Clomiphene Citrate Plus Gonadotropins and GnRH Antagonist Versus Flexible GnRH Antagonist Protocol Versus Microdose GnRH Agonist Protocol in Poor Responders Undergoing IVF
1 other identifier
interventional
250
1 country
1
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_4
Started Jan 2014
Shorter than P25 for phase_4
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
January 1, 2014
CompletedFirst Submitted
Initial submission to the registry
July 22, 2014
CompletedFirst Posted
Study publicly available on registry
July 28, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 1, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
November 1, 2014
CompletedJuly 28, 2014
July 1, 2014
9 months
July 22, 2014
July 24, 2014
Conditions
Outcome Measures
Primary Outcomes (1)
Clinical pregnancy rate
Time Frame: until 12th gestational week
Secondary Outcomes (1)
implantation rate
Time Frame: until 12th gestational week
Study Arms (3)
Clomiphene citrate
EXPERIMENTALDaily FSH and LH plus Cetrorelix
EXPERIMENTALTriptorelin plus daily FSH and LH
EXPERIMENTALInterventions
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
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.
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.
Eligibility Criteria
You may qualify if:
- 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).
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Bioromalead
Study Sites (1)
Bioroma
Rome, Rome, 00197, Italy
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- SINGLE
- Who Masked
- PARTICIPANT
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 22, 2014
First Posted
July 28, 2014
Study Start
January 1, 2014
Primary Completion
October 1, 2014
Study Completion
November 1, 2014
Last Updated
July 28, 2014
Record last verified: 2014-07