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

Primary Purpose

Infertility

Status
Completed
Phase
Not Applicable
Locations
Spain
Study Type
Interventional
Intervention
Autologous mitochondria with ICSI
STANDARD ICSI PROCEDURE
Sponsored by
Instituto Valenciano de Infertilidad, IVI VALENCIA
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Infertility

Eligibility Criteria

18 Years - 42 Years (Adult)FemaleDoes not accept healthy volunteers

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.

Sites / Locations

  • IVI Valencia

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

ICSI with mitochondria

Control ICSI without mitochondria

Arm Description

Half of the Metaphase II oocytes retrieved after the controlled ovarian stimulation will be randomized to this group and autologous mitochondria from the patient's ovarian cortex will be introduced into the oocyte during the intracytoplasmic sperm injection in the vitro fertilization treatment.

The other half of the metaphase II oocytes retrieved after the controlled ovarian stimulation will be randomized to this group and will not receive autologous mitochondria during the intracytoplasmic sperm injection (ICSI) in the vitro fertilization treatment. Control Group

Outcomes

Primary Outcome Measures

Rate of ongoing pregnancy

Secondary Outcome Measures

Full Information

First Posted
October 21, 2015
Last Updated
August 22, 2017
Sponsor
Instituto Valenciano de Infertilidad, IVI VALENCIA
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1. Study Identification

Unique Protocol Identification Number
NCT02586298
Brief Title
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

2. Study Status

Record Verification Date
August 2017
Overall Recruitment Status
Completed
Study Start Date
October 2015 (Actual)
Primary Completion Date
March 2017 (Actual)
Study Completion Date
July 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Instituto Valenciano de Infertilidad, IVI VALENCIA

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Infertility

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare Provider
Allocation
Randomized
Enrollment
59 (Actual)

8. Arms, Groups, and Interventions

Arm Title
ICSI with mitochondria
Arm Type
Experimental
Arm Description
Half of the Metaphase II oocytes retrieved after the controlled ovarian stimulation will be randomized to this group and autologous mitochondria from the patient's ovarian cortex will be introduced into the oocyte during the intracytoplasmic sperm injection in the vitro fertilization treatment.
Arm Title
Control ICSI without mitochondria
Arm Type
Active Comparator
Arm Description
The other half of the metaphase II oocytes retrieved after the controlled ovarian stimulation will be randomized to this group and will not receive autologous mitochondria during the intracytoplasmic sperm injection (ICSI) in the vitro fertilization treatment. Control Group
Intervention Type
Other
Intervention Name(s)
Autologous mitochondria with ICSI
Intervention Description
Autologous mitochondria during the intracytoplasmic sperm injection (ICSI) process will be added to this randomized group of oocytes.
Intervention Type
Other
Intervention Name(s)
STANDARD ICSI PROCEDURE
Intervention Description
STANDARD ICSI PROCEDURE
Primary Outcome Measure Information:
Title
Rate of ongoing pregnancy
Time Frame
12 weeks

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
42 Years
Accepts Healthy Volunteers
No
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: Low or abnormal Fertilization Rate despite semen count > 3 million/mL. 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. 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. All cases without embryo transfer due to any chromosomal abnormality detected through PGD or PGS techniques. 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Elena Labarta, MD PhD
Organizational Affiliation
Gynecologist Specialist TRA, IVI Valencia
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Antonio Pellicer, MD PhD
Organizational Affiliation
Gynecologist specialist TRA, President IVI Valencia
Official's Role
Principal Investigator
Facility Information:
Facility Name
IVI Valencia
City
Valencia
ZIP/Postal Code
46015
Country
Spain

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
30477915
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.
Results Reference
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Autologous Mitochondrial Transfer in ICSI to Improve Oocyte and Embryo Quality in IVF Patients. Pilot Study

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