Best Treatment for Women With Both (Polycystic Ovary Syndrome) PCOS and Subclinical Hypothyroidism

Female Infertility Clinical Trial

Official title:

Letrozole Alone vs. Letrozole Plus Levothyroxine for Ovulation Induction in Infertile Women With Both (Polycystic Ovary Syndrome) PCOS and Sub-clinical Hypothyroidism.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06041204
• Other study ID #: Gyne2021
• Status: Recruiting
• Phase: N/A
• Start date: May 6, 2021
• Est. completion date: May 28, 2025

Study information

• Verified date: June 2024
• Source: Al-Azhar University
• Contact: Muhamed Alhagrasy, M.D.
• Phone: 01017313413
• Email: MuhamedAhmed.216[@]azhar.edu.eg
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: May 28, 2025
• Est. primary completion date: April 30, 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 20 Years to 40 Years

Eligibility

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

Related Conditions & MeSH terms

• Female Infertility
• Hypothyroidism
• Infertility
• Infertility, Female
• Polycystic Ovary Syndrome
• Subclinical Hypothyroidism
• Syndrome

Intervention

Drug:
• Letrozole 2.5mg
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.
• Levothyroxine 25 Mcg (0.025 Mg) Oral Tablet
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

Country	Name	City	State
Egypt	Al-Hussein University Hospital	Cairo

Sponsors (1)

Lead Sponsor	Collaborator
Muhamed Ahmed Abdelmoaty Muhamed Alhagrasy

Country where clinical trial is conducted

Egypt, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pregnancy rate	Biochemical evidence of pregnancy by positive urine or serum ß-hCG test.	Assessed at the end of each cycle. the cycles are 6. Each cycle is 28 days.
Primary	Live birth rate	The number of deliveries that resulted in a live born baby, documented by hospital delivery records.	Through study completion average 1 year.
Secondary	Ovulation rate	Evidence of ovulation by ultrasound monitoring of dominant follicle development and serum progesterone level > 3 ng/mL in mid-luteal phase.	Assessed at the end of each cycle. the cycles are 6. Each cycle is 28 days.
Secondary	Miscarriage rate	Loss of clinical pregnancy before 20 weeks gestation, confirmed by ultrasound or histopathology.	Through study completion average 1 year.
Secondary	Menstrual regularity	Normal ovulatory menstrual cycles defined as cycle length 21-35 days.	Through study completion average 1 year.
Secondary	Side effects	Participant reports of adverse effects of letrozole or levothyroxine, graded per standard criteria.	Through study completion average 1 year.