameter quantitatively (Table 2). However, the type plasma and lipid serum. Spermatozoa have a greater propor-
of statistical analysis and the design used in each study were tion of neutral lipids with insignificant diacylglycerol levels
different. Three studies reported serum lipid levels associ- [41]. Cholesterol is present in seminal plasma of species like
ated with sperm morphology [29–31]. Schisterman et al.’s humans; hence the synthesis and metabolism of lipids can
study reported that two lipid parameters (triglycerides, free affect their reproduction.
cholesterol) affected sperm morphology [29]. The study by The correlation between triglycerides level to seminal
Hagiuda et al. said that the sperm morphology of patients plasma and sperm quality exists. The non-esterified fatty
with hypertriglyceridemia and normal triglycerides differed acids in seminal plasma and sperm suggest then male infer-
significantly [30]. In contrast, the hypertriglyceridemia tility can be affected by lipid metabolism [30]. Lipids play
group reported having average sperm counts that tended a significant role in molecular processes for reproduction;
to be higher than those in the normal group. Meanwhile, for example, cholesterol is the primary substrate for ster-
research by Liu et al. said that all serum lipid profiles affect oid synthesis and affects the hormonal steroidogenesis and
sperm morphology [32]. milieu in both women and men [31, 42]. However, when
Another parameter that was found to be significant was sperm parameters are changed due to elevation of fatty acids
motility; this was reported in one study [31] and then in and triglycerides. Hence, gamete maturation within a lipid-
one significant study of semen volume [30]. One study rich environment impacts oocytes and spermatozoa, conse-
by Dupont et al. did not perform semen analysis but only quently affecting fertility in men.
compared lipid levels in the fertile and infertile groups; the Five of all the studies analyzed reported a significant
results reported that HDL levels were different in these two relationship between lipid levels and semen parameters.
groups; the fertile group had lower HDL levels (1.25 (1.18, Three sperm parameters that are always attentive to are
1.13)) than the infertile group [32]. While the rest of the sperm count, motility, and normal morphology. Dupont
study reported that there was no significant relationship et al. reported that HDL levels differed in the sub fertile and
between serum lipids and semen parameters [33, 34]. fertile groups without examining semen parameters in the
two groups [32]. This report has many weaknesses though
significant. However, it remains to be considered that HDL
Discussion contributes to a male’s fertility profile. The research sample
of Dupont et al. reported having a history of self-reporting
Lipids serum are laboratory parameters that are easy to tobacco consumption which is sometimes underestimated.
check and available in almost all centres. Lipid serum pro- So this self-reporting tends to cause a bias in the research
files are measures when predicting cardiovascular risks and results.
are now part of most routine tests. Many studies revealed Along with HDL, Ferlin et al. also reported that HDL
that abdominal obesity or metabolic syndrome harmed affects the number of spermatozoa. In addition to HDL
sperm parameters [35–37]. Along with the increase in obe- parameters, LDL and triglycerides were also reported to give
sity rates and cardiovascular risks, infertility in men also different results on the number of spermatozoa [43]. Against
increases. What is interesting to investigate is the significant sperm count parameters, triglycerides and very-low-density
correlation between these serum lipid parameters and male lipoprotein were also positively correlated with sperm con-
infertility (in this case, semen parameters). This systematic centration [34].

13
Table 1  Characteristics of included studies
Author, year Study Country origin Sample size Sample criteria Age (mean ± SD or Lipid serum parameters Semen parameters Quality
median (IQR)) of study

Dupons et al., 2019 Case Control France Fertile = 100 Infertile: primary Infertile: 33.3 (32.2, Total cholesterol NR 9
Infertile = 96 idiopathic infertil- 34.3) HDL
Reproductive Sciences

