Clinical trial NCT00756028: Short Versus Long Protocol for IVF and IVF+ICSI
Official title: Short Versus Long IVF-treatment. A Prospective, Consecutive and Randomized Comparative Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Infertility
Ovarian Hyperstimulation Syndrome
Quality of Life
Live Birth
Keywords: OHSS
quality of life
IVF
ICSI
GnRH-agonist
GnRH-antagonist
Lead sponsor: Hvidovre University Hospital
Sponsor class: OTHER
First posted: 2008-09-19
Enrollment: 1099
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 39
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Frequency of Ovarian Hyperstimulation Syndrome (OHSS)
timeFrame: 3 years
Secondary outcomes:
measure: Quality of life during treatment
timeFrame: 3 years
measure: Live births
timeFrame: 3 years
measure: Gene expression profiles of granulosa and cumulus cells
timeFrame: 3 years
measure: Estradiol and vascular endothelial growth factor concentrations in follicular fluid.
timeFrame: 3 years
Other outcomes:
Locations:
city: Dronninglund
country: Denmark
facility: Dronninglund Fertility Clinic
city: Hvidovre
country: Denmark
facility: Fertility Clinic, Hvidovre Hospital
Study officials:
affiliation: Hvidovre University Hospital
name: Thue Bryndorf
role: STUDY_CHAIR
affiliation: Hvidovre University Hospital
name: Helle Meinertz
role: STUDY_CHAIR
affiliation: Hvidovre University Hospital
name: Peter Hornnes
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.