Clomiphene Citrate in Combination With Gonadotropins for Ovarian Stimulation in Women With Poor Ovarian Response.

Phase 2

• Conditions: Female Infertility
• Interventions: Drug: Clomiphene citrate; Drug: Gonadotropins

• Registration Number: NCT02237755
• Lead Sponsor: University of Athens

Brief Summary

Coadministration of various drugs used for ovarian stimulation can increase the efficiency of IVF especially in poor responders. The investigators hypothesize that ovarian response of those patients could improve by using combination of clomiphene citrate with gonadotropins in infertile women with poor response to gonadotrophin administration only.

Detailed Description

Patients diagnosed with poor ovarian response will be included in the study. The definition of poor response was based on the presence of at least one of the following criteria: Age \> 40 years old, day 2 FSH \>9.5 mIU/ml, AMH \< 2ng/ml ,at least one previous COH with less than 3 oocytes retrieved, at least one cancelled attempt due to poor response, estradiol less than 500 pg/ml on the day of HCG. All patients will be counseled regarding their prognosis and other treatment options including oocyte donation as well as adoption were also presented and discussed in detail. Early follicular phase FSH, estradiol (E2) and Anti-Mullerian Hormone (AMH) will be measured prior to the initiation of treatment. Women in the Clomiphene group will receive 100-150 mg of Clomiphene citrate once per day for 5 days in combination with gonadotropins according to short GnRH-antagonist protocol: all women will have measurements of serum FSH and estradiol and a pelvic sonogram on the second day of their cycle. Providing that serum FSH is \< 17 mIU/ml and estradiol is \< 70 pg/ml on day 2 , ovarian stimulation will be initiated with 100-150 mg of Clomiphene citrate in combination with 450 IU of gonadotropins either in the form of a combination of highly purified urinary FSH and LH or with a combination of Rec FSH and Rec LH. All patients will be re-evaluated on day 5 of the stimulation, and dosage adjustments will be made and the antagonists (Cetrorelix or ganirelix 0.25 mg/day) will be initiated. When at least 2 follicles reach an average diameter of 17 mm, final oocyte maturation will be triggered with 10,000IU of hCG ( Pregnyl, Organon, Greece Inc.). Oocyte retrieval will be performed 34 to 36 hours later. All patients will undergo ICSI. Patients with successful fertilization will have embryo transfer under sonographic guidance on day 3 after retrieval. Women in the Gonadotropin group will receive only gonadotropins according to short GnRH-antagonist protocol as it was mentioned above.

Study Timeline

• Status Verified: 2014-09
• Study First Submitted: 2014-09-09
• Study First Submitted QC: 2014-09-09
• Last Update Submitted: 2014-09-09
• Study First Posted: 2014-09-11
• Last Update Posted: 2014-09-11
• Study Start: 2014-10
• Primary Completion: 2014-11
• Study Completion: 2015-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 50

Inclusion Criteria

• Women with poor response to ovarian stimulation. The definition of poor response was based on the presence of at least one of the following criteria: Age > 40 years old, day 2 FSH >9.5 mIU/ml, AMH < 2ng/ml ,at least one previous COH with less than 3 oocytes retrieved, at least one cancelled attempt due to poor response, estradiol less than 500 pg/ml on the day of HCG.

Exclusion Criteria

• All other women that do not fulfill the above mentioned criteria

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Clomiphene citrate	Gonadotropins	Administration of Clomiphene citrate in combination with gonadotropins according to a short stimulation GnRH antagonists protocol.
Gonadotropins	Gonadotropins	Patients in this group will be stimulated according to a short stimulation protocol with gonadotropins and GnRH antagonists.
Clomiphene citrate	Clomiphene citrate	Administration of Clomiphene citrate in combination with gonadotropins according to a short stimulation GnRH antagonists protocol.
Gonadotropins	Clomiphene citrate	Patients in this group will be stimulated according to a short stimulation protocol with gonadotropins and GnRH antagonists.

Primary Outcome Measures

Name	Time	Method
Clinical pregnancy	14 days after embryo transfer	At the completion of the ovarian stimulation patients that will proceed to transfer and have a positive pregnancy test will have sonographic evaluation for confirmation of clinical pregnancy.