Condition category
Pregnancy and Childbirth
Date applied
17/08/2018
Date assigned
30/08/2018
Last edited
17/07/2020
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting
Publication status
Results

Plain English Summary

Background and study aims
In the last decade, research has shown that microorganisms may have an impact on the outcome of assisted reproductive procedures such as IVF or IVF-ICSI. Microorganisms, together with their genetic information and the environment in which they live and interact is called the microbiome. One common type of bacteria that lives in the vagina is Lactobacillus. Studies have shown that the presence of Lactobacillus during assisted reproductive procedures can have a positive impact on the outcome. However, using the microbiome as a way of predicting the outcome of these procedures has not yet been investigated. This study aims to develop a method of using the microbiome to identify women with low, mid and high chances of becoming pregnant prior to the start of IVF or IVF-ICSI treatment. Having the ability to predict this may help couples to make decisions about whether to continue these treatments.

Who can participate?
Females aged 20-44 with a male partner, who have been indicated for IVF or IVF-ICSI

What does the study involve?
Participants will be asked to
Participants will receive a sampling protocol and collect a vaginal swab and urine sample by themselves in the IVF centre. The swab and the urine sample will take place once and have to be taken within the two months prior to the embryo transfer.
The urine sample collection will be obtained according to a standard ‘clean catch’ protocol, including washing hands thoroughly, cleaning the urinary opening with towelettes and collecting a midstream specimen in a sterile container. Vaginal samples will be taken with FLOQSwabs™. The participants will be instructed to insert the swab 3-5 centimetres beyond the vaginal orifice, and move the swab around along the vaginal wall for 10-15 seconds.

What are the possible benefits and risks of participating?
This research may not directly benefit the participants, since the test result is not shared with the participants during the study. However, the participants may help us to develop a predictive test based on the urogenital microbiome and hopefully this will contribute to a personalised medicine approach in the future. There are no known risks to participants taking part in this study.

Where is the study run from?
Division Reproductive Endocrinology and Infertility, Department Obstetrics and Gynaecology, Erasmus University Medical Centre, Rotterdam (The Netherlands) (lead centre) and 7 other centres in The Netherlands

When is the study starting and how long is it expected to run for?
July 2014 to December 2018

Who is funding this study?
1. NGI Pre-Seed (The Netherlands)
2. RedMedTech (The Netherlands)
3. STW (The Netherlands)
4. Eurostars VALBIOME (Belgium)

Who is the main contact?
Dr Rivka Koedooder
r.koedooder@erasmusmc.nl

Trial website

N/A

Contact information

Type

Scientific

Primary contact

Miss Rivka Koedooder

ORCID ID

http://orcid.org/0000-0002-0233-6312

Contact details

Dr. Molewaterplein 40
Rotterdam
3015 CD
Netherlands

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

METC 2014-455

Study information

Scientific title

Analysis of the microbiome to determine the predictive accuracy of the urogenital microbiome for IVF/IVF-ICSI outcome prediction in IVF/IVF-ICSI patients

Acronym

ReceptIVFity

Study hypothesis

The urogenital microbiome can be used as predictor for IVF/IVF-ICSI outcome.

Ethics approval

The protocol was approved by the Institutional Medical Ethical Review Board of all participating centres, the coordinating centre was Erasmus University Medical Centre, Rotterdam, The Netherlands (MEC-2014-455). Date of approval: 15/08/2014

Study design

Observational prospective multi-centre cohort study

Primary study design

Observational

Secondary study design

Cohort study

Trial setting

Hospitals

Trial type

Diagnostic

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet

Condition

In vitro fertilisation (IVF) and intracytoplasmic sperm injection (IVF-ICSI)

Intervention

A microbiome profiling intervention based on a urinary sample and a vaginal swab obtained prior to the start of the IVF or IVF/ICSI treatment. The ultimate goal will be to develop a predictive algorithm that enables identification of the group of women with a low, mid and high chance to become pregnant prior to the start of the IVF or IVF-ICSI treatment. Predictive knowledge of the microbiome profile may enable couples to make a more substantiated decision on whether to continue treatment or not. Hence, the unnecessary physical and emotional burden of a failed IVF or IVF-ICSI treatment can be avoided.
Participants will receive a sampling protocol and collect the samples by themselves in the IVF centre.
The urine sample collection will be obtained according to a standard ‘clean catch’ protocol, including washing hands thoroughly, cleaning the urinary opening with towelettes and collecting a midstream specimen in a sterile container. Vaginal samples will be taken with FLOQSwabs™. The participants will be instructed to insert the swab 3-5 centimetres beyond the vaginal orifice, and move the swab around along the vaginal wall for 10-15 seconds.
The sampling will take place once and the swab and the urine sample have to be taken within the 2 months prior to the embryo transfer.

