NCT00883766

Brief Summary

The aim of this study is to compare two different IVF-stimulation protocols in patients affected by PCOS: the use of a Gonadotropin-releasing hormone (GnRH) - antagonist starting on day 1 of controlled ovarian hyperstimulation (COH) versus a standard long agonist protocol; in order to assess whether it affects the number and quality of Metaphase II (MII) oocytes while reducing the risk of hyperstimulation. Since PCOS patients are also likely to be insulin resistant we also aim to evaluate how metformin affects tha IVF stimulation outcome.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
172

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started Apr 2009

Typical duration for not_applicable

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

April 1, 2009

Completed
16 days until next milestone

First Submitted

Initial submission to the registry

April 17, 2009

Completed
3 days until next milestone

First Posted

Study publicly available on registry

April 20, 2009

Completed
3.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2012

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2012

Completed
Last Updated

July 20, 2012

Status Verified

October 1, 2010

Enrollment Period

3.2 years

First QC Date

April 17, 2009

Last Update Submit

July 19, 2012

Conditions

Polycystic Ovary SyndromeIn Vitro Fertilization

Keywords

Polycystic Ovary SyndromeGnRH AntagonistLong Agonist ProtocolOHSS

Outcome Measures

Primary Outcomes (1)

  • Number of Oocytes MII retrieved per patient

    1 Day

Secondary Outcomes (3)

  • Fertilization rates

    24 hours after pick-up

  • Clinical pregnancy rates

    4 weeks after pick-up

  • Incidence of OHSS

    From ovulation triggering to two weeks after pick-up

Study Arms (2)

Long agonist protocol

ACTIVE COMPARATOR
Other: Controlled ovarian hyperstimulation for IVF with a long agonist protocol

Antagonist protocol

EXPERIMENTAL
Other: Controlled ovarian hyperstimulation for IVF with an antagonist protocol

Interventions

Controlled ovarian hyperstimulation for IVF with a long agonist protocolOTHER

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)

Long agonist protocol
Controlled ovarian hyperstimulation for IVF with an antagonist protocolOTHER

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)

Antagonist protocol

Eligibility Criteria

Age18 Years - 37 Years
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • PCOS patients according to the Rotterdam consensus 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

You may not qualify if:

  • Congenital adrenal hyperplasia
  • Cushing's syndrome
  • Androgen-producing tumours
  • Hyperprolactinaemia and thyroid dysfunction
  • Age \> 38 years
  • Serum FSH levels \> 10 mIU/ml

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Institut Universitari Dexeus

Barcelona, Barcelona, 08028, Spain

Location

Related Publications (7)

  • 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.

    PMID: 16123051BACKGROUND

  • 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.

    PMID: 11925376BACKGROUND

  • 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.

    PMID: 17347165BACKGROUND

  • 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.

    PMID: 14678281BACKGROUND

  • 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.

    PMID: 12524053BACKGROUND

  • 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.

    PMID: 17767003BACKGROUND

  • 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.

    PMID: 16501038BACKGROUND

Related Links

MeSH Terms

Conditions

Polycystic Ovary Syndrome

Condition Hierarchy (Ancestors)

Ovarian CystsCystsNeoplasmsOvarian DiseasesAdnexal DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital DiseasesGonadal DisordersEndocrine System Diseases

Study Officials

  • Fulvia Mancini, M.D. PhD

    Department of Obstetric, Gynecology and Reproductive Medicine

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER

Study Record Dates

First Submitted

April 17, 2009

First Posted

April 20, 2009

Study Start

April 1, 2009

Primary Completion

June 1, 2012

Study Completion

June 1, 2012

Last Updated

July 20, 2012

Record last verified: 2010-10

Locations

ES(1)