Antagonist/Letrozole in Poor Responders

Yazd Research & Clinical Center for Infertility

Status and phase: Completed; Phase 2; Phase 1

Conditions: Ovarian Stimulation

Treatments: Drug: oral contraceptive (Marvelone); Drug: letrozole; Drug: GnRH agonist (buserelin); Drug: recombinant FSH or hMG; Drug: ganirelix acetate

Study type: Interventional

Funder types: Other

Identifiers

NCT00823004

1969yazdRCCI

Details and patient eligibility

About

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.

Full 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.

Enrollment: 120 patients

Sex: Female

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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120 participants in 2 patient groups

1

Active Comparator group

Description:

A/L: Poor responders who will receive letrozole and GnRH antagonist for ovarian stimulation

Treatment:

Drug: ganirelix acetate

Drug: recombinant FSH or hMG

Drug: letrozole

Drug: oral contraceptive (Marvelone)

2

Active Comparator group

Description:

MF: In this arm poor responders are treated by microdose GnRH agonist flare protocol

Treatment:

Drug: recombinant FSH or hMG

Drug: GnRH agonist (buserelin)

Drug: oral contraceptive (Marvelone)