Keywords
Cardiovascular diseases, Infertility, Fertility, Uric Acid, CK (MB), HDL, LDL hs-CRP
This article is included in the Datta Meghe Institute of Higher Education and Research collection.
Scientists and medical experts are beginning to understand the significant role that a woman’s past reproductive experiences play in her potential risk of developing heart disease. Reproductive history is seldom considered when assessing the cardiovascular risk. Infertility, high blood pressure, and hypertension are risk factors for heart disease. Additional analyses were conducted to determine whether the apparent increase in risk could be influenced by other risk factors associated with infertility such as irregular menstruation, thyroid conditions, and waist circumference.
This study aimed to investigate the association between cardiovascular risk and infertility in women and those who are fertile. The objectives of this study were to estimate the levels of serum creatinine kinase (MB) in both infertile and fertile control groups, as well as to estimate the LDL and HDL levels in the same groups. The study group comprised 78 participants, of which 39 were fertile and 39 were infertile. CK (MB), HDL, LDL, Uric acid, and high sensitivity C reactive Protein (hs-CRP) levels were analyzed.
In this study, we discuss how infertility may share common pathways with cardiovascular diseases. Numerous mechanisms may be involved in mediating infertility, including ovulatory abnormalities, endometriosis, and uterine fibroids. For example, in addition to having lower HDL levels, women with polycystic ovary syndrome (PCOS) are more likely to have higher levels of total cholesterol, triglycerides, and LDL. PCOS patients typically exhibit elevated UA levels and hyperuricemia, which are commonly associated with increased androgen levels.
Cardiovascular diseases, Infertility, Fertility, Uric Acid, CK (MB), HDL, LDL hs-CRP
Participants in the prospective Women Health Organization study who had gone through menopause self-reported if they had tried becoming pregnant for a minimum of a year.
Female infertility, which can be caused by conditions including PCOD, obesity, thyroid problems, and endometriosis, is likely to increase the risk of cardiovascular disease (CVD), according to a growing body of studies. This study aimed to determine whether there is a connection between infertility and cardiovascular disease (CVD). This information demonstrates the correlation between a few reproductive factors and an increased risk of cardiovascular disease.
Despite the lack of comprehensive data, there is mounting evidence that infertility increases the risk of cardiovascular disease. Therefore, it is uncertain if heart failure (HF) is more likely to occur after infertility. Researchers and health professionals are beginning to realize the importance of a woman’s prior reproductive experiences in the future risk of developing heart disease. Reproductive history is rarely considered when determining the cardiovascular risk. Infertility is regarded as a risk factor for heart disease, along with conditions such as high blood pressure and hypertension. Further analyses were carried out, according to the researchers, to ascertain whether other risk factors linked to infertility, such as irregular menstruation, thyroid issues, and waist circumference, could be responsible for the apparent increase in risk.
Approximately 30–40 percent of infertile couples go undiagnosed, meaning that no evident abnormalities are found after basic therapies, such as sperm analysis and testing for ovulation and tubal patency.1,2 For couples who are infertile for unknown reasons, fecundity might be difficult. Several underlying causes, including age, endocrine problems, mild to moderate endometriosis, oxidative stress, and decreased endometrial receptivity, can contribute to infertility.3
Atherosclerosis is recognized as the principal cause of elevated risk of cardiovascular diseases. Globally, cardiovascular disease (CVD) is one of the leading causes of illness and death. It’s widely accepted that inflammation significantly influences atherosclerosis.4,5 Inflammatory factors, including CRP, transforming growth factor-1, interleukin-6, and monocyte/macrophage colony-stimulating factor, have been linked to atherosclerosis. High-sensitivity CRP (hs-CRP) is a biochemical risk factor of myocardial infarction in healthy individuals. It’s a biomarker of persistent, minimal inflammation that is elevated in people with unstable CVD.6,7 Metabolic syndrome, characterized by diabetes, insulin resistance, abdominal obesity, and dyslipidemia, is also associated with high hs-CRP levels.8 Reproductive hormones also affect the serum UA levels. Although controversy exists regarding the relationship between different hormones and UA levels, it is commonly acknowledged that hyperuricemia and elevated serum UA levels are directly correlated with elevated testosterone levels. Testosterone can influence the performance of the renal UA reabsorption system by altering the expression of certain proteins.9 Homocysteine and lipids are two of the 12 baseline laboratory markers, and hs-CRP is the most reliable indicator of the risk of cardiovascular events. Testosterone may also elevate blood UA levels by promoting the hepatic metabolism of purine nucleotides.10 Women with polycystic ovary syndrome (PCOS) often have elevated UA levels and hyperuricemia, which are associated with elevated androgen levels.11 The relationship between the risk of CVD and the subtypes of female factors involves numerous mechanisms, including ovulatory abnormalities, endometriosis, and uterine fibroids. For example, women with PCOS, in addition to having lower HDL levels, are more likely to have higher levels of total cholesterol, triglycerides, and LDL.12,13 The three hyperandrogenic Rotterdam phenotypes have higher BMIs,14,15 which may be attributed to metabolic syndrome.16,17 Hyperandrogenic phenotypes have a worse cardiometabolic profile.18 Infertility and cardiovascular disease may thus be linked with hyperandrogenism, dyslipidemia, obesity, and insulin resistance potentially playing a role.19–21 Among the 12 baseline laboratory markers, including lipids and homocysteine, hs-CRP level was the most accurate predictor of CVD risk. The characteristics of metabolic syndrome include diabetes, insulin resistance, abdominal obesity, dyslipidemia, and high hs-CRP levels. Researchers found that postmenopausal CHD was not independently correlated with a history of infertility or the root cause of infertility. However, coronary heart disease was positively associated with either “always having irregular menses” or “occasionally having irregular menses.” Therefore, individuals with monthly irregularities may bear a higher risk of cardiovascular disease (CVD) among research participants who self-report infertility.22 One of the limitations of this study is that the researchers did not remotely and retrospectively assess premenopausal cardiovascular events and risk factors to determine the history of infertility and its cause. Women with low ovarian reserves have high triglycerides, LDL, and HDL, along with elevated values of HOMA-IR (indicating insulin resistance) and CRP (a biomarker of inflammation), similar to those with PCOS.23 Thus, the cascade of cardiovascular illnesses may be mediated by dyslipidemia, chronic inflammation,24 and insulin resistance in females with early ovarian insufficiency. Previous studies on patients with endometriosis have shown that serum lipoprotein (a) and triglycerides are higher, but blood HDL and LDL levels are equivalent to those of controls with similar ages and amounts of body fat.25
This study discusses how infertility may share common pathways with cardiovascular diseases. This study aimed to investigate the relationship between unexplained female infertility and cardiovascular diseases, as assessed by risk markers such as CK (MB), LDL, HDL, serum uric acid, and hs-CRP.
1° Risk marker
To estimate the levels of serum creatine kinase (MB), infertility, and fertility control.
To estimate the LDL level in Infertile and Fertile Control.
To estimate the HDL level in Infertile and Fertile Control.
2° Risk marker
To estimate the level of serum Uric Acid in Infertile and Fertile Control.
To estimate the level of hs- CRP in Infertile and Fertile Control.
The study was conducted among the general population of the Vidarbha District at AVBRH Hospital. This study aimed to explore the connection between infertility and cardiovascular diseases in young women. In addition to having lower HDL levels, women with PCOS may also be more likely to exhibit higher levels of total cholesterol, triglycerides, and LDL. c PCOS patients typically demonstrate elevated UA levels and hyperuricemia, which are frequently associated with increased androgen levels. A relationship is expected to exist between cardiovascular diseases and infertility.
This study was conducted at Acharya Vinoba Bhave Rural Hospital (AVBRH), Sawangi Meghe, and Wardha.
This study comprised 78 gynecological and IVF patients, all of whom were aged >25 years, encompassing both infertile and fertile women. The infertile women in this study experienced at least two IVF failures and were aged <40 years.
Women experiencing chromosomal abnormalities, genetic abnormalities, uterine abnormalities, hematological or immunological disorders, Diabetes, Hypertension, Cancer and Also embryos that arise from maternal and paternal abnormalities will be excluded.
The main objective of this study was to compare 39 healthy controls and 39 infertile participants.
This study aimed to evaluate the levels of CK (MB), HDL, LDL, and hs-CRP in fertile and infertile individuals. Additionally, we investigated the cardiovascular risks faced by both pregnant and infertile women. It is expected that infertile women will have a much greater number of these. In addition, infertile women have decreased HDL levels.
This cross-sectional study was conducted in cooperation with Acharya Vinoba Bhave Rural Hospital (AVBRH), Sawangi Wardha, at Jawaharlal Nehru Medical College (JNMC), Sawangi Wardha, in the Central Laboratory Division of the Department of Biochemistry, from 2022 to 2025. 39 women in all will be registered as cases and 39 women in good health will be enrolled as controls. Only women between the ages of 25 and 40 years were included in this research. All ethical procedures will be followed before and throughout the trial, and written consent will be obtained at the time of sample collection. Women with chromosomal abnormalities, genetic abnormalities, uterine abnormalities, hematological or immunological disorders, Diabetes, Hypertension, and Cancer as well as embryos that arise from such maternal and paternal abnormalities will be excluded from the study.
The antecubital location on the right arm was chosen primarily for blood sample collection. A tourniquet, cotton, syringe, and rubbing alcohol were used to puncture the area. About three to four inches above the venipuncture site, a tourniquet was applied. Next, the region was cleaned with cotton and alcohol and a needle was inserted. Samples were collected in a simple vial (up to 5 mL) in accordance with the specifications. The tourniquet was removed and cotton was applied to stop bleeding after the sample had been collected. The patient’s name and the name of the test were then written in the vial. The material will be sent to the biochemistry processing lab once it has been labelled. To prepare the sample in the laboratory, the serum was first separated using a REMI R-8C Plus centrifuge set to 3000 rpm for five–seven minutes. The levels of Creatine Kinase (CK-MB), LDL, HDL, UA, and hs-CRP were measured using a Vitros 5600 dry chemistry analyzer manufactured by Ortho Clinical Diagnostics.
For statistical analysis, SPSS software for windows version 27.0 will be used.
Statically significance will be defined at p<0.001.
Random sampling was used to take all the required steps to control bias at all levels.
Sample size: 78 Patients
Zα/2 is the level of significance at 5% i.e., 95% confidence interval = 1.96.
Z1−α/2 = 1.96 at 5% level of significance
P = % infertility related to cardiovascular diseases in women = 28%
Study reference: Ref. 26.
A total of 78 participants will be needed in the study, of which 39 will be women and 39 will be healthy controls.
To determine the relative differences between and across groups, the data will be analyzed using the appropriate chi-square test, and a certified statistician will use the proper statistical approach to analyze the research results. All responses were calculated using the software version 4.3. Outcome variables (creatine kinase (CK-MB) [IU/L], HDL [mg/dL], LDL [mg/dL], hs-CRP [mg/dL], and UA [mg/dL]) were first tested for normality for the quantitative measurement of the mean and standard deviation (SD). Positional average (median) statistics will be used to search for skewed distributions and calculate the interquartile range (IQR). For the qualitative evaluation, every binary and categorical variable was explained in terms of frequency and percentages. R software (R: The R Project for Statistical Computing (r-project.org)), version 4.3.2, free of cost, was used to compute the results of all statistical studies.
At the 5% level of significance (p < 0.05), The inferential statistics for assessing the significant difference in the outcome variables will be assessed. The data for the outcome variable will be transformed into a normal distribution using a mathematical technique if it displays a non-normal distribution for quantitative assessment.
If data persists with a non-normal distribution, we will use alternative non-parametric tests (Chi-square, Mann-Whitney U, and Wilcoxon tests). Outcome variables (creatinine kinase (CK-MB) [IU/L], HDL [mg/dL], LDL [mg/dL], hs-CRP [mg/dL], and UA [mg/dL]) were subjected to a t-test (independent) to determine the significance of the mean.
The primary aim of this study was to compare 39 healthy controls with 39 infertile individuals.
This study aimed to assess CK (MB), HDL, LDL, and hs-CRP levels in both fertile and infertile participants. To explore the cardiovascular risk associated with both infertile and fertile women. These levels are expected to be significantly higher in infertile women. HDL levels were lower in infertile women.
This study is the cross sectional study, the main purpose of this study is to compare 39 healthy control with 39 infertile individuals.
This study aimed to assess CK (MB), HDL, LDL, and hs-CRP levels in both fertile and infertile participants. To explore the cardiovascular risk associated with both infertile and fertile women. at the analytical level we found that Female infertility, which can be caused by conditions including PCOD, obesity, thyroid problems, and endometriosis, is likely to increase the risk of cardiovascular disease (CVD), according to a growing body of studies. This study aimed to ascertain whether a link exists between cardiovascular disease (CVD) and infertility. These data support an association between certain reproductive variables that pose a higher risk of cardiovascular disease. Sun et al., did a study concluded that women with diminished ovarian reserves have elevated triglyceride and LDL levels and decreased HDL levels. They also exhibit elevated levels of HOMA-IR, an indicator of insulin resistance, and hs-CRP, a measure of inflammation. Because of the small effect size, it is challenging to ascertain whether infertility is linked to a minor increase in CVD risk markers for all infertile women. BMI and waist circumference were the most strongly correlated CVD risk factors that among the women who reported a history of infertility. Previous studies on endometriosis patients have shown that serum lipoprotein and triglycerides are higher, but blood HDL and LDL levels are equivalent to those of controls of similar ages.27 Wenyi Xu et al., did a study to concluded that a concise summary of the association between uric acid and female reproductive diseases as new information is added, our understanding of uric acid’s function in the reproductive system is expanding. Reproductive hormones also affect serum UA levels. Although there is considerable disagreement on the issue of specific hormones and UA levels, the prevailing view is that high testosterone levels are strongly associated with elevated serum UA levels and hyperuricemia. High UA levels and hyperuricaemia are common in PCOS patients and are usually accompanied by hyperandrogenaemia.28–30 Eugster and Vingerhoets et al. categorized infertile women and couples using qualitative studies. For example, achieving pregnancy does not necessarily restore normalcy in the lives of infertile individuals. A literature review reported that pregnancy for people undergoing IVF is more stressful than for people without fertility problems but found no evidence of lower self-esteem for those who became pregnant via IVF.31,32 Amanuel Abajobi, et al., in report in review literature conducted a study from 1990 to 2015 on cardiovascular diseases, involving 422 million cases. Of these, 17 million cases resulted in cardiovascular death. This finding indicates that cardiovascular disease is a major global cause of death, underscoring its significance in global disease burden studies.33 Earl S. et al., investigated the risk of future health problems related to female infertility. They compared the impact of sterility on the future health trajectory of fertile individuals with that of those who experienced early death. Researchers found that reproductive status could significantly affect health outcomes at different life stages, suggesting potential opportunities for risk management and surveillance.34,35 From this, we learned that there was no correlation between cardiovascular illness and infertility in women in their middle years. However, after reaching middle age, there is potential for infertility, and it is likely that women may develop cardiovascular diseases after menopause. Because this research is ongoing, we cannot draw any conclusions.
Based on the observations, outcomes, and interpretation of the findings of the study, a conclusion will be made.
This study was approved by the Institutional Ethics Committee of Datta Meghe Institute of Higher Education and Research (DU) has granted its approval to the study protocol DMIHER (DU)/IEC/2023/1105 Date: 01/07/2023.
Figshare: STROBE checklist for ASSOCIATION BETWEEN INFERTILITY AND RISK OF CARDIOVASCULAR DISEASES IN YOUNG WOMEN.
This project contains the following extended data:
https://doi.org/10.6084/m9.figshare.24947499.v1
Data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).
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