PICSI Impact on Euploidy in Assisted Reproduction

Sperm Hyaluronic Binding Selection (PICSI): Impact on Embryo Aneuploid Status in Assisted Human Reproduction

Hyaluronic acid (HA) is a major component of the cumulus complex surrounding oocytes. Intracytoplasmic sperm injection (ICSI) involves injection of a selected sperm into the oocyte. Embryologists select sperm with normal morphology and progressive motility. Physiologic intracytoplasmic sperm injection (PICSI) involves sperm selection for ICSI based on hyaluronan binding. Mature sperm which bind to HA have greater genomic integrity and reduced levels of DNA fragmentation. Earlier observational studies demonstrated improved outcomes in assisted reproductive technologies (ART) including improved clinical pregnancy rates, decreased miscarriage rates and higher live birth rates. A large multicentre randomized trial, the HABSelect trial, which included over 2,500 couples, found that PICSI did not improve term (>37 weeks gestation) live birth rates compared to standard ICSI. However, mechanistic analysis of the data from the HABSelect trial showed a significant reduction in miscarriage rates, most notable in couples where the woman was aged over 37 years where a significant reduction in miscarriage rate was seen (40% with ICSI vs 15% with PICSI). A 2021 retrospective sibling oocyte study, including 45 cycles, compared fertilisation and embryo development and found higher fertilisation rate in PICSI cycles. No difference was observed in clinical pregnancy rates; miscarriage rates and live birth rates were not reported. We aim to prospectively study PICSI vs standard ICSI in sibling oocytes to investigate if PICSI improves embryological and ART outcomes, particularly fertilisation rate, embryo euploid status and miscarriage rate, where the female patient is aged over 35 years.

Study Overview

• Status: Recruiting
• Conditions: Infertility
• Intervention / Treatment: Device: PICSI

• Study Type: Interventional
• Enrollment (Estimated): 142
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Louise E Glover, PhD; Phone Number: 353 + 15567900; Email: lglover@merrionfertility.ie

Study Locations

• Ireland
  • Dublin, Ireland, D02 NH93
    • Recruiting
    • Merrion Fertility Clinic
    • Contact: Louise E Glover, PhD; Phone Number: 353 + 15567900; Email: lglover@merrionfertility.ie
    • Contact: David Crosby, MD
    • Contact: Louise Glover, PhD
    • Contact: Sarah Petch, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Couples undergoing a planned ICSI-PGT-A cycle using their own fresh gametes
• Female age > 35 years and/or Male age > 40 years
• Minimum of two mature eggs at time of egg maturity assessment

Exclusion Criteria:

• Couples undergoing a planned IVF cycle (even if converted to ICSI)
• Patients using donor gametes for an ICSI cycle
• Patients using frozen gametes for an ICSI cycle

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Standard ICSI; ICSI performed using standard sperm selection methods.
Experimental: PICSI; ICSI performed using sperm selected based on hyaluronan binding (PICSI® dish, Cooper Surgical).	Device: PICSI; The PICSI® dish is a CE marked medical device containing dots of a HA hydrogel (Cooper Surgical).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Euploidy rates	Primary outcome is rate of euploid embryos per cycle after preimplantation genetic testing for aneuploidy (PGT-A)	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fertilisation rates	Defined as number of 2PNs per oocyte injected	24-48 hours
Blastocyst development and rate	Assessed on day 5 and day 6 according to Gardner grading system.	5 and 6 days
Positive hCG rate	Defined as detection of urinary human chorionic gonadotropin (hCG) per embryo transfer cycles.	6-7 weeks
Clinical pregnancy rate	Defined as number of fetal heartbeats/ gestational sacs identified by ultrasonographic visualisation at 6-7 weeks gestation per cycles started, oocyte retrievals or embryo transfer cycles.	6-7 weeks
Miscarriage rate	Defined as number of spontaneous losses of an intra-uterine pregnancy prior to 22 completed weeks of gestational age per embryo transfer cycles.	up to 22 weeks
Live birth rate	Defined as number of live births at ≥37 weeks gestation per embryo transfer cycles	37-42 weeks

Collaborators and Investigators

• Sponsor: Merrion Fertility Clinic
• Investigators: Study Director: David Crosby, MD, Merrion Fertility Clinic and the National Maternity Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2024
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): January 1, 2029

Study Registration Dates

• First Submitted: August 1, 2024
• First Submitted That Met QC Criteria: September 17, 2024
• First Posted (Estimated): September 19, 2024

Study Record Updates

• Last Update Posted (Estimated): September 19, 2024
• Last Update Submitted That Met QC Criteria: September 17, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Sperm; Aneuploidy; PICSI
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Infertility
• Other Study ID Numbers: MFC3

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No