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

NCT ID: NCT02372279

Last Updated: 2021-06-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

TERMINATED

Clinical Phase

NA

Total Enrollment

193 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-02-28

Study Completion Date

2021-03-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Placenta; Implantation

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

OTHER

Blinding Strategy

DOUBLE

Participants Caregivers

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

No embryo observation (NEO)

Study group. No embryonic observation from day one to day five of embryo development.

Group Type NO_INTERVENTION

No interventions assigned to this group

Embryo observation (EO)

Control group. Conventional embryonic observations performed in day two, three and five of embryo development.

Group Type EXPERIMENTAL

Embryo observation

Intervention Type OTHER

In EO group, conventional observations will be made.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Embryo observation

In EO group, conventional observations will be made.

Intervention Type OTHER

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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).
Minimum Eligible Age

18 Years

Maximum Eligible Age

50 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Instituto Bernabeu

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Jorge Ten Morro

Ph.D. Embryologist

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Jorge Ten Morro, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Instituto Bernabeu

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Instituto Bernabeu

Alicante, , Spain

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Spain

References

Explore related publications, articles, or registry entries linked to this study.

Alpha Scientists in Reproductive Medicine and ESHRE Special Interest Group of Embryology. The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting. Hum Reprod. 2011 Jun;26(6):1270-83. doi: 10.1093/humrep/der037. Epub 2011 Apr 18.

Reference Type BACKGROUND
PMID: 21502182 (View on PubMed)

Fujiwara M, Takahashi K, Izuno M, Duan YR, Kazono M, Kimura F, Noda Y. Effect of micro-environment maintenance on embryo culture after in-vitro fertilization: comparison of top-load mini incubator and conventional front-load incubator. J Assist Reprod Genet. 2007 Jan;24(1):5-9. doi: 10.1007/s10815-006-9088-3. Epub 2006 Dec 13.

Reference Type BACKGROUND
PMID: 17160731 (View on PubMed)

Gardner DK, Lane M, Stevens J, Schlenker T, Schoolcraft WB. Blastocyst score affects implantation and pregnancy outcome: towards a single blastocyst transfer. Fertil Steril. 2000 Jun;73(6):1155-8. doi: 10.1016/s0015-0282(00)00518-5.

Reference Type BACKGROUND
PMID: 10856474 (View on PubMed)

Bernabeu R, Roca M, Torres A, Ten J. Indomethacin effect on implantation rates in oocyte recipients. Hum Reprod. 2006 Feb;21(2):364-9. doi: 10.1093/humrep/dei343. Epub 2005 Nov 10.

Reference Type BACKGROUND
PMID: 16284067 (View on PubMed)

Herrero J, Tejera A, Albert C, Vidal C, de los Santos MJ, Meseguer M. A time to look back: analysis of morphokinetic characteristics of human embryo development. Fertil Steril. 2013 Dec;100(6):1602-9.e1-4. doi: 10.1016/j.fertnstert.2013.08.033. Epub 2013 Sep 29.

Reference Type BACKGROUND
PMID: 24083877 (View on PubMed)

Zhang JQ, Li XL, Peng Y, Guo X, Heng BC, Tong GQ. Reduction in exposure of human embryos outside the incubator enhances embryo quality and blastulation rate. Reprod Biomed Online. 2010 Apr;20(4):510-5. doi: 10.1016/j.rbmo.2009.12.027. Epub 2009 Dec 28.

Reference Type BACKGROUND
PMID: 20129824 (View on PubMed)

Kirkegaard K, Kesmodel US, Hindkjaer JJ, Ingerslev HJ. Time-lapse parameters as predictors of blastocyst development and pregnancy outcome in embryos from good prognosis patients: a prospective cohort study. Hum Reprod. 2013 Oct;28(10):2643-51. doi: 10.1093/humrep/det300. Epub 2013 Jul 30.

Reference Type BACKGROUND
PMID: 23900207 (View on PubMed)

Steptoe PC, Edwards RG. Birth after the reimplantation of a human embryo. Lancet. 1978 Aug 12;2(8085):366. doi: 10.1016/s0140-6736(78)92957-4. No abstract available.

Reference Type BACKGROUND
PMID: 79723 (View on PubMed)

Bognar Z, Csabai TJ, Pallinger E, Balassa T, Farkas N, Schmidt J, Gorgey E, Berta G, Szekeres-Bartho J, Bodis J. The effect of light exposure on the cleavage rate and implantation capacity of preimplantation murine embryos. J Reprod Immunol. 2019 Apr;132:21-28. doi: 10.1016/j.jri.2019.02.003. Epub 2019 Mar 4.

Reference Type BACKGROUND
PMID: 30852462 (View on PubMed)

Barberet J, Chammas J, Bruno C, Valot E, Vuillemin C, Jonval L, Choux C, Sagot P, Soudry A, Fauque P. Randomized controlled trial comparing embryo culture in two incubator systems: G185 K-System versus EmbryoScope. Fertil Steril. 2018 Feb;109(2):302-309.e1. doi: 10.1016/j.fertnstert.2017.10.008. Epub 2017 Nov 23.

Reference Type BACKGROUND
PMID: 29175066 (View on PubMed)

Armstrong S, Bhide P, Jordan V, Pacey A, Marjoribanks J, Farquhar C. Time-lapse systems for embryo incubation and assessment in assisted reproduction. Cochrane Database Syst Rev. 2019 May 29;5(5):CD011320. doi: 10.1002/14651858.CD011320.pub4.

Reference Type BACKGROUND
PMID: 31140578 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32098536 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

InstitutoBernabeu

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.