PGT-A Evaluates Advanced Sperm Selection in Embryos From High Teratozoospermia Males

Next Generation Sequencing of Embryos for Testing the Efficacy of Advanced Sperm Selection Techniques in Males With High Teratozoospermia Index

In this study of 264 couples, sperm selection techniques in males with high teratozoospermia index and sperm DNA fragmentation significantly increased fertilization, blastocyst development rates, and maintained comparable embryo euploidy rates through preimplantation genetic testing, suggesting the efficiency of these techniques in improving assisted reproductive outcomes.

Study Overview

• Status: Completed
• Conditions: Infertility; Teratozoospermia; Sperm DNA Fragmentation
• Intervention / Treatment: Device: Sperm Selection

Detailed Description

Couples seeking infertility treatment are becoming more frequent. Paternal factor shows one of the infertility causes which may have a negative impact on reproductive outcomes. Intracytoplasmic sperm injection (ICSI) is thought to be the most effective way to treat infertility. Sperm morphology evaluation is a reliable predictor of male fertility while teratozoospermia index (TZI) is a unique expression of sperm morphological assessment. A higher rate of abnormal sperm morphology tends to have higher sperm chromosomal abnormality rates. The choice of high-quality sperm through sperm selection techniques is expected to improve ICSI outcomes. In this study, a total number of 264 couples were included and divided into 3 groups: (1) Males have normal TZI (Control group: 111 males have TZI <1.6), (2) Males with high TZI and no sperm selection techniques are performed (NO-SS group: 63 males have TZI >1.8), and (3) Males with high TZI and sperm selection techniques are performed (SS-group: 90 males have TZI >1.8). The TZI was significantly (P<0.000) higher in the NO-SS and SS-group as compared to the control group. The percentage of sperm DNA fragmentation SDF in the males of the SS group was significantly higher than the controls and NO-SS group (P=0.000). The fertilization (P=0. 039) and blastocyst development rates (P= 0. 041) are significantly higher in the SS group as compared to the NO-SS group in females aged <35. A total of 1072 embryos were tested for preimplantation genetic testing for aneuploidy using NGS, although higher SDF in the males of the SS group, the embryo euploidy rates show that there is no significant difference between the SS group (56.35±3.46%) as compared to the control group (54.54±3.24%) and the NO-SS group (57.45±4.57%). In general, we found that sperm selection techniques are efficient techniques in increasing fertilization, blastocyst development rates, and euploidy rate in males with high teratozoospermia index and sperm DNA fragmentation combined.

• Study Type: Interventional
• Enrollment (Actual): 264
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • Maadi
    • Cairo, Maadi, Egypt, 11728
      • Ganin Fertility Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Males diagnosed with normal and high teratozoospermia index.
2. Males with Mild to moderate OTA (oligoteratoasthenozoospermia).
3. Males aged 18-60 years.
4. Female aged 18-40 years.
5. Case must have PGT-A for all of her blastocysts.
6. Normo responder (> 5 mature oocytes).
7. 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 ICSI.

Exclusion Criteria:

1. Leukocytospermia.
2. Presence of varicocele.
3. Known genetic abnormality.
4. Use of sperm or oocyte donors.
5. Use of gestational carrier.
6. Presence of any of the endometrial factors that affect embryo implantation such as hydrosalpings, adenomyosis or previous uterine infection.
7. 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: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control; 111 Males have normal Teratozoospermia index (TZI) less than 1.6. Semen processing is done by double layer density gradient method only.
Experimental: Sperm selection group PICSI or MACS (SS-Group); 90 Males with high TZI and sperm selection techniques such as PICSI or MACS are performed. Semen processing is done by double layer density gradient method followed by: (1) In case of PICSI: 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. Individual bound sperm selection is done followed by ICSI. or (2) In case of 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 ICSI.	Device: Sperm Selection; Sperm selection using physiological intracytoplasmic sperm injection (PICSI dish) or magnetic-activated cell sorting (MACS) for selecting sperm with high-quality, better morphology and lower DNA fragmentation.
No Intervention: No sperm selection group (NO SS-Group); 63 Males with high TZI more than 1.8 and no sperm selection techniques are performed. Semen processing is done by double layer density gradient method only.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Euploidy rate	Defined as the proportion of euploid blastocysts	15 days post ICSI
Aneuploidy rate	Defined as the proportion of aneuploid blastocysts	15 days post ICSI
Fertilization rate	Defined as the proportion of fertilizaed oocytes	1 day
Blastocyst development rate	Defined as the proportion of blastocysts formed on day 5 or 6	5-6 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Low mosaic rate	Defined as the proportion of low mosaic blastocysts	15 days post ICSI
High mosaic rate	Defined as the proportion of high mosaic blastocysts	15 days post ICSI
Blastocyst quality rate	Defined as the assessment of blastocyst quality according to Gardner's criteria into: good, fair or poor	5-6 days

Collaborators and Investigators

• Sponsor: Ganin Fertility Center
• Investigators: Study Director: Hosam Zaki, MSc, FRCOG, Ganin Fertility Center; Study Chair: Mohamed Nasreldin, MSc., Ganin Fertility Center; Principal Investigator: Hanan Ramadan, PhD, Cairo University; Principal Investigator: Maiada Moustafa, PhD, Helwan University; Principal Investigator: Mohamed Abas, MBB, Cairo University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2023
• Primary Completion (Actual): September 1, 2023
• Study Completion (Actual): September 1, 2023

Study Registration Dates

• First Submitted: January 21, 2024
• First Submitted That Met QC Criteria: January 29, 2024
• First Posted (Actual): January 30, 2024

Study Record Updates

• Last Update Posted (Actual): January 30, 2024
• Last Update Submitted That Met QC Criteria: January 29, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: PGT-A; Sperm DNA fragmentation; Sperm selection; Euploidy rate; Teratozoospermia index
• Additional Relevant MeSH Terms: Infertility, Male; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Infertility; Teratozoospermia
• Other Study ID Numbers: GFC-008

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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