Embryo Growth DisorderACIDOFIVNCT04456478
Impact of PH Values of the Embryo Culture Medium on Success of in Vitro Fertilization (IVF)
A study testing pH at 7.38 ± 0.02 and pH at 7.22 ± 0.02 in people with Embryo Growth Disorder and Humans, run by University Hospital, Toulouse at 3 sites in France.
Trial summary
The objective of this study is to compare, through a multicentric randomized trial, the impact of two pH values in the embryo culture medium on the clinical results of In Vitro Fertilization (IVF) process and especially the impact on live birth delivery rate. Read more about this study
- Who is it for?
- Ages 18 to 40 years, women only
- Conditions the study is for
- Embryo Growth Disorder, Humans, Pregnancy
- What is being tested?
- pH at 7.38 ± 0.02 and pH at 7.22 ± 0.02
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 429 participants
- Where
- 3 sitesFrance
- Study dates
- 14 Oct 2020to 19 Jun 2024
- Phase
- Interventional
- 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 40 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Couples whose woman is 18 to 40 years old and man is 18 to 60 at the time of inclusion.
- Infertile couple with a medical indication of IVF-ICSI according to criteria applied in each center.
- First or second ICSI attempt with fresh embryo transfer.
- Signature of informed consent by both partners of the couple
- Affiliation to a social security scheme or equivalent for both partners of the couple.
- Fitting the inclusion criteria for IVF according the the French law.
Who cannot join
- Use of spermatozoa extracted by testicular biopsy.
- Freeze-al strategy (without fresh embryo transfer) decided before embryo culture
- Absence of mature oocyte (metaphase II) at the day of the puncture
- Uterine pathology affecting implantation (uterine malformation, diffuse adenomyosis ...)
- One of the two partners (or both) is (are) infected with HIV, HCV or HBV in the year before the inclusion
- One of the two partners (or both) is (are) in safeguarding justice, under guardianship or trusteeship.
- Couple having already participated once in the study.
- Couple enrolled in another interventional clinical study
Trial locations and contacts
3 sites in 1 country.
France3 sites
CHU de BORDEAUX
Bordeaux
Centre AMP BIOPYRENEES
Pau
CHU de TOULOUSE
Toulouse
About this study
Official title: Randomized Trial in Assisted Reproductive Technology : Impact of PH Values of the Embryo Culture Medium on Live Birth Rate After in Vitro Fertilization (IVF)
The objective of this study is to compare, through a multicentric randomized trial, the impact of two pH values in the embryo culture medium on the clinical results of In Vitro Fertilization (IVF) process and especially the impact on live birth delivery rate.
Read the detailed description
Despite progress in Assisted Reproductive Technology (ART), the livebirth rate per oocyte retrieval during In Vitro Fertilization (IVF) remain relatively low (15 à 25%). This is in part due to the sensitivity of the preimplantation embryo to its environment. Indeed, there is growing evidence that culture conditions during IVF are critical not only for the development of pre- and post-implantation embryo, but also for long-term health effects; and numerous animal data suggest the importance of pH control in the IVF culture medium. Maintaining the intercellular pH (pHi) is one of the vital roles of embryo homeostasis since pHi regulates many cellular processes. Indeed, variations in pHi can affect embryonic development. Although the embryo has biochemical systems to regulate its pHi, these systems can be overtaken. Under the conditions of IVF embryo culture, the extracellular pH (pHe) in a culture medium is the result of a balance between CO2 concentration in the incubator and bicarbonate concentration in the culture medium (determined by the medium manufacturer). The recommendations of the manufacturers of embryo culture media are to maintain a pHe slightly higher (generally between 7.2 and 7.4) than the pHi (estimated between 7.1 to 7.2) to compensate for the acidification due to cell metabolism. However, as the pH scale is logarithmic, a pHe variation of 7.2 to 7.4 corresponds to a decrease in the concentration of H+ ions by a factor of 1.6 in the medium. Actually, there is no clinical data to know what is the ideal pH to apply to a culture medium during IVF.
This is a clinical study comparing two pH values in the culture medium of embryos obtained by IVF, randomized, multicentric (3 centers), patient-blinded, in groups parallel to the ratio 1: 1. IVF-ICSI will be performed according to the usual procedure and the day of the oocyte puncture, the embryologist will proceed to the 1: 1 randomization: culture of the oocytes and embryos in the culture medium with a pH at 7.38 ± 0.02 or a pH at 7.22 ± 0.02.
In case of pregnancy after embryo transfer, patients will be followed until delivery.
- Conditions
- Embryo Growth Disorder, Humans, Pregnancy
- Being tested
- pH at 7.38 ± 0.02, pH at 7.22 ± 0.02
- Keywords
- pH, embryo culture, In Vitro Fertilization, live birth rate, randomized trial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
pH at 7.38 ± 0.02Procedure or surgery
In the 3 centers of the study, IVF-ICSI will be performed according to the usual procedure: ovarian stimulation, oocyte retrieval, sperm microinjection by ICSI, embryo culture in Global® Total HSA medium, embryo selection and transfer at day 3. The day of the oocyte puncture, the embryologist will proceed to the 1: 1 randomization: culture of the embryos in a medium with a pH at 7.38 ± 0.02. We have chosen to study specifically the early stages of fertilization and embryo development (until day 3), stages for which extracellular pH control is more critical because the intracellular pH regulatory mechanisms are somewhat limited and could be exceeded.
pH at 7.22 ± 0.02Procedure or surgery
In the 3 centers of the study, IVF-ICSI will be performed according to the usual procedure: ovarian stimulation, oocyte retrieval, sperm microinjection by ICSI, embryo culture in Global® Total HSA medium, embryo selection and transfer at day 3. The day of the oocyte puncture, the embryologist will proceed to the 1: 1 randomization: culture of the embryos in a medium with a pH at 7.22 ± 0.02. We have chosen to study specifically the early stages of fertilization and embryo development (until day 3), stages for which extracellular pH control is more critical because the intracellular pH regulatory mechanisms are somewhat limited and could be exceeded.
| Study group | Role | What they receive |
|---|---|---|
| pH 7.38 ± 0.02 | Active comparator | IVF-ICSI will be performed according to the usual procedure and the day of the oocyte puncture, the embryologist will proceed to the culture of the oocytes and embryos in the culture medium with a pH at 7.38 ± 0.02 Receives: Procedure: pH at 7.38 ± 0.02 |
| pH 7.22 ± 0.02 | Experimental | IVF-ICSI will be performed according to the usual procedure and the day of the oocyte puncture, the embryologist will proceed to the culture of the oocytes and embryos in the culture medium with a pH at 7.22 ± 0.02 Receives: Procedure: pH at 7.22 ± 0.02 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Live birth delivery rate
Number of deliveries that resulted in at least one live birth (gestational age ≥ 22 weeks) / Number of oocyte retrievals
Measured: month 9
Secondary outcomes (9)
Fertilization rate
Number of 2PN zygotes at day 1 post-injection / Number of matures injected oocytes
Measured: day 1
Cleavage rate
Number of embryos with at least 2 blastomeres at day 2 / Number of diploid zygotes at day 1 post-injection
Measured: day 2
Percentage of top embryos
Number of 7 to 10-blastomeres embryos at day 3 with less than 10% fragments / Total number of embryos at day 3
Measured: day 3
Embryo freezing rate
Number of frozen embryos / Total number of obtained embryos
Measured: day 6
Implantation rate
Number of gestational sacs observed with ultrasonography (5 weeks after embryo transfer) divided by the number of embryos transferred (expressed as a percentage)
Measured: week 5
Clinical ongoing pregnancy rate by transfer
Number of pregnancies diagnosed by ultrasonographic of at least one fetus with a discernible heartbeat at 5 weeks after embryo transfer / Number of embryo transfers
Measured: week 5
Clinical ongoing pregnancy rate by oocyte retrieval
Number of pregnancies diagnosed by ultrasonographic of at least one fetus with a discernible heartbeat at 5 weeks after embryo transfer / Number of oocyte retrieval
Measured: week 5
Miscarriage rate
Number of spontaneous loss of an intrauterine pregnancy prior to 22 completed weeks of gestational age / Number of pregnancies
Measured: week 22
Malformation rate diagnosed at birth
Number of malformations according to Eurocat classification (in total and in Eurocat subgroups) / Total number of newborns
Measured: month 9
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jul 2020
- Study start14 Oct 2020
- Primary completion19 Jun 2024
- Study completion19 Jun 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Embryo Growth DisorderStudies of the same condition, open and under way.
- More trials run by University Hospital, ToulouseThe sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Multicentric randomized blinded trial
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 429 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Toulouse
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Nicolas GATIMEL, ph, Principal investigator, University Hospital, Toulouse
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04456478
- Sponsor's protocol ID
- RC31/19/0503
- Other IDs
- 2020-A00221-38
- Acronym
- ACIDOFIV
- Status last verified
- Jan 2025
- First submitted
- 29 Jun 2020
- Last updated
- 13 Jan 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Trial in Assisted Reproductive Technology : Impact of PH Values of the Embryo Culture Medium on Live Birth Rate After in Vitro Fertilization (IVF)
- ClinicalTrials.gov ID
- NCT04456478
- Acronym / sponsor ID
- ACIDOFIV / RC31/19/0503
- Conditions
- Embryo Growth Disorder, Humans, Pregnancy
- Keywords
- pH, embryo culture, In Vitro Fertilization, live birth rate, randomized trial
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 429 participants (actual)
- Lead sponsor
- University Hospital, ToulouseUniversity, hospital or other
- Study start
- 14 Oct 2020 (actual)
- Primary completion
- 19 Jun 2024 (actual)
- Study completion
- 19 Jun 2024 (actual)
- First posted
- 2 Jul 2020 (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.
The objective of this study is to compare, through a multicentric randomized trial, the impact of two pH values in the embryo culture medium on the clinical results of In Vitro Fertilization (IVF) process and especially the impact on live birth delivery rate.
Detailed description
Despite progress in Assisted Reproductive Technology (ART), the livebirth rate per oocyte retrieval during In Vitro Fertilization (IVF) remain relatively low (15 à 25%). This is in part due to the sensitivity of the preimplantation embryo to its environment. Indeed, there is growing evidence that culture conditions during IVF are critical not only for the development of pre- and post-implantation embryo, but also for long-term health effects; and numerous animal data suggest the importance of pH control in the IVF culture medium. Maintaining the intercellular pH (pHi) is one of the vital roles of embryo homeostasis since pHi regulates many cellular processes. Indeed, variations in pHi can affect embryonic development. Although the embryo has biochemical systems to regulate its pHi, these systems can be overtaken. Under the conditions of IVF embryo culture, the extracellular pH (pHe) in a culture medium is the result of a balance between CO2 concentration in the incubator and bicarbonate concentration in the culture medium (determined by the medium manufacturer). The recommendations of the manufacturers of embryo culture media are to maintain a pHe slightly higher (generally between 7.2 and 7.4) than the pHi (estimated between 7.1 to 7.2) to compensate for the acidification due to cell metabolism. However, as the pH scale is logarithmic, a pHe variation of 7.2 to 7.4 corresponds to a decrease in the concentration of H+ ions by a factor of 1.6 in the medium. Actually, there is no clinical data to know what is the ideal pH to apply to a culture medium during IVF.
This is a clinical study comparing two pH values in the culture medium of embryos obtained by IVF, randomized, multicentric (3 centers), patient-blinded, in groups parallel to the ratio 1: 1. IVF-ICSI will be performed according to the usual procedure and the day of the oocyte puncture, the embryologist will proceed to the 1: 1 randomization: culture of the oocytes and embryos in the culture medium with a pH at 7.38 ± 0.02 or a pH at 7.22 ± 0.02.
