Prospective Randomized Study to Evaluate the Effect of Embryonic Observation on the Gestation (PROdE) (PROdE)

June 21, 2021 updated by: Jorge Ten Morro, Instituto Bernabeu

Prospective Randomized Study to Evaluate the Effect of Embryonic Observation on the Live Birth Rate (LBR)

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

193

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • Alicante, Spain, 03016
        • Instituto Bernabeu

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: No embryo observation (NEO)
Study group. No embryonic observation from day one to day five of embryo development.
Experimental: Embryo observation (EO)
Control group. Conventional embryonic observations performed in day two, three and five of embryo development.
Other: Embryo observation
In EO group, conventional observations will be made.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Live Birth Rate
Time Frame: Nine months after treatment.
The number of deliveries that resulted in a live born neonate, expressed per 100 embryos
Nine months after treatment.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Positive hCG rate
Time Frame: 14 days after oocyte retrieval.
Number of treatments with a level of BhCG >5 mUI/mL, assessed in serum.
14 days after oocyte retrieval.
Implantation rate
Time Frame: 6-7 weeks after oocyte retrieval.
Number of gestational sacs observed divided by the number of embryos transferred. expressed as a percentage, %.
6-7 weeks after oocyte retrieval.
Ongoing pregnancy rate
Time Frame: 12 weeks after B-hCG positive test
Defined as a pregnancy with a detectable heart rate at 12 weeks of gestation or beyond.
12 weeks after B-hCG positive test
Miscarriage rate
Time Frame: From 12 weeks after gestation to delivery
Loss of a pregnancy after 12 weeks of gestation.
From 12 weeks after gestation to delivery
Fertilization rate
Time Frame: 16-18 hours after microinjection or insemination
Number of fertilized oocytes out of the total microinjected or inseminated.
16-18 hours after microinjection or insemination
Blastocyst formation rate on day 5
Time Frame: 5 days after microinjection or insemination.
Number of embryos that reach the blastocyst stage at day 5
5 days after microinjection or insemination.
Blastocyst quality
Time Frame: 5 days after microinjection or insemination.
The assessment of blastocyst morphology in several grades
5 days after microinjection or insemination.
Number of usable blastocysts
Time Frame: 5 days after microinjection or insemination.
Number of blastocysts transferred and frozen.
5 days after microinjection or insemination.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Instituto Bernabeu

Investigators

  • Principal Investigator: Jorge Ten Morro, Ph.D., Instituto Bernabeu

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 1, 2015

Primary Completion (Actual)

March 1, 2021

Study Completion (Actual)

March 1, 2021

Study Registration Dates

First Submitted

February 20, 2015

First Submitted That Met QC Criteria

February 20, 2015

First Posted (Estimate)

February 26, 2015

Study Record Updates

Last Update Posted (Actual)

June 23, 2021

Last Update Submitted That Met QC Criteria

June 21, 2021

Last Verified

June 1, 2021

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • InstitutoBernabeu

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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