Clomiphene Citrate Plus Gonadotropins and GnRH Antagonist Versus Flexible GnRH Antagonist Protocol Versus Microdose GnRH Agonist Protocol in Poor Responders Undergoing IVF

NCT ID: NCT02201914

Last Updated: 2014-07-28

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 250 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-01-31
• Study Completion Date: 2014-11-30

Brief Summary

Poor ovarian response to stimulation in IVF cycles is a challenging and frustrating condition, due to its poor prognosis in terms of chances of pregnancy and live births. Various ovarian stimulation regimens have been tried to overcome these obstacles. A simple approach is increase the dose of the gonadotropin administration, but the results in terms of pregnancy rate are very low Another commonly used stimulation regimen is the microdose GnRH agonist protocol, which takes advantage of the initial rise in endogenous gonadotropins that follows the agonist administration in the early follicular phase and subsequently prevents a premature LH surge, with fewer cycle cancellations. However, their application in poor responders, even if in small doses and for a limited period, has been questioned as they may cause oversuppression of ovarian function, leading to a prolonged cycle and increased treatment costs without improving the outcomes.

Recently, GnRH antagonists were introduced in ART treatment. They are effective in preventing a premature LH surge and allow for a more natural recruitment of follicles in the follicular phase in a non-suppressed ovary, offering a potential alternative in the treatment of these patients. However, randomized studies evaluating the efficacy of this regimen in poor responders did not show any improvements in pregnancy rates. Current approach have included the addition of oral agents such us clomiphene citrate (CC) to gonadotropins. Some authors have investigated the role of CC in addition to low dose of gonadotropins in mild stimulation regimen, demonstrating that, despite a small number of retrieved oocytes, good quality embryos were produced with a subsequent improvement in the fertilization rate, clinical pregnancy rate and live birth rate. The only study that evaluate the efficacy of CC in addition to high doses of gonadotropins in poor responders showed improving in number of retrieved oocytes, transferred embryos and biochemical pregnancy; however, clinical pregnancy rate and live birth rate remained low and showed no measurable increase.

The aim of this study was to compare the efficacy of the CC as an adjunctive to a high dose of gonadotropins in cycles with antagonist protocols with the microdose GnRH agonist and flexible antagonist protocols in women who responded poorly to ovarian stimulation, to determine whether this protocol may improve IVF outcomes, offering a valid alternative in poor responder patients treatment.

Conditions

Poor Responders; IVF; Clomiphene Citrate; GnRH Agonist; GnRH Antagonist

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Clomiphene citrate

Group Type: EXPERIMENTAL

Clomiphene citrate

Intervention Type: DRUG

patients receive clomiphene citrate 100 mg daily starting on day 2 for 5 days and 450 IU recombinant FSH and 225 IU recombinant LH daily starting on day 5; Cetrorelix 0,25 mg was administered daily when one or more follicle reached 13-14 mm in diameter until the hCG injection

Daily FSH and LH plus Cetrorelix

Group Type: EXPERIMENTAL

Daily FSH and LH plus Cetrorelix

Intervention Type: DRUG

Women receive an initial daily dose of 450 IU recombinant FSH and 225 IU recombinant LH starting on day 3; Cetrorelix 0,25 mg was administered daily when one or more follicle reached 13-14 mm in diameter until the hCG injection.

Triptorelin plus daily FSH and LH

Group Type: EXPERIMENTAL

Triptorelin plus daily FSH anh LH

Intervention Type: DRUG

women receive short-acting Triptorelin 0,05 mg daily starting on day 1 until the hCG injection and 450 IU recombinant FSH and 225 IU recombinant LH daily starting on day 2.

Interventions

Clomiphene citrate

patients receive clomiphene citrate 100 mg daily starting on day 2 for 5 days and 450 IU recombinant FSH and 225 IU recombinant LH daily starting on day 5; Cetrorelix 0,25 mg was administered daily when one or more follicle reached 13-14 mm in diameter until the hCG injection

Intervention Type: DRUG

Daily FSH and LH plus Cetrorelix

Women receive an initial daily dose of 450 IU recombinant FSH and 225 IU recombinant LH starting on day 3; Cetrorelix 0,25 mg was administered daily when one or more follicle reached 13-14 mm in diameter until the hCG injection.

Intervention Type: DRUG

Triptorelin plus daily FSH anh LH

women receive short-acting Triptorelin 0,05 mg daily starting on day 1 until the hCG injection and 450 IU recombinant FSH and 225 IU recombinant LH daily starting on day 2.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• poor responders in a previous IVF cycle at least 3 months before at our center and undergoing a new IVF attempt with at least two of the following criteria : I) age > 40 years old; II) basal follicular stimulation hormone (FSH) > 12 mIU/ml; III) three or fewer oocytes retrieved in the previous IVF cycle; IV) low estradiol levels on the day of human chorionic gonadotropin (hCG) administration (< 1500 pmol/ml).

Exclusion Criteria

• body mass index > 30
• biochemical and ultrasound evidence of polycystic ovary syndrome
• stage III-IV endometriosis
• inflammatory or autoimmune disorders
• metabolic disease
• infertility medications within the past two months

• Minimum Eligible Age: 25 Years
• Maximum Eligible Age: 44 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Bioroma

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Bioroma

Rome, Rome, Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Mauro Schimberni, MD

Role: CONTACT

bioroma@bioroma.net

+39063334266

Facility Contacts

Mauro Schimberni, MD

Role: primary

bioroma@bioroma.net

+39063334266

Other Identifiers

BRM003

Identifier Type: -

Identifier Source: org_study_id