Polycystic Ovary Syndrome (PCOS) and In Vitro Fertilization (IVF): A Comparison Between Standard Long Protocol Versus an Antagonist Protocol Starting on Day 1
NCT ID: NCT00883766
Last Updated: 2012-07-20
Study Results
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Basic Information
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TERMINATED
NA
172 participants
INTERVENTIONAL
2009-04-30
2012-06-30
Brief Summary
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Detailed Description
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Our results are in accordance with this meta-analysis. Therefore, if the pregnancy and abortion rates in PCOS and controls do not differ, the main problem when dealing with PCOS in IVF is OHSS. This condition can be approached by using an antagonist instead of an agonist, by changing the kind of ovulation trigger and by co-treating patients with metformin.
* One of the currently debatable issues regarding the use of GnRH antagonists refers to the timing of GnRH antagonist initiation. A fixed protocol starting antagonist arbitrarily on Day 6 of stimulation has been used in all introductory comparative trials employing a daily antagonist administration (2). Following these trials, a flexible antagonist initiation by a follicle of 14-15 mm has been evaluated. Currently, initiation of antagonist in the early follicular phase in PCOS patients has been performed by Lainas and coll. (3) who treated patients with PCOS either with a long GnRH agonist scheme or a fixed day-1 GnRH antagonist protocol and concluded that initiation of GnRH antagonist concomitantly with recombinant FSH on day 1 is associated with an earlier follicular growth and a different hormonal environment during the follicular phase when compared with the long agonist protocol. This may lead to a reduction in the incidence of OHSS.
* Over the past 15 years, it has become increasingly recognized that insulin resistance is central to the pathogenesis of the PCOS (4). Metformin, a biguanide insulin-lowering agent, has been extensively investigated in the management of PCOS. Two recent systematic reviews (5, 6) demonstrated that metformin improves reproductive function of some women with PCOS. Metformin also appeared to improve the outcomes of ovulation induction therapies when combined with clomiphene and gonadotrophin. Tang et al. recently studied PCOS overweight patients undergoing IVF to whom they administered 850 mg bid or placebo 28 days prior to the stimulation (7). They concluded that short-term co-treatment with metformin for patients with PCOS undergoing IVF/ICSI cycles does not improve the response to stimulation but significantly improves the pregnancy outcome and reduces the risk of OHSS.
The aim of this study is to verify if using an antagonist the number and quality of MII oocytes is equal compared to a standard long agonist protocol while reducing the risk of hyperstimulation.
Outcome measures:
Primary endpoints:
* Oocytes MII Secondary endpoints
* Fertilization rates
* Pregnancy rates
* Miscarriage rates
* Incidence of OHSS
Conditions
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Long agonist protocol
Controlled ovarian hyperstimulation for IVF with a long agonist protocol
Day 1 of 1st menstruation: OC for 18-21 days (Microdiol ®) + Metformin (Dianben ®) 850 x 2/day if: BMI\>30, HOMA \>3.8, G/I ratio \<4.5
Day 18-24 of cycle: Leuprorelin (Procrin ®) 0.1 s.c. for 14-21 days
Day 1 of 2nd menstruation (=Day 1 COH cycle): Hormonal profile (FSH, LH, E2, Pg, T, SHBG), Ultrasonography to exclude cyst \>10 mm
Day 2of COH cycle: rFSH (Gonal F ®) 150 IU/day for 4 days; Leuprorelin (Procrin ®) 0.1 s.c. (and following days)
Day 7 of COH (and following): Measure FSH, LH, E2, Pg + Ultrasound
Day before HCG: stop rFSH
Day HCG: measure FSH, LH, E2, Pg, administer 250 mcg Choriogonadotropin-alfa ( Ovitrelle®)
Day of pick-up: Follicular fluid from 1st follicle to be centrifuged and stored at -20°C
Day 7 after pick-up: ultrasound, patient evaluation.
Day 14 after pick-up: HCG in blood
Day 28 after pick-up: Ultrasound to visualize heart beat if pregnancy test positive
(OC= oral contraceptive; COH= Controlled Ovarian Hyperstimulation)
Antagonist protocol
Controlled ovarian hyperstimulation for IVF with an antagonist protocol
Day 1 of pre COH-cycle: OC for 18-21 days (Microdiol ®) + Metformin (Dianben ®) 850 x 2/day if: BMI\>30, HOMA \>3.8, G/I ratio \<4.5
Day 3 of free-pill interval: Hormonal profile (FSH, LH, E2, Pg, T, SHBG), Ultrasonography to exclude cyst \>10 mm
Day 5 of free-pill interval (=Day 1 COH cycle): Cetrorelix acetate (Cetrotide®) 0.25 mg s.c. + rFSH (Gonal F ®) 150 IU/day (and following days)
Day 3-4-10 of COH cycle: measure FSH, LH, E2, Pg + ECO
Day before HCG: stop rFSH + cetrorelix
Day HCG: measure FSH, LH, E2, Pg, administer 250 mcg Choriogonadotropin-alfa ( Ovitrelle®)
Day of pick-up: Follicular fluid from 1st follicle to be centrifuged and stored at -20°C
Day 7 after pick-up: ultrasound, patient evaluation.
