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Does Cardiometabolic Health Determine IVF Treatment Outcomes?
Infertility is a global health concern that affects approximately 50 million people worldwide or those with the inability to start an integrated family . It has been defined as the failure to conceive (as in pregnancy) after continuous non-contraceptive intercourse for twelve months or longer and subjected to several implications in terms of culturally, socially and also economically . The prevalence rate varied across geographic factors , wherein the UK has been estimated at 12-14% while developing countries including Asia reported to 3.5-16%. In western-Africa however, the incidence of infertility is quite high at 50% , . As with the difference of incidence in the geographic regions, the causes of infertility too vary in accordance. In Western countries such as the UK or US, the main cause of infertility is increased age while in Africa the main cause has been attributed to the high prevalence of sexually transmitted diseases . These rates of increased prevalence have thus increased the need for assisted reproductive techniques (ART) such as In-vitro Fertilisation (IVF) .
Another very important causative factor for infertility that has been warranting IVF is the presence of obesity in women of the childbearing age . In the UK figures demonstrate that 29% of the women aged 16-44 years of age are overweight with BMI of >25kg/m2 but <30kg/m2, while 19% were obese, i.e., >30kg/m2 . Contrastingly in the US more than two-thirds of women of reproductive age have been found to be obese . Obesity is not only a leading cause of infertility but has also been found to have implications for the outcomes of IVF . The main implicating factors of obesity include the development Polycystic Ovaries (PCOS), along with anovulatory fertility and ovulatory subfertility –. Beside this, obesity has also been known to have negative impacts on the oocyte quality and early embryo growth ,  and is strongly related to premature birth and the birth of a macrosomic neonate .
One of the major repercussions of obesity remains cardiometabolic risk (CMR) and subsequently metabolic syndrome (MS). In view of this there exists a strong association between MS and the development of insulin resistance (IR) (akin to diabetes) and coronary artery disease (CAD)  which defines the concept of CMR. Apart from this, obese women also suffer from other factors of CMR such as hypertension, altered lipid profiles (elevated LDL, dyslipidaemia) and inflammation , , . However, it is not clear how far cardiometabolic health has been associated with IVF success. Chang et al.  have demonstrated the association of IR to assisted reproduction outcomes. The study findings revealed that while hyperinsulinemia and IR do not cause changes in oocyte and embryo development, rather it bears a negative association with the endometrial function and the implantation process. Similarly, the study by Salzer  postulated that the mechanism of IR in obese pregnant women is strongly associated with the development of hypertension due to the excess weight which leads to an increase in the sympathetic activity.
Hypertension has in turn been demonstrated to cause defects in placentation and therefore, it is hypothesised that it does play an important role in IVF outcomes . On the other hand, dyslipidaemia and altered lipid profiles, are known to alter the development of oocytes, in terms of the size, number and the quality. Evidence suggests that among obese pregnant women with dyslipidaemia have smaller oocytes than those who do not but these findings are based on few studies . However, the more substantial evidence is required to associate dyslipidaemia and the outcomes of IVF.
The other factors associated with obesity, pregnancy and IVF outcomes are the intake of gonadotropins to increase follicle stimulation. Studies showed that this, in turn, leads to the reduction of Estradiol (E2) levels which is suggestive that obesity does play a role in the impaired metabolism of gonadotropins too , . Thus, it can be stated that although obesity is a causative factor for negative outcomes of IVF, it is still a reversible process . However, approaching obesity in terms of a reduced BMI and weight loss is a long drawn process and one that may or may not be successful. Therefore, it is imperative to look into whether treating the various CMR factors can improve the outcomes of IVF.
In line with this, the study by Jinno at al  demonstrated that metformin can be used to adequately correct IR, thereby improve the outcome of IVF. Similarly, Tso et al.  also showed similar findings where the author demonstrated that metformin can decrease IR and also reduce the risk of Ovarian Hyperstimulation Syndrome (OHSS). On thecontrary , other studies (for example , ) consider myoinositol as a viable alternative to adjuvant therapy for reduction of IR. Rosiglitazone has been suggested to not only reduce the effects of lipotoxicity caused by dyslipidaemia in obese pregnant women, but also enhances the quality of the oocyte, embryo, and other ovarian functions , .
Despite the above positive findings, it is important to note, that British Fertility Society (BFS) does not still recommend the use of adjuvants in IVF due to lack of substantial evidence. The guidelines however further state that metformin may be considered as an adjuvant (although not expressly recommended) . Further, it is noted that especially for dyslipidaemia statins are still not recommended, even though they have demonstrated to have no teratogenic effects in pregnancy –. Although CMR factors do have an association with the outcome of IVF and that the correction of these factors may enable for better IVF outcomes but it is still inconclusive due to lack of substantial evidence. Therefore, the area of providing adjuvants in the form of pharmacological therapy during the IVF treatment procedure needs to be explored further.
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