ity, age < 45 years, Fertile: 34.4 (33.7, LDL


no severe oligozoo- 35.1) Triglycerides
spermia (< 5 million/
ml), no history of
undescended testis,
varicocele, or infec-
tion, no female
factors, female part-
ner < 38 years old
Fertile: volunteers, a
spontaneously con-
ceived Childs, time to
pregnancy less than
12 months, a female
partner < 38 years old
Schisterman et al., 2014 Cohort Prospective USA 501 The male who discon- 31.8 ± 4.9 Cholesterol Semen Volume 8
tinuing contraception, Free Cholesterol Sperm Concentration
not medically or Phospholipids Total Motility
surgically sterile, aged Triglycerides Morphology
18–51 years old Total Lipid DNA fragmentation
index
Osadchuk et al., 2020 Case–control Russia Normal semen = 55 Male volunteers aged 37.8 ± 10.9 Total cholesterol Semen volume 7
Impaired semen = 35 23–63 years old, Triglycerides Sperm concentration
absent from alcohol HDL Total motility
2–3 days, excluded LDL Progressive motility
for chronic or acute Vitality
disease history and
infection
Hagiuda et al., 2012 Cohort prospective Japan 167 Males who were sus- 36.5 ± 5.73 Triglyceride Sperm concentration 7
pected infertile with Total motility
aged 22–46 years old Morphology
Lu et al., 2016 Cohort Prospective China 631 Male fertile aged 29.37 ± 4.48 Total cholesterol Sperm concentration 9
18–55 years old, Triglycerides Progressive motility
stopping use con- HDL Morphology
traception, excluded LDL
for alcohol drink- Free fatty acid
ers, heavy smokers,
chronic disease infec-
tion of urogenital,
varicocele, or other
andrology histories

13
Reproductive Sciences

The interaction between lipids and sperm production has


of study
Quality
a complex and uncertain mechanism. The first mechanism
that impacts spermatogenesis is decreased testosterone levels
8

7
(hypogonadism) which leads to disturbances in spermatogen-

Sperm concentration
Progressive motility
esis so that the number of sperm formed decreases. Intrates-
Lipid serum parameters Semen parameters

ticular testosterone is indispensable in the process of sper-

Total motility
Sperm count

Morphology
matogenesis. Decreased testosterone in the case of increased
lipids can occur in several ways. One of them is the involve-
ment of leptin. Leptin levels elevation in hypogonadotropic
hypogonadism suggesting possible leptin resistance [44, 45].
In addition, in the case of obesity, where there is an increase
in the lipid profile, there is also an increase in the cytokine
Total cholesterol

Total cholesterol

TNF-alpha. TNF-alpha will elevate IL-6, IL-8, and COX2


Triglycerides

Triglycerides

expression in the hypothalamus and a macrophage infiltration


associated with a decrease in circulating gonadotropins that
VLDL
HDL

HDL
LDL

LDL

may lead to impaired spermatogenesis [46].


Other mechanism is an increase in oestrogen is also
suspected, but this is more common in the obese dyslipi-
Age (mean ± SD or

daemia group. There is an aromatization of testosterone


median (IQR))

into excess oestrogen: adipose tissue increases circulating


oestrogens and exaggerated feedback inhibition of GnRH-
31.7 ± 7.9

31(18,70)

gonadotropin secretion [47]. The last mechanism involved


in hypogonadism on dyslipidaemia is insulin resistance.
Dyslipidaemia can be another potential risk for metabolic
lem, smoking history
pituitary or testicular
of testicular cancer,
Male with no history

drug use that affect

function, no record

syndrome; nevertheless, dyslipidaemia is also associated


of andrology prob-

over 18 years old


Healthy male aged
orchiectomy, no

with insulin resistance [48]. GnRH neurons and kisspeptin


Sample criteria

neurons express insulin receptors [49, 50], and mice with a


selective neuronal knockout for insulin receptors show an
increased body mass and hypogonadotropic hypogonadism
[51]. However, the question that is difficult to answer is the
lipid parameters that impact sperm parameters.
Liu et al. reported that increased cholesterol such as tri-
glycerides and very-low-density lipoprotein would positively
Country origin Sample size

correlate with sperm motility [31]. In addition, the study


by Hagiuda et al. reported that there were significant dif-
5177

7601

ferences in sperm morphology between the hypertriglyc-


eridemia group and the normal group [30]. However, the
unique thing is that the hypertriglyceridemia group was said
to have a higher normal sperm morphology than the normal
Taiwan

triglyceride group. Liu et al. reported that all lipid profiles


Italy

correlated with sperm morphology, especially very-low-den-


sity lipoprotein [31]. Meanwhile, Schisterman et al. said that
Cross-sectional

lipid parameters such as triglycerides negatively correlate


Retrospective

with sperm morphology [29].


The involvement of lipids in sperm differentiation is still
Study

debated. The assumption is that lipids in the serum will


transport to the seminal plasma so that an increase in serum
lipids will cause an increase in lipids in the plasma seminal.
Table 1  (continued)

Lipids are needed in sperm differentiation to a certain extent.


Ferlin et al., 2019

Liu et al., 2016

The amount of cholesterol in sperm varies enormously in


Author, year

humans, even among ejaculates [25]; conversely, the fraction


of cholesterol present within sperm membranes is widely
linked to sperm morphology [26] and fertility potential [25].

