J Infertil Reprod Biol, 2020, Volume 8, Issue 3, Pages: 61-65. https://doi.org/10.47277/JIRB/8(3)/61  
Alterations in Lipid Profile and Indices of  
Atherogenicity among Infertile Women Seeking  
Conception by Assisted Reproductive Technology  
1
*
1
2
Mathias Abiodun Emokpae , Claudius Osakhuemen Eromosele , Hope Oluwadara Ajibade  
1
Department of Medical Laboratory Science, School of Basic Medical Sciences, University of Benin, Benin City, Nigeria  
Department of Medical Laboratory Science, College of Natural and Applied Sciences, Achievers University, Owo, Nigeria  
2
Received: 18/06/2020  
Accepted: 09/08/2020  
Published: 20/09/2020  
Abstract  
Female infertility is common all over the world and lipid disorders are suggested to play a role. This study aimed to evaluate  
the plasma lipid profile and indices of atherogenicity among infertile women attending assisted reproductive technology clinics.  
Serum lipid profile (total cholesterol, triglycerides, low- density lipoprotein cholesterol, high- density lipoprotein cholesterol, and  
calculated indices of atherogenicity were determined in 140 infertile women and 50 healthy age-matched women of proven fertility.  
The lipid profile was assayed by the spectrophotometric method using reagents supplied by Randox Laboratories, Crumlin, Antrim,  
UK. The means values of measured parameters were compared between cases and controls by unpaired Students-test. The results  
showed that age (p<0.001), total cholesterol, triglycerides, low-density lipoprotein, AIP, some cardiac risk ratios, and atherogenic  
coefficients were significantly higher (p<0.001) while high-density cholesterol was significantly lower (p<0.001) among infertile  
women than control subjects. The difference in the mean body mass index between the cases and controls was not significant. The  
calculated indices of atherogenicity except high density/low-density ratio were significantly higher among infertile women seeking  
assisted reproductive technology for conception than control subjects. The higher indices of atherogenicity among this group of  
subjects might predispose them to cardiovascular diseases. Therefore, routine evaluation of lipid profile and indices of  
atherogenicity is suggested.  
Keywords: Female, Fertilization, Infertility, Lipids, Reproductive techniques  
Introduction  
The need to identify risk factors and serum markers of  
atherosclerosis in the process of early detection and  
prediction of risk for cardiovascular diseases (CVD) is  
gaining increasing attention. Mathematical models are used  
to calculate how much atherogenic low-density lipoprotein  
cholesterol (LDL-c) is driving the progression of  
atherosclerosis (1). Cardiac risk ratio (CRR) is the ratio of  
total cholesterol value to high-density lipoprotein  
cholesterol (HDL-c) value (2,3), atherogenic coefficient  
parameters (6, 7).  
Female infertility is common all over the world with  
couples experiencing significant financial and emotional  
burdens. Even though several factors are implicated in  
infertility (8), lipid disorders are suggested to play a role.  
Some authors have reported that fertility potential among  
couples with abnormal lipids was lower with a fecundability  
Odds ratio (FOR) and high total cholesterol in both males  
and females (9). Infertile women seeking conception by  
assisted fertilization technology may be at increased risk of  
cardiovascular disease because they are administered with  
exogenous gonadotropins. Ovulation induction by  
exogenous gonadotropins is some of the commonest causes  
of lipoprotein modifications (10). Individualized  
gonadotropin dosage to reduce adverse effects of excessive  
ovarian response or poor response has been advocated (11).  
Also, derangement in lipid concentrations can impact  
negatively on the basic function that requires cholesterol.  
Hence dyslipidemia may be a major determinant in the  
progression of infertility (12). Some authors have reported  
(
AC) is calculated by subtracting the value of HDL-c from  
total cholesterol, all divided by HDL-c value while  
Atherogenic index of plasma (AIP) is defined as logarithm  
[log] of the ratio of plasma concentration of triglycerides to  
HDL-C and is strongly correlated with CVD risks (4).  
