Best Treatment for Women With Both (Polycystic Ovary Syndrome) PCOS and Subclinical Hypothyroidism
Letrozole Alone vs. Letrozole Plus Levothyroxine for Ovulation Induction in Infertile Women With Both (Polycystic Ovary Syndrome) PCOS and Sub-clinical Hypothyroidism.
Muhamed Ahmed Abdelmoaty Muhamed Alhagrasy
200 participants
May 6, 2021
INTERVENTIONAL
Conditions
Summary
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.
Eligibility
Inclusion Criteria11
- 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 Criteria13
- 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
Interventions
Participants 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.
Participants 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.
Locations(1)
View Full Details on ClinicalTrials.gov
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NCT06041204