Antagonist/Letrozole in Poor Responders

Phase 1

Completed

• Conditions: Ovarian Stimulation
• Interventions: Drug: letrozole; Drug: GnRH agonist (buserelin); Drug: oral contraceptive (Marvelone); Drug: recombinant FSH or hMG; Drug: ganirelix acetate

• Registration Number: NCT00823004
• Lead Sponsor: Yazd Research & Clinical Center for Infertility

Brief Summary

Failure to respond to controlled ovarian hyperstimulation (COH) is still a major concern in assisted reproduction and there is no consensus on the ovarian stimulation choice regime for poor responders.

Aim: To evaluate and compare the efficacy of a microdose GnRH agonist flare (MF) and a GnRH antagonist/letrozole (A/L) protocols in poor responders undergoing in vitro fertilization (IVF).

Methods: One hundred eighty poor responder patients will be randomized to an ovarian stimulation protocol with either a MF or a letrozole and high dose FSH/hMG and flexible GnRH antagonist protocol.

Detailed Description

All women receive 21 days of an oral contraceptive. A MF protocol will be used for ovarian stimulation in 90 patients. Three days after the last pill, a GnRH-agonist buserelin (Suprefact, Aventis Pharma, Frankfurt, Germany) 50 µg SC twice daily will be initiated and two days after that, recombinant FSH (Gonal-F, Serono, Aubonne, Switzerland) or hMG (Merional, IBSA, Lugano, Switzerland) 300-450 IU/day will be administered. Ninetyty patients will be assigned to an A/L protocol. After oral contraceptive withdrawal bleeding on day 3 of cycle, recombinant FSH or hMG 300-450 IU/day will be initiated and letrozole (Femara, Novartis, East Hanover, NJ) 5 mg/day will be administered for 5 days. When the dominant follicle reached 14 mm in mean diameter, ganirelix acetate (Antagon, Organon, West Orange, NJ) 0.25 mg SC daily will be started.

Patients weill be monitored by serial vaginal ultrasonography and measurement of serum E2 level. When at least two follicles with a mean diameter of 18 mm will be achieved hCG (Pregnyl, Organon, Oss, the Netherlands) 10000 IU will be administered. Cycle cancellation will be considered when fewer than two follicles with normal growth pattern weill be noted.

Oocyte retrieval will be performed 34-36 hours after hCG administration. Conventional IVF or intracytoplasmic sperm injection (ICSI) will be performed as appropriate. Embryos with 4-6 equally sized blastomers on day 2 with ≤ 20% fragmentation and no multinucleation will be considered top quality embryos. Embryos with 2-6 equally or unequally blastomers with ≤20% fragmentation and no multinucleation will be considered good quality embryos. Embryos will be transferred on day 2 or 3 under ultrasound guidance, with a C.C.D. embryo transfer catheter ( Laboratoire C.C.D., Paris, France). Luteal support with progesterone in oil (Progesterone, Aburaihan Co., Tehran, Iran) 100 mg daily IM will be started on the day of oocyte retrieval.

Serum β-hCG level will be measured 14 days after embryo transfer and a transvaginal ultrasonography will be performed 3 weeks after positive β-hCG for documentation of gestational sac and fetal heart activity. Clinical pregnancy will be considered as the presence of a gestational sac with fetal heart activity.

Study Timeline

• Study Start: 2008-06
• Study First Submitted: 2009-01-14
• Study First Submitted QC: 2009-01-14
• Study First Posted: 2009-01-15
• Primary Completion: 2009-02
• Study Completion: 2009-10
• Status Verified: 2013-12
• Last Update Submitted: 2013-12-20
• Last Update Posted: 2013-12-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 120

Inclusion Criteria

• at least one previous failed IVF cycle in which three or fewer follicles with a mean diameter of 16 mm were achieved, and/or
• serum E2 level measured on the day of hCG administration was ≤500 pg/ml

Exclusion Criteria

• day 3 serum FSH level ≥12 mIU/mL
• there is no age limit

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
2	GnRH agonist (buserelin)	MF: In this arm poor responders are treated by microdose GnRH agonist flare protocol
2	recombinant FSH or hMG	MF: In this arm poor responders are treated by microdose GnRH agonist flare protocol
1	letrozole	A/L: Poor responders who will receive letrozole and GnRH antagonist for ovarian stimulation
1	oral contraceptive (Marvelone)	A/L: Poor responders who will receive letrozole and GnRH antagonist for ovarian stimulation
1	recombinant FSH or hMG	A/L: Poor responders who will receive letrozole and GnRH antagonist for ovarian stimulation
1	ganirelix acetate	A/L: Poor responders who will receive letrozole and GnRH antagonist for ovarian stimulation
2	oral contraceptive (Marvelone)	MF: In this arm poor responders are treated by microdose GnRH agonist flare protocol

Primary Outcome Measures

Name	Time	Method
pregnancy rate	5 weeks

Secondary Outcome Measures

Name	Time	Method
stimulation outcomes	2 weeks

Trial Locations

Locations (1)

Research and clinical center for infertility; 🇮🇷 Yazd, Iran, Islamic Republic of