Letrozole Alone vs. Letrozole Plus Levothyroxine for Ovulation Induction in Infertile Women With Both (Polycystic Ovary Syndrome) PCOS and Sub-clinical Hypothyroidism.
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- Pregnancy rate
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 20 Years 至 40 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Letrozole Group
Participants randomized to letrozole group will take 5mg tablets orally daily for 5 days starting on day 3 of cycle. Dose can be adjusted up to 7.5mg based on ovulation response, maintained for subsequent cycles. Treatment continues for up to 6 ovulatory cycles or until pregnancy occurs. Ovulation assessed by follicular monitoring and progesterone. Compliance monitored by pill counts and diary. Routine antenatal care if pregnant. Adverse effects monitored per guidelines. Participants followed for multiple pregnancies. Tablets taken at same time each day. Maximum treatment period is 6 months.
干预措施: Letrozole 2.5mg (Drug)
Letrozole plus levothyroxine
Participants randomized to this group will take letrozole tablets at same dose and schedule as letrozole only group. In addition, they will take levothyroxine tablets orally once daily. Levothyroxine dose will start at 25mcg and be titrated based on TSH level, with a target TSH in the normal range. Participants will take levothyroxine at approximately same time each day. Letrozole dosing and schedule as described for other group. Treatment continues for up to 6 ovulatory cycles or until pregnancy occurs. Ovulation assessed by follicular monitoring and progesterone. Compliance monitored by pill counts, TSH levels and diary. Routine antenatal care if pregnant. Adverse effects monitored per guidelines. Participants followed for multiple pregnancies. Maximum treatment period is 6 months.
干预措施: Letrozole 2.5mg (Drug)
Letrozole plus levothyroxine
Participants randomized to this group will take letrozole tablets at same dose and schedule as letrozole only group. In addition, they will take levothyroxine tablets orally once daily. Levothyroxine dose will start at 25mcg and be titrated based on TSH level, with a target TSH in the normal range. Participants will take levothyroxine at approximately same time each day. Letrozole dosing and schedule as described for other group. Treatment continues for up to 6 ovulatory cycles or until pregnancy occurs. Ovulation assessed by follicular monitoring and progesterone. Compliance monitored by pill counts, TSH levels and diary. Routine antenatal care if pregnant. Adverse effects monitored per guidelines. Participants followed for multiple pregnancies. Maximum treatment period is 6 months.
干预措施: Levothyroxine 25 Mcg (0.025 Mg) Oral Tablet (Drug)
结局指标
主要结局
Pregnancy rate
时间窗: Assessed at the end of each cycle. the cycles are 6. Each cycle is 28 days.
Biochemical evidence of pregnancy by positive urine or serum β-hCG test.
Live birth rate
时间窗: Through study completion average 1 year.
The number of deliveries that resulted in a live born baby, documented by hospital delivery records.
次要结局
- Ovulation rate(Assessed at the end of each cycle. the cycles are 6. Each cycle is 28 days.)
- Miscarriage rate(Through study completion average 1 year.)
- Menstrual regularity(Through study completion average 1 year.)
- Side effects(Through study completion average 1 year.)
研究者
Muhamed Ahmed Abdelmoaty Muhamed Alhagrasy
lecturer and consultant at Obstetrics and Gynecology Department.
Al-Azhar University