Short Versus Long Protocol for IVF and IVF+ICSI

NCT ID: NCT00756028

Last Updated: 2016-01-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 1099 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-01-31
• Study Completion Date: 2015-12-31

Brief Summary

Purpose: Comparing a GnRH agonist and an antagonist protocol for IVF/ICSI with regard to

1. frequency of ovarian hyperstimulation syndrome (OHSS) (1. outcome measure)

2. quality of life (2. outcome measure)

3. live birth rate (2. outcome measure)

4. gene expression profiles of granulosa and cumulus cells, and concentrations of estradiol and vascular endothelial growth factor in follicular fluid(not only compared between GnRH agonist and antagonist protocol, but also between patients with OHSS and no OHSS and patients becoming pregnant and not becoming pregnant (2. outcome measure), and

5. number of oocytes removed per treatment, number of embryo transfers per treatment and number of spontaneous abortions per treatment (these three parameters are tertiary outcome measures).

In addition to the above mentioned efficacy outcome measures the safety outcome measure "frequency of known side-effects" will be compared between the two protocols.

Detailed Description

Patients: 1100 patients are randomized prospectively to either treatment. Stratification: =<36 y/>36 y, IVF/ICSI, and treatment centre.

Methods: OHSS is quantified by consecutive measurements of weight, abdominal diameter, ultrasound measurements of ascites and ovarian volume, paraclinical parameters, and by a systematic patient questionnaire. Furthermore it is registered if the patients have been hospitalized and/or have had ascites drainage performed due to OHSS. Data from the first 100 patients are used together with Golans OHSS-classification, to make a more precise definition of OHSS. This definition is applied prospectively on data from the remaining patients.

Quality of life is gauged by a questionnaire. Child birth rate is ascertained by a pregnancy response questionnaire and by obtaining data from the Danish National Birth Registry.

Statistics: The study is designed to be able to show a 50% reduction of OHSS comparing short to long protocol.

Conditions

Infertility; Ovarian Hyperstimulation Syndrome; Quality of Life; Live Birth

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

Patients receiving short protocol IVF/ICSI-treatment. Intervention pharmacon: GnRH-antagonist (Orgalutran®: Ganirelix)

Group Type: EXPERIMENTAL

Patients receiving short protocol IVF/ICSI-treatment.

Intervention Type: DRUG

Injection s.c. Orgalutran® (Ganirelix)0.25 mg once daily from day 5 of FSH-stimulation until HCG-day

2

Patients receiving long protocol IVF/ICSI-treatment. Intervention pharmacon: GnRH-agonist (Synarela®: Nafarelin)

Group Type: ACTIVE_COMPARATOR

Long protocol

Intervention Type: DRUG

Patients receiving long protocol IVF/ICSI-treatment. Intervention pharmacon: GnRH-agonist (Synarela®:Nafarelin)

Interventions

Patients receiving short protocol IVF/ICSI-treatment.

Injection s.c. Orgalutran® (Ganirelix)0.25 mg once daily from day 5 of FSH-stimulation until HCG-day

Intervention Type: DRUG

Long protocol

Patients receiving long protocol IVF/ICSI-treatment. Intervention pharmacon: GnRH-agonist (Synarela®:Nafarelin)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• All patients referred for infertility receiving their first IVF or IVF+ICSI treatment

Exclusion Criteria

• Previous IVF or IVF+ICSI-treatment
• Uterine anomalies
• It is necessary to perform direct sperm aspiration from husband's/partner's testicles
• Allergy to one of the intervention products
• Patient is 40 years or above

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 39 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Peter Hornnes, MD, DMSc

OTHER

Sponsor Role: lead

Responsible Party

Peter Hornnes, MD, DMSc

MD, DMSc

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Thue Bryndorf

Role: STUDY_CHAIR

Hvidovre University Hospital

Helle Meinertz

Role: STUDY_CHAIR

Hvidovre University Hospital

Peter Hornnes

Role: PRINCIPAL_INVESTIGATOR

Hvidovre University Hospital

Locations

Dronninglund Fertility Clinic

Dronninglund, , Denmark

Fertility Clinic, Hvidovre Hospital

Hvidovre, , Denmark

Countries

Denmark

References

Toftager M, Sylvest R, Schmidt L, Bogstad J, Lossl K, Praetorius L, Zedeler A, Bryndorf T, Pinborg A. Quality of life and psychosocial and physical well-being among 1,023 women during their first assisted reproductive technology treatment: secondary outcome to a randomized controlled trial comparing gonadotropin-releasing hormone (GnRH) antagonist and GnRH agonist protocols. Fertil Steril. 2018 Jan;109(1):154-164. doi: 10.1016/j.fertnstert.2017.09.020. Epub 2017 Nov 23.

Reference Type: DERIVED

PMID: 29175067 (View on PubMed)

Toftager M, Bogstad J, Lossl K, Praetorius L, Zedeler A, Bryndorf T, Nilas L, Pinborg A. Cumulative live birth rates after one ART cycle including all subsequent frozen-thaw cycles in 1050 women: secondary outcome of an RCT comparing GnRH-antagonist and GnRH-agonist protocols. Hum Reprod. 2017 Mar 1;32(3):556-567. doi: 10.1093/humrep/dew358.

Reference Type: DERIVED

PMID: 28130435 (View on PubMed)

Toftager M, Bogstad J, Bryndorf T, Lossl K, Roskaer J, Holland T, Praetorius L, Zedeler A, Nilas L, Pinborg A. Risk of severe ovarian hyperstimulation syndrome in GnRH antagonist versus GnRH agonist protocol: RCT including 1050 first IVF/ICSI cycles. Hum Reprod. 2016 Jun;31(6):1253-64. doi: 10.1093/humrep/dew051. Epub 2016 Apr 8.

Reference Type: DERIVED

PMID: 27060174 (View on PubMed)

Other Identifiers

KvL

Identifier Type: -

Identifier Source: org_study_id