In case of pregnancy after embryo transfer, patients will be followed until delivery.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- Model description
- Multicentric randomized blinded trial
| Arm | Type | Receives |
|---|---|---|
| pH 7.38 ± 0.02 | Active comparator | Procedure: pH at 7.38 ± 0.02IVF-ICSI will be performed according to the usual procedure and the day of the oocyte puncture, the embryologist will proceed to the culture of the oocytes and embryos in the culture medium with a pH at 7.38 ± 0.02 |
| pH 7.22 ± 0.02 | Experimental | Procedure: pH at 7.22 ± 0.02IVF-ICSI will be performed according to the usual procedure and the day of the oocyte puncture, the embryologist will proceed to the culture of the oocytes and embryos in the culture medium with a pH at 7.22 ± 0.02 |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Couples whose woman is 18 to 40 years old and man is 18 to 60 at the time of inclusion.
- Infertile couple with a medical indication of IVF-ICSI according to criteria applied in each center.
- First or second ICSI attempt with fresh embryo transfer.
- Signature of informed consent by both partners of the couple
- Affiliation to a social security scheme or equivalent for both partners of the couple.
Key exclusion criteria (8 listed)
- Use of spermatozoa extracted by testicular biopsy.
- Freeze-al strategy (without fresh embryo transfer) decided before embryo culture
- Absence of mature oocyte (metaphase II) at the day of the puncture
- Uterine pathology affecting implantation (uterine malformation, diffuse adenomyosis ...)
- One of the two partners (or both) is (are) infected with HIV, HCV or HBV in the year before the inclusion
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| pH at 7.38 ± 0.02In the 3 centers of the study, IVF-ICSI will be performed according to the usual procedure: ovarian stimulation, oocyte retrieval, sperm microinjection by ICSI, embryo culture in Global® Total HSA medium, embryo selection and transfer at day 3. The day of the oocyte puncture, the embryologist will proceed to the 1: 1 randomization: culture of the embryos in a medium with a pH at 7.38 ± 0.02. We have chosen to study specifically the early stages of fertilization and embryo development (until day 3), stages for which extracellular pH control is more critical because the intracellular pH regulatory mechanisms are somewhat limited and could be exceeded. | Procedure or surgery | pH 7.38 ± 0.02 |
| pH at 7.22 ± 0.02In the 3 centers of the study, IVF-ICSI will be performed according to the usual procedure: ovarian stimulation, oocyte retrieval, sperm microinjection by ICSI, embryo culture in Global® Total HSA medium, embryo selection and transfer at day 3. The day of the oocyte puncture, the embryologist will proceed to the 1: 1 randomization: culture of the embryos in a medium with a pH at 7.22 ± 0.02. We have chosen to study specifically the early stages of fertilization and embryo development (until day 3), stages for which extracellular pH control is more critical because the intracellular pH regulatory mechanisms are somewhat limited and could be exceeded. | Procedure or surgery | pH 7.22 ± 0.02 |
Primary outcome
Live birth delivery rate
Time frame: month 9
Number of deliveries that resulted in at least one live birth (gestational age ≥ 22 weeks) / Number of oocyte retrievals
9 secondary outcomes
Fertilization rate
Time frame: day 1
Cleavage rate
Time frame: day 2
Percentage of top embryos
Time frame: day 3
Embryo freezing rate
Time frame: day 6
Implantation rate
Time frame: week 5
Clinical ongoing pregnancy rate by transfer
Time frame: week 5
Clinical ongoing pregnancy rate by oocyte retrieval
Time frame: week 5
Miscarriage rate
Time frame: week 22
Malformation rate diagnosed at birth
Time frame: month 9
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2025.
Related trials for Embryo Growth Disorder
Recruiting
Ovarian PRP Injections for Improved Embryo Quality Using Embryo Quality Score
Infertility, Poor Ovarian Reserve
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.
Nicolas GATIMEL, ph principal investigator
University Hospital, Toulouse
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing pH at 7.38 ± 0.02 and pH at 7.22 ± 0.02 in people with Embryo Growth Disorder and Humans, run by University Hospital, Toulouse at 3 sites in France.
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 6 inclusion and 8 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: finished, as of the sponsor's last update on 13 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in France. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Live birth delivery rate (time frame: month 9). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 13 Jan 2025.