L-Carnitine and Clomiphene Citrate for Induction of Ovulation in Women With Polycystic Ovary Syndrome

Study Overview
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Brief Summary
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The purpose of the study to assess the efficacy of adding L-carnitine to clomiphene citrate for increasing the ovulation and the pregnancy rate in women with PCOS.

Detailed Description
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A total of 106 women with the diagnosis of PCOS based on the European Society of Human Reproduction and Embryology/ American Society for Reproductive Medicine (ESHRE/ASRM) guidelines criteria (Rotterdam Criteria, 2003) will be randomly assigned using a computer-generated randomization sheet and they will be distributed into two groups: Group L (53 patients): This group will receive oral clomiphene citrate (Clomid, Global Napi Pharmaceuticals (GNP), Egypt) (50 mg tablet, two times per day) from the third day of the cycle until the seventh day of the cycle plus oral carnitine supplementation (Carnivita Forte, Eva Pharma, Egypt) (1g tablet, three times per day) from the third day of the cycle until the day of the pregnancy test. Group C (53 patients): This group will receive oral clomiphene citrate only (Clomid, Global Napi Pharmaceuticals (GNP), Egypt) (50 mg tablet, two times per day) from the third day of the cycle until the seventh day of the cycle. Serum FSH, LH & free testosterone concentrations will be measured on day 3 (basal) of the cycle. Trans-vaginal folliculometry will be performed on all women on days 7 and 9 of the cycle and then individualized according to the response. When one leading follicle attains a diameter of 17mm or more, the endometrial thickness will be measured and 10,000 IU of Human chorionic gonadotropin (hCG) will be given (im injection; Pregnyl, organon, Holland). Timed intercourse will be advised after 36-48 hours from the night of hCG administration for 2 successive days. Ovulation success will be confirmed by transvaginal ultrasound which will show that the leading follicle has collapsed, and some fluid appeared in the Douglas pouch. Serum progesterone will be measured on day 8 post hCG injection, ovulation will be confirmed if the serum progesterone level is ≥ 5 ng/ml (Leiva et al., 2015). Luteal-phase support will not be provided in both groups. Pregnancy test will be done in the form of testing the level of beta hCG in the blood after 14 days once the success of the ovulation process has been confirmed.

Official Title
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L-Carnitine and Clomiphene Citrate for Induction of Ovulation in Women With Polycystic Ovary Syndrome

Conditions
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Polycystic Ovary Syndrome

Intervention / Treatment
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* Drug: oral clomiphene citrate
* Drug: oral carnitine supplementation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ranging from 18-35 years. Normal Hysterosalpingo-graphy (HSG). Normal Semen analysis of the husband. Diagnosed with PCOS based on the (ESHRE/ASRM) guidelines criteria (Rotterdam Criteria 2003). Exclusion Criteria: Patient's refusal. Male factors of infertility and/or abnormal HSG. Hyperprolactinemia (prolactin ≥ 22 ng/dl). FSH on day 3 > 15 mIU/mL. Gross ovarian pathology diagnosed by ultrasound.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A total of 106 women with the diagnosis of PCOS based on the European Society of Human Reproduction and Embryology/ American Society for Reproductive Medicine (ESHRE/ASRM) guidelines criteria (Rotterdam Criteria, 2003) will be randomly assigned using a computer-generated randomization sheet and they will be distributed into two groups: Group L (53 patients): This group will receive oral clomiphene citrate (Clomid, Global Napi Pharmaceuticals (GNP), Egypt) (50 mg tablet, two times per day) from the third day of the cycle until the seventh day of the cycle plus oral carnitine supplementation (Carnivita Forte, Eva Pharma, Egypt) (1g tablet, three times per day) from the third day of the cycle until the day of the pregnancy test. Group C (53 patients): This group will receive oral clomiphene citrate only (Clomid, Global Napi Pharmaceuticals (GNP), Egypt) (50 mg tablet, two times per day) from the third day of the cycle until the seventh day of the cycle.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group L<br>This group will receive oral clomiphene citrate (Clomid, Global Napi Pharmaceuticals (GNP), Egypt) (50 mg tablet, two times per day) from the third day of the cycle until the seventh day of the cycle plus oral carnitine supplementation (Carnivita Forte, Eva Pharma, Egypt) (1g tablet, three times per day) from the third day of the cycle until the day of the pregnancy test. | Drug: oral clomiphene citrate<br>* oral clomiphene citrate 50 mg tablet, two times per day will be received from the third day of the cycle until the seventh day of the cycle.<br>* Other names: clomid;Drug: oral carnitine supplementation<br>* oral carnitine supplementation 1g tablet, three times per day will be received from the third day of the cycle until the day of the pregnancy test.<br>* Other names: Carnitiva Forte;|
| Active Comparator: Group C<br>This group will receive oral clomiphene citrate only (Clomid, Global Napi Pharmaceuticals (GNP), Egypt) (50 mg tablet, two times per day) from the third day of the cycle until the seventh day of the cycle. | Drug: oral clomiphene citrate<br>* oral clomiphene citrate 50 mg tablet, two times per day will be received from the third day of the cycle until the seventh day of the cycle.<br>* Other names: clomid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ovulation success by trans-vaginal ultrasound | Ovulation success will be confirmed by transvaginal ultrasound which will show that the leading follicle has collapsed, and some fluid appeared in the Douglas pouch. | 36-48 hours after night of hCG administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum progesterone | Serum progesterone will be measured on day 8 post hCG injection, ovulation will be confirmed if the serum progesterone level is ≥ 5 ng/ml. | Day 8 post hCG injection | 
| Clinical pregnancy | Pregnancy test will be done in the form of testing the level of beta hCG in the blood after 14 days once the success of the ovulation process has been confirmed. | 14 days after hCG administration |