However, the information in the literature that has examined  
the association between indices of atherogenicity and  
infertility in women seeking pregnancy via assisted  
reproductive technology is scanty (5). Indices of  
atherogenicity are said to be critical indices that better  
predict cardiovascular risk than values of lipid profile  
*Corresponding authors: Mathias Abiodun Emokpae, Department of Medical Laboratory Science, School of Basic Medical  
Sciences, University of Benin, Benin City, Nigeria, Email: mathias.emokpae@uniben.edu  
61  
J Infertil Reprod Biol, 2020, Volume 8, Issue 3, Pages: 61-65. https://doi.org/10.47277/JIRB/8(3)/61  
that in human in-vitro, abnormal maternal serumlipid profile  
minimum of 140 samples and 50 controls were recruited for  
the study.  
was associated with poorer oocyte quality, ovarian function,  
and embryo development (12). This is an indication of a  
potential reduction in fertility (13). The incidence of  
dyslipidemia among infertile subjects is on the increase all  
over the world. Many of its possible causes are not  
associated with hormonal imbalance but, hyperlipidemia can  
be linked to various hormonal diseases such as diabetes,  
polycystic ovary syndrome, and metabolic syndrome.  
Besides the clinical symptoms of cardiovascular disease,  
dyslipidemia and the associated syndromes have also been  
associated with infertility (14, 15).  
Atherosclerotic disease is a chronic and degenerative  
process that begins slowly probably during infancy. It is a  
disease with a wide range of clinical manifestation which  
may be asymptomatic or may eventually manifest as  
cardiovascular disease. The inflammatory process and the  
accompanying oxidative stress contribute to the mechanisms  
of the development of atherosclerosis (16). The incidence of  
atherosclerosis may differ according to the stage of the  
disease, individual patient race, age, sex, and environmental  
factors (16). A study has shown that Nigerians seemed to  
have an unfavorable risk profile for CVD which was not  
obvious using simple lipid profile parameters (17). This  
study aimed to determine the lipid profile and indices of  
atherogenicity among infertile women seeking assisted  
reproductive technology.  
Sample Collection  
Under strict aseptic precautions, 5mL of fasting venous  
blood was obtained from each of the participants into a  
lithium heparin bottle. Blood samples were collected at  
baseline coinciding with Days 2-4 of women menstrual  
cycles and before ovarian stimulation and administration  
gonadotropins. Samples were centrifuged at a speed of  
3000rpm for 5 minutes and plasma was separated. The  
plasma recovered was transferred to a fresh tube for  
determination of lipid profile.  
Sample Analysis  
Triglyceride, total cholesterol, and HDL-c were  
determined by the spectrophotometric method using  
reagents kits supplied by Randox Laboratories, Crumlin,  
Antrim, UK. Indices of atherogenicity were calculated as  
indicated in the introduction section and LDL-c was  
calculated using Friedewald et al. (20) formula.  
Statistical Analysis  
All data analysis was performed using SPSS. 21.0  
Software (SPSS, Chicago, IL). Continuous variables were  
expressed as means ±standard deviation and analyzed using  
the independent Student t-test. A p-value of less than 0.05  
was considered to be statistically significant.  
Materials and Methods  
This is a cross-sectional study of women seeking  
conception via Assisted Reproductive Technology. The  
subjects comprised of 140 infertile women aged 36.8±0.35,  
body mass index 24.8±0.01, and 50 healthy women of  
proven fertility and aged 30.0±0.02, body mass index  
Results  
A total of 190 women were recruited in the study. This  
comprised of 140 infertile women seeking assisted  
reproductive technology and 50 healthy women of proven  
fertility as controls. Table 1 describes the demographic  
characteristics of the study population. The mean ages of the  
study population were significantly higher (p<0.001) than  
control subjects. There was no significant difference in the  
means body mass index (BMI) and the age of onset of  
menstruation (Menarche) between the cases and controls.  
Table 2 shows the pattern of lipid profile and indices of  
atherogenicity among the study population compared with  
controls. The mean HDL-c level was significantly lower  
24.03±0.01 who served as controls.  
