RCT of niPGT for Aneuploidy and Morphology Compared With Morphology Alone in IVF

NCT04474522 | Completed DMC

• 1 other identifier: UW 20-248
• Study Type: interventional
• Target: 517
• Locations: 1 country
• Sites: 1

Brief Summary

This study is to compare the efficacy in embryo selection based on morphology alone compared to morphology and non-invasive preimplantation genetic testing for aneuploidy (NIPGT-A) in infertile women undergoing in vitro fertilization (IVF). We supposed the embryo selection based on morphology and NIPGT-A results in a higher live birth rate and a lower miscarriage rate in IVF as compared with that based on morphology alone. Therefore we would like to conduct a double-blind randomized controlled trial. Infertile women undergoing IVF will be enrolled. The spent culture medium (SCM) of each blastocyst will be frozen individually. They will be randomized into two groups: (1) the intervention group based on morphology and NIPGT-A and (2) the control group based on morphology alone. In the control group, blastocysts with the best quality morphology will be replaced first. In the intervention group, blastocysts with the best morphology and euploid result of SCM will be replaced first.The primary outcome is a live birth per the first embryo transfer. We would like to compare live birth rates and miscarriage rates between the two groups.

Conditions

Preimplantation Diagnosis

Outcome Measures

Primary Outcomes (1)

• Live birth

  Birth beyond 22 weeks of gestation per the first FET

  Number of live births beyond 22 weeks of gestation

Secondary Outcomes (10)

• Cumulative live birth rate

  Number of pregnancies leading to live birth within 6 months of randomization

• Time to pregnancy

  1 year

• Positive urine pregnancy test

  Positive urine pregnancy test 14 days after embryo transfer

• Clinical pregnancy

  6 weeks

• Ongoing pregnancy

  10 weeks

Study Arms (2)

intervention group using morphology and NIPGT-A

ACTIVE COMPARATOR

Both morphology and NIPGT-A result will be used to prioritize the sequence of embryo transfer in the intervention group.

Genetic: Non-invasive Preimplantation genetic testing for aneuploidy status

control group based on morphology alone

NO INTERVENTION

Morphology only will be used to prioritize the sequence of embryo transfer in the intervention arm.

Interventions

Non-invasive Preimplantation genetic testing for aneuploidy status GENETIC

In the intervention group, comprehensive chromosome screening using NGS will be performed according to the recommendations of the company in all SCM samples. Sequence of replacement shall be altered by the NiPGT result after morpholgy.

intervention group using morphology and NIPGT-A

Eligibility Criteria

• Age: 18 Years - 43 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Women aged less than 43 years at the time of ovarian stimulation
• At least two blastocysts suitable for freezing on day 5 or 6 after oocyte retrieval

You may not qualify if:

• Less than two blastocysts suitable for freezing on day 5 or 6 after oocyte retrieval;
• Women undergoing PGT for monogenic diseases or structural rearrangement of chromosomes;
• Use of donor oocytes;
• Hydrosalpinx shown on pelvic scanning and not surgically treated

Sponsors & Collaborators

• The University of Hong Kong: lead

Study Sites (1)

Department of Obstetrics and Gynaecology

Hong Kong, Hong Kong, China

Location

Related Publications (12)

• Spandorfer SD, Davis OK, Barmat LI, Chung PH, Rosenwaks Z. Relationship between maternal age and aneuploidy in in vitro fertilization pregnancy loss. Fertil Steril. 2004 May;81(5):1265-9. doi: 10.1016/j.fertnstert.2003.09.057.

  PMID: 15136087 BACKGROUND

• Hassold T, Hall H, Hunt P. The origin of human aneuploidy: where we have been, where we are going. Hum Mol Genet. 2007 Oct 15;16 Spec No. 2:R203-8. doi: 10.1093/hmg/ddm243.

  PMID: 17911163 BACKGROUND

• Nybo Andersen AM, Wohlfahrt J, Christens P, Olsen J, Melbye M. Maternal age and fetal loss: population based register linkage study. BMJ. 2000 Jun 24;320(7251):1708-12. doi: 10.1136/bmj.320.7251.1708.

  PMID: 10864550 BACKGROUND

• Mastenbroek S, Twisk M, van der Veen F, Repping S. Preimplantation genetic screening: a systematic review and meta-analysis of RCTs. Hum Reprod Update. 2011 Jul-Aug;17(4):454-66. doi: 10.1093/humupd/dmr003. Epub 2011 Apr 29.

  PMID: 21531751 BACKGROUND

• Yang Z, Liu J, Collins GS, Salem SA, Liu X, Lyle SS, Peck AC, Sills ES, Salem RD. Selection of single blastocysts for fresh transfer via standard morphology assessment alone and with array CGH for good prognosis IVF patients: results from a randomized pilot study. Mol Cytogenet. 2012 May 2;5(1):24. doi: 10.1186/1755-8166-5-24.

  PMID: 22551456 BACKGROUND

• Scott RT Jr, Upham KM, Forman EJ, Hong KH, Scott KL, Taylor D, Tao X, Treff NR. Blastocyst biopsy with comprehensive chromosome screening and fresh embryo transfer significantly increases in vitro fertilization implantation and delivery rates: a randomized controlled trial. Fertil Steril. 2013 Sep;100(3):697-703. doi: 10.1016/j.fertnstert.2013.04.035. Epub 2013 Jun 1.

  PMID: 23731996 BACKGROUND

• Forman EJ, Hong KH, Ferry KM, Tao X, Taylor D, Levy B, Treff NR, Scott RT Jr. In vitro fertilization with single euploid blastocyst transfer: a randomized controlled trial. Fertil Steril. 2013 Jul;100(1):100-7.e1. doi: 10.1016/j.fertnstert.2013.02.056. Epub 2013 Mar 30.

  PMID: 23548942 BACKGROUND

• Fiorentino F, Biricik A, Bono S, Spizzichino L, Cotroneo E, Cottone G, Kokocinski F, Michel CE. Development and validation of a next-generation sequencing-based protocol for 24-chromosome aneuploidy screening of embryos. Fertil Steril. 2014 May;101(5):1375-82. doi: 10.1016/j.fertnstert.2014.01.051. Epub 2014 Mar 6.

  PMID: 24613537 BACKGROUND

• Evans J, Hannan NJ, Edgell TA, Vollenhoven BJ, Lutjen PJ, Osianlis T, Salamonsen LA, Rombauts LJ. Fresh versus frozen embryo transfer: backing clinical decisions with scientific and clinical evidence. Hum Reprod Update. 2014 Nov-Dec;20(6):808-21. doi: 10.1093/humupd/dmu027. Epub 2014 Jun 10.

  PMID: 24916455 BACKGROUND

• Lee E, Illingworth P, Wilton L, Chambers GM. The clinical effectiveness of preimplantation genetic diagnosis for aneuploidy in all 24 chromosomes (PGD-A): systematic review. Hum Reprod. 2015 Feb;30(2):473-83. doi: 10.1093/humrep/deu303. Epub 2014 Nov 28.

  PMID: 25432917 BACKGROUND

• Munne S, Kaplan B, Frattarelli JL, Child T, Nakhuda G, Shamma FN, Silverberg K, Kalista T, Handyside AH, Katz-Jaffe M, Wells D, Gordon T, Stock-Myer S, Willman S; STAