Autologous Mitochondrial Transfer in ICSI to Improve Oocyte and Embryo Quality in IVF Patients. Pilot Study

Infertility Clinical Trial

Official title:

Autologous Mitochondrial Transfer as a Complementary Technique to ICSI to Improve Oocyte and Embryo Quality in IVF Patients. Pilot Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02586298
• Other study ID #: 1501-VLC-005-AP
• Status: Completed
• Phase: N/A
• First received: October 21, 2015
• Last updated: August 22, 2017
• Start date: October 2015
• Est. completion date: July 2017

Study information

• Verified date: August 2017
• Source: Instituto Valenciano de Infertilidad, IVI VALENCIA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 59
• Est. completion date: July 2017
• Est. primary completion date: March 2017
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 42 Years

Eligibility

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.

Related Conditions & MeSH terms

• Infertility

Intervention

Other:
• Autologous mitochondria with ICSI
Autologous mitochondria during the intracytoplasmic sperm injection (ICSI) process will be added to this randomized group of oocytes.
• STANDARD ICSI PROCEDURE
STANDARD ICSI PROCEDURE

Locations

Country	Name	City	State
Spain	IVI Valencia	Valencia

Sponsors (1)

Lead Sponsor	Collaborator
Instituto Valenciano de Infertilidad, IVI VALENCIA

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of ongoing pregnancy		12 weeks