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

NCT02586298 | Completed

• 1 other identifier: 1501-VLC-005-AP
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 1

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.

Conditions

Infertility

Outcome Measures

Primary Outcomes (1)

• Rate of ongoing pregnancy

  12 weeks

Study Arms (2)

ICSI with mitochondria

EXPERIMENTAL

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.

Other: Autologous mitochondria with ICSI

Control ICSI without mitochondria

ACTIVE COMPARATOR

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

Other: STANDARD ICSI PROCEDURE

Interventions

Autologous mitochondria with ICSI OTHER

Autologous mitochondria during the intracytoplasmic sperm injection (ICSI) process will be added to this randomized group of oocytes.

ICSI with mitochondria

STANDARD ICSI PROCEDURE OTHER

STANDARD ICSI PROCEDURE

Control ICSI without mitochondria

Eligibility Criteria

• Age: 18 Years - 42 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Instituto Valenciano de Infertilidad, IVI VALENCIA: lead

Study Sites (1)

IVI Valencia

Valencia, 46015, Spain

Location

Related Publications (1)

• 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.

  PMID: 30477915 DERIVED

MeSH Terms

Conditions

Infertility

Interventions

Sperm Injections, Intracytoplasmic

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Fertilization in Vitro; Reproductive Techniques, Assisted; Reproductive Techniques; Therapeutics; Investigative Techniques

Study Officials

• Elena Labarta, MD PhD

  Gynecologist Specialist TRA, IVI Valencia

  STUDY DIRECTOR

• Antonio Pellicer, MD PhD

  Gynecologist specialist TRA, President IVI Valencia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2015
• First Posted: October 26, 2015
• Study Start: October 1, 2015
• Primary Completion: March 1, 2017
• Study Completion: July 1, 2017
• Last Updated: August 23, 2017

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)