Prospective, Randomized Trial Comparing ICSI to Insemination for Non-Male Factor Patients Undergoing PGT-A

NCT05548101 | Unknown

• 1 other identifier: ICSI
• Study Type: interventional
• Target: 500
• Locations: 0 countries
• Sites: N/A

Brief Summary

Intracytoplasmic sperm injection (ICSI) is a procedure performed during in vitro fertilization (IVF) in which a single sperm is injected directly into an oocyte. This procedure was developed for male factor infertility due to its requirement for a very small number of viable sperm. However, its use has expanded and is now recommended for IVF cycles in which preimplantation genetic testing for aneuploidies (PGT-A) is performed on blastocysts. We hypothesize that the ICSI procedure may interfere with the normal meiosis II process that occurs during fertilization, and lead to a higher rate of aneuploid blastocysts. In our study we will randomly assign non-male factor infertility patients to either conventional insemination or ICSI and compare the rate of karyotypically normal embryos in each group.

Conditions

Infertility

Keywords

Infertility; ICSI; Intracytoplasmic Sperm Injection; non-male factor infertility; IVF; In Vitro Fertilization; PGT-A

Outcome Measures

Primary Outcomes (1)

• Rate of karyotypically normal blastocysts

  Aneuploidy will be defined as an abnormal number of chromosomes. Mosaicism will be defined as 30-70% mosaicism, whereas less than 30% mosaicism will be considered euploidy, and greater than 70% mosaicism will be considered aneuploidy. PGT-A outcomes will be analyzed for percentage of euploid, aneuploid, mosaic, and no result embryos. Rate of karyotypically normal blastocysts will be defined as the number of euploid blastocysts divided by the number of normally fertilized (2PN) embryos in that group. We will also assess the number of euploid embryos as a percentage of the total number of inseminated or injected oocytes.

  2 weeks after oocyte retrieval

Secondary Outcomes (2)

• Rate of blastocyst development

  1 week after oocyte retrieval

• Fertilization rate

  1 day after oocyte retrieval

Study Arms (2)

Conventional Insemination

NO INTERVENTION

Oocytes will be fertilized via conventional insemination: Oocytes will be washed with multipurpose handling medium (MHM) plus 0.5% human serum albumin (HSA). Excess cumulus cells and blood will be trimmed. Oocytes will be transferred to a dish containing Irvine Scientific Continuous Cell Culture Complete Medium with two oocytes per dish. The dish will then be transferred to the incubator. Insemination will occur 4-6 hours post-retrieval. Sperm will be collected as a fresh specimen and washed with Irvine Scientific Continuous Single Culture-NX. Sperm concentration and motility will be assessed before and after washing according to WHO 6th edition criteria. Sperm will be prepared to achieve a concentration of 200,000 sperm per 100 microliter drop. 6 drops of prepared sperm will be added to each dish.

Intracytoplasmic Sperm Injection (ICSI)

ACTIVE COMPARATOR

Oocytes will be fertilized via ICSI: Oocytes will be washed with multipurpose handling medium (MHM) plus 0.5% human serum albumin (HSA). Excess cumulus cells and blood will be trimmed. Oocytes will be transferred to a dish containing Irvine Scientific Continuous Cell Culture Complete Medium with two oocytes per dish. The dish will then be transferred to the incubator. Oocytes will be immediately exposed to hyaluronidase to strip the cumulus and coronal cells. Embryologists will assess the maturation status under inverted microscopy. ICSI will be performed on all mature metaphase II oocytes 4 hours after retrieval. Injected oocytes will then be placed in a fresh culture dish and returned to the incubator.

Procedure: ICSI

Interventions

ICSI PROCEDURE

Using the injecting pipet, one sperm will be isolated. Using the tip of the injecting pipet, the sperm tail will be broken by trapping it between the pipet and bottom of the dish. The sperm will be picked up in the pipet. The oocyte will be positioned so the polar body is at the 12 o'clock or 6 o'clock position. The sperm injecting pipet will be positioned at the 3 o'clock position of the oocyte. The injecting pipet will be advanced into the oocyte cytoplasm and the cytoplasm will be gently aspirated until the oocyte membrane breaks. The sperm will then be injected into the cytoplasm of the oocyte. The pipet will then be withdrawn from the oocyte.