Inclusion criteria  
All healthy women attending an ART clinic seeking  
pregnancy by ART. Apparently healthy Women between the  
ages of 25-45 without menses (anovulatory) and other  
histories of infertility and not on contraceptives were  
enrolled.  
(
p<0.001) among the infertile women than the fertile  
Exclusion criteria  
Those Women < 45 who are still menstruating and are on  
contraceptives and those above 45 years were excluded.  
controls. On the other hand, total cholesterol, triglyceride,  
LDL-c, VLDL-c, AIP, cardiac risk ratios except for HDL-  
c/LDL-c ratio, and AC were significantly higher (p<0.001)  
among infertile women than control subjects.  
Ethical Consideration  
The protocol of the study was reviewed and approved by  
the Health Research ethics committee of the Lagos State  
Ministry of Health, Lagos State, Nigeria (Reference HM  
Discussion  
Female infertility is a social menace and has an  
economic, social, and psychological impact on the  
individual, and the society. Infertile women seeking  
conception by assisted reproductive techniques are treated  
with recombinant follicle-stimulating hormone to stimulate  
their ovaries to produce oocytes as well as human chorionic  
gonadotropins (hCG). These exogenous hormones have  
been reported to increase lipid concentrations. It is very  
important to know the lipid profile levels and indices of  
1208/255 dated 23rd June 2018). Informed consent was  
sought from the participant to indicate voluntary  
participation in this study.  
Sample Size Determination  
The sample size (N) was calculated using sample size  
determination formula for health studies (18) and a 10%  
prevalence of female infertility in Nigeria (19). Therefore a  
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Table 1: Demographic characteristics of study population  
Variables  
Infertile women (n=140)  
Controls (n=50)  
Age(years)  
Body mass index(Kg/m )  
Menarche (Years)  
Irregular menstruation  
Gynecological surgery  
Physical activity  
35.9±0.35  
24.8±0.5  
13.1±1.0  
40(28.6%)  
50(35.7%)  
120(85.7)  
02(1.4)  
30.0±0.01  
24.03±0.2  
13.0±0.2  
0(0%)  
03(06%)  
32(64%)  
0(0%)  
3
Cigarette smoking  
Alcohol Consumption  
10(7.1%)  
15(30%)  
Table 2: Comparison of Lipid profile parameters and atherogenic indices between infertile and fertile women  
Parameters  
Infertile Women (n=140)  
Fertile Women (n=50)  
P Value  
Triglycerides(mmol/L)  
Total Cholesterol(mmol/L)  
HDL-c(mmol/L)  
LDL-c(mmol/L)  
VLDL-c(mmol/L)  
AIP  
1.72±0.02  
5.70±0.01  
0.89±0.02  
3.90±0.02  
082±0.02  
0.52±0.001  
1.60±0.07  
5.46±0.02  
1.16±0.02  
3.60±0.02  
0.73±0.02  
0.29±0.001  
0.001  
0.001  
0.001  
0.001  
0.001  
0.001  
Cardiac Risk Ratios  
TC/HDL-c  
LDL-c/HDL-c  
HDL-c/LDL-c  
AC  
6.38±0.04  
4.35±0.05  
0.22±0.06  
5.39±0.06  
4.69±0.03  
3.11±0.04  
0.32±0.04  
3.72±0.04  
0.001  
0.001  
0.5  
0.001  
HDL-c=High Density Lipoprotein cholesterol; LDL-c= Low-Density Lipoprotein cholesterol; VLDL-c=Very Low-Density Lipoprotein cholesterol; AIP=atherogenic  
index of plasma lipid; atherogenic coefficient  
atherogenicity to predict cardiovascular risk and fecundity  
potential.  
(24, 25). In this study, there was no significant difference in  
the means of BMI between infertile women and control  
subjects. However, BMI was reported to be negatively  
associated with the number of normally fertilized oocytes,  
cleavage embryos, and good quality embryos. It was  
reported that high BMI may adversely influence the  
pregnancy rate of IVF in subjects with endometriosis (12).  
