Clomiphene Citrate Plus Gonadotropins and GnRH Antagonist Versus Flexible GnRH Antagonist Protocol Versus Microdose GnRH Agonist Protocol in Poor Responders Undergoing IVF

IVF Clinical Trial

Official title:

Clomiphene Citrate Plus Gonadotropins and GnRH Antagonist Versus Flexible GnRH Antagonist Protocol Versus Microdose GnRH Agonist Protocol in Poor Responders Undergoing IVF: a Randomized Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02201914
• Other study ID #: BRM003
• Status: Recruiting
• Phase: Phase 4
• First received: July 22, 2014
• Last updated: July 24, 2014
• Start date: January 2014
• Est. completion date: November 2014

Study information

• Verified date: July 2014
• Source: Bioroma
• Contact: Mauro Schimberni, MD
• Phone: +39063334266
• Email: bioroma[@]bioroma.net
• Is FDA regulated: No
• Health authority: Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
• Study type: Interventional

Clinical Trial Summary

Poor ovarian response to stimulation in IVF cycles is a challenging and frustrating condition, due to its poor prognosis in terms of chances of pregnancy and live births. Various ovarian stimulation regimens have been tried to overcome these obstacles. A simple approach is increase the dose of the gonadotropin administration, but the results in terms of pregnancy rate are very low Another commonly used stimulation regimen is the microdose 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. However, their application in poor responders, even if in small doses and for a limited period, has been questioned as they may cause oversuppression of ovarian function, leading to a prolonged cycle and increased treatment costs without improving the outcomes.

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, offering a potential alternative in the treatment of these patients. However, randomized studies evaluating the efficacy of this regimen in poor responders did not show any improvements in pregnancy rates. Current approach have included the addition of oral agents such us clomiphene citrate (CC) to gonadotropins. Some authors have investigated the role of CC in addition to low dose of gonadotropins in mild stimulation regimen, demonstrating that, despite a small number of retrieved oocytes, good quality embryos were produced with a subsequent improvement in the fertilization rate, clinical pregnancy rate and live birth rate. The only study that evaluate the efficacy of CC in addition to high doses of gonadotropins in poor responders showed improving in number of retrieved oocytes, transferred embryos and biochemical pregnancy; however, clinical pregnancy rate and live birth rate remained low and showed no measurable increase.

The aim of this study was to compare the efficacy of the CC as an adjunctive to a high dose of gonadotropins in cycles with antagonist protocols with the microdose GnRH agonist and flexible antagonist protocols in women who responded poorly to ovarian stimulation, to determine whether this protocol may improve IVF outcomes, offering a valid alternative in poor responder patients treatment.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 250
• Est. completion date: November 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 25 Years to 44 Years

Eligibility

Inclusion Criteria:

• poor responders in a previous IVF cycle at least 3 months before at our center and undergoing a new IVF attempt 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 within the past two months

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Clomiphene Citrate
• GnRH Agonist
• GnRH Antagonist
• IVF
• Poor Responders

Intervention

Drug:
• Clomiphene citrate
patients receive clomiphene citrate 100 mg daily starting on day 2 for 5 days and 450 IU recombinant FSH and 225 IU recombinant LH daily starting on day 5; Cetrorelix 0,25 mg was administered daily when one or more follicle reached 13-14 mm in diameter until the hCG injection
• Daily FSH and LH plus Cetrorelix
Women receive an initial daily dose of 450 IU recombinant FSH and 225 IU recombinant LH starting on day 3; Cetrorelix 0,25 mg was administered daily when one or more follicle reached 13-14 mm in diameter until the hCG injection.
• Triptorelin plus daily FSH anh LH
women receive short-acting Triptorelin 0,05 mg daily starting on day 1 until the hCG injection and 450 IU recombinant FSH and 225 IU recombinant LH daily starting on day 2.

Locations

Country	Name	City	State
Italy	Bioroma	Rome

Sponsors (1)

Lead Sponsor	Collaborator
Bioroma

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical pregnancy rate		Time Frame: until 12th gestational week	Yes
Secondary	implantation rate		Time Frame: until 12th gestational week	Yes