Clinical trial NCT04456478: Impact of PH Values of the Embryo Culture Medium on Success of in Vitro Fertilization (IVF)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Embryo Growth Disorder
Humans
Pregnancy
Keywords: pH
embryo culture
In Vitro Fertilization
live birth rate
randomized trial
Lead sponsor: University Hospital, Toulouse
Sponsor class: OTHER
First posted: 2020-07-02
Enrollment: 429
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multicentric randomized blinded trial
Primary purpose: OTHER

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Live birth delivery rate
timeFrame: month 9
Secondary outcomes:
measure: Fertilization rate
timeFrame: day 1
measure: Cleavage rate
timeFrame: day 2
measure: Percentage of top embryos
timeFrame: day 3
measure: Embryo freezing rate
timeFrame: day 6
measure: Implantation rate
timeFrame: week 5
measure: Clinical ongoing pregnancy rate by transfer
timeFrame: week 5
measure: Clinical ongoing pregnancy rate by oocyte retrieval
timeFrame: week 5
measure: Miscarriage rate
timeFrame: week 22
measure: Malformation rate diagnosed at birth
timeFrame: month 9
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: CHU de BORDEAUX
city: Pau
country: France
facility: Centre AMP BIOPYRENEES
city: Toulouse
country: France
facility: CHU de TOULOUSE
Study officials:
affiliation: University Hospital, Toulouse
name: Nicolas GATIMEL, ph
role: PRINCIPAL_INVESTIGATOR
References: