Clinical trial NCT02372279: Prospective Randomized Study to Evaluate the Effect of Embryonic Observation on the Gestation (PROdE)
Official title: Prospective Randomized Study to Evaluate the Effect of Embryonic Observation on the Live Birth Rate (LBR)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Placenta; Implantation
Keywords: Embryo development
Implantation
In vitro fertilization
Lead sponsor: Instituto Bernabeu
Sponsor class: OTHER
First posted: 2015-02-26
Enrollment: 193
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: In a conventional in vitro fertilization (IVF) cycle, daily microscopic observation of embryos outside the incubator to assess their morphology and establish a selection process is performed. In this way it is possible to know which embryo or embryos have greater implantantion capacity and will be transferred to the uterus to obtain a viable pregnancy. However, these observations can produce deleterious effects on embryo development due to changes in temperature, pH and osmolarity of the culture media, as well as a negative effect of direct light microscope for observation. This project aims to test the hypothesis that non-embryonic observation produces a beneficial effect on embryo quality until day 5 of development (blastocyst stage) and, therefore, on rates of implantation and ongoing gestation, compared with the conventional protocol of observations under the inverted microscope on days two, three and five of development.

Detailed description: The present study is a prospective double-blind randomised controlled trial (RCT) approved by a local Ethics Committe. Summarily, in the control group we did three embryo observations outside the incubator as we usually do in our conventional protocol: day 2, day 3 and day 5, just before ET; in the study group we performed a unique embryo observation on day 5 before ET. All the subjects that participated in the study were informed and gave us their consent to take part on it.

The inclusion criteria of the study were: first cycle of ART treatment with conventional IVF or ICSI with donated eggs, normal uterine cavity and a single or double embryo transfer, always performed on day 5 at blastocyst stage.

The exclusion criteria were the following: patients above 50 years old, patients that were diagnosed with recurrent implantation failure (RIF) and/or recurrent pregnancy loss (RPL) or uterine pathologies, body mass index \>30 kg/m2, the use of seminal samples coming from donors or testicular origin and cycles that included preimplantational genetic testing (PGT).

LBR was the main outcome of our study, defined as the number of deliveries that resulted in a live born neonate, expressed per 100 embryo transfers (Zegers- Hochschild et al., 2009). Secondary efficacy endpoints were positive hCG rate (\>5 mUI/mL, assessed in serum 14 days after oocyte retrieval), implantation rate (number of gestational sacs observed divided by the number of embryos transferred, expressed as a percentage, %), ongoing pregnancy rate, defined as a pregnancy with a detectable heart rate at 12 weeks of gestation or beyond and miscarriage (loss of a pregnancy after 12 weeks of gestation).

In addition, we assessed the next IVF laboratory parameters: fertilization rate, blastocyst formation rate on day 5, blastocyst quality, number of transferred embryos and number of usable blastocysts (number of blastocysts transferred and frozen).

The sample size calculation was based on the primary outcome. We assumed a live birth rate of 40% in the control group, compared to 50% in the non-observational group deduced from previous studies. By applicating the sample size calculation program, 776 patients (388 per group) were required in order to detect a risk difference (RD) of 10% between the two groups in the final analysis, with a power of 80% at a two-sided, adjusted alpha-level of 0.05. A follow-up loss rate of 10% was estimated.

Eligibility criteria: Inclusion Criteria:

* First cycle of ART treatment with conventional IVF or ICSI with donated eggs.
* Normal uterine cavity and a single or double embryo transfer, always performed on day 5 at blastocyst stage.

Exclusion Criteria:

* Patients above 50 years old, patients that were diagnosed with recurrent implantation failure (RIF) and/or recurrent pregnancy loss (RPL) or uterine pathologies,
* Body mass index \>30 kg/m2.
* The use of seminal samples coming from donors or testicular origin.
* Cycles that included preimplantational genetic testing (PGT).

Primary outcomes:
measure: Live Birth Rate
timeFrame: Nine months after treatment.
Secondary outcomes:
measure: Positive hCG rate
timeFrame: 14 days after oocyte retrieval.
measure: Implantation rate
timeFrame: 6-7 weeks after oocyte retrieval.
measure: Ongoing pregnancy rate
timeFrame: 12 weeks after B-hCG positive test
measure: Miscarriage rate
timeFrame: From 12 weeks after gestation to delivery
measure: Fertilization rate
timeFrame: 16-18 hours after microinjection or insemination
measure: Blastocyst formation rate on day 5
timeFrame: 5 days after microinjection or insemination.
measure: Blastocyst quality
timeFrame: 5 days after microinjection or insemination.
measure: Number of usable blastocysts
timeFrame: 5 days after microinjection or insemination.
Other outcomes:
Locations:
city: Alicante
country: Spain
facility: Instituto Bernabeu
Study officials:
affiliation: Instituto Bernabeu
name: Jorge Ten Morro, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Kalleas D, McEvoy K, Horne G, Roberts SA, Brison DR. Live birth rate following undisturbed embryo culture at low oxygen in a time-lapse incubator compared to a high-quality benchtop incubator. Hum Fertil (Camb). 2022 Feb;25(1):147-153. doi: 10.1080/14647273.2020.1729423. Epub 2020 Feb 26.