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

Sponsor

University of Athens (Other)

Overall Status

Unknown status

CT.gov ID

NCT02237755

Collaborator

Lito Maternity Hospital (Other)

Enrollment

Arms

Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Female Infertility	Drug: Clomiphene citrate Drug: Gonadotropins	Phase 2/Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Prospective Randomized Trial on the Effect of Clomiphene Citrate Administration in Women With Poor Ovarian Reserve Undergoing Controlled Ovarian Stimulation for IVF. Impact on Stimulation Characteristics and Pregnancy Outcome.

Study Start Date :

Oct 1, 2014

Anticipated Primary Completion Date :

Nov 1, 2014

Anticipated Study Completion Date :

Dec 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Clomiphene citrate Administration of Clomiphene citrate in combination with gonadotropins according to a short stimulation GnRH antagonists protocol.	Drug: Clomiphene citrate clomiphene citrate 100mg/day will be added to the standard gonadotropin regiment Other Names: Clomiphene citrate 50 mg/tab Cerpafar 50 mg/tab Drug: Gonadotropins All patients will be stimulated with a fixed GnRH-antagonist protocol. Ovarian stimulation will be initiated 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. Other Names: Menopur 75IU , Gonal
Active Comparator: Gonadotropins Patients in this group will be stimulated according to a short stimulation protocol with gonadotropins and GnRH antagonists.	Drug: Clomiphene citrate clomiphene citrate 100mg/day will be added to the standard gonadotropin regiment Other Names: Clomiphene citrate 50 mg/tab Cerpafar 50 mg/tab Drug: Gonadotropins All patients will be stimulated with a fixed GnRH-antagonist protocol. Ovarian stimulation will be initiated 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. Other Names: Menopur 75IU , Gonal

Arm

Intervention/Treatment

Active Comparator: Clomiphene citrate

Administration of Clomiphene citrate in combination with gonadotropins according to a short stimulation GnRH antagonists protocol.

Drug: Clomiphene citrate

clomiphene citrate 100mg/day will be added to the standard gonadotropin regiment

Other Names:

Clomiphene citrate 50 mg/tab

Cerpafar 50 mg/tab

Drug: Gonadotropins

All patients will be stimulated with a fixed GnRH-antagonist protocol. Ovarian stimulation will be initiated 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.

Other Names:

Menopur 75IU , Gonal

Active Comparator: Gonadotropins

Patients in this group will be stimulated according to a short stimulation protocol with gonadotropins and GnRH antagonists.

Drug: Clomiphene citrate

clomiphene citrate 100mg/day will be added to the standard gonadotropin regiment

Other Names:

Clomiphene citrate 50 mg/tab

Cerpafar 50 mg/tab

Drug: Gonadotropins

Other Names:

Menopur 75IU , Gonal

Outcome Measures

Primary Outcome Measures

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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 50 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

University of Athens
Lito Maternity Hospital

Investigators

Study Chair: Nikos Vlahos, Assoc. Prof., University of Athens, 2nd Department of Obstetrics and Gynecology
Principal Investigator: Olga Triantafyllidou, MD, University of Athens School of Medicine