Antagonist/Letrozole in Poor Responders

NCT ID: NCT00823004

Last Updated: 2013-12-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

120 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-06-30

Study Completion Date

2009-10-31

Brief Summary

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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

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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.

Conditions

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Ovarian Stimulation

Keywords

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controlled ovarian hyperstimulation pregnancy rate Poor responders GnRH antagonist GnRH agonist letrozole in vitro fertilization

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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1

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

Group Type ACTIVE_COMPARATOR

letrozole

Intervention Type DRUG

letrozole 5mg/day from day 3 to day 7 of menstrual cycle

oral contraceptive (Marvelone)

Intervention Type DRUG

oral contraceptive, first 21 days

recombinant FSH or hMG

Intervention Type DRUG

recombinant FSH or hMG 300-450 IU/day

ganirelix acetate

Intervention Type DRUG

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)

2

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

Group Type ACTIVE_COMPARATOR

oral contraceptive (Marvelone)

Intervention Type DRUG

oral contraceptive, first 21 days

GnRH agonist (buserelin)

Intervention Type DRUG

50 µg SC twice daily

recombinant FSH or hMG

Intervention Type DRUG

recombinant FSH or hMG 300-450 IU/day

Interventions

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letrozole

letrozole 5mg/day from day 3 to day 7 of menstrual cycle

Intervention Type DRUG

oral contraceptive (Marvelone)

oral contraceptive, first 21 days

Intervention Type DRUG

GnRH agonist (buserelin)

50 µg SC twice daily

Intervention Type DRUG

recombinant FSH or hMG

recombinant FSH or hMG 300-450 IU/day

Intervention Type DRUG

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)

Intervention Type DRUG

Other Intervention Names

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letrozole (Femara, Novartis, East Hanover, NJ) Marvelon suprefact Gonal F Merional Antagon

Eligibility Criteria

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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
Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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Yazd Research & Clinical Center for Infertility

OTHER

Sponsor Role lead

Responsible Party

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homa oskouian

fellowship

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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homa oskouian, M.D.

Role: PRINCIPAL_INVESTIGATOR

Research and clinical center for infertility

robab davar, MD

Role: PRINCIPAL_INVESTIGATOR

Research and clinical center for infertility

Locations

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Research and clinical center for infertility

Yazd, Yazd Province, Iran

Site Status

Countries

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Iran

Other Identifiers

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1969yazdRCCI

Identifier Type: -

Identifier Source: org_study_id