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

Sponsor

Muhamed Ahmed Abdelmoaty Muhamed Alhagrasy (Other)

Overall Status

Recruiting

CT.gov ID

NCT06041204

Collaborator

(none)

500

Enrollment

Location

Arms

30.8

Anticipated Duration (Months)

16.2

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
PCOS (Polycystic Ovary Syndrome) of Bilateral Ovaries Subclinical Hypothyroidism Female Infertility	Drug: Letrozole 2.5mg Drug: Levothyroxine 25 Mcg (0.025 Mg) Oral Tablet	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

500 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Participant)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

May 6, 2021

Anticipated Primary Completion Date :

Oct 1, 2023

Anticipated Study Completion Date :

Nov 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 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.	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.
Experimental: 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.	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. Drug: 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. Other Names: levothyroxine 25

Arm

Intervention/Treatment

Active Comparator: 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.

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.

Experimental: 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.

Drug: Letrozole 2.5mg

Drug: 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.

Other Names:

levothyroxine 25

Outcome Measures

Primary Outcome Measures

Pregnancy rate [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 [Through study completion average 1 year.]
The number of deliveries that resulted in a live born baby, documented by hospital delivery records.

Secondary Outcome Measures

Ovulation rate [Assessed at the end of each cycle. the cycles are 6. Each cycle is 28 days.]
Evidence of ovulation by ultrasound monitoring of dominant follicle development and serum progesterone level > 3 ng/mL in mid-luteal phase.
Miscarriage rate [Through study completion average 1 year.]
Loss of clinical pregnancy before 20 weeks gestation, confirmed by ultrasound or histopathology.
Menstrual regularity [Through study completion average 1 year.]
Normal ovulatory menstrual cycles defined as cycle length 21-35 days.
Side effects [Through study completion average 1 year.]
Participant reports of adverse effects of letrozole or levothyroxine, graded per standard criteria.

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 40 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Al-Hussein University Hospital	Cairo		Egypt	11633

Sponsors and Collaborators

Muhamed Ahmed Abdelmoaty Muhamed Alhagrasy

Investigators

Principal Investigator: Muhamed Alhagrasy, M.D., Al-Azhar University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Muhamed Ahmed Abdelmoaty Muhamed Alhagrasy, lecturer and consultant at Obstetrics and Gynecology Department., Al-Azhar University

ClinicalTrials.gov Identifier:

NCT06041204

Other Study ID Numbers:

Gyne2021

First Posted:

Sep 18, 2023

Last Update Posted:

Sep 18, 2023

Last Verified:

Sep 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Muhamed Ahmed Abdelmoaty Muhamed Alhagrasy, lecturer and consultant at Obstetrics and Gynecology Department., Al-Azhar University

Letrozole

Levothyroxine

PCOS

Subclinical hypothyroidism

Additional relevant MeSH terms:

Polycystic Ovary Syndrome

Study Results

No Results Posted as of Sep 18, 2023