13
Table 2  Qualitative analyses of included study
Author, Year Results Conclusion

Dupont et al., 2019 Total Cholesterol Total Cholesterol Infertile: 5.2 (5.02,5.38) There is HDL has a sig-
fertile: 5.2 HDL: 1.38 (1.32, 1.44) none nificant difference
(5.01,5.40) LDL: 3.24 (3.06, 3.41) infor- between fertile and
Reproductive Sciences

HDL: 1.25 (1.18, Triglycerides: mation infertile groups


1.13) 1.20 (1.06, 1.33) about (p < 0.008)
LDL: 3.28 (3.09, semen
3.47) param-
Triglycerides: 1.42 eters
(1.23, 1.62)
Schisterman et al., Spearmen correlation between Cholesterol and semen volume (r = -0.004), total lipid and semen volume (r = -0.001), triglycerides and bicephalic morphology There is a nega-
2014 (r = -0.001), free cholesterol and sperm head with acrosome (r = -0.043), sperm head area (r = -0.008), sperm head perimeter (r = -0.005), phospholipids and tive correlation
sperm head with acrosome (r = -0.014), sperm head area (r = -0.002) between several
lipids and semen
parameters, espe-
cially morphology
Osadchuk et al., Lipid param- Lipid parameters impaired semen group (mmol/l) (mean (SD)) Overall No reliable cor-
2020 eters normozoo- Triglycerides: 1.40 (0.81) semen relation was found
spermia group Total cholesterol: 4.55 (1.24) param- between serum
(mmol/l) (mean HDL: 1.21 (0.42 eters total cholesterol,
(SD)) LDL: 2.70 (1.15) (mean triglyceride, high
Triglycerides: 1.31 (SE)) and low-density
(0.64) Semen lipoprotein choles-
Total cholesterol: volume: terol, and semen
4.40 (0.88) 3.3 parameters
HDL: 1.14 (0.36) (1.8)
LDL: 2.69 (0.92) Sperm
concen-
tration:
55.81
(45.77)
Progres-
sive
motil-
ity: 45.0
(26.5)
Normal
mor-
phol-
ogy:
6.95
(2.98)

13

Table 2  (continued)
Author, Year Results Conclusion

13
Hagiuda et al., Semen parameters in normal triglycerides (mean ± SD) Semen parameters in hyper triglycerides (mean ± SD) There is a signifi-
2012 Sperm concentration: 12.6 ± 8.60, Sperm concentration: 13.4 ± 7.87, cant difference in
Motility: 39.9 ± 18.0 Motility: 41.9 ± 15.8 morphology
Normal morphology: 10.1 ± 5.50 Normal morphology: 12.2 ± 5.82 between the
normal and
hypertryglic-
erides group
(p = 0.0386)
Lu et al., 2016 Overall Lipid serum (mmol/L) (Mean (SD)) Overall Semen parameters (mean (SD)) There was no
Triglycerides: 1.75 (1.67) Sperm concentration (­ 106/ml): 57.15 (44.67) significant cor-
Total cholesterol: 4.54 (1.00) Progressive motility (%): 33.14 (13.06) relation between
LDL: 2.55 (0.74) Total motility (%): 45.61 (18.42) serum lipids
HDL: 1.26 (0.29) Normal sperm morphology (%): 4.31 (1.69) levels and semen
parameters
Ferlin et al., 2019 Lipid parameters (mean ± SD) Semen parameters (mean ± SD) There is a sig-
Triglycerides (mg/dl): 111 ± 46 Sperm concentration: 30.1 ± 38.7 nificant difference
HDL: 51 ± 14 Progressive motility: 28.3 ± 21.0 between lipid
LDL: 110 ± 41 Normal morphology: 15.1 ± 12.7 levels (HDL,
Total cholesterol: 183 ± 38 LDL, and triglyc-
erides) and sperm
count (p = 0.01,
p = 0.008,
p = 0.019, respec-
tively)
Liu et al., 2017 There is a positive correlation between sperm concentration with triglyceride and very-low-density lipoprotein (adjusted p = 0.001 and p = 0.005, The men with
total sperm motility and progressive motility was increased with increasing low‐density lipoprotein and cholesterol levels (both adjusted p = 0.008 increased total
and p < 0.001), lipid profile and normal sperm morphology, especially low‐density lipoprotein and cholesterol with statistical significance (adjusted cholesterol were
p = 0.017 and p = 0.021) positively corre-
lated with sperm
motility. There
is a correlation
between all lipid
profiles and sperm
morphology
Reproductive Sciences
Reproductive Sciences