Day 14 after pick-up: HCG in blood
Day 28 after pick-up: Ultrasound to visualize heart beat if pregnancy test positive (OC= oral contraceptive; COH= Controlled Ovarian Hyperstimulation)
Interventions
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Controlled ovarian hyperstimulation for IVF with a long agonist protocol
Day 1 of 1st menstruation: OC for 18-21 days (Microdiol ®) + Metformin (Dianben ®) 850 x 2/day if: BMI\>30, HOMA \>3.8, G/I ratio \<4.5
Day 18-24 of cycle: Leuprorelin (Procrin ®) 0.1 s.c. for 14-21 days
Day 1 of 2nd menstruation (=Day 1 COH cycle): Hormonal profile (FSH, LH, E2, Pg, T, SHBG), Ultrasonography to exclude cyst \>10 mm
Day 2of COH cycle: rFSH (Gonal F ®) 150 IU/day for 4 days; Leuprorelin (Procrin ®) 0.1 s.c. (and following days)
Day 7 of COH (and following): Measure FSH, LH, E2, Pg + Ultrasound
Day before HCG: stop rFSH
Day HCG: measure FSH, LH, E2, Pg, administer 250 mcg Choriogonadotropin-alfa ( Ovitrelle®)
Day of pick-up: Follicular fluid from 1st follicle to be centrifuged and stored at -20°C
Day 7 after pick-up: ultrasound, patient evaluation.
Day 14 after pick-up: HCG in blood
Day 28 after pick-up: Ultrasound to visualize heart beat if pregnancy test positive
(OC= oral contraceptive; COH= Controlled Ovarian Hyperstimulation)
Controlled ovarian hyperstimulation for IVF with an antagonist protocol
Day 1 of pre COH-cycle: OC for 18-21 days (Microdiol ®) + Metformin (Dianben ®) 850 x 2/day if: BMI\>30, HOMA \>3.8, G/I ratio \<4.5
Day 3 of free-pill interval: Hormonal profile (FSH, LH, E2, Pg, T, SHBG), Ultrasonography to exclude cyst \>10 mm
Day 5 of free-pill interval (=Day 1 COH cycle): Cetrorelix acetate (Cetrotide®) 0.25 mg s.c. + rFSH (Gonal F ®) 150 IU/day (and following days)
Day 3-4-10 of COH cycle: measure FSH, LH, E2, Pg + ECO
Day before HCG: stop rFSH + cetrorelix
Day HCG: measure FSH, LH, E2, Pg, administer 250 mcg Choriogonadotropin-alfa ( Ovitrelle®)
Day of pick-up: Follicular fluid from 1st follicle to be centrifuged and stored at -20°C
Day 7 after pick-up: ultrasound, patient evaluation.
Day 14 after pick-up: HCG in blood
Day 28 after pick-up: Ultrasound to visualize heart beat if pregnancy test positive (OC= oral contraceptive; COH= Controlled Ovarian Hyperstimulation)
Eligibility Criteria
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Inclusion Criteria
* Presence of both ovaries
* Absence of endometriomas detected at ultrasound
* FSH \< 10 IU/L on day 3 of the cycle
* E2 \< 80 pg/mL, and Pg \< 1.6 ng/mL at initiation of stimulation
Exclusion Criteria
* Cushing's syndrome
* Androgen-producing tumours
* Hyperprolactinaemia and thyroid dysfunction
* Age \> 38 years
* Serum FSH levels \> 10 mIU/ml
18 Years
37 Years
FEMALE
No
Sponsors
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Fundacion Dexeus
OTHER
Responsible Party
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Departamento de Obstetricia, Ginecologia y Reproducción
Principal Investigators
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Fulvia Mancini, M.D. PhD
Role: PRINCIPAL_INVESTIGATOR
Department of Obstetric, Gynecology and Reproductive Medicine
Locations
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Institut Universitari Dexeus
Barcelona, Barcelona, Spain
Countries
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References
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Heijnen EM, Eijkemans MJ, Hughes EG, Laven JS, Macklon NS, Fauser BC. A meta-analysis of outcomes of conventional IVF in women with polycystic ovary syndrome. Hum Reprod Update. 2006 Jan-Feb;12(1):13-21. doi: 10.1093/humupd/dmi036. Epub 2005 Aug 25.
Al-Inany H, Aboulghar M. GnRH antagonist in assisted reproduction: a Cochrane review. Hum Reprod. 2002 Apr;17(4):874-85. doi: 10.1093/humrep/17.4.874.
Lainas TG, Petsas GK, Zorzovilis IZ, Iliadis GS, Lainas GT, Cazlaris HE, Kolibianakis EM. Initiation of GnRH antagonist on Day 1 of stimulation as compared to the long agonist protocol in PCOS patients. A randomized controlled trial: effect on hormonal levels and follicular development. Hum Reprod. 2007 Jun;22(6):1540-6. doi: 10.1093/humrep/dem033. Epub 2007 Mar 8.
Tsilchorozidou T, Overton C, Conway GS. The pathophysiology of polycystic ovary syndrome. Clin Endocrinol (Oxf). 2004 Jan;60(1):1-17. doi: 10.1046/j.1365-2265.2003.01842.x. No abstract available.
Costello MF, Eden JA. A systematic review of the reproductive system effects of metformin in patients with polycystic ovary syndrome. Fertil Steril. 2003 Jan;79(1):1-13. doi: 10.1016/s0015-0282(02)04554-5.
Moll E, van der Veen F, van Wely M. The role of metformin in polycystic ovary syndrome: a systematic review. Hum Reprod Update. 2007 Nov-Dec;13(6):527-37. doi: 10.1093/humupd/dmm026. Epub 2007 Sep 1.
Tang T, Glanville J, Orsi N, Barth JH, Balen AH. The use of metformin for women with PCOS undergoing IVF treatment. Hum Reprod. 2006 Jun;21(6):1416-25. doi: 10.1093/humrep/del025. Epub 2006 Feb 24.
Related Links
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Related Info
Other Identifiers
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DEX002
Identifier Type: -
Identifier Source: org_study_id