Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT05721495 |
| Other study ID # |
PI-0353-2016 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
September 1, 2017 |
| Est. completion date |
November 30, 2022 |
Study information
| Verified date |
January 2023 |
| Source |
University Hospital Virgen de las Nieves |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Single embryo transfer decreases the multiple pregnancy rate and its complications. However,
studies are needed to help increase the effectiveness of this technique to increase its use,
which undoubtedly improves the safety of our patients.
Objectives:
To assess the results of IVF / ICSI cycles with single embryo transfer, in terms of both
pregnancy and live birth rates, comparing a group of patients in which an elective delayed
cryotransfer of an embryo without fresh transfer is performed (experimental group ), with
patients in whom a fresh embryo is transferred electively.
Methodology:
A prospective randomized clinical trial with two arms in parallel, not blinded, including 138
couples using an IVF / ICSI cycle at the Reproduction Unit of the Hospital Universitario
Virgen de las Nieves de Granada. The inclusion criteria classify them as having a good
reproductive prognosis, and the patients will follow an ovulation treatment protocol with
GnRH agonists or antagonists. Couples will undergo an IVF / ICSI cycle, randomly assigned to:
- Group I (experimental): fresh transfer is not performed, the best quality embryo is
cryopreserved. Elective transfer in a later cycle of the cryopreserved embryo.
- Group II (control): fresh transfer of the best quality embryo.
Description:
The study has been designed as a prospective, randomized, two-arm, parallel, unblinded study,
during which the investigators will include 138 couples (69 in each group) of IVF / ICSI
users. Cycles canceled or punctured but without embryo transfer (either due to not obtaining
oocytes, non-fertilization or arrest of embryonic development) will not be included in the
study. The assignment of the couples to each of the groups will be carried out by means of a
consecutive random sampling procedure. The randomization list will be created specifically
for this project and will be kept safely by someone not included in the research team:
- Group I (experimental): fresh transfer is not performed, the best quality embryo is
cryopreserved. Elective transfer in a later cycle of the cryopreserved embryo.
- Group II (control): fresh transfer of the best quality embryo.
Subjects of study:
Patients who come to the Human Reproduction Unit of the Virgen de las Nieves University
Hospital to perform a first or second cycle of IVF / ICSI. Couples will be selected according
to inclusion criteria that classify them as good reproductive prognosis (which is consistent
with the usual eSET practice).
Couples will be able to participate in the study for only one cycle. Each couple will be
interviewed to explain the characteristics of the study and will be given an Information
Sheet. Written informed consent must be obtained from each couple. The person outside the
research team who is guarding the randomization list will assign the corresponding treatment
group.
Before starting the study, ethical approval was processed by the Ethics Committee through the
Ethics Portal for Biomedical Research of Andalusia.
For the objective of assesing the null hypothesis that includes the equality of live birth
rates in the group of women who undergo an elective deferred transfer of a single embryo and
the group who undergo elective transfer of a fresh embryo, a power of 80% has been
established to detect statistically significant differences by means of a bilateral
Chi-square test for two independent samples, taking into account that the level of
significance is 5%, and assuming that the proportion in the group of women who undergo a
fresh transfer is 50.9%, the proportion in the group of women who receive the deferred
elective transfer is 78%, and that the proportion of women with respect to the total is 50%,
it will be necessary to include 48 women in each group, with the objetive to obtain 96
experimental units in the study. Taking into account that the expected dropout rate is three
out of ten women, it will be necessary to include 69 women per group. The 138 women will be
assigned to one of the groups using a random procedure, following a sequence of random
numbers generated by specific software (Epidat, Epidemiological Data Analysis Program
Tabulated. Version 3.1).
Methodology The patients must follow an ovulation stimulation treatment, in order to achieve
multiple follicular development. A so-called "long analog" GnRH agonist protocol will be
used. This consists of administering from day 22 of the cycle 0.1 mg / day of GnRH analog
(Decapeptyl 0.1; Lasa, Barcelona, Spain) until the day on which the administration of
gonadotropin is started, in which the dose is reduced at 50% until the day of hCG. After
10-14 days of administration of the agonist, the pituitary restraint is checked by means of
ovarian vaginal ultrasound (absence of follicles and cysts) and serum estradiol determination
(<50 pg / mL). If this medical hypophysectomy is confirmed, 300 IU of recombinant FSH (FSHr)
is administered per day (Gonal F, Serono, Madrid, Spain) for two days, and 150 IU of FSHr
from the 3rd to the 7th day. On this day, ultrasound monitoring of follicular development and
serum estradiol determination are performed in order to once again adjust the dose of rFSH to
each patient. Once the follicular response is adequate (more than 3 ovarian follicles greater
than 18 mm in diameter), ovulation is triggered using 6,500 IU of hCG (Ovitrelle, Merck,
Darmstadt, Germany).
IVF / ICSI and embryo culture will then be performed. To perform sperm microinsemination
(ICSI) it is necessary to remove the cumulus and radiated crown from the oocyte. To
decumulate, the crown-oocyte cluster complex is submerged in a solution with 80 IU / mL of
hyaluronidase (HYASE, IVF Science Scandinavia, Gothenburg, Sweden) for 10-20 seconds,
aspirating the complex several times using a pasteur pipette. The microinsemination technique
is performed under an inverted microscope with Eppendorf and Narishigue micromanipulators and
microinjectors. In Vitro Fertilization (IVF) is performed in a five-well plate, depositing
0.5 mL of IVF medium (Vitrolife, Sweden) and 0.5 mL of Ovoil (Vitrolife, Sweden) in each
well. Five cumulus are left per well and 100,000 sperm / mL are added. In both cases, the
oocytes are cultured in a Thermo-Fisher incubator, within a morphokinetic platform
(PrimoVision) that takes photographs of them every 5-10 minutes. The following days are
evaluated for classification, choosing the one with the best implantation potential according
to the division times measured by morphokinetics and the morphological criteria of the
Spanish Association for the Study of Reproduction Biology (ASEBIR) reviewed in 2015.
The embryo transfer will be carried out in group 2 on the third day choosing the best embryo
according to the previous criteria. In group 1, the embryos will be cryopreserved by
vitrification, selecting the best one for delayed transfer. The commercial vitrification
media (Medicult Vitrification, Denmark) and the storage device will be Cryoleaf (McGill
Cryoleaf, Medicult, Denmark). All cryopreserved embryos will be stored in liquid nitrogen at
-196ºC in storage cylinders (Air Liquide, France). The day before cryotransfer the embryo is
devitrified, using the thawing kit (Medicult Warming, Denmark). At the end, the embryo is
washed in G2 medium (Vitrolife), leaving it in culture until the next day, after evaluating
the embryo quality and cryosurvival (percentage of lysed cells). The woman's endometrium is
prepared by treatment with estradiol valerate and progesterone. On the day of cryotransfer,
embryo quality is assessed again, with emphasis on embryo division. Cryotransfer is performed
using the same technique as transfer.
Study limitations The project has been carried out taking into account the resources
available in the Human Reproduction Unit of the University Hospital Virgen de las Nieves, and
therefore there do not seem to be any limitations in this regard.
The study could be completed by performing a preimplantation genetic diagnosis to determine
if there are embryonic genetic alterations prior to intrauterine transfer, but this technique
is not yet performed in our Unit. Likewise, blastocyst transfer can increase pregnancy rates,
but by increasing the cancellation rate of embryo transfer, so it is not routinely performed
in our Unit.