However, small number study looks into the specific rela- be excluded. Many studies measure semen parameters such
tionships between serum cholesterol or other lipid profiles as sperm count, motility, and morphology, but not many
and sperm quality. Testicular cholesterol composed 26.50% have investigated sperm DNA.
of total lipid, glycerides 28.50%, and phospholipids 45% The relationship between serum lipids and sperm
[52]. The lipid content of the sperm membrane altered dra- parameters may remain unanswered. However, obesity
matically throughout spermatogenesis, sperm maturation, was linked to higher serum lipid levels, leading to higher
capacitation, and acrosome reaction [53]. These changes seminal plasma lipid levels. Therefore we concluded that
presumably depended on the transfer of cholesterol and lipid serum might impact sperm quality primarily through
phospholipids between sperm and seminal plasma [54]. aberrant lipid metabolism in the male reproductive system.
Several investigations have identified a connection It's likely that unusual lipid levels in the male reproduc-
between sperm membrane lipid composition and seminal tive system directly cause poor semen quality. In addition,
plasma [55] and increased phospholipid levels in seminal research with similar objectives should also analyse exer-
plasma in oligozoospermia and azoospermia patients [56]. cise habits and dietary patterns in the future.
However, Liu et al. also suggested it's possible that the lipids Male with metabolic diseases, particularly dyslipidae-
in seminal plasma aren't derived from blood [31]. Epithe- mia, may be prescribed statins, which can lower testos-
lial cells in the male reproductive tract could be the source. terone levels and interfere with reproduction [61]. A pilot
This raises how lipids in seminal plasma are regulated and study about the use of atorvastatin in healthy men revealed
where they come from [56]. But what is certain is that the that at least one altered semen parameter in 35% of the
increase of lipids levels in the seminal plasma will affect subjects during atorvastatin treatment, and in 65% of the
sperm quality. subjects after withdrawal [41]. Contrary, a large-scale ret-
The mechanism involved in sperm abnormalities is an rospective study suggested that there are no deleterious
increase in reactive oxygen species (ROS), which ulti- effects from statin use on conventional semen parameters
mately causes disturbances in spermatogenesis such as [62]. We assume that normal lipid level is required for
sperm count, sperm motility, and morphology. ROS also a good semen parameters, but excess or deficiency will
even affects DNA damage. ROS can disrupt DNA integrity worsen them. Apart from that, controlling hyperlipidaemia
by causing deletions, cross-links, frameshifts, and chromo- not only improves sperm but also maintains the overall
somal rearrangements by modifying nucleic bases [57]. All quality of life expectancy [63].
these because their plasma membranes contain huge lev-
els of polyunsaturated fatty acids (PUFA) [58], and their
cytoplasm contains deficient concentrations of scavenging
enzymes [59], spermatozoa are particularly sensitive to the Conclusion
damage produced by excessive ROS. These intracellular
antioxidant enzymes cannot protect the plasma membrane The association between serum lipids and semen param-
that surrounds the acrosome and tail, leaving spermatozoa eters is still unclear. However, five of seven studies that
to rely on the seminal plasma for protection. The increase in researched these two variables reported that serum lipids
ROS can occur because ­H2O2 peroxidation the lipid compo- have the potential to influence the quality of semen param-
nent. Actually, lipids are part of the sperm. However, if the eters. A study with a more appropriate design and suffi-
lipids in the seminal plasma are too excessive, peroxidation cient length of time is needed to confirm the correlation
will cause an excess of ROS [60]. Excess ROS will lead to between these two variables. While waiting, there is no
sperm damage and apoptosis (abortive). harm in providing an intervention to stabilize blood lipid
Other reports have reported otherwise, Liu et al. and levels to improve sperm quality and a more decent quality
Osadchuk et al. said no significant correlation between of life.
serum lipid parameters and sperm parameters [31, 33].
This is in line with the statement of Liu et al. that it is very Author Contribution  CP: conceptualizing a systematic review study;
CP and BA: perform study searches in database; CP and BA: selecting
likely that the selection of participants who are members and extracting data from each eligible study; RM, AR, and AA: validate
of the study tends to be biased and not random, especially the results of the selection and extraction of data that has been col-
with a cross-sectional design [31]. If you want to see the lected; CP, AR, and RM: wrote the manuscript; AA and DD: reviewing
effect of exposure, lipids with sperm parameters, a cohort the manuscript; and all authors: finalized the manuscript.
design with a baseline sperm examination would be better
Data Availability  There is no data support this article.
and prioritized. The sampling place for ejaculation col-
lection also needs to be considered because it can affect Code Availability  No code was used nor generated in this study.
(bias) sperm results. In addition, genetic risk factors such
as familial hypercholesterolemia or ApoE genotype should