Also known as: Intracytoplasmic Sperm Injection

Intracytoplasmic Sperm Injection (ICSI)

Eligibility Criteria

• Age: 18 Years - 39 Years
• Gender Eligibility Details: There must be a female partner to undergo oocyte retrieval and a male partner to provide sperm for insemination.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Female partner aged 18-39 years old with at least 10 oocytes following retrieval
• Male partner with initial semen analysis with greater than or equal to 16 million sperm/mL, greater than or equal to 42% motile sperm, greater than or equal to 16.4 million total motile sperm, greater than or equal to 30% progressive motility, and greater than or equal to 4% normal morphology (as defined by WHO 6th edition)

You may not qualify if:

• Fertilization failure or more than one implantation failure from previous IVF cycles
• Male factor infertility as defined by sperm concentration less than 16 million sperm/mL, motility less than 42%, total motile count less than 16.4 million, progressive motility less than 30%, or normal morphology less than 4%
• Female partner over age 39 years old
• Female partner with 9 or fewer oocytes following retrieval
• Singe gene analysis by preimplantation genetic testing for monogenic disorders (PGT-M) being performed
• ICSI being performed for any reason other than PGT-A

Sponsors & Collaborators

• Texas Fertility Center: lead
• Ovation Fertility: collaborator

Related Publications (6)

• Practice Committees of the American Society for Reproductive Medicine and the Society for Assisted Reproductive Technology. Electronic address: asrm@asrm.org. Intracytoplasmic sperm injection (ICSI) for non-male factor indications: a committee opinion. Fertil Steril. 2020 Aug;114(2):239-245. doi: 10.1016/j.fertnstert.2020.05.032. Epub 2020 Jul 9.

  PMID: 32654822 BACKGROUND

• Palmerola KL, Vitez SF, Amrane S, Fischer CP, Forman EJ. Minimizing mosaicism: assessing the impact of fertilization method on rate of mosaicism after next-generation sequencing (NGS) preimplantation genetic testing for aneuploidy (PGT-A). J Assist Reprod Genet. 2019 Jan;36(1):153-157. doi: 10.1007/s10815-018-1347-6. Epub 2018 Oct 25.

  PMID: 30362056 BACKGROUND

• Niu X, Long J, Gong F, Wang W. Does ICSI for in vitro fertilization cause more aneuploid embryos? Mol Cytogenet. 2020 Jul 1;13:27. doi: 10.1186/s13039-020-00497-z. eCollection 2020.

  PMID: 32636925 BACKGROUND

• Swearman HK, Liperis G, Crittlendon J, Sjoblom C. Fertilization by ICSI results in significantly higher aneuploidy rates compared to IVF, in embryos analysed by next generation sequencing (NGS) or comparative genome hybridization (CGH) array. ASRM Poster Session Volume 110, Issue 4, Supplement, E346-347. 2018 Sep.

  BACKGROUND

• Deng J, Kuyoro O, Zhao Q, Behr B, Lathi RB. Comparison of aneuploidy rates between conventional in vitro fertilization and intracytoplasmic sperm injection in in vitro fertilization-intracytoplasmic sperm injection split insemination cycles. F S Rep. 2020 Jul 27;1(3):277-281. doi: 10.1016/j.xfre.2020.07.006. eCollection 2020 Dec.

  PMID: 34223256 BACKGROUND

• Kandil H, Agarwal A, Saleh R, Boitrelle F, Arafa M, Vogiatzi P, Henkel R, Zini A, Shah R. Editorial Commentary on Draft of World Health Organization Sixth Edition Laboratory Manual for the Examination and Processing of Human Semen. World J Mens Health. 2021 Oct;39(4):577-580. doi: 10.5534/wjmh.210074. Epub 2021 Jun 11. No abstract available.

  PMID: 34169684 BACKGROUND

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

• Kaylen Silverberg, MD

  Texas Fertility Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Madeline R Kaye, MD

CONTACT

7168603989; madeline@txfertility.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Patient will be blinded to use of ICSI versus conventional insemination
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Model Details: prospective randomized controlled clinical trial

Study Record Dates

• First Submitted: September 16, 2022
• First Posted: September 21, 2022
• Study Start: November 1, 2022
• Primary Completion: November 1, 2023
• Study Completion: November 1, 2023
• Last Updated: September 21, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share