Randomized Controlled Trial of Combined Letrozole and Clomid (CLC II) Versus Letrozole Alone for Women With Anovulation

Prior treatment

• Current use of hormonal contraception; use of any type of combined contraceptive or oral progestins within the past month; or use of hormonal implants or depo progestins within the past 3 months
• Use of medications known to affect reproductive function or metabolism or that are an absolute contraindication during pregnancy within the past month
• If patients are suspected based on clinical findings for other etiologies that mimic PCOS, work up must be completed to exclude other etiologies prior to enrollment (i.e. Cushing's syndrome, androgen-secreting tumor)

Other illness

• Uncorrected thyroid disease
• Medical conditions in which avoiding pregnancy is recommended until under improved control: poorly controlled Type 1 or Type 2 diabetes, poorly controlled hypertension
• Contraindications to clomiphene citrate: hypersensitivity to clomiphene citrate or any of its components, history of liver disease or known liver disease, unknown cause of abnormal uterine bleeding, or intracranial lesion
• Contraindications to letrozole: hypersensitivity to letrozole or any of its components

Other

• Current pregnancy
• Other known cause of infertility: endometriosis, tubal factor, uterine abnormalities
• Untreated hyperprolactinemia

• Willing to comply with all study procedures and be available for the duration of the study
• Diagnosis of infertility: Inability of couple to achieve successful pregnancy after 12 months of regular time unprotected intercourse in women less than 35 years of age; and after 6 months of regular intercourse without use of contraception in women 35 years and older. Women that have anovulation or oligomenorrhea are also considered to meet diagnosis of infertility, without meeting the time constraints described above.
• Diagnosis of polycystic ovary syndrome based on Revised Rotterdam criteria.
• Ability to have regular intercourse during the ovulation induction phase of the study.
• Partner with a normal sperm concentration of 15 million/mL and with normal motility of \>40% according to World Health Organization cutoff points or greater than 10 million total motile sperm count OR has fathered a pregnancy in the past.