13
Reproductive Sciences

Declarations  13. Belloc S, Cohen-Bacrie M, Amar E, et  al. High body mass
index has a deleterious effect on semen parameters except
morphology: results from a large cohort study. Fertil Steril.
Ethics Approval  This study did not involve human participants, their
2014;102:1268–73. https://​doi.​org/​10.​1016/j.​fertn​stert.​2014.​
data or biological material, and therefore no ethics approval was
07.​1212.
needed.
14. Tsao C-W, Liu C-Y, Chou Y-C, et al. Exploration of the associa-
tion between obesity and semen quality in a 7630 male population.
Consent to Participate  This study did not involve human participants,
PLoS ONE. 2015;10: e0119458. https://​doi.​org/​10.​1371/​journ​al.​
their data or biological material, and therefore no consent to participate
pone.​01194​58.
was needed.
15. Attaman JA, Toth TL, Furtado J, et al. Dietary fat and semen
quality among men attending a fertility clinic. Hum Reprod.
Consent for Publication  This study did not involve human participants,
2012;27:1466–74. https://​doi.​org/​10.​1093/​humrep/​des065.
their data or biological material, and therefore no consent to publica-
16. Mendiola J, Torres-Cantero AM, Moreno-Grau JM, et al. Food
tion was needed.
intake and its relationship with semen quality: a case-control
study. Fertil Steril. 2009;91:812–8. https://​doi.​org/​10.​1016/j.​fertn​
Conflict of Interest  The authors declare no competing interests. stert.​2008.​01.​020.
17. Liu C-Y, Chou Y-C, Chao JC-J, et al. The association between
dietary patterns and semen quality in a general asian population
of 7282 males. PLoS ONE. 2015;10: e0134224. https://​doi.​org/​
10.​1371/​journ​al.​pone.​01342​24.
References 18. Miller WL, Auchus RJ. The molecular biology, biochemistry, and
physiology of human steroidogenesis and its disorders. Endocr
1. Boivin J, Bunting L, Collins JA, Nygren KG. International esti- Rev. 2011;32:81–151. https://​doi.​org/​10.​1210/​er.​2010-​0013.
mates of infertility prevalence and treatment-seeking: potential 19. Gwynne JT, Strauss JF 3rd. The role of lipoproteins in ster-
need and demand for infertility medical care. Hum Reprod. oidogenesis and cholesterol metabolism in steroidogenic
2007;22:1506–12. https://​doi.​org/​10.​1093/​humrep/​dem046. glands. Endocr Rev. 1982;3:299–329. https://​doi.​org/​10.​1210/​
2. Glazer CH, Bonde JP, Eisenberg ML, et al. Male infertility and edrv-3-​3-​299.
risk of nonmalignant chronic diseases: a systematic review of the 20. Xu Q, Lin H-Y, Yeh S-D, et al. Infertility with defective sper-
epidemiological evidence. Semin Reprod Med. 2017;35:282–90. matogenesis and steroidogenesis in male mice lacking androgen
https://​doi.​org/​10.​1055/s-​0037-​16035​68. receptor in Leydig cells. Endocrine. 2007;32:96–106. https://​doi.​
3. Eisenberg ML, Li S, Brooks JD, et al. Increased risk of cancer in org/​10.​1007/​s12020-​007-​9015-0.
infertile men: analysis of U.S. claims data. J Urol. 2015;193:1596– 21. Rulli SB, Ahtiainen P, Mäkelä S, et al. Elevated steroidogenesis,
601. https://​doi.​org/​10.​1016/j.​juro.​2014.​11.​080. defective reproductive organs, and infertility in transgenic male
4. Latif T, Kold Jensen T, Mehlsen J, et al. Semen quality as a pre- mice overexpressing human chorionic gonadotropin. Endocrinol-
dictor of subsequent morbidity: a Danish cohort study of 4,712 ogy. 2003;144:4980–90. https://​doi.​org/​10.​1210/​en.​2003-​0403.