Intervention type

Procedure/Surgery

Phase

Drug names

Primary outcome measure

To assess the specificity and sensitivity of the urinary and vaginal microbiome composition for the prediction of embryo implantation failure of a consecutive IVF or IVF-ICSI procedure.
1. The composition of the urinary and vaginal samples, assessed by Next Generation Sequencing and the IS-pro technique within the 2 months prior to the embryo transfer
2. Ongoing pregnancy (defined as an intrauterine embryo/foetus with detection of cardiac activity on transvaginal ultrasound between 7-9 weeks of gestation after fresh embryo transfer)
3. Sensitivity - the proportion of women who become pregnant who test mid or high chance to become pregnant based on microbiome analysis using urinary and vaginal samples (true positive (TP) / (TP + false negative (FN)))
4. Specificity - the proportion of women who do not become pregnant who test low chance to become pregnant based on microbiome analysis using urinary and vaginal samples (true negative (TN) / (TN + false positive (FP)))

Secondary outcome measures

N/A

Overall trial start date

08/07/2014

Overall trial end date

01/12/2018

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Female
2. Indication for an IVF or IVF-ICSI procedure
3. Aged 20-44 years
4. Willing to provide a urine sample and a vaginal swab
5. Willing to provide informed consent
6. Male partner

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

300

Total final enrolment

192

Participant exclusion criteria

1. No transferable embryos after IVF or IVF-ICSI
2. Indication for emergency IVF because of cancer or other reasons
3. AFS (American Fertility Society) III/IV classified endometriosis and pre-treatment with a GnRH (gonadotropin-releasing hormone) analogue
4. >3 weeks use of hormonal contraceptives 3 months prior to start IVF or IVF-ICSI
5. Pregnant previously to the start of the IVF or IVF-ICSI (including miscarriage)
6. Hormonal treatments 3 months prior to start IVF or IVF-ICSI
7. Use of sperm donation

Recruitment start date

02/06/2015

Recruitment end date

09/04/2016

Locations

Countries of recruitment

Netherlands

Trial participating centre

Erasmus University Medical Centre
Division of Reproductive Medicine Department of Obstetrics and Gynaecology Erasmus University Medical Centre Wytemaweg 80
Rotterdam
3015 CN
Netherlands

Trial participating centre

Radboud University Medical Centre
Division of Reproductive Medicine Department of Obstetrics and Gynaecology Geert Grooteplein Zuid 10
Nijmegen
6525 GA
Netherlands

Trial participating centre

Isala Kliniek
Isala Voortplantingscentrum Dokter Spanjaardweg 29
Zwolle
8025 BT
Netherlands

Trial participating centre

VU University Medical Centre
Division of Reproductive Medicine Department of Obstetrics and Gynaecology De Boelelaan 1117
Amsterdam
1081 HV
Netherlands

Trial participating centre

Sint Elisabeth Ziekenhuis
Division of Reproductive Medicine Department of Obstetrics and Gynaecology Hilvarenbeekseweg 60
Tilburg
5022 GC
Netherlands

Trial participating centre

VivaNeo Medisch Centrum Kinderwens
Simon Smitweg 16
Leiderdorp
2353 GA
Netherlands

Trial participating centre

University Medical Centre Utrecht
Division of Reproductive Medicine Department of Obstetrics and Gynaecology Heidelberglaan 100
Utrecht
3584 CX
Netherlands

Trial participating centre

Maastricht Universitair Medisch Centrum+
Division of Reproductive Medicine Department of Obstetrics and Gynaecology P. Debyelaan 25
Maastricht
6229 HX
Netherlands

Sponsor information

Organisation

Erasmus University Medical Centre

Sponsor details

Dr. Molewaterplein 40
Rotterdam
3015 CD
Netherlands

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Not defined

Funder name

Netherlands Genomics Initiative

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

RedMedTech

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Stichting voor de Technische Wetenschappen

Alternative name(s)

Technology Foundation STW

Funding Body Type

unknown

Funding Body Subtype

Location

Funder name

Eurostars

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

The results of the determination of the urinary microbiome and vaginal microbiome using NGS and IS-pro will be published in a scientific journal in 2018.
The results of the predictive accuracy of the urogenital microbiome as predictor for IVF/IVF-ICSI outcome will be published in a scientific journal in 2018.

IPD sharing statement:
The datasets generated during and/or analysed during the current study will be available upon request from r.koedooder@erasmusmc.nl. This will contain anonymised data after our primary data are published, but only if formally requested so we can control the nature of the analyses.

Intention to publish date

01/09/2018

Participant level data

Available on request

Basic results (scientific)

Publication list

2019 results in https://pubmed.ncbi.nlm.nih.gov/31119299/ (added 17/07/2020)

Publication citations

Additional files

Editorial Notes

17/07/2020: The following changes were made to the trial record: 1. Publication reference added. 2. The total final enrolment was added.