Clinical trial NCT02586298: Autologous Mitochondrial Transfer in ICSI to Improve Oocyte and Embryo Quality in IVF Patients. Pilot Study
Official title: Autologous Mitochondrial Transfer as a Complementary Technique to ICSI to Improve Oocyte and Embryo Quality in IVF Patients. Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Infertility
Lead sponsor: Instituto Valenciano de Infertilidad, IVI VALENCIA
Sponsor class: OTHER
First posted: 2015-10-26
Enrollment: 59
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 42
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The principle objective is to improve embryo quality through autologous micro-injection of mitochondria isolated from Ovarian stem cells into the oocytes themselves, as a complementary ICSI technique in patients with low embryo quality in previous IVF cycles and in those who did not bear children.

This improvement in embryo quality will be determined through on-going pregnancy rate after treatment and/or improvement in embryo quality according to morphological (ASEBIR-"Association for the study of Biology in Reproductive Science), morphokinetic criteria and in Preimplantation Genetic Screening.

Using an adaptive design, retrieved oocytes of approximately 60 patients will be randomized in the first part of the study to two treatment groups; standard ICSI procedure without mitochondrial supplementation and ICSI with autologous mitochondrial supplementation. Following an interim analysis of outcomes, an additional 130 patients may be added, for a total of 190 patients.


Eligibility criteria: Inclusion Criteria:

* The patients must have read, understood and signed the ICF.
* Age ≤ 42 years.
* Serum AMH ≥ 4 pM/L.
* Previous IVF cycle with 5 or more metaphase II oocytes after retrieval
* BMI \< 30.
* Will undergo an IVF cycle with arrays in Preimplantation Genetic Screening.
* Semen sample with concentrations exceeding 3 million/mL progressive motile sperm.

Present with a history of at least one previous cycle of IVF with embryo transfer and no pregnancy due to low embryo quality. Low embryo quality is understood as \> 70% of the embryos obtained being included in the worst prognosis category according to any of the following criteria:

1. Low or abnormal Fertilization Rate despite semen count \> 3 million/mL.
2. Deficient quality embryos according to morphological criteria established by ASEBIR:

   i. Embryo D2 and D3: classified as Type C or Type D according to ASEBIR criteria.

   ii. Embryo D5 or blastocyst: Inner cell mass absent, with few cells and difficult differentiation, Trophectoderm with very few cells. Type C or D of ASEBIR.
3. Embryos of deficient quality according to morphokinetic criteria established (28) for EmbryoScope Time-Lapse if this incubator has been used.

   i.Category 4: Embryos of 1 or 2 pronuclei (PN) formed from 1 to 2 cells at 27h, from 2 to 6 cells on D2 and 4 or \>8 cells or morula on D3. The embryo can present with asymmetrical and multinucleated blastomeres. Degree of fragmentation \< 50%.

   ii. Category 5: Embryo with any number of cells at 27h, on D2 and D3. Asymmetrical, multinucleated blastomeres and any degree of fragmentation. Atretic embryos and those with arrested embryo development belong to this category.
4. All cases without embryo transfer due to any chromosomal abnormality detected through PGD or PGS techniques.
5. All cases without transfer due to the presence of embryos that present a blockage of embryo development before D3.

If the morphological quality criteria established under points 2, 3 and 4 give contradictory results, the result obtained through PGD/PGS (point 4) will prevail over the morphokinetic parameters (point 3) and this, in turn, will prevail over the classic morphological criteria (point 2).

Exclusion Criteria:

* Formal contraindication for ovarian cortex biopsy or follicle puncture.
* Severe male factor (concentration\<3 million/mL of progressive motile sperm).
* Any characteristic incompatible with carrying out a new IVF cycle at IVI Valencia.

Primary outcomes:
measure: Rate of ongoing pregnancy
timeFrame: 12 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Valencia
country: Spain
facility: IVI Valencia
Study officials:
affiliation: Gynecologist Specialist TRA, IVI Valencia
name: Elena Labarta, MD PhD
role: STUDY_DIRECTOR
affiliation: Gynecologist specialist TRA, President IVI Valencia
name: Antonio Pellicer, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Labarta E, de Los Santos MJ, Herraiz S, Escriba MJ, Marzal A, Buigues A, Pellicer A. Autologous mitochondrial transfer as a complementary technique to intracytoplasmic sperm injection to improve embryo quality in patients undergoing in vitro fertilization-a randomized pilot study. Fertil Steril. 2019 Jan;111(1):86-96. doi: 10.1016/j.fertnstert.2018.09.023. Epub 2018 Nov 24.