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
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
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)