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

Primary Purpose

PCOS (Polycystic Ovary Syndrome) of Bilateral Ovaries, Subclinical Hypothyroidism, Female Infertility

Status
Recruiting
Phase
Not Applicable
Locations
Egypt
Study Type
Interventional
Intervention
Letrozole 2.5mg
Levothyroxine 25 Mcg (0.025 Mg) Oral Tablet
Sponsored by
Muhamed Ahmed Abdelmoaty Muhamed Alhagrasy
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for PCOS (Polycystic Ovary Syndrome) of Bilateral Ovaries focused on measuring Letrozole, Levothyroxine, PCOS, Subclinical hypothyroidism

Eligibility Criteria

20 Years - 40 Years (Adult)FemaleDoes not accept 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

Sites / Locations

  • Al-Hussein University HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Letrozole Group

Letrozole plus levothyroxine

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Full Information

First Posted
September 5, 2023
Last Updated
September 11, 2023
Sponsor
Muhamed Ahmed Abdelmoaty Muhamed Alhagrasy
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1. Study Identification

Unique Protocol Identification Number
NCT06041204
Brief Title
Best Treatment for Women With Both (Polycystic Ovary Syndrome) PCOS and Subclinical Hypothyroidism
Official Title
Letrozole Alone vs. Letrozole Plus Levothyroxine for Ovulation Induction in Infertile Women With Both (Polycystic Ovary Syndrome) PCOS and Sub-clinical Hypothyroidism.
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 6, 2021 (Actual)
Primary Completion Date
October 1, 2023 (Anticipated)
Study Completion Date
November 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Muhamed Ahmed Abdelmoaty Muhamed Alhagrasy

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
PCOS (Polycystic Ovary Syndrome) of Bilateral Ovaries, Subclinical Hypothyroidism, Female Infertility
Keywords
Letrozole, Levothyroxine, PCOS, Subclinical hypothyroidism

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
500 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Letrozole Group
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Letrozole plus levothyroxine
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Letrozole 2.5mg
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Levothyroxine 25 Mcg (0.025 Mg) Oral Tablet
Other Intervention Name(s)
levothyroxine 25
Intervention Description
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.
Primary Outcome Measure Information:
Title
Pregnancy rate
Description
Biochemical evidence of pregnancy by positive urine or serum β-hCG test.
Time Frame
Assessed at the end of each cycle. the cycles are 6. Each cycle is 28 days.
Title
Live birth rate
Description
The number of deliveries that resulted in a live born baby, documented by hospital delivery records.
Time Frame
Through study completion average 1 year.
Secondary Outcome Measure Information:
Title
Ovulation rate
Description
Evidence of ovulation by ultrasound monitoring of dominant follicle development and serum progesterone level > 3 ng/mL in mid-luteal phase.
Time Frame
Assessed at the end of each cycle. the cycles are 6. Each cycle is 28 days.
Title
Miscarriage rate
Description
Loss of clinical pregnancy before 20 weeks gestation, confirmed by ultrasound or histopathology.
Time Frame
Through study completion average 1 year.
Title
Menstrual regularity
Description
Normal ovulatory menstrual cycles defined as cycle length 21-35 days.
Time Frame
Through study completion average 1 year.
Title
Side effects
Description
Participant reports of adverse effects of letrozole or levothyroxine, graded per standard criteria.
Time Frame
Through study completion average 1 year.

10. Eligibility

Sex
Female
Gender Based
Yes
Gender Eligibility Description
This study will only enroll female participants. Patients must be of reproductive age with intact uteri and ovaries to meet the inclusion criteria. The study aims to induce ovulation for conception in infertile women with PCOS and subclinical hypothyroidism. As such, only individuals biologically born as females and currently identifying as women will be eligible. All enrolled participants must have functioning ovaries and intact reproductive organs capable of sustaining a pregnancy. Patients who have undergone surgical sterilization procedures like tubal ligation or hysterectomy will be excluded. Confirmation of female gender will be through medical history, physical examination, and review of medical records if needed. Pregnancy tests will be done at screening and before each treatment cycle. The reproductive status, ovaries and uterus will be assessed by medical history, physical examination and imaging like ultrasound when indicated.
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Muhamed Alhagrasy, M.D.
Phone
01017313413
Email
MuhamedAhmed.216@azhar.edu.eg
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Muhamed Alhagrasy, M.D.
Organizational Affiliation
Al-Azhar University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Al-Hussein University Hospital
City
Cairo
ZIP/Postal Code
11633
Country
Egypt
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Muhamed A Alhagrasy, M.D.
Phone
00201017313413
Email
MuhamedAhmed.216@azhar.edu.eg

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
To protect participant confidentiality, individual-level data from this study will not be made publicly available. However, de-identified aggregated data and results can be shared with other researchers upon request after publication. Any data provided will be limited, non-identifiable, and subject to a data use agreement to ensure participant privacy. Only select excerpts needed to validate findings will be shared under approved research objectives. The investigators reserve the right to reject requests that may compromise anonymity. We aim to promote transparency through controlled data access rather than public availability of the full dataset due to re-identification risks for participants.

Learn more about this trial

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

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