Genetic Screening and Assisted Oocyte Activation in Couples with Diminished/aberrant Embryonic Development.

NCT ID: NCT03354013

Last Updated: 2024-09-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-01-15
• Study Completion Date: 2022-09-09

Brief Summary

This is an interventional comparative study at the Department of Reproductive Medicine at Ghent University Hospital. Patients with previous embryo developmental problems are eligible for the study. Patients will undergo an ICSI-AOA treatment and will also be screened for genes important in the oocyte activation and embryonic development process. Also, the calcium releasing pattern of the patients' spermatozoa will be investigated.

Detailed Description

Assisted Oocyte Activation (ICSI-AOA) will be the treatment for these patients to overcome their previous embryo developmental problems. This protocol artificially induces calcium rises in the oocyte, which mimics the natural oocyte activation process induced by the sperm factor PLCzeta. If 6 or more mature oocytes are collected at oocyte retrieval, 50%ICSI and 50% ICSI-AOA will be applied to all oocytes. The best embryo(s) will be transferred back. Rest embryo(s) will be vitrified for future cycles. Patients will be followed up.

Furthermore, an additional sperm sample will be produced to investigate the calcium inducing pattern of the patients' spermatozoa. Thereby, mouse and/or human (research-donated control oocytes) will be pre-incubated with a Ca2+ sensitive dye. Next, human spermatozoa will be injected into these mouse/human oocytes and the calcium pattern will be recorded under an inverted epifluorescence microscope.

Both partners will give a saliva sample to screen for mutations possible genes involved in oocyte activation and embryo development.

Conditions

Embryo; Embryo Disorder; Genetic Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

AOA, genetic screening, calcium pattern

Clinical setting: Patients will undergo ICSI-AOA. Furthermore, patients will give a saliva sample to do genetic screening. Genes important during oocyte activation and embryo development will be investigated.

Also, calcium pattern analysis of the patients' spermatozoa will be executed.

Group Type: EXPERIMENTAL

AOA

Intervention Type: PROCEDURE

100% ICSI-AOA will be performed.

Genetic screening

Intervention Type: DIAGNOSTIC_TEST

Patients will donate a saliva sample. Genetic screening will take place for PLCzeta (male) and Dux4 (male and female). Also other possible genes involved in embryo development could be tested.

Calcium pattern analysis

Intervention Type: DIAGNOSTIC_TEST

Male patients will donate a sperm sample. Calcium pattern analysis will take place by injecting the patients' sperm into mouse and/or human (in vitro matured) oocytes (research-donated control oocytes). This will estimate the sperm capability to induce calcium oscillations in the oocyte.

Interventions

AOA

100% ICSI-AOA will be performed.

Intervention Type: PROCEDURE

Genetic screening

Patients will donate a saliva sample. Genetic screening will take place for PLCzeta (male) and Dux4 (male and female). Also other possible genes involved in embryo development could be tested.

Intervention Type: DIAGNOSTIC_TEST

Calcium pattern analysis

Male patients will donate a sperm sample. Calcium pattern analysis will take place by injecting the patients' sperm into mouse and/or human (in vitro matured) oocytes (research-donated control oocytes). This will estimate the sperm capability to induce calcium oscillations in the oocyte.

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• patients with one or more previous ICSI cycles (UZ Gent) AND
• patients with:
• complete developmental arrest (no transfer), or
• complete developmental delay (no morula/blastocyst on Day 5), or
• significantly reduced blastocyst formation (≤15%)
• willing and able to give informed consent

Exclusion Criteria

• patients which went for oocyte or sperm donation
• patients with severe male infertility or low fertilization (<33%) after ICSI
• cycles requiring surgical sperm recovery procedures

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Ghent

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Petra De Sutter, M.D; PhD

Role: PRINCIPAL_INVESTIGATOR

University Ghent

Björn Heindryckx, Prof.; PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Ghent

Locations

Ghent University Hospital

Ghent, East-Flandres, Belgium

Countries

Belgium

References

Cardona Barberan A, Bonte D, Boel A, Thys V, Paredis R, Machtelinckx F, De Sutter P, De Croo I, Leybaert L, Stoop D, Coucke P, Vanden Meerschaut F, Heindryckx B. Assisted oocyte activation does not overcome recurrent embryo developmental problems. Hum Reprod. 2023 May 2;38(5):872-885. doi: 10.1093/humrep/dead051.

Reference Type: DERIVED

PMID: 36931261 (View on PubMed)

Other Identifiers

2017/0819

Identifier Type: OTHER

Identifier Source: secondary_id

B670201732853

Identifier Type: -

Identifier Source: org_study_id