Impact of Human Embryo Culture System on Live Birth (AGRUPADO)

Improvement of Live Birth Rate With a New Standardized Human Embryo Culture System: a Prospective, Randomized, Controlled Trial

Previous studies in human and different mammals have proved that the embryo group culture (in the same culture medium drop) using a reduced volume is associated with a better embryo development. This is due to the effect of different autocrine and paracrine factors secreted by the embryos. Besides, previous studies with embryos from human and other mammals have shown that a high oxygen concentration may have a negative effect on embryo quality due to the generation of reactive oxygen species, which cause oxidative stress. The embryo culture at low oxygen tension is correlated to better success rates in IVF/ICSI treatments.

The purpose of this study is to evaluate the combined effect of the embryo group culture and the low oxygen tension on the embryo development and the results of the IVF/ICSI treatments. The specific goal is to compare the embryo group culture in a reduced volume of medium at a low oxygen tension (5%) with the standard individual culture at an atmospheric oxygen tension (20%). The first culture condition will be applied in a K-MINC incubator (COOK Medical®), whereas the second condition will be applied using a Heracell incubator (Heraeus®).

Study Overview

• Status: Completed
• Conditions: Embryo Culture
• Intervention / Treatment: Procedure: New Culture Condition; Procedure: Standard Culture Condition

• Study Type: Interventional
• Enrollment (Actual): 182
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Seville
    • Sevilla, Seville, Spain, 41011
      • IVI Sevilla

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 38 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• <38 years (with own oocytes) / <45 years (with oocyte donation).
• First treatment with own oocytes / any treatment with oocyte donation.
• ≥10 oocytes with a diameter of ≥10 mm.

Exclusion Criteria:

• Diseases that affect endometrial receptivity: endometriosis, hydrosalpinx, ovarian hyperstimulation syndrome, obesity, endocrinopathies, thrombophilia, congenital or acquired uterine anomalies.
• Patients under a treatment with genetic preimplantation diagnosis.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: New Culture Condition; Intervention group embryos cultured grouped under low oxygen tension in benchtop incubators.	Procedure: New Culture Condition; Intervention group embryos cultured grouped (5 embryos per drop) under low oxygen tension (5%) in benchtop incubators.
Active Comparator: Standard Culture Condition; Control group embryos cultured individually under atmospheric oxygen tension in large-box incubators.	Procedure: Standard Culture Condition; Control group embryos cultured individually (1 embryo per drop) under atmospheric oxygen tension (20%) in large-box incubators.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical pregnancy rate	Confirmed when a gestational sac with heartbeat was observed in the uterus by ultrasound examination, performed 2-3 weeks after the positive result of the beta-hCG pregnancy test.	April 2013 - October 2016

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Implantation rate	Number of embryos implanted per number of embryos transferred	April 2013 - October 2016
Live birth rate	Number of newborns per pregnancy achieved	April 2013 - October 2016

Other Outcome Measures

Outcome Measure	Time Frame
Fecundation rate	April 2013 - October 2016
Mean number of viable embryos	April 2013 - October 2016
Blastocyst rate	April 2013 - October 2016
Mean number of embryos transferred	April 2013 - October 2016
Live Birth rate per embryos transferred	April 2013 - October 2016
Multiple pregnancy rate	April 2013 - October 2016
Clinical miscarriage rate	April 2013 - October 2016

Collaborators and Investigators

• Sponsor: IVI Sevilla
• Investigators: Study Chair: Myriam Ruiz, MSc, IVI Sevilla; Study Director: Manuel Fernandez-Sánchez, PhD, IVI Sevilla

Publications and helpful links

General Publications

• Ruiz M, Santamaria-Lopez E, Blasco V, Hernaez MJ, Caligara C, Pellicer A, Fernandez-Sanchez M, Prados N. Effect of Group Embryo Culture under Low-Oxygen Tension in Benchtop Incubators on Human Embryo Culture: Prospective, Randomized, Controlled Trial. Reprod Sci. 2020 Jul;27(7):1522-1533. doi: 10.1007/s43032-020-00150-5. Epub 2020 Jan 28.

Study record dates

Study Major Dates

• Study Start (Actual): July 23, 2013
• Primary Completion (Actual): November 17, 2015
• Study Completion (Actual): October 1, 2016

Study Registration Dates

• First Submitted: July 17, 2013
• First Submitted That Met QC Criteria: July 17, 2013
• First Posted (Estimate): July 19, 2013

Study Record Updates

• Last Update Posted (Actual): April 25, 2018
• Last Update Submitted That Met QC Criteria: April 24, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: grouped embryo culture; embryo density; low oxygen; benchtop incubator; culture condition
• Other Study ID Numbers: IVISEV-003AGR

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No