Female Infertility, PCOS (Polycystic Ovary Syndrome) of Bilateral Ovaries, Subclinical Hypothyroidism
Conditions
Keywords
Letrozole, Levothyroxine, PCOS, Subclinical hypothyroidism
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.
Interventions
DRUGLetrozole 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.
DRUGLevothyroxine 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.
Sponsors
Muhamed Ahmed Abdelmoaty Muhamed Alhagrasy
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
FEMALE
Age
20 Years to 40 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Egypt
Contacts
Primary ContactMuhamed Alhagrasy, M.D.
Outcome results
None listed