The most prevalent cause of infertility with anovulatory cycles is polycystic ovarian syndrome (PCOS), which affects 15-20% of infertile women. Stein and Leventhal published the first description of this illness in 1931. It is a condition marked by insulin resistance, oligomenorrhea, increased androgen release from the ovaries, anovulation/oligo- anovulation and various clinical symptoms such hirsutism, acne and oligomenorrhoea [1,2].
Genetic and environmental variables are thought to have a role in the complex aetiology of PCOS, which has not yet been fully understood. It is believed that issues with insulin receptors and post-receptor elements of the insulin signalling pathway are the cause of the resistance to insulin. Approximately 80% of PCOS patients with central obesity and 30% to 40% of PCOS patients who are slim experience hyperinsulinemia as a result of insulin resistance. Higher free androgen concentration, increased free androgen response to LH and increased levels of IGF-I in the bloodstream all contribute to hyperandrogenism caused by hyperinsulinemia. In anovulatory infertile PCOS, insulin-sensitizing medications have been explored alongside oral ovulation induction medications since hyperinsulinemia frequently contributes to the pathophysiology of the condition [1,3].
Among insulin sensitizers, metformin and Myo-inositol have been studied most extensively. The mechanism of action of the two is different [1].
Biguanides like metformin are frequently recommended to treat type II diabetes. Metformin works by lowering insulin-induced fatty acid oxidation, increasing insulin sensitivity and reducing hepatic gluconeogenesis. Metformin has demonstrated promise in the treatment of PCOS as an insulin sensitizer. More recent research has demonstrated that the symptoms of acne, hirsutism, menstrual irregularities, anovulatory infertility, androgen profile, BMI and incidence of diabetes can be addressed by treating IR with metformin, despite early ambiguous results. One of the drawbacks of using metformin for PCOS patients is that its effectiveness can rely on the precise phenotypic manifestation of the condition and scientists are yet unable to determine who will benefit the most. Additionally, metformin has a well-established side effect profile that includes gastrointestinal complaints (nausea, diarrhoea, abdominal pain), vitamin B12 deficiency and lactic acidosis, all of which may prevent some women from tolerating the medication.
However, it is the first insulin- sensitizing drug to be used in PCOS women to investigate the role of insulin resistance in the pathogenesis of the syndrome and there is evidence that it may have metabolic, endocrine and reproductive benefits [2-4].
It has also been demonstrated that myo-inositol, an isomerized and dephosphorylated precursor of glucose-6- phosphate, can increase insulin sensitivity. Researchers have looked at the hypothesis that the development of IR in PCOS may be influenced by an intracellular shortage of D-chiro-inositol (DCI), a myo-inositol metabolite found in muscle, fat and theca cells. Inositol phosphoglycan (IPG), a substance that promotes insulin action, is created by DCI. It has been demonstrated that women with PCOS and IR have higher urine DCI clearance along with impaired DCI-IPG release in response to insulin. Therefore, supplementation with myo-inositol and/or DCI may address a number of variables that contribute to the development of IR in PCOS patients, improving treatment results. Myo-inositol functions as the second messenger of the insulin signal and lowers hyperinsulinemia, improves ovarian function, lowers the LH/FSH ratio and lowers serum androgens through the membrane-associated sodium-dependent inositol co-transporter GLUT4. A study on PCOS demonstrates improved ovulation, decreased hyperandrogenaemia and restored fertility following Myo-inositol therapy. It improves follicle and oocyte development as well as the quality of the oocytes and embryos. Numerous studies support the idea that myoinositol is a safe and effective choice for treating PCOS patients because there are no negative effects in the recommended concentrations. On the other hand, people with PCOS who are more easily compliant have better outcomes when it comes to managing their metabolic parameters, hyperandrogenism and ovulation [2-4].
The emphasis on myo-inositol is relatively new, compared to metformin, which is the traditional and most often used drug to treat PCOS. The two insulin sensitizers have different modes of action; thus, they may function synergistically when combined to enhance metabolic and reproductive outcomes in PCOS women who are having trouble getting pregnant [1,4].
In the study done by Pramod et al. [1], better results in terms of clinical fertility rates were observed in the group that was given a combination of myoinositol with metformin as compared the group who was given only Myoinositol.
In a study conducted by Chirania et al. [4] in PCOS patients with menstrual irregularities achieved regular menses on their own and most patients with infertility issues conceived.
Another study by Rani et al. [5] also reported that the ovulation rate was significantly higher in metformin plus myo- inositol group and the pregnancy rate was higher in metformin plus myo-inositol group.
So, we can say that a combination of insulin sensitizers, such as metformin and myoinositol, is advised to treat the metabolic and endocrine anomalies of insulin-resistant PCOS, which promote ovarian folliculogenesis, enhance ovulation and lessen the long-term health risk of PCOS. Insulin sensitizers enhance ovulatory and hyperandrogenaemia processes [3,5].
In a study conducted by Thakur [6], they found a significant improvement in parameters like irregular menstruation, skin changes, rate of conception, LH/FSH ratio, sensitivity to insulin and HOMA-IR after six months of treatment in cases that were given a combination of metformin and myoinositol than myoinositol and metformin individually.
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