Clomiphene Citrate (CC) Co-treatment With HP Urinary FSH vs HP Urinary FSH in CC-resistant PCOS

Study Overview
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Brief Summary
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To test whether adding small doses of HP urinary FSH to standard regimen of clomiphene citrate in clomiphene resistant PCOS well yield better results in terms of better ovulation rate,lower follicle number, less consumption of HP urinary FSH,lower treatment cost , better pregnancy rate, lower multiple pregnancy rates compared with the exclusive use of HP urinary FSH in these cases.

Detailed Description
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To test whether CC co- treatment with chronic low dose HP uFSH vs chronic low dose HP uFSH in CC resistant PCOS will yield better results in terms of ,ovulation rate, lower follicle number,lower HP uFSH dose ,better outcome in terms of pregnancy rates, better cost-effectiveness ratio, lower multiple pregnancy rates,lower cycle cancellation.

Official Title
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Clomiphene Citrate Co-treatment With Low Dose HP Urinary FSH vs. HP Urinary FSH Step-up Protocol for Clomiphene-citrate Resistant PCOS Anovulatory Infertility: Randomized Controlled Trial

Conditions
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Polycystic Ovary Syndrome

Intervention / Treatment
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* Drug: Step-up HP u FSH
* Drug: Clomiphine citrate plus low dose uFSH


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: CC resistant PCOS Infertile Females Age 18-38 Exclusion Criteria: Hyperprolactinaemia Cushing syndrome Adult onset adrenal hyperplasia Age >38 Other infertility factors in the couple than PCOS: male factor,tubal factor,edometriosis

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 38 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Clomiphene Citrate plus HP uFSH<br>Starting from the 2nd day of the cycle Clomiphene Citrate( CC)50 mg tablets are given in 100 mg daily dose for 5 days together with an low dose HP uFSH (half ampoule: 37.5 IU) given im daily for 8-10 days. | Drug: Clomiphine citrate plus low dose uFSH<br>* Clomiphene citrate 50 mg tab oral tablets(Clomid 50 mg tablets Global Napi , Egypt) two tablets(100 mg) /day are started from the 2nd day of cycle for 5 days togeteher with 37.5 IU HP uFSH (Fostimone 75 IU IBSA)/day for 8 days and may be extended to 10-12 days until leading follicle diameter reaches 18 mm<br>|
| Active Comparator: Step-up HP uFSH<br>HP uFSH started in doses of half ampole (37.5 )IU daily from the 2nd day of cycle for 7 days ,then dose is stepped-up to one ampoule ( 75 IU) for 7 days then the one and a half amps (112.5) IU /day until follicular diameter reaches 18 mm mean diameter | Drug: Step-up HP u FSH<br>* HP u FSH (Fostimone 75 IU ,IBSA Institut Biochimique SA-CH 6903 Lugano) in doses of 37.5 IU (half ampole) im /day statrted from second day of the cycle for 7 days ,then increased to 75 IU for another 7 days ,then to 112.5 IU (one and half ampoule) untilleading follicle mean diameter reaches 18 mm<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ovulation rate | IF CC Co-treatment with low dose step-up HP urinary(u)FSH results in similar or higher ovulation rate compared with step-up low dose HP uFSH | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Live birth rate | % of of cases that result in live birth > 20 weeks pregnancy | 6 months | 
| number of follicles sized 16 mm or more mean diameter in both ovaries at the time of hCG | To test if CC-co treatment with low dose HP uFSH results in lower number of follicles 16 mm mean diameter or more at time of triggerring ovulation compared with low dose HP uFSH | 3 months | 
| Endometrial thickness | Measuring endometrial thickness in mm in both study arms at the time of ovulation trigerring to see if there is difference | 3 months | 
| serum Estradiol(E2) | serum level of E2 is measured in both groups at the time of ovulation triggerring to test for differences | 3 months | 
| incidence of multiple pregnancy | To test if CC-co treatment with low dose HP uFSH results in lower or higher incidence of multiple pregnancies compared with low dose HP uFSH | 3 months | 
| costs per cycle | costs of drugs used to induce ovulation in each arm of the study in Egyptian pounds The cost of HP uFSH per cycle was calculated by multiplying the cost of a single IU with the mean number of FSH IU used per cycle. Add to this the cost of clomiphene citrate in the relevant arm | 3 months | 
| cost effectiveness ratio | The cost-effectiveness ratio is calculated multiplying the cost per cycle by the total number of cycles performed in each arm then dividing the result for the number of clinical pregnancies obtained in the arm during the trial. | 6 months | 
| clinical and biochemical predictors of response to treatment |  | 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PCOS, Clomiphene resistance, ovulation induction, low dose uFSH, uFSH step-up protocol