To investigate if the use of different stimulation protocols / GnRH-analogues affects embryo developmental kinetics after IVF treatment. We hypothesize that GnRH analogues differentially affect embryo development through differences in follicular…
ID
Source
Brief title
Condition
- Sexual function and fertility disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The aim of the study is to analyze the effect of the GnRH analogue used on
embryo developmental kinetics. The main study parameter is the time needed from
completion of the first cleavage division until reaching the 4-cell stage,
determined by retrospective analysis of time lapse recordings.
Secondary outcome
Secondary study parameters on embryo developmental kinetics will be the time
interval between:
- Disappearance of the pronuclei and first cleavage of the embryo, as well as
reaching the 2-cell, 4-cell and 8-cell stage;
- Completion of first cleavage and reaching the 3-cell and 8-cell stage;
- The 3-cell and 4-cell stage.
We will also analyze embryo morphology on Day 3 and determine the proportion of
good quality embryos, as defined by embryos with 8 cells, <20% fragmentation,
equally sized blastomeres and no irregularities observed in the cytoplasm. For
the embryo that is selected for transfer, the implantation potential will be
recorded.
Background summary
Selection of the best embryo for transfer is the key to achieve high
implantation rates and is still largely based on morphological assessments at
fixed time points. Newly emerging techniques, enabling safe time-lapse
photography of embryo development, demonstrate that morphological changes occur
rapidly around the time of cell division, with an initial increase in
fragmentation, followed by re-uptake. Therefore, if observed at the wrong
moment, good quality embryos can be erroneously classified as poor quality.
During a previous randomized trial, comparing the effect of ovarian stimulation
protocols with GnRH agonist or GnRH antagonist co-treatment on embryo
aneuploidy rates, we made observations indicating that GnRH antagonist embryos
may be developmentally delayed in reaching the 8-cell stage on Day 3. If
confirmed, optimal timing of embryo morphology assessment may be different from
what is routine practice in labs optimized for GnRH agonist stimulation
protocols. Morphological selection of GnRH antagonist embryos may thus occur at
a suboptimal moment and lead to selection of the *wrong* embryo. Optimizing
timing of embryo morphology assessment for GnRH antagonist embryos may thus
result in improved embryo implantation rates.
Study objective
To investigate if the use of different stimulation protocols / GnRH-analogues
affects embryo developmental kinetics after IVF treatment. We hypothesize that
GnRH analogues differentially affect embryo development through differences in
follicular growth during stimulation. To chart these changes, we aim to perform
time-lapse photography using the EmbryoScope* on embryos from IVF patients,
randomized for either GnRH-agonist or antagonist co-treatment. To analyze
underlying molecular pathways, mRNA and protein expression of a panel of
relevant genes will be assayed in cumulus cells from individual oocytes in
relation to the analogue used. Furthermore we will perform RNA-sequencing. To
explain variations in gene expression, we will also assay epigenetic
programming in these cumulus cells.
Study design
Prospectively randomized multicenter interventional trial in 82 women
undergoing IVF treatment.
Randomization to one of two routinely applied ovarian stimulation protocols:
(1) GnRH agonist long stimulation protocol with daily administration of
recombinant FSH.
(2) GnRH antagonist stimulation protocol starting with administration of rFSH
on cycle day 5, with GnRH antagonist treatment start on stimulation day 1.
Study burden and risks
This study will not interfere with the standard IVF and embryo transfer
procedures, except that embryos will be cultured in the EmbryoScope*. Available
data from international studies and our own validation show that this is a safe
incubator for human embryos and may even improve culture conditions. Cumulus
cells are normally discarded. The study will not negatively affect pregnancy
rates, nor will it affect the women*s or children*s health. Insight gained from
this study will help increase our understanding of factors influencing embryo
development and may improve embryo selection and IVF outcomes for future IVF
patients.
Dr. Molewaterplein 40
Rotterdam 3015 GD
NL
Dr. Molewaterplein 40
Rotterdam 3015 GD
NL
Listed location countries
Age
Inclusion criteria
Female age <= 37 years
BMI < 32 kg/m2
Regular cycle (25-35 days)
Partner with normal semen parameters (Volume: >= 1.5 ml, concentration: >15*10^6/ml, progressively motile sperm > 32%, so with a VCM >= 7.2)
Standard indication for IVF
Undergoing first or second IVF cycle
Exclusion criteria
Indication for ICSI
Endometriosis
Expected poor response
One previous IVF treatment not resulting in embryo transfer
Medical contra indication for pregnancy or IVF treatment
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
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In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2011-005919-91-NL |
| CCMO | NL37697.000.12 |