The aim of the study is to show non-inferiority of a short, flare-up GnRH-agonist protocol to the GnRH-antagonist protocol, both with OC pill pre-treatment, in women undergoing in vitro fertilisation (IVF) or intracellular sperm injection (ICSI)…
ID
Source
Brief title
Condition
- Sexual function and fertility disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is the incidence of premature LH surges, defined as a
serum LH value > 10 IU/l, with or without a rise in progesterone, defined as a
value > 1 ng/ml (> 3.18 nmol/l).
Secondary outcome
Secondary endpoints include incidence of premature urine LH surges, follicular
development, number of oocytes and (top-quality) embryo*s, embryo metabolomics,
endometrial thickness, hormone levels (LH, FSH, oestradiol, progesterone),
(signs of) ovarian hyperstimulation syndrome (OHSS), cancellation rate,
fertilisation rate, implantation rate, ongoing pregnancy rate and live birth
rate. In addition, (hypo-oestrogenic) adverse events and total dose and
duration of GnRH analogue and gonadotrophin treatment will be assessed.
Background summary
In contrast to the long gonadotrophin releasing hormone (GnRH)-agonist
protocol, the GnRH-antagonist protocol is associated with the occurrence of
premature luteinizing hormone (LH) surges. In clinical practice, pre-treatment
with oral contraceptive (OC) pill is given to enhance follicle synchronisation
and, as a consequence, to minimize premature ovulation, although the latter is
still reported to occur. A so called short or flare-up GnRH-agonist protocol is
also used in clinical practice as patient-friendly alternative to the long
protocol. Little is known on the incidence of premature LH surges under this
protocol; and whether these can be pre-empted by OC pill pre-treatment.
To date, no comparison has been made between the short GnRH-agonist protocol
versus the GnRH-antagonist protocol, both combined with OC pill pre-treatment
with respect to their efficacy in preventing premature LH surges.
Study objective
The aim of the study is to show non-inferiority of a short, flare-up
GnRH-agonist protocol to the GnRH-antagonist protocol, both with OC pill
pre-treatment, in women undergoing in vitro fertilisation (IVF) or
intracellular sperm injection (ICSI) treatment with gonadotrophins. Primary
endpoint will be the incidence of premature serum LH surges.
Study design
The study has an open, prospective, multi-centre, parallel two-arm randomised
controlled design.
Intervention
1. Flare-up GnRH-agonist protocol with OC pill pre-treatment. OC pill is given
during 21±3 days of the preceding cycle. On day two of the menses after
withdrawal of the OC pill of the following cycle, triptorelin is started,
accompanied at day three by HP-hMG in a fixed dose of 150 IU. Both are given
until criteria for hCG administration are met.
2. GnRH-antagonist protocol with OC pill pre-treatment. OC pill is given during
21±3 days of the preceding cycle. On day three of the menses of the following
cycle, HP-hMG (fixed dose of 150 IU) is started and accompanied by cetrorelix
at day six of gonadotrophin administration, both given until criteria for hCG
administration are met.
Study burden and risks
This study is ethically justified, since the study has a non-inferiority design
relative to currently used treatment. During this study every participant has
an equal chance to profit from the possible benefits. The measurements during
this study will be combined as much as possible with the routine
investigations. All medication used in this study is registered for the given
indication and used in clinical practice for years. During the entire study
period possible side effects and severe adverse events will be monitored and
evaluated.
Combining the short, GnRH-agonist and *antagonist protocol with OC pill
pre-treatment probably leads to better synchronization of follicular
development and possibly better effectiveness. No untoward effects on the
treatment results (chance to become pregnant) are envisaged. Possible benefits
are improving patient comfort by minimizing the number of GnRH-analogue
injections.
Amstelveenseweg 601
1081 JC Amsterdam
NL
Amstelveenseweg 601
1081 JC Amsterdam
NL
Listed location countries
Age
Inclusion criteria
- IVF or ICSI treatment (first, second or third cycle)
- Signed informed consent
Exclusion criteria
- Women aged over 39 years
- Women with a single ovary
- Known poor responders, defined as women with a follicle count of < 4 follicles > 14 mm in a previous IVF/ICSI treatment cycle
- History or evidence of polycystic ovary syndrome (PCOS) or incipient ovarian failure (IOF)
- Severe endometriosis, stage III/IV, needing Surrey stimulation protocol
- Women with known contraindications for oral OCs
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2010-022171-56-NL |
| CCMO | NL32470.029.10 |