Clomiphene Citrate (CC)/Gonadotropin/Gonadotropin Releasing Hormone (GnRH) Antagonist Versus Gonadotropin/GnRH Agonist

Sponsor

Yazd Research & Clinical Center for Infertility (Other)

Overall Status

Completed

CT.gov ID

NCT00830492

Collaborator

(none)

200

Enrollment

Location

Arms

Duration (Months)

18.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Objective: To compare the efficacy of using mild ovarian stimulation protocol and conventional stimulation protocol in IVF outcome.

Design: Prospective randomized trial

Setting: University IVF setting. Patient(s): The study compromised a total 200 subinfertile couple that women had regulary menstruation.

Intervention(s): Patients were randomized to treatment clomiphene citrate, gonadotropin and GnRH antagonist (100 patients) or GnRH agonist and gonadotropin ( 100 patients).

Main outcome measure: Clinical pregnancy rate.

Key Words: clomiphene citrate, GnRH agonist, GnRH antagonist, in vitro fertilization, pregnancy rate.

Condition or Disease	Intervention/Treatment	Phase
Ovarian Stimulation	Drug: clomiphene citrate Procedure: Ultrasound Drug: GnRH antagonist Drug: gonadotopin (HMG) Drug: buserelin Drug: rFSH	Phase 4

Study Design

Study Type:

Interventional

Anticipated Enrollment :

200 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Investigator)

Primary Purpose:

Treatment

Official Title:

Comparisin CC/Gonadotropin/GnRH Antagonist and Gonadotropin/GnRH Agonist in IVF Outcome.

Study Start Date :

Jan 1, 2008

Actual Primary Completion Date :

Dec 1, 2008

Actual Study Completion Date :

Dec 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 2 In group A (n=100), the patients were stimulated conventional. They desensitized with buserelin (suprefact, Aventis, Frankfurt, Germany) 500µg subcutaneously (S.C.) everyday for menstrual cycle 21, until the baseline evaluation, which takes place in the first few days of menstruation. If baseline levels of estradiol (<50 pg/ml ) had been achieved, then the dose of buserelin would be reduced to 250µg and ovarian stimulation would commence with 150-225 IU recombinant FSH (r_FSH) (Gonal F, Serono, Aubnne, Switzerland) S.C.	Procedure: Ultrasound cycle day 8 Drug: buserelin Buserelin (suprefact, Aventis, Frankfurt, Germany) 500µg subcutaneously (S.C.) everyday for menstrual cycle 21, until the baseline evaluation, which takes place in the first few days of menstruation. If baseline levels of estradiol (<50 pg/ml ) had been achieved, then the dose of buserelin would be reduced to 250µg. Drug: rFSH 150-225 IU recombinant FSH (r_FSH) (Gonal F, Serono, Aubnne, Switzerland) S.C.
Experimental: clomiphen/gonadotropin/GnRH antagonist Patients in group B ( n=100 ) were stimulated clomiphene citrate ( ) 100 mg from cycle day three through seven and continuous gonadotropin stimulation with of r_FSH 75 IU daily from cycle day 5. Ultrasound in two group was performed on 8 cycle day. In group B 0.25 mg GnRH antagonist (Ganirelix , Organon ,Netherland ) daily was started with dominant follicle ≥14mm and in this day 75 IU human menopoasl gonadotropin (HMG) (Menogon, ferring, pharmacenticals , Germany ) increased to the initial gonadotropin . LH assessment on the day of starting antagonist was performed and if LH was >15 IU/L , cycle was cancelled. Human chorionic gonadotropin 10000 IU ((pregnyl, Organon, Oss, the Netherlands ) was given when 1 to 3 follicles reached 18 mm	Drug: clomiphene citrate 100 mg from cycle day 3 through 7 Procedure: Ultrasound cycle day 8 Drug: GnRH antagonist Daily, started with dominant follicle greater than 14 mm (Ganirelix , Organon, Netherlands). Drug: gonadotopin (HMG) 75 IU human menopausal gonadotropin (Menogon, ferring, pharmacenticals , Germany)

Arm

Intervention/Treatment

Active Comparator: 2

In group A (n=100), the patients were stimulated conventional. They desensitized with buserelin (suprefact, Aventis, Frankfurt, Germany) 500µg subcutaneously (S.C.) everyday for menstrual cycle 21, until the baseline evaluation, which takes place in the first few days of menstruation. If baseline levels of estradiol (<50 pg/ml ) had been achieved, then the dose of buserelin would be reduced to 250µg and ovarian stimulation would commence with 150-225 IU recombinant FSH (r_FSH) (Gonal F, Serono, Aubnne, Switzerland) S.C.

Procedure: Ultrasound

cycle day 8

Drug: buserelin

Buserelin (suprefact, Aventis, Frankfurt, Germany) 500µg subcutaneously (S.C.) everyday for menstrual cycle 21, until the baseline evaluation, which takes place in the first few days of menstruation. If baseline levels of estradiol (<50 pg/ml ) had been achieved, then the dose of buserelin would be reduced to 250µg.

Drug: rFSH

150-225 IU recombinant FSH (r_FSH) (Gonal F, Serono, Aubnne, Switzerland) S.C.

Experimental: clomiphen/gonadotropin/GnRH antagonist

Patients in group B ( n=100 ) were stimulated clomiphene citrate ( ) 100 mg from cycle day three through seven and continuous gonadotropin stimulation with of r_FSH 75 IU daily from cycle day 5. Ultrasound in two group was performed on 8 cycle day. In group B 0.25 mg GnRH antagonist (Ganirelix , Organon ,Netherland ) daily was started with dominant follicle ≥14mm and in this day 75 IU human menopoasl gonadotropin (HMG) (Menogon, ferring, pharmacenticals , Germany ) increased to the initial gonadotropin . LH assessment on the day of starting antagonist was performed and if LH was >15 IU/L , cycle was cancelled. Human chorionic gonadotropin 10000 IU ((pregnyl, Organon, Oss, the Netherlands ) was given when 1 to 3 follicles reached 18 mm

Drug: clomiphene citrate

100 mg from cycle day 3 through 7

Procedure: Ultrasound

cycle day 8

Drug: GnRH antagonist

Daily, started with dominant follicle greater than 14 mm (Ganirelix , Organon, Netherlands).

Drug: gonadotopin (HMG)

75 IU human menopausal gonadotropin (Menogon, ferring, pharmacenticals , Germany)

Outcome Measures

Primary Outcome Measures

clinical pregnancy rate [2 weeks]
ovarian stimulation safety [3weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 35 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

female patient age 18-35 years, presence of a regular and proven ovulatory menstruation cycle with a length of 26-35 days
basal FSH <10 IU/L and body mass index (BMI) of 18-30 (kg/m²)
Indication for IVF were unexplained infertility, mild male factor, tubal factor, early stage endometriosis and cervical factor