Validation test (“ReceptIVFity-test”) to predict the chance of pregnancy with IVF or IVF-ICSI treatment based on bacteria composition
| ISRCTN | ISRCTN83157250 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN83157250 |
| Secondary identifying numbers | METC 2014-455 |
- Submission date
- 17/08/2018
- Registration date
- 30/08/2018
- Last edited
- 06/09/2023
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Pregnancy and Childbirth
Plain English summary of protocol
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
Contact information
Scientific
Dr. Molewaterplein 40
Rotterdam
3015 CD
Netherlands
 ORCID ID |
0000-0002-0233-6312 |
|---|
Study information
| Study design | Observational prospective multi-centre cohort study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Cohort study |
| Study setting(s) | Hospital |
| Study type | Diagnostic |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet |
| 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 |
| Study acronym | ReceptIVFity |
| Study objectives | The urogenital microbiome can be used as predictor for IVF/IVF-ICSI outcome. |
| Ethics approval(s) | 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 |
| Health condition(s) or problem(s) studied | 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 |
| 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 | There are no secondary outcome measures |
| Overall study start date | 08/07/2014 |
| Completion date | 01/12/2018 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 20 Years |
| Upper age limit | 44 Years |
| Sex | Female |
| Target number of participants | 300 |
| Total final enrolment | 192 |
| Key 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 |
| Key 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 |
| Date of first enrolment | 02/06/2015 |
| Date of final enrolment | 09/04/2016 |
Locations
Countries of recruitment
- Netherlands
Study participating centres
Department of Obstetrics and Gynaecology
Erasmus University Medical Centre
Wytemaweg 80
Rotterdam
3015 CN
Netherlands
Department of Obstetrics and Gynaecology
Geert Grooteplein Zuid 10
Nijmegen
6525 GA
Netherlands
Dokter Spanjaardweg 29
Zwolle
8025 BT
Netherlands
Department of Obstetrics and Gynaecology
De Boelelaan 1117
Amsterdam
1081 HV
Netherlands
Department of Obstetrics and Gynaecology
Hilvarenbeekseweg 60
Tilburg
5022 GC
Netherlands
Leiderdorp
2353 GA
Netherlands
Department of Obstetrics and Gynaecology
Heidelberglaan 100
Utrecht
3584 CX
Netherlands
Department of Obstetrics and Gynaecology
P. Debyelaan 25
Maastricht
6229 HX
Netherlands
Sponsor information
Hospital/treatment centre
Dr. Molewaterplein 40
Rotterdam
3015 CD
Netherlands
"ROR" |
https://ror.org/018906e22 |
|---|
Funders
Funder type
Not defined
No information available
No information available
Private sector organisation / Trusts, charities, foundations (both public and private)
- Alternative name(s)
- Technology Foundation STW, Technologiestichting STW, Dutch Technology Foundation, Dutch Technology Foundation STW, STW
- Location
- Netherlands
Government organisation / National government
- Alternative name(s)
- EUREKA Eurostars
- Location
- Belgium
Results and Publications
| Intention to publish date | 01/09/2018 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| 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 plan | 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. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 04/06/2019 | 17/07/2020 | Yes | No |
| Protocol article | 07/12/2018 | 06/09/2023 | Yes | No |
Editorial Notes
06/09/2023: Publication reference added.
17/07/2020: The following changes were made to the trial record:
1. Publication reference added.
2. The total final enrolment was added.
