Long Acting FSH Plus Antagonist Versus Daily FSH Plus Antagonist Versus Short Agonist Protocol in Poor Responders Undergoing IVF

Long Acting FSH Plus GnRH Antagonist Versus Daily FSH Plus GnRH Antagonist Versus Short Agonist Regimens in Poor Responder Patients Undergoing IVF: a Randomized Study.

Despite the progression in assisted reproductive technology (ART), poor ovarian response to controlled ovarian stimulation remains a challenge for clinicians and a source of distress for patients. Multiple strategies have been tried to overcome these obstacles. The increase of the gonadotropin administration have been associated with a very low pregnancy rate. The introduction of 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, have improved cycle parameters and increased pregnancy rate. 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. However, the randomized studies comparing the efficacy of these two regimens reported conflicting and nonsignificant results. Moreover, more recently adjuvant therapies for COH such as growth hormone therapy or pyridostigmine, oral L-arginine, and transdermal testosterone failed to improve IVF outcomes. Recently, the new treatment option with corifollitropin alfa, able to keep the circulating FSH level above the threshold necessary to support multi-follicular growth for an entire week, in a GnRH antagonist protocol seems to have a potential beneficial effect in poor responders.

The aim of this study is to compare long-acting FSH/GnRH antagonist with daily FSH/GnRH antagonist with short GnRH agonist protocol on IVF outcome in poor responder patients .

Study Overview

• Status: Unknown
• Conditions: Female Infertility; Poor Responder
• Intervention / Treatment: Drug: Long acting FSH and GnRH antagonist; Drug: Daily FSH and GnRH antagonist; Drug: Triptorelin and recombinant FSH

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 4

Contacts and Locations

Study Locations

• Italy
  • Rome, Italy, 00197
    • Recruiting
    • Bioroma
    • Contact: Mauro Schimberni; Phone Number: +39063334266; Email: bioroma@bioroma.net
    • Principal Investigator: Mauro Schimberni

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 44 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• women 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 (gonadotropins, clomiphene citrate) within the past two months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Long acting FSH and GnrH antagonist; Woman in long acting FSH and GnRH antagonist arm receive an initial dose of 150 mcg Corifollitropin alfa on second day of the menstrual cycle followed by a fixed daily dose of 0.25 mg of GnRH antagonist on day 7 of the cycle onwards. On the ninth day of the cycle, a daily fixed dose of 300 IU of recombinant FSH will be administered until the day of ovulation triggering.	Drug: Long acting FSH and GnRH antagonist; Woman in long acting FSH and GnRH antagonist arm receive an initial dose of 150 mcg Corifollitropin alfa on second day of the menstrual cycle followed by a fixed daily dose of 0.25 mg of GnRH antagonist on day 7 of the cycle onwards. On the ninth day of the cycle, a daily fixed dose of 300 IU of recombinant FSH will be administered until the day of ovulation triggering.
EXPERIMENTAL: daily FSH and GnRH antagonist; Woman in daily FSH and GnRH antagonist arm receive a fixed dose of 300 IU of recombinantFSH starting 3 day of the menstrual cycle followed by a fixed daily dose of 0.25 mg of GnRH antagonist on day 7 of the cycle onwards until the day of ovulation triggering.	Drug: Daily FSH and GnRH antagonist; Woman in daily FSH and GnRH antagonist arm receive a fixed dose of 300 IU of recombinantFSH starting 3 day of the menstrual cycle followed by a fixed daily dose of 0.25 mg of GnRH antagonist on day 7 of the cycle onwards until the day of ovulation triggering.
EXPERIMENTAL: Triptorelin and recombinant FSH; Women in triptorelin and recombinant FSH arm receive a fixed dose of 0.05 mg of triprorelin from the 1 day of the menstrual cycle followed by a fixed dose of 300 IU of recombinant FSH starting 3 day until the day of HCG administration.	Drug: Triptorelin and recombinant FSH; Women in Triptorelin and recombinant FSH arm receive a fixed dose of 0.05 mg of Triprorelin from the 1 day of the menstrual cycle followed by a fixed dose of 300 IU of recombinant FSH starting 3 day untill the day of HCG administration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Clinical pregnancy rate	Time Frame: until 12th gestational week

Secondary Outcome Measures

Outcome Measure	Time Frame
Implantation rate	Time Frame: until 12th gestational week

Collaborators and Investigators

• Sponsor: Bioroma
• Investigators: Principal Investigator: Mauro Schimberni, MD, Bioroma

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (ANTICIPATED): November 1, 2014
• Study Completion (ANTICIPATED): December 1, 2014

Study Registration Dates

• First Submitted: February 20, 2014
• First Submitted That Met QC Criteria: February 21, 2014
• First Posted (ESTIMATE): February 25, 2014

Study Record Updates

• Last Update Posted (ESTIMATE): February 25, 2014
• Last Update Submitted That Met QC Criteria: February 21, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Keywords: Poor responders, IVF, GnRH agonist, GnRH antagonist, recombinant FSH
• Additional Relevant MeSH Terms: Infertility; Infertility, Female; Physiological Effects of Drugs; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Luteolytic Agents; Triptorelin Pamoate; Prolactin Release-Inhibiting Factors
• Other Study ID Numbers: BRM001