The biologic mechanism by which lipids and  
lipoproteins affect successful reproduction is the role lipids  
play in ovarian steroidogenesis (8, 23). Others have  
suggested that the dysregulation of insulin which disrupts  
ovarian function may be implicated (26). A 50% increased  
risk of myocardial infarction or coronary heart disease was  
reported among women with menstrual irregularities in  
comparison with those who had normal cycles from the ages  
of 20 to 35 years (27). The results show that infertile females  
have significantly higher triglycerides compared to control.  
Some authors reported that high triglycerides levels are  
found in both obese and non-obese women suffering from  
infertility (28). High serum levels of total cholesterol and  
LDL-c in infertile women is an indication disproportionate  
steroidogenesis that may be taking place and this could be  
the reason for infertility. This agrees with a study that  
observed that women with different causes of infertility had  
increased total cholesterol levels (29).  
In this study, plasma concentrations of triglycerides,  
total cholesterol, LDL-c, VLDL-c, and the indices of  
atherogenicity except for HDL-c/LDL-c ratio were  
significantly higher while HDL-c was significantly lower  
among infertile women than controls.  
The observed results are consistent with previous studies  
(
8, 10, 12). Wang et al. (12) evaluated lipid profile levels in  
infertile women and associated their levels with oocyte and  
embryo qualities. The authors reported that the quality of  
embryo may be associated with lipid abnormalities in  
infertile females. They observed a negative association of  
embryo quality with triglycerides, total cholesterol, and  
LDL-c levels. The level of HDL-c correlated positively with  
embryo quality (12). The important role of HDL cholesterol  
in the process of mammalian female reproduction has been  
aptly demonstrated in knockout (SR-BI KO) female mice.  
The experimental study showed that a high incidence of  
exencephaly with female bias in embryos lacking SR-BI as  
associated with abnormal HDL metabolism (21). Besides, it  
was reported that HDL-c exhibit a vital cytoprotective effect  
on oocytes and surrounding granulosa cells (22). The study  
by Wang et al (12) is an indication that an adequate level of  
HDL-c is required for the development of oocytes to the  
embryo. This protective effect of HDL-c may be attributed  
to the delivery of cholesterol to corpus luteum as a substrate  
for the biosynthesis of progesterone by both HDL-c and  
LDL-c (23).  
It was suggested that lipid may be used as a marker of  
fertility. In the United States of America, it was  
recommended that adults over the age of 20 years undergo  
lipid profile screening every 5 years as this will enable the  
identification of reduced fecundity (30). Although  
cholesterol is a precursor of steroid hormones, a high level  
The increasing incidence of the negative effect of raised  
body mass index (BMI) on IVF outcomes has been reported  
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of it can cause infertility in females (31). Abnormality of  
7. Emokpae MA, Arogundade A, Adumaya SC. Use of the  
atherogenic index of plasma in evaluating the potential  
cardioprotective effects of red wine consumption: Studies in  
LDL-c had not been consistently reported in some cases of  
infertility. Even those with normal LDL-c levels had shown  
increase VLDL-c relative to the control group (32). A  
significantly higher index of atherogenicity was observed  
among infertile women when compared with the fertile  
group. This implies that infertile women have a higher risk  
of developing cardiovascular diseases than the fertile group.  
This is particularly important because Black Africans are  
known to have lower lipid levels than Caucasians (33).  
Therefore, the use of lipid levels to diagnose cardiovascular  
diseases in Africans may be misleading. Glew et al. (17)  
reported that they were able to differentiate patients with  
stroke from normal individuals via the use of cardiac risk  
ratios. The need to identify prospective women seeking  
intervention via assisted reproductive technology who are at  
risk of CVD cannot be overemphasized.  
Nigerian  
Young  
adult  
volunteers.  
Biokemistri.  
2013;25(3):118-23.  
8. Abbasi M. Nanoparticles as a promising Innovative  
Treatment Towards Infertility. Journal of Infertility and  
Reproductive Biology. 2017;5(1):1-4.  
9. Schisterman EF, Mumford SL, Browne RW, et al. Lipid  
concentrations and couple fecundity: the LIFE study.  
Journal of Clinical Endocrinology and Metabolism,  
2014;99:2786-94.  
10. Brizzi P, Dessole S, Tonolo G, et al. Effect of ovarian  
stimulation on plasma lipid and apolipoprotein  
concentrations in  
undergoing IVF/embryo  
BioMedicine Online. 2003;7(3):309-12.  
a
population of infertile women  
transfer. Reproductive  
11. Mannem HM, Agarwal SA, Nayak C, et al. Prediction of  
Ovarian Response with Ovarian Response Prediction index  
Conclusion  
(
Orpi) during controlled Ovarian stimulation in IVF. Journal  
Plasma triglyceride, total cholesterol, LDL-c, and  
indices of atherogenicity (except HDL-c/LDL-c ratio) were  
significantly higher while HDL-c was significantly lower  
among infertile women seeking conception via assisted  
reproduction. It is suggested that this group of women may  
benefit from periodic lipid profiles and indices of  
atherogenicity determination for fertility potential and/or  
CVD risk assessments.  
of Infertility and Reproductive Biology. 2020;8(3):33-37.  
2. Wang S, Wang J, Jiang Y, Jiang W. Association between  
blood lipid level and embryo quality during in vitro  
fertilization. Medicine. 2020;99:13(e19665).  
3. Sozen I, Arici A: Hyperinsulinism and its interaction with  
hyperandrogenism in polycystic ovary syndrome. Obstetrics  
and Gynecology Survey. 2000;55:321-8.  
1
1
1
1
4. Ben-Shlomo I, Grinbaum  
E, Levinger U. Obesity-  
associated infertility-the earliest known description.  
Reproductive Biomedicine Online. 2008;17(1):5-6.  
5. Chughtai B, Lee RK, Te AE, Kaplan SA. Metabolic  
syndrome and sexual dysfunction. Current Opinion in  
Urology. 2011;21(6):514-8.  
16. Melo AS, Rosa-e-Silva JC, Poli-Neto OB, et al. Unfavorable  
lipid profile in women with endometriosis. Fertility and  
Sterility. 2010;93(7):2433-6.  
Acknowledgments  
The contribution of Prof. O. Giwa-Osagie and his team  
during this study is appreciated.  
Conflicts of interest  
The authors declare that there is no conflicts of interest.  
References  
17. Glew RH, Okolie H, Crossey M, et al. Serum lipid profiles  
and homocysteine levels in adults with stroke or Myocardial  
Infarction in the town of Gombe in Northern Nigeria. Journal  
of Health Population and Nutrition. 2004;22:341-7.  
18. Lwange SK, Lemeshow S. Sample size determination in  
health studies; a practical manual. IRIS, World Health  
Organization. 1991.  
19. Menuba I, Ugwu E, Obi S, et al. Clinical management and  
therapeutic outcome of infertile couples in southeast Nigeria.  
Therapeutics Clinical Risk Management. 2014;10: 763-768.  
20. Friedewald WT, Levy RL, Fredrickson DS. Estimation of  
the concentration of low-density lipoprotein cholesterol in  
plasma without use of preparative ultracentrifuge. Clinical  
Chemistry. 1972;10:499-502.  
1
.
Rajab TMA. Comparative study for the atherogenic index of  
plasma (AIP) in patients with type 2 diabetes mellitus, β-  
thalassemia, and hypothyroidism. International Journal of  
Chemistry Research. 2012;2:1-9.  
2
3
4
.
.
.
Castelli WP. Cholesterol and lipids in the risk of coronary  
artery disease- the Framingham Heart Study. Canadian  
Journal of Cardiology. 1988;4:5-10.  
John D, Brunzell MD. Lipoprotein management in patients  
with cardiometabolic risk. Journal of American College of  
Cardiologists. 2008;51:1512-4.  
Dobi´asov´a M, Urbanov´a, Z, Sam´anek, M. Relations  
between particle size of HDL and LDL lipoproteins and  
cholesterol esterification rate. Physiological Research.  
2
005;54:159-65.  
21. Santander NG, Contreras-Duarte S, Awad MF, et al.  
Developmental abnormalities in mouse embryos lacking the  
HDL receptor SR-BI. Human Molecular Genetics. 2013;  
22:1086-96.  
22. Browne RW, Bloom MS, Shelly WB, et al. Follicular fluid  
high-density lipoprotein-associated micronutrient levels are  
associated with embryo fragmentation during IVF. Journal  
of Assisted Reproduction and Genetics. 2009;26:557-60.  
5
6
.
.
Cai G, Shi G, Xue S, Lu W. The atherogenic index of plasma  
is a strong and independent predictor for coronary artery  
disease in the Chinese Han population. Medicine  
(
Baltimore). 2017;96:8058.  
Khazaal MS. Atherogenic index of plasma as a parameter in  
predicting cardiovascular risk in males compared to the  
conventional dyslipidemic indices. Karbala Journal of  
Medicine. 2013;6:1506-31.  
64  
J Infertil Reprod Biol, 2020, Volume 8, Issue 3, Pages: 61-65. https://doi.org/10.47277/JIRB/8(3)/61  
2
2
3. Fujimoto VY, Kane JP, Ishida BY, et al. High-density  
lipoprotein metabolism and human embryo. Human  
Reproduction Update. 2010;16:20-38.  
4. Bailey AP, Hawkins LK, Missmer SA, et al. Effect of  
body mass index on in vitro fertilization outcomes in  
women with polycystic ovary syndrome. American  
Journal  
of  
Obstetrics  
and  
Gynecology.  
2014;211:163.e1-6.  
2
2
5. Garalejic E, Arsic B, Radakovic J, et al. A preliminary  
evaluation of the influence of body mass index on in  
vitro fertilization outcome in nonobese endometriosis  
patients. BMC Women’s Health. 2017;17;17:112.  
6. Robker RL, Akison LK, Bennett BD, et al: Obese  
women exhibit differences in ovarian metabolites,  
hormones, and gene expression compared with  
moderate-weight women. Journal of Clinical  
Endocrinology and Metabolism. 2009;94:1533-40.  
7. Parikh NI, Jeppson RP, Berger JS, et al: Reproductive  
Risk Factors and Coronary Heart Disease in the  
Women’s Health Initiative Observational Study.  
Circulation. 2016;133(22):2149-58.  
8. Marther K , Kwan F, Corenblum B. Hyperinsulinemia  
in polycystic ovary syndrome correlates with increased  
cardiovascular risk independent of obesity. Fertility and  
Sterility. 2000; 73(1):150-6.  
9. Fiances, SG, David, GG. Basic and Clinical  
Endocrinology: Disorder of lipoprotein catabolism in  
female infertility. (6th ed). New York: McGraw-Hill,  
2
2
2
3
2001;20:7230-5.  
0. National Institutes of Health. Third report of the  
National Cholesterol Education Program (NCEP) expert  
panel on detection, evaluation, and treatment of high  
blood cholesterol in adults (Adult Treatment Panel III).  
Executive Summary. NIH Publication No. 01-3670,  
2001.  
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3
1. Centers for Disease Control. Prospective parents with  
high cholesterol levels could be in for a long wait to  
become pregnant. Journal of Clinical Endocrinology and  
Metabolism. 2014;1:1-2.  
2. Pirwany IR, Fleming R, Greer IA, et al. Lipids and  
lipoprotein subfractions in women with PCOS:  
Relationship to metabolic and endocrine parameters.  
Clinical Endocrinology. 2001;54:447-53.  
3. Ademuyinwa O, Ugbaja RN, Rotimi, SO. Plasma lipid  
profile atherogenic and coronary risk indices in some  
Residents of Abeokuta in South-Western Nigeria.  
Biochemistry. 2008;20:85-91.  
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