InfertilityNCT03436758
Validation of Addition of Uterine Fluid to Human Embryo Culture Medium
An observational study of Infertility, run by IVI Murcia at 1 site in Spain.
Trial summary
Infertility or infertility affects about 15% of couples of reproductive age. It is estimated that 80 million people around the world suffer from this problem. Assisted reproduction techniques (ART) use culture media (during in vitro fertilization or early embryo development) with protein sources that are very… Read more about this study
- Who is it for?
- Ages 18 to 39 years
- Conditions the study is for
- Infertility
- How many people
- 27 participants
- Where
- 1 siteSpain
- Study dates
- 30 Jan 2018to 31 Dec 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 39 years
- All sexes
- Adult
Study population: infertility couples
Who may be able to join
- Couples in icsi treatment
- Woman:
- BMI between 17 and 30.Under controlled ovarian stimulation and at least 8 metaphase II oocytes collected
- Man:
- Sperm concentration higher than 5 million sperm / ml
Who cannot join
- Woman:
- Diagnosis of endometriosis Uterine pathology that compromises embryonic development Patients undergoing treatment for repeat abortion or implantation failures Abnormal karyotype Patients included in the Pre-Implantation Genetic Diagnosis (DPI) program
- Male:
- Men whit abnormal karyotype, High values of DNA fragmentation Abnormal FISH (Fluorescence in situ Hybridization) Sperm from epididymal aspirate or testicular biopsy
Trial locations and contacts
1 site in 1 country.
Spain1 site, 1 recruiting
- Recruiting
IVI Murcia
Murcia, 30007
Juan Carlos Martinez Soto, MD, PhD, +34666676183, JuanCarlos.Martinez@ivi.es
About this study
Infertility or infertility affects about 15% of couples of reproductive age. It is estimated that 80 million people around the world suffer from this problem. Assisted reproduction techniques (ART) use culture media (during in vitro fertilization or early embryo development) with protein sources that are very different from natural sources. This media could produce an added stress to the gametes and embryos that could cause epigenetic alterations and health effects during adult life.
Our working hypothesis is based on studies in animal models (pig and cow), in which it was observed that the culture media with reproductive fluids used as additives instead of conventional sources of proteins (such as serum albumin) , produce embryos with an epigenetic profile closer to that of embryos generated in the maternal oviduct. Moreover, with these fluids, blastocysts obtained have a greater number of cells and hatchability than those produced with serum albumin alone.
Read more
Therefore, the University of Murcia, with an extensive experience in this area, and the IVI Murcia (Valencian Infertility Institute) research team have come together to launch this research project in order to determine the advantages of the use of human reproductive fluids as additives in embryonic culture media. To do this, 2 specific objectives are proposed,:
- Creation of the first collection of human uterine fluid samples for Assisted Reproduction use.
- To evaluate the use of uterine fluid as a media supplement in the culture media for assisted reproduction techniques, by evaluating embryo quality cultured with autologous fluid from voluntary patients (autologous culture)
This achievement would allow us the development of protocols in the nearest ART physiological conditions which represent not only a technical challenge but a biomedical responsibility that must be addressed to prevent future diseases of the offspring.
Read the detailed description
- Creation of the first collection of human uterine fluid samples for Assisted Reproduction use. Female reproductive system will be collected at the Virgen de la Arrixaca University Clinical Hospital from surgical pieces of patients undergoing surgical procedures. IVI Murcia Clinics uterine fluids from oocyte donors will be collected. These fluids will be store in the Arrixaca Hospital Biobank for future researches.
