Impact of pH Values of the Embryo Culture Medium on Success of In Vitro Fertilization (IVF)

Pregnancy Clinical Trial

— ACIDOFIV  

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04456478
• Other study ID #: RC31/19/0503
• Secondary ID: 2020-A00221-38
• Status: Recruiting
• Phase: N/A
• Start date: October 14, 2020
• Est. completion date: April 2025

Study information

• Verified date: August 2023
• Source: University Hospital, Toulouse
• Contact: Nicolas GATIMEL, ph
• Phone: 05 67 77 10 08
• Email: gatimel.n[@]chu-toulouse.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 622
• Est. completion date: April 2025
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Embryo Growth Disorder
• Growth Disorders
• Humans
• Pregnancy

Intervention

Procedure:
• pH at 7.38 ± 0.02
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 ± 0.02
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.

Locations

Country	Name	City	State
France	CHU de BORDEAUX	Bordeaux
France	Centre AMP BIOPYRENEES	Pau
France	CHU de TOULOUSE	Toulouse

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Toulouse

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Live birth delivery rate	Number of deliveries that resulted in at least one live birth (gestational age = 22 weeks) / Number of oocyte retrievals	month 9
Secondary	Fertilization rate	Number of 2PN zygotes at day 1 post-injection / Number of matures injected oocytes	day 1
Secondary	Cleavage rate	Number of embryos with at least 2 blastomeres at day 2 / Number of diploid zygotes at day 1 post-injection	day 2
Secondary	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	day 3
Secondary	Embryo freezing rate	Number of frozen embryos / Total number of obtained embryos	day 6
Secondary	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)	week 5
Secondary	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	week 5
Secondary	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	week 5
Secondary	Miscarriage rate	Number of spontaneous loss of an intrauterine pregnancy prior to 22 completed weeks of gestational age / Number of pregnancies	week 22
Secondary	Malformation rate diagnosed at birth	Number of malformations according to Eurocat classification (in total and in Eurocat subgroups) / Total number of newborns	month 9