Condition category
Pregnancy and Childbirth
Date applied
06/04/2016
Date assigned
21/04/2016
Last edited
11/04/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Assisted reproductive technology (ART) is a group of methods that are used to help infertile couples. For example, during in vitro fertilisation (IVF), eggs are removed from a woman's body and mixed with sperm to make embryos, which are then put back into the woman's body. Intra-cytoplasmic sperm injection (ICSI) differs from conventional IVF in that a single sperm is injected directly into an egg. In natural conditions the egg and embryo are subjected to ever changing dynamic processes. However, routine ART today involve the use of static in vitro culture systems. The aim of this study is to determine whether there is any difference in the viability of embryos after in vitro culture under static and mechanical micro-vibration conditions.

Who can participate?
Woman aged from 23 to 44 years with infertility

What does the study involve?
The woman’s eggs are retrieved and inseminated with her partner’s sperm through conventional IVF and ICSI techniques. Couples are offered the choice of either standard routine culture of the eggs and embryos, or culture with mechanical agitation (micro-vibration) of the culture medium. Embryo development rates are assessed on the day of transfer (Day 2, Day 3 or Day 5).

What are the possible benefits and risks of participating?
Not provided at time of registration

Where is the study run from?
Endokrinologikum Ulm, Praxisklinik Frauenstraße (Germany)

When is the study starting and how long is it expected to run for?
January 2010 to December 2015

Who is funding the study?
Cologne University (Germany)

Who is the main contact?
Dr Vladimir Isachenko
v.isachenko@yahoo.com

Trial website

Contact information

Type

Scientific

Primary contact

Dr Vladimir Isachenko

ORCID ID

Contact details

University Maternal Hospital
Kerpener Str. 34
Cologne
50931
Germany
+49 (0)221 478 4924
v.isachenko@yahoo.com

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

In vitro culture and transfer of 9,624 embryos from 4,435 patients: micro-vibration increases baby-take-home rate

Acronym

Study hypothesis

In natural conditions the egg and embryo are subjected to ever changing dynamic processes. However, the routine assisted reproductive technologies today involve the use of static in vitro culture systems. The objective was to determine whether there is any difference in the viability of embryos after in vitro culture under static and mechanical micro-vibration condition.

Ethics approval

The Ethical Commissions of Medical Faculties of universities Ulm (12/11/2011, permission 321/10-UBB/bal) and Cologne (20/11/2013, permission 13-147)

Study design

Observational cohort study

Primary study design

Observational

Secondary study design

Cohort study

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

In vitro fertilization

Intervention

Patients with infertility were stimulated for in vitro fertilization-cycle (IVF) or intracytoplasmic spermatozoa injection-cycle (ICSI) with triptorelin (Decapeptyl®, Ferring, Kiel, Germany) and recombinant FSH (Puregon®, MSD Sharp & Dohme GmbH, Haar, Germany or Menogon®, MerckSerono GmbH, Darmstadt, Germany or Gonal-f®, MerckSerono GmbH, Darmstadt, Germany) according to the "short" protocol. Ovulation was induced by the administration of 5000 IU of HCG (Brevactid®, Ferring GmbH, Kiel, Germany) and oocytes were retrieved 34 – 36 hours later and inseminated with the partner’s sperm through conventional IVF and ICSI techniques.

Couples were offered the choice of the in-vitro culture of oocytes and embryos according to the standard routine or with mechanical agitation (micro-vibration) until transplantation. Written informed consent was obtained from all the participating couples.

Only two embryos per patient were cultured, as according to German law no more than three pronuclear oocytes/embryos from one patient (usually two) can be cultured in vitro and all cultured oocytes/embryos must be later transferred to the patient independently of the developmental rate of these embryos.

Oocytes for the culture of pronuclear embryos were obtained from 4435 informed patients aged 26–46 years (median age 32.8). Pronuclear embryos (two per patient) were cultured in vitro under two different conditions: Group 1 (n = 4821), without mechanical agitation of the culture medium (standard routine conditions); and Group 2 (n = 4803), with mechanical agitation (44 Hz delivered over 5 s once every hour and acceleration (660 mV/g at 3.3 V: X = ±1.0g, Y = ±0.7g, Z = ±0.15g)).

Mechanical agitation was achieved using the newly developed device Viboviduct 1500 (SimSoTec GmbH, Cologne, Germany, www.vibration-oviduct.com). This device before using was calibrated by measurement of vibration with a special device PCE-VT 2700 (PCE Instruments UK Ltd., Southampton, U.K.). Viboviduct 1500 generates micro-vibrations with a special electric motor with low electromagnetic noise. The generated vibrations are forwarded directly to the plate with Petri dishes. Harmful high frequencies are damped and smoothed by the intelligent control software developed on the microprocessor. The control software monitors the motor movements. Petri dishes with embryos are fixed on the plate. The device is designed and developed for use in a CO2 incubator.

Embryo development rates were determined on the day of transfer (Day 2, Day 3 or Day 5). The embryos were cultured in 50 µl of culture medium (Sage, Los Angeles, CA, USA) under mineral oil (Sigma, St. Louis, MO, USA) for their transfer.

The embryo on Day 2 and 3 quality system used to grade of the embryos was described by Steer et al. as follows: Grade A, equal sized symmetrical blastomeres; Grade B, uneven blastomeres with < 10 % fragmentation; Grade C, 10 - 50 % blastomeric fragmentation; and Grade D, > 50 % blastomeric fragmentation. Day 5 embryos were graded according to Veeck and Zaninovic.

Embryo transfer (one to three embryos per patient) was performed on Day 2, Day 3, or Day 5 after retrieval of oocytes. Pregnancy was defined as an increase in serum hCG concentration (20 IU/L) determined on 11 and 13 – 15 days after embryo transfer. Clinical pregnancy was recorded when the fetal sac was visualized on an ultrasound on gestational weeks seven to eight.

Intervention type

Procedure/Surgery

Phase

Drug names

Primary outcome measures

Embryo development rates determined on the day of transfer (Day 2, Day 3 or Day 5)

Secondary outcome measures

N/A

Overall trial start date

01/01/2010

Overall trial end date

01/12/2015

Reason abandoned

Eligibility

Participant inclusion criteria

Woman age from 23 to 44 years with infertility

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

4,435

Participant exclusion criteria

The wish of the patient

Recruitment start date

04/01/2010

Recruitment end date

16/12/2015

Locations

Countries of recruitment

Germany

Trial participating centre

Endokrinologikum Ulm, Praxisklinik Frauenstraße
Department of Reproductive Medicine Christian-Lauritzen Institute Frauenstr. 51
Ulm
89073
Germany

Sponsor information

Organisation

Cologne University Maternal Hospital (Germany)

Sponsor details

Kerpener Str. 34
Cologne
50931
Germany
+49 (0)221 478 4990
peter.mallmann@uk-koeln.de

Sponsor type

Research organisation

Website

Funders

Funder type

University/education

Funder name

Cologne University (Germany)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

The manuscript has been submitted for publication

Intention to publish date

Participant level data

Available on request

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes