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.

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 tha t 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.

Written consent will be obtained at the time of sample collection.