Sperm Selection by Either PICSI or MACS in Cases With Abnormal Sperm DNA Fragmentation Index for ICSI

PICSI vs. MACS for Abnormal Sperm DNA Fragmentation ICSI Cases: a Prospective Randomized Trial

On the day of ICSI, choosing the best sperm by either PICSI or magnetic activated cell sorting (MACS) in cases with abnormal DNA is not fully investigated. This study helps in solving this problem by using two known techniques to achieve that purpose.

Study Overview

• Status: Completed
• Conditions: Sperm DNA Fragmentation
• Intervention / Treatment: Other: PICSI; Other: MACS

Detailed Description

Sperm DNA fragmentation has shown a negative correlation with fertilization rate, embryo quality, and implantation rate. And a positive correlation with miscarriage rate in the 1st trimester.

Sperm selection methods like PICSI and MACS have been developed for selecting a healthy mature non apoptotic sperm with healthy membrane for Oocyte injection so as to obtain best embryo quality and achieve higher ongoing pregnancy rates.

A sperm selection technique based on sperm membrane binding to hyaluronic acid (PICSI Dish), the main substrate of the oocyte zonapellucida, could improve the likelihood of obtaining better sperm for ICSI with non fragmented DNA. Another sperm selection technique based on Magnetic activated cell sorting (MACS) that depends on the binding of protein Annexin V to phosphatidylserine which is a marker for apoptosis, giving a resulting (eluted) spermatozoa without DNA fragmentation.

In order to determine which sperm selection technique is better for dealing with DNA fragmentation patients we need to study both techniques on two different groups of patients

• Study Type: Interventional
• Enrollment (Actual): 396
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt
    • Ganin Fertility Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Males diagnosed of abnormal DNA fragmentation index ( > 19%).
• Males with mild to moderate OTA (oligoteratoasthenozoospermia).
• Male aged 18-60 years.
• Female aged 18-40 years.
• Normo responder ( > 5 mature oocytes)
• Male will have to refrain from ejaculation no less than 1 day but no greater than 3 days prior semen specimen production on day of oocyte retrieval

Exclusion Criteria:

Males with normalDNA fragmentation index (<19%)at the initial assessment.

• Leukocytospermia
• Presence of varicocele.
• Known genetic abnormality
• Use of sperm donation or cryopreserved sperm
• Use of Oocyte donation
• Use of gestational carrier
• Presence of any of the endometrial factors that affect embryo implantation such as hydrosalpings, adenomyosis or previous uterine infection
• Any contradictions to undergoing in vitro fertilization or gonadotropin stimulation

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
Experimental: PICSI; Semen processing is done by double layer density gradient method followed by adding Sperm to the dot of hyaluronan on the PICSI dish, within minutes the bound sperm are attached by their acrosome to the surface of the dot. Selecting an individual bound sperm with enhanced genetic and developmental integrity ensures that the sperm selected is the optimal sperm from the sample for oocyte injection	Other: PICSI; sperm selection using PICSI dish for selecting sperm with lower DNA fragmentation index
Active Comparator: MACS; Semen processing is done by double layer density gradient method. The resulted pellet is labeled with annexin V microbeads followed by separation on MACS Column, the eluted fraction contains non apoptotic sperm suitable for Oocyte injection.	Other: MACS; sperm selection using MACS for selecting sperm with lower DNA fragmentation index

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ongoing pregnancy rate	Defined as the proportion of pregnancies that completed more than 20 weeks of gestation	20 weeks of gestation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of cleavage rate	Defined as the proportion of cleaved embryos on day 3 over the injected oocytes	3 days
Comparison of Blastulation rate	Defined as the proportion of blastocysts formed on day 5 or 6 over the cleaved embryos on day 3	5-6 days
Comparison of Blastocyst quality rate	Defined as the assessment of blastocyst quality according to Gardner's criteria into: good, fair or bad in terms of percentage of the total formed blastocysts	5-6 days
Comparison of Pregnancy rate	Defined as clinical pregnancy per transfer	14 days following embryo transfer
Comparison of implantation rate	Defined as number of gestational sacs with fetal heart beat, shown by ultrasound in gestational week 6 over number of embryo transferred.	6- 8 weeks following embryo transfer

Collaborators and Investigators

• Sponsor: Ganin Fertility Center
• Collaborators: The Cleveland Clinic; University of the Western Cape
• Investigators: Study Chair: Hosam Zaki, MSc, FRCOG, Ganin Fertility Center, Cairo, Egypt; Principal Investigator: Eman Hasanen, BSc, Ganin Fertility Center, Cairo, Egypt; Principal Investigator: Khaled El Qusi, BSc, Ganin Fertility Center, Cairo, Egypt; Principal Investigator: Abd El Ghafar Hussin, BSc, Ganin Fertility Center, Cairo, Egypt; Principal Investigator: Salma El Tanbouly, BSc, Ganin Fertility Center, Cairo, Egypt; Study Director: Ashok Agarwal, PhD, American Center of Reproductive Medicine, Cleveland Clinic; Principal Investigator: Ralph Henkel, PhD, University of the Western Cape; Principal Investigator: Hanaa Alkhader, Ganin Fertility Center, Cairo, Egypt

Publications and helpful links

General Publications

• Benchaib M, Braun V, Lornage J, Hadj S, Salle B, Lejeune H, Guerin JF. Sperm DNA fragmentation decreases the pregnancy rate in an assisted reproductive technique. Hum Reprod. 2003 May;18(5):1023-8. doi: 10.1093/humrep/deg228.
• Baldi and Muratori (2013) Genitic Damage in Human Spermatozoa. USA, NY : Springer Science & Business Media.
• Hasanen E, Elqusi K, ElTanbouly S, Hussin AE, AlKhadr H, Zaki H, Henkel R, Agarwal A. PICSI vs. MACS for abnormal sperm DNA fragmentation ICSI cases: a prospective randomized trial. J Assist Reprod Genet. 2020 Oct;37(10):2605-2613. doi: 10.1007/s10815-020-01913-4. Epub 2020 Aug 8.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2017
• Primary Completion (Actual): March 30, 2019
• Study Completion (Actual): March 30, 2019

Study Registration Dates

• First Submitted: January 7, 2018
• First Submitted That Met QC Criteria: January 7, 2018
• First Posted (Actual): January 12, 2018

Study Record Updates

• Last Update Posted (Actual): July 21, 2020
• Last Update Submitted That Met QC Criteria: July 18, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: DFI; PICSI; MACS; SDF; sperm selection
• Other Study ID Numbers: GFC - 002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No