men with long-term follow-up. Am J Epidemiol. 2017;186:910–7. 22. Whitfield M, Pollet-Villard X, Levy R, et al. Posttesticular sperm
https://​doi.​org/​10.​1093/​aje/​kwx067. maturation, infertility, and hypercholesterolemia. Asian J Androl.
5. Boeri L, Capogrosso P, Ventimiglia E, et al. Undiagnosed predia- 2015;17:742–8. https://​doi.​org/​10.​4103/​1008-​682X.​155536.
betes is highly prevalent in primary infertile men - results from a 23. Gupta RS, Dixit VP. Effect of dietary cholesterol on spermatogen-
cross-sectional study. BJU Int. 2019;123:1070–7. https://​doi.​org/​ esis. Z Ernahrungswiss. 1988;27:236–43. https://d​ oi.o​ rg/1​ 0.1​ 007/​
10.​1111/​bju.​14558. BF020​19512.
6. Glazer CH, Bonde JP, Giwercman A, et  al. Risk of diabetes 24. Purohit A, Daradka HM. Effect of mild hyperlipidaemia on tes-
according to male factor infertility: a register-based cohort study. ticular cell population dynamics in albino rats. Indian J Exp Biol.
Hum Reprod. 2017;32:1474–81. https://​doi.​org/​10.​1093/​humrep/​ 1999;37:396–8.
dex097. 25. Sugkraroek P, Kates M, Leader A, Tanphaichitr N. Levels of
7. Salonia A, Matloob R, Gallina A, et al. Are infertile men less cholesterol and phospholipids in freshly ejaculated sperm and
healthy than fertile men? Results of a prospective case-control Percoll-gradient-pelletted sperm from fertile and unexplained
survey. Eur Urol. 2009;56:1025–31. https://​doi.​org/​10.​1016/j.​ infertile men. Fertil Steril. 1991;55:820–7.
eururo.​2009.​03.​001. 26. Meseguer M, Garrido N, Martínez-Conejero JA, et al. Role of
8. Del Giudice F, Kasman AM, Ferro M, et al. Clinical correla- cholesterol, calcium, and mitochondrial activity in the susceptibil-
tion among male infertility and overall male health: a system- ity for cryodamage after a cycle of freezing and thawing. Fertil
atic review of the literature. Investig Clin Urol. 2020;61:355–71. Steril. 2004;81:588–94. https://​doi.​org/​10.​1016/j.​fertn​stert.​2003.​
https://​doi.​org/​10.​4111/​icu.​2020.​61.4.​355. 09.​035.
9. Groos S, Krause W, Mueller UO. Men with subnormal sperm 27. Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020
counts live shorter lives. Soc Biol. 2006;53:46–60. https://​doi.​ statement: An updated guideline for reporting systematic reviews.
org/​10.​1080/​19485​565.​2006.​99891​16. BMJ. 2021; 372. https://​doi.​org/​10.​1136/​bmj.​n71.
10. Eisenberg ML, Li S, Behr B, et al. Semen quality, infertility and 28. Wells GA, O’Connell D, Peterson J, Welch V, Losos M, Tugwell
mortality in the USA. Hum Reprod. 2014;29:1567–74. https://d​ oi.​ P, Shea B. Newcastle-Ottawa quality assessment scale. Ottawa
org/​10.​1093/​humrep/​deu106. Hosp Res Institute. 2014; 2–4.
11. Glazer CH, Eisenberg ML, Tøttenborg SS, et al. Male factor 29. Schisterman EF, Mumford SL, Chen Z, et al. Lipid concentrations
infertility and risk of death: a nationwide record-linkage study. and semen quality: the LIFE study. Andrology. 2014;2:408–15.
Hum Reprod. 2019;34:2266–73. https://​doi.​org/​10.​1093/​humrep/​ https://​doi.​org/​10.​1111/j.​2047-​2927.​2014.​00198.x.
dez189. 30. Hagiuda J, Ishikawa H, Furuuchi T, et al. Relationship between
12. Tournaye H, Krausz C, Oates RD. Novel concepts in the aetiology dyslipidaemia and semen quality and serum sex hormone lev-
of male reproductive impairment. Lancet Diabetes Endocrinol. els: an infertility study of 167 Japanese patients. Andrologia.
2017;5:544–53. https://d​ oi.o​ rg/1​ 0.1​ 016/S
​ 2213-8​ 587(16)3​ 0040-7. 2014;46:131–5. https://​doi.​org/​10.​1111/​and.​12057.

13
Reproductive Sciences

31. Liu C-Y, Chou Y-C, Lin S-H, et al. Serum lipid profiles are associ- 47. Kim ED, McCullough A, Kaminetsky J. Oral enclomiphene citrate
ated with semen quality. Asian J Androl. 2017;19:633–8. https://​ raises testosterone and preserves sperm counts in obese hypo-
doi.​org/​10.​4103/​1008-​682X.​195240. gonadal men, unlike topical testosterone: restoration instead of
32. Dupont C, Faure C, Daoud F, et al. Metabolic syndrome and replacement. BJU Int. 2016;117:677–85. https://​doi.​org/​10.​1111/​
smoking are independent risk factors of male idiopathic infer- bju.​13337.
tility. Basic Clin Androl. 2019;29:1–7. https://​doi.​org/​10.​1186/​ 48. Novida H, Murtiwi S, Tjokroprawiro A, et al. Po317 are there
s12610-​019-​0090-x. any correlations between ratio Ldl-C/Hdl-C and lipoprotein(a)
33. Osadchuk L, Tipisova E, Kleshchev M, et al. Study of semen with insulin resistance in type 2 diabetes patients with abdominal
quality, reproductive hormone levels, and lipid levels in men from obesity? Diabetes Res Clin Pract. 2014;106:S208–9. https://​doi.​
Arkhangelsk, a city in North of European Russia. Am J Mens org/​10.​1016/​s0168-​8227(14)​70611-4.
Health. 2020;14:1557988320939714. https://​doi.​org/​10.​1177/​ 49. Divall SA, Williams TR, Carver SE, et al. Divergent roles of
15579​88320​939714. growth factors in the GnRH regulation of puberty in mice. J Clin
34. Jin-Chun L, Jing J, Yao Q, et al. Relationship between lipids lev- Invest. 2010;120:2900–9. https://​doi.​org/​10.​1172/​JCI41​069.
els of serum and seminal plasma and semen parameters in 631 50. Qiu X, Dowling AR, Marino JS, et al. Delayed puberty but normal
Chinese subfertile men. PLoS One. 2016;11:e0146304. https://​ fertility in mice with selective deletion of insulin receptors from
doi.​org/​10.​1371/​journ​al.​pone.​01463​04. Kiss1 cells. Endocrinology. 2013;154:1337–48. https://​doi.​org/​
35. Michalakis K, Mintziori G, Kaprara A, et al. The complex interac- 10.​1210/​en.​2012-​2056.
tion between obesity, metabolic syndrome and reproductive axis: 51. Brüning JC, Gautam D, Burks DJ, et al. Role of brain insulin
a narrative review. Metabolism. 2013;62:457–78. https://​doi.​org/​ receptor in control of body weight and reproduction. Science.
10.​1016/j.​metab​ol.​2012.​08.​012. 2000;289:2122–5. https://d​ oi.o​ rg/1​ 0.1​ 126/s​ cienc​ e.2​ 89.5​ 487.2​ 122.
36. Leisegang K, Udodong A, Bouic PJD, Henkel RR. Effect of the 52. Sheriff DS. The lipid composition of human testis in patients
metabolic syndrome on male reproductive function: a case-con- with bilateral varicocele as cause of infertility. Andrologia.
trolled pilot study. Andrologia. 2014;46:167–76. https://​doi.​org/​ 1982;14:150–3. https://​doi.​org/​10.​1111/j.​1439-​0272.​1982.​tb031​
10.​1111/​and.​12060. 17.x.
37. Ventimiglia E, Capogrosso P, Colicchia M, et al. Metabolic 53. Keber R, Rozman D, Horvat S. Sterols in spermatogenesis and
syndrome in white European men presenting for primary cou- sperm maturation. J Lipid Res. 2013;54:20–33. https://​doi.​org/​
ple’s infertility: investigation of the clinical and reproductive 10.​1194/​jlr.​R0323​26.
burden. Andrology. 2016;4:944–51. https://​d oi.​o rg/​1 0.​1 111/​ 54. Scolari S, Müller K, Bittman R, et al. Interaction of mammalian
andr.​12232. seminal plasma protein PDC-109 with cholesterol: implications
38. Calonge RN. Lipid dysregulation in seminal and follicular fluids for a putative CRAC domain. Biochemistry. 2010;49:9027–31.
could be related with male and female infertility. Endocrinol Int https://​doi.​org/​10.​1021/​bi101​257c.
J. 2018;6:65–71. https://​doi.​org/​10.​15406/​emij.​2018.​06.​00156. 55. Huacuja L, Delgado NM, Calzada L, et al. Exchange of lipids
39. Feingold KR. Obesity and dyslipidemia. In: Feingold KR, Anawalt between spermatozoa and seminal plasma in normal and patho-
B, Boyce A, et al (eds). South Dartmouth (MA); 2000. logical human semen. Arch Androl. 1981;7:343–9. https://d​ oi.o​ rg/​
40. Foucaut A-M, Faure C, Julia C, et al. Sedentary behavior, physical 10.​3109/​01485​01810​89993​29.
inactivity and body composition in relation to idiopathic infertility 56. Selvaraj S, Aruldhas MM, Govindarajulu P. Normospermic, oli-
among men and women. PLoS ONE. 2019;14: e0210770. https://​ gospermic and azoospermic men. 1957.
doi.​org/​10.​1371/​journ​al.​pone.​02107​70. 57. Thomson LK, Fleming SD, Aitken RJ, et al. Cryopreservation-
41. Pons-Rejraji H, Brugnon F, Sion B, et al. Evaluation of atorv- induced human sperm DNA damage is predominantly medi-
astatin efficacy and toxicity on spermatozoa, accessory glands ated by oxidative stress rather than apoptosis. Hum Reprod.
and gonadal hormones of healthy men: a pilot prospective clini- 2009;24:2061–70. https://​doi.​org/​10.​1093/​humrep/​dep214.
cal trial. Reprod Biol Endocrinol. 2014;12:65. https://​doi.​org/​10.​ 58. Alvarez JG, Storey BT. Differential incorporation of fatty acids
1186/​1477-​7827-​12-​65. into and peroxidative loss of fatty acids from phospholipids of
42. Gianfrilli D, Ferlin A, Isidori AM, et al. Risk behaviours and human spermatozoa. Mol Reprod Dev. 1995;42:334–46. https://​
alcohol in adolescence are negatively associated with testicular doi.​org/​10.​1002/​mrd.​10804​20311.
volume: results from the Amico-Andrologo survey. Andrology. 59. Aitken RJ, Roman SD. Antioxidant systems and oxidative stress
2019;7:769–77. https://​doi.​org/​10.​1111/​andr.​12659. in the testes. Adv Exp Med Biol. 2008;636:154–71. https://​doi.​
43. Ferlin A, Garolla A, Ghezzi M, et al. Sperm count and hypo- org/​10.​1007/​978-0-​387-​09597-4_9.
gonadism as markers of general male health. Eur Urol Focus. 60. Sanocka D, Kurpisz M. Reactive oxygen species and sperm cells.
2021;7:205–13. https://​doi.​org/​10.​1016/j.​euf.​2019.​08.​001. Reprod Biol Endocrinol. 2004;2:1–7. https://​doi.​org/​10.​1186/​
44. van Rossum CTM, Hoebee B, van Baak MA, et al. Genetic vari- 1477-​7827-2-​12.
ation in the leptin receptor gene, leptin, and weight gain in young 61. La Vignera S, Condorelli RA, Vicari E, Calogero AE. Statins
Dutch adults. Obes Res. 2003;11:377–86. https://d​ oi.o​ rg/1​ 0.1​ 038/​ and erectile dysfunction: a critical summary of current evidence.
oby.​2003.​51. J Androl. 2012;33:552–8. https://​doi.​org/​10.​2164/​jandr​ol.​111.​
45. Kwon O, Kim KW, Kim M-S. Leptin signalling pathways in hypo- 015230.
thalamic neurons. Cell Mol Life Sci. 2016;73:1457–77. https://​ 62. Keihani S, Martin C, Craig JR, et al. Semen parameters are unaf-
doi.​org/​10.​1007/​s00018-​016-​2133-1. fected by statin use in men evaluated for infertility. Andrologia.
46. Morelli A, Sarchielli E, Comeglio P, et al. Metabolic syndrome 2018;50:1–6. https://​doi.​org/​10.​1111/​and.​12995.
induces inflammation and impairs gonadotropin-releasing hor- 63. Pramudya D, Tjokroprawiro A, Murtiwi S, et al. Po335 Corre-
mone neurons in the preoptic area of the hypothalamus in rabbits. lation Between Lipid Profiles and Body Mass Index in Patients
Mol Cell Endocrinol. 2014;382:107–19. https://d​ oi.o​ rg/1​ 0.1​ 016/j.​ With Type Ii Diabetes Mellitus. Diabetes Res Clin Pract.
mce.​2013.​09.​017. 2014;106:S219. https://​doi.​org/​10.​1016/​s0168-​8227(14)​70629-1.

13

You might also like