- Validation of the addition of uterine fluid to human embryonic culture media:
Couples undergoing assited Reproduction Treatment in IVI Murcia will be asked for their inclusion in this study. Uterine fluid will be take 48 hours after peak of LH (luteinizing hormone), in natural cycle. Oocytes from these patients, will be divided into two groups: Half of the zygotes of each patient, control group, will be grown in the conditions usually used in the clinic, and the other half, experimental group, will add 1-5% of uterine fluid from the patient (v / v)
On day 3 and on day 5 of culture the quality of the embryos in both groups will be assessed according to the usual criteria of the clinic and the best quality and highest probability of implantation will be transferred, following the usual clinical practice. The samples of uterine fluid, after the initial processing in the IVI-Murcia clinic will be transferred to the Department of Physiology of the University of Murcia where they will be fractionated to perform a quality control according to the following specifications:
Uterine fluid pH 7.0-7.6 Osmolarity (mOsm / kg) 260-320 Endotoxin (EU / mL) <0.15 Sterility No growth
Only samples that meet these criteria will continue to be part of the study
- Conditions
- Infertility
- Keywords
- uterine fluids, Biobank, culture medium
- Medical subject headings
- Infertility
What is being measured
The primary outcome is the main question the study is designed to answer.
embryo quality
Number of embryo with A or B quality according to ASEBIR (Spanish association for the study of the biology of reproduction) criteria
Measured: embryo quality will be analyze on day 3 and 5 after fertilization
Secondary outcomes (4)
Pregnancy rate
serum levels of chorionic gonadotropin Beta (Beta-hCG)
Measured: between 14-16 days after fertilization
ongoing pregnancy
ultrasonography
Measured: 16-18 week after fertilization
implantation rate
number of embryos implanted/number of embryos transferred x100
Measured: 24 days after fertilization
pregnancy loss rate
number of miscarriages/ number of ongoing pregnancy x100
Measured: 10 days after B-hCG evaluation at end of pregnancy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2018
- Study start30 Jan 2018
- Primary completion30 Oct 2019 (estimated)
- Study completion31 Dec 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for InfertilityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 27 participants (estimated)
Sponsor and investigators
- Lead sponsor
- IVI Murcia
- Sponsor type
- University, hospital or other
- Collaborators
- Universidad de Murcia
- Responsible party
- Sponsor
- Investigators
- Jose Landeras, MD, Principal investigator, IVI-RMA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03436758
- Sponsor's protocol ID
- 1607-MUR-055-JL
- Status last verified
- Feb 2018
- First submitted
- 12 Feb 2018
- Last updated
- 19 Feb 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Coy P, Jimenez-Movilla M, Garcia-Vazquez FA, Mondejar I, Grullon L, Romar R. Oocytes use the plasminogen-plasmin system to remove supernumerary spermatozoa. Hum Reprod. 2012 Jul;27(7):1985-93. doi: 10.1093/humrep/des146. Epub 2012 May 3.
PubMed 22556378Aviles M, Gutierrez-Adan A, Coy P. Oviductal secretions: will they be key factors for the future ARTs? Mol Hum Reprod. 2010 Dec;16(12):896-906. doi: 10.1093/molehr/gaq056. Epub 2010 Jun 28.
PubMed 20584881Belva F, Bonduelle M, Roelants M, Michielsen D, Van Steirteghem A, Verheyen G, Tournaye H. Semen quality of young adult ICSI offspring: the first results. Hum Reprod. 2016 Dec;31(12):2811-2820. doi: 10.1093/humrep/dew245. Epub 2016 Oct 5.
PubMed 27707840Chiu PC, Chung MK, Koistinen R, Koistinen H, Seppala M, Ho PC, Ng EH, Lee KF, Yeung WS. Cumulus oophorus-associated glycodelin-C displaces sperm-bound glycodelin-A and -F and stimulates spermatozoa-zona pellucida binding. J Biol Chem. 2007 Feb 23;282(8):5378-88. doi: 10.1074/jbc.M607482200. Epub 2006 Dec 27.
PubMed 17192260Coy P, Canovas S, Mondejar I, Saavedra MD, Romar R, Grullon L, Matas C, Aviles M. Oviduct-specific glycoprotein and heparin modulate sperm-zona pellucida interaction during fertilization and contribute to the control of polyspermy. Proc Natl Acad Sci U S A. 2008 Oct 14;105(41):15809-14. doi: 10.1073/pnas.0804422105. Epub 2008 Oct 6.
PubMed 18838686Coy P, Grullon L, Canovas S, Romar R, Matas C, Aviles M. Hardening of the zona pellucida of unfertilized eggs can reduce polyspermic fertilization in the pig and cow. Reproduction. 2008 Jan;135(1):19-27. doi: 10.1530/REP-07-0280.
PubMed 18159080Gabler C, Chapman DA, Killian GJ. Expression and presence of osteopontin and integrins in the bovine oviduct during the oestrous cycle. Reproduction. 2003 Dec;126(6):721-9.
PubMed 14748691
Study at a glance
From the registry record, last updated by the sponsor on 19 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Validation of Addition of Uterine Fluid to Human Embryo Culture Medium
- ClinicalTrials.gov ID
- NCT03436758
- Acronym / sponsor ID
- 1607-MUR-055-JL
- Conditions
- Infertility
- Keywords
- uterine fluids, Biobank, culture medium
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 27 participants (estimated)
- Lead sponsor
- IVI MurciaUniversity, hospital or other
- Collaborators
- Universidad de Murcia
- Study start
- 30 Jan 2018 (actual)
- Primary completion
- 30 Oct 2019 (estimated)
- Study completion
- 31 Dec 2019 (estimated)
- First posted
- 19 Feb 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Infertility or infertility affects about 15% of couples of reproductive age. It is estimated that 80 million people around the world suffer from this problem. Assisted reproduction techniques (ART) use culture media (during in vitro fertilization or early embryo development) with protein sources that are very different from natural sources. This media could produce an added stress to the gametes and embryos that could cause epigenetic alterations and health effects during adult life.
Our working hypothesis is based on studies in animal models (pig and cow), in which it was observed that the culture media with reproductive fluids used as additives instead of conventional sources of proteins (such as serum albumin) , produce embryos with an epigenetic profile closer to that of embryos generated in the maternal oviduct. Moreover, with these fluids, blastocysts obtained have a greater number of cells and hatchability than those produced with serum albumin alone.
Therefore, the University of Murcia, with an extensive experience in this area, and the IVI Murcia (Valencian Infertility Institute) research team have come together to launch this research project in order to determine the advantages of the use of human reproductive fluids as additives in embryonic culture media. To do this, 2 specific objectives are proposed,:
- Creation of the first collection of human uterine fluid samples for Assisted Reproduction use.
- To evaluate the use of uterine fluid as a media supplement in the culture media for assisted reproduction techniques, by evaluating embryo quality cultured with autologous fluid from voluntary patients (autologous culture)
This achievement would allow us the development of protocols in the nearest ART physiological conditions which represent not only a technical challenge but a biomedical responsibility that must be addressed to prevent future diseases of the offspring.
Detailed description
- Creation of the first collection of human uterine fluid samples for Assisted Reproduction use. Female reproductive system will be collected at the Virgen de la Arrixaca University Clinical Hospital from surgical pieces of patients undergoing surgical procedures. IVI Murcia Clinics uterine fluids from oocyte donors will be collected. These fluids will be store in the Arrixaca Hospital Biobank for future researches.
- Validation of the addition of uterine fluid to human embryonic culture media:
Couples undergoing assited Reproduction Treatment in IVI Murcia will be asked for their inclusion in this study. Uterine fluid will be take 48 hours after peak of LH (luteinizing hormone), in natural cycle. Oocytes from these patients, will be divided into two groups: Half of the zygotes of each patient, control group, will be grown in the conditions usually used in the clinic, and the other half, experimental group, will add 1-5% of uterine fluid from the patient (v / v)
On day 3 and on day 5 of culture the quality of the embryos in both groups will be assessed according to the usual criteria of the clinic and the best quality and highest probability of implantation will be transferred, following the usual clinical practice. The samples of uterine fluid, after the initial processing in the IVI-Murcia clinic will be transferred to the Department of Physiology of the University of Murcia where they will be fractionated to perform a quality control according to the following specifications:
Uterine fluid pH 7.0-7.6 Osmolarity (mOsm / kg) 260-320 Endotoxin (EU / mL) <0.15 Sterility No growth
Only samples that meet these criteria will continue to be part of the study
Study design
- Observational model
- Case only
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 39 years
- Sex
- All
- Age groups
- Adult
- Study population
- infertility couples
Key inclusion criteria (5 listed)
- Couples in icsi treatment
- BMI between 17 and 30.Under controlled ovarian stimulation and at least 8 metaphase II oocytes collected
- Sperm concentration higher than 5 million sperm / ml
Key exclusion criteria (4 listed)
- Woman:
- Diagnosis of endometriosis Uterine pathology that compromises embryonic development Patients undergoing treatment for repeat abortion or implantation failures Abnormal karyotype Patients included in the Pre-Implantation Genetic Diagnosis (DPI) program
- Men whit abnormal karyotype, High values of DNA fragmentation Abnormal FISH (Fluorescence in situ Hybridization) Sperm from epididymal aspirate or testicular biopsy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
embryo quality
Time frame: embryo quality will be analyze on day 3 and 5 after fertilization
Number of embryo with A or B quality according to ASEBIR (Spanish association for the study of the biology of reproduction) criteria
4 secondary outcomes
Pregnancy rate
Time frame: between 14-16 days after fertilization
ongoing pregnancy
Time frame: 16-18 week after fertilization
implantation rate
Time frame: 24 days after fertilization
pregnancy loss rate
Time frame: 10 days after B-hCG evaluation at end of pregnancy
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Feb 2018.
- Background: PubMed 22556378Coy P, Jimenez-Movilla M, Garcia-Vazquez FA, Mondejar I, Grullon L, Romar R. Oocytes use the plasminogen-plasmin system to remove supernumerary spermatozoa. Hum Reprod. 2012 Jul;27(7):1985-93. doi: 10.1093/humrep/des146. Epub 2012 May 3.
- Results publication: PubMed 20584881Aviles M, Gutierrez-Adan A, Coy P. Oviductal secretions: will they be key factors for the future ARTs? Mol Hum Reprod. 2010 Dec;16(12):896-906. doi: 10.1093/molehr/gaq056. Epub 2010 Jun 28.
- Results publication: PubMed 27707840Belva F, Bonduelle M, Roelants M, Michielsen D, Van Steirteghem A, Verheyen G, Tournaye H. Semen quality of young adult ICSI offspring: the first results. Hum Reprod. 2016 Dec;31(12):2811-2820. doi: 10.1093/humrep/dew245. Epub 2016 Oct 5.
- Results publication: PubMed 17192260Chiu PC, Chung MK, Koistinen R, Koistinen H, Seppala M, Ho PC, Ng EH, Lee KF, Yeung WS. Cumulus oophorus-associated glycodelin-C displaces sperm-bound glycodelin-A and -F and stimulates spermatozoa-zona pellucida binding. J Biol Chem. 2007 Feb 23;282(8):5378-88. doi: 10.1074/jbc.M607482200. Epub 2006 Dec 27.
- Results publication: PubMed 18838686Coy P, Canovas S, Mondejar I, Saavedra MD, Romar R, Grullon L, Matas C, Aviles M. Oviduct-specific glycoprotein and heparin modulate sperm-zona pellucida interaction during fertilization and contribute to the control of polyspermy. Proc Natl Acad Sci U S A. 2008 Oct 14;105(41):15809-14. doi: 10.1073/pnas.0804422105. Epub 2008 Oct 6.
- Results publication: PubMed 18159080Coy P, Grullon L, Canovas S, Romar R, Matas C, Aviles M. Hardening of the zona pellucida of unfertilized eggs can reduce polyspermic fertilization in the pig and cow. Reproduction. 2008 Jan;135(1):19-27. doi: 10.1530/REP-07-0280.
- Results publication: PubMed 14748691Gabler C, Chapman DA, Killian GJ. Expression and presence of osteopontin and integrins in the bovine oviduct during the oestrous cycle. Reproduction. 2003 Dec;126(6):721-9.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jose Landeras, MD principal investigator
IVI-RMA
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Infertility, run by IVI Murcia at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 19 Feb 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Juan C Martinez-Soto, PhD (+34968200031 ext. 16523, juancarlos.martinez@ivi.es), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
embryo quality (time frame: embryo quality will be analyze on day 3 and 5 after fertilization). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03436758, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Feb 2018.