Antagonist/Letrozole in Poor Responders

Ovarian Stimulation Clinical Trial

Official title:

GnRH Antagonist /Letrozole Versus Microdose GnRH Agonist Flare Protocol in Poor Responders Undergoing in Vitro Fertilization

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00823004
• Other study ID #: 1969yazdRCCI
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: January 14, 2009
• Last updated: December 20, 2013
• Start date: June 2008
• Est. completion date: October 2009

Study information

• Verified date: December 2013
• Source: Yazd Research & Clinical Center for Infertility
• Contact: n/a
• Is FDA regulated: No
• Health authority: Iran: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: October 2009
• Est. primary completion date: February 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: N/A and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Ovarian Stimulation

Intervention

Drug:
• letrozole
letrozole 5mg/day from day 3 to day 7 of menstrual cycle
• oral contraceptive (Marvelone)
oral contraceptive, first 21 days
• GnRH agonist (buserelin)
50 µg SC twice daily
• recombinant FSH or hMG
recombinant FSH or hMG 300-450 IU/day
• ganirelix acetate
GnRH antagonist (ganirelix acetate) when a leading follicle reaches a mean diameter of 14 mm, 0.25 mg per day (Antagon, Organon, West Orange, NJ)

Locations

Country	Name	City	State
Iran, Islamic Republic of	Research and clinical center for infertility	Yazd

Sponsors (1)

Lead Sponsor	Collaborator
Yazd Research & Clinical Center for Infertility

Country where clinical trial is conducted

Iran, Islamic Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	pregnancy rate		5 weeks	Yes
Secondary	stimulation outcomes		2 weeks	Yes