Sodium-Glucose Co-Transporter-2 Inhibitors as Adjuvant Therapy With Letrozole in Induction of Ovulation

Inclusion Criteria: Pre-menopausal women aged 20-40 with primary or secondary infertility and PCOS which render them unable to become pregnant. Diagnosis of PCOS will based on European Society of Human Reproduction and Embryology/American Society for Reproductive Medicine (ESHRE/ASRM) criteria, the diagnosis is made when at least two of the following criteria are met: oilgo and/or anovulation (infrequent or no ovulation), clinical and/or biochemical signs of hyperandrogenism including hirsutism, acne and/or increased testosterone levels or polycystic ovaries on ultrasound (defined as those containing at least 12 follicles measuring 2-9 mm in diameter arranged peripherally around an echo-dense stroma and/or with increased ovarian volume of at least 10 ml). Exclusion Criteria: Other causes of hyperandrogenism mimic PCOS such as congenital adrenal hyperplasia, Cushing's syndrome, or androgen secreting tumors are excluded. Persistent hyperprolactinemia, thyroid dysfunction defined as TSH \< 0.2 mIU/ML or \>5.5 mIU/mL) or patients with menopausal levels of FSH (\> 15 mIU/mL) (A normal level within the last year is adequate for enter the study). Liver disease is defined as AST or ALT \> 2 times normal or total bilirubin \>2.5 mg/dL, kidney disease defined as BUN \> 30 mg/dL or serum creatinine\> 1.4 mg/dL or significant anemia defined as Hemoglobin \< 10 mg/dL. Women with Type I or II diabetes mellitus who are poorly controlled (defined as a HA1c level \> 7.0%). Untreated poorly controlled hypertension is defined as a systolic blood pressure ≥ 160 mm Hg or a diastolic ≥ 100 mm Hg obtained on two measures obtained at least 60 minutes apart. History of deep venous thrombosis, pulmonary embolus, or cerebrovascular accident. Women who have undergone a bariatric surgery procedure in the recent past (\<12 months) and are in a period of acute weight loss or have been advised against pregnancy by their bariatric surgeon. Presence of any urinary symptom such as frequency, urgency, or bloody micturition. In case of metabolic acidosis, osteoporosis, endometrial hyperplasia, or endometrial neoplasia. Women who had gonadotropin induction, ovarian drilling before or women with hypergonadotropic hypogonadism or functional ovarian cysts (\> 5cm). Criteria of IVF/ICSI as poor Response, no Eggs or ectopic pregnancy. Women who receive antidiabetic medications such as insulin, thiazolidinediones, acarbose, or sulfonylureas are likely to confound the effects of study medication or who are currently receiving metformin XR for a diagnosis of Type I or Type II diabetes or for PCOS are also specifically excluded. Concomitant use of medication that could interfere with the absorption, metabolism, and excretion of drugs involved in the study as the use of Furosemide, cimetidine increase metformin concentration and nifedipine enhances the absorption of metformin.