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

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

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.

Study Overview

• Status: Completed
• Conditions: Polycystic Ovary Syndrome
• Intervention / Treatment: Drug: Clomiphine citrate plus low dose uFSH; Drug: Step-up HP u FSH

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 174
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • Dekahlia
    • Mansoura, Dekahlia, Egypt
      • Mansoura Integrated Fertility Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 38 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Clomiphene Citrate plus HP uFSH; 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; 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
Active Comparator: Step-up HP uFSH; 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; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Mansoura Integrated Fertility Center
• Investigators: Study Chair: Mohamad E Ghanem, MD, Mansoura Integrated Fertility Center; Study Director: Mohammad A Emam, MD, Mansoura Integrated Fertility Center; Principal Investigator: Mohamad E Ghanem, MD, Mansoura Integrated Fertility Center

Publications and helpful links

General Publications

• Palomba S, Falbo A, Zullo F. Management strategies for ovulation induction in women with polycystic ovary syndrome and known clomifene citrate resistance. Curr Opin Obstet Gynecol. 2009 Dec;21(6):465-73. doi: 10.1097/GCO.0b013e328332d188.
• Gorry A, White DM, Franks S. Infertility in polycystic ovary syndrome: focus on low-dose gonadotropin treatment. Endocrine. 2006 Aug;30(1):27-33. doi: 10.1385/ENDO:30:1:27.
• Ghanem ME, Elboghdady LA, Hassan M, Helal AS, Gibreel A, Houssen M, Shaker ME, Bahlol I, Mesbah Y. Clomiphene citrate co-treatment with low dose urinary FSH versus urinary FSH for clomiphene resistant PCOS: randomized controlled trial. J Assist Reprod Genet. 2013 Nov;30(11):1477-85. doi: 10.1007/s10815-013-0090-2. Epub 2013 Sep 7. Erratum In: J Assist Reprod Genet. 2014 Apr;31(4):505-6.

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (Actual): September 1, 2012
• Study Completion (Actual): September 1, 2012

Study Registration Dates

• First Submitted: September 29, 2010
• First Submitted That Met QC Criteria: September 29, 2010
• First Posted (Estimate): September 30, 2010

Study Record Updates

• Last Update Posted (Estimate): May 30, 2013
• Last Update Submitted That Met QC Criteria: May 29, 2013
• Last Verified: May 1, 2013

More Information

Terms related to this study

• Keywords: PCOS; ovulation induction; Clomiphene resistance; low dose uFSH; uFSH step-up protocol
• Additional Relevant MeSH Terms: Neoplasms; Endocrine System Diseases; Ovarian Cysts; Cysts; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Polycystic Ovary Syndrome
• Other Study ID Numbers: MansouraIFC1