The goal of this randomized controlled trial is to compare letrozole alone versus letrozole plus levothyroxine for ovulation induction in infertile women with both PCOS and subclinical hypothyroidism. The main questions it aims to answer are:

Is letrozole plus levothyroxine superior to letrozole alone in achieving ovulation in these patients? Does combining levothyroxine with letrozole lead to higher pregnancy and live birth rates compared to letrozole alone?

Participants will be randomized into two groups:

Group 1 will receive letrozole only, starting at 2.5 mg daily from day 3 to 7 of the menstrual cycle. The dose will be increased up to 7.5 mg if no ovulation occurs, for a maximum treatment period of 6 months or until pregnancy is achieved.

Group 2 will receive letrozole at the same doses as group 1 plus 25 mcg levothyroxine daily.

Inclusion Criteria:

Age between 20-40 years

BMI between 18-35 kg/m2

Meet diagnostic criteria for PCOS based on the Rotterdam consensus criteria and ESHRE/ASRM modifications (2018):

Oligo- and/or anovulation Clinical and/or biochemical signs of hyperandrogenism Polycystic ovaries on ultrasound

Subclinical hypothyroidism defined as TSH level between 5-10 mIU/L with normal free T4

Infertility duration ≥ 1 year

Intact ovaries and uterus, confirmed by physical exam and imaging

Normal semen analysis in male partner

No tubal or peritoneal factor contributing to infertility

Effective contraception if not attempting conception

Willing and able to provide informed consent

Exclusion Criteria:

Known thyroid disease or on thyroid medications

Abnormal thyroid function tests other than subclinical hypothyroidism

Hyperprolactinemia

Presence of other causes of infertility such as:

Moderate to severe male factor infertility Bilateral tubal occlusion or peritoneal factors Stage III-IV endometriosis Ovarian failure or insufficiency (high FSH or low AMH)

Previous diagnosis of any type of congenital adrenal hyperplasia

Uncontrolled diabetes (HbA1C >8%)

History of deep vein thrombosis or thromboembolic events

Any contraindication to letrozole or levothyroxine

Previous use of letrozole or levothyroxine in past 6 months

Current or suspected pregnancy

Breastfeeding

Inability to comply with treatment and follow-up procedures

This study will only enroll female participants. Patients must be of reproductive age with intact uteri and ovaries to meet the inclusion criteria.

The study aims to induce ovulation for conception in infertile women with PCOS and subclinical hypothyroidism. As such, only individuals biologically born as females and currently identifying as women will be eligible.

All enrolled participants must have functioning ovaries and intact reproductive organs capable of sustaining a pregnancy. Patients who have undergone surgical sterilization procedures like tubal ligation or hysterectomy will be excluded.

Confirmation of female gender will be through medical history, physical examination, and review of medical records if needed. Pregnancy tests will be done at screening and before each treatment cycle.

The reproductive status, ovaries and uterus will be assessed by medical history, physical examination and imaging like ultrasound when indicated.

To protect participant confidentiality, individual-level data from this study will not be made publicly available. However, de-identified aggregated data and results can be shared with other researchers upon request after publication. Any data provided will be limited, non-identifiable, and subject to a data use agreement to ensure participant privacy. Only select excerpts needed to validate findings will be shared under approved research objectives. The investigators reserve the right to reject requests that may compromise anonymity. We aim to promote transparency through controlled data access rather than public availability of the full dataset due to re-identification risks for participants.