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.
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Parallel
Letrozole 2.5mg
DrugParticipants will receive 2.5mg letrozole tablets orally daily for 5 days starting on day 3 of menstrual cycle. The 2.5mg dose will be maintained for at least the first 3 cycles. If no ovulation after 3 cycles, dose cautiously increased up to 7.5mg maximum. Once minimum ovulation dose determined, it will be continued for up to 6 cycles total or until pregnancy occurs. Compliance monitored by pill counts and diary. Ovulation assessed by follicular monitoring and progesterone levels. Routine antenatal care if pregnant. Adverse effects monitored and managed per guidelines. Participants followed for multiple pregnancies. Maximum treatment duration is 6 ovulatory cycles or 6 months. Tablets taken at same time each day.
Levothyroxine 25 Mcg (0.025 Mg) Oral Tablet
DrugParticipants will take letrozole at same doses as letrozole only group. Also receive levothyroxine starting at 25mcg orally once daily, titrated by 25mcg every 4 weeks to reach normal TSH, maximum 100mcg daily. Once appropriate dose determined to normalize TSH, it is maintained throughout treatment period. Compliance monitored by pill counts, TSH levels, and diary. Treatment continues for up to 6 ovulatory cycles or until pregnancy, whichever is first, maximum 6 months. Ovulation assessed by monitoring and progesterone. Routine antenatal care if pregnant. Adverse effects monitored and managed per guidelines. Participants followed for multiple pregnancies. Letrozole and levothyroxine taken daily at same time. All other procedures same as letrozole only group.
Pregnancy rate
Biochemical evidence of pregnancy by positive urine or serum β-hCG test.
Live birth rate
The number of deliveries that resulted in a live born baby, documented by hospital delivery records.
Ovulation rate
Evidence of ovulation by ultrasound monitoring of dominant follicle development and serum progesterone level \> 3 ng/mL in mid-luteal phase.
Miscarriage rate
Loss of clinical pregnancy before 20 weeks gestation, confirmed by ultrasound or histopathology.
Menstrual regularity
Normal ovulatory menstrual cycles defined as cycle length 21-35 days.
Side effects
Participant reports of adverse effects of letrozole or levothyroxine, graded per standard criteria.
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Muhamed Ahmed Abdelmoaty Muhamed Alhagrasy
Lead sponsor
Al-Azhar University
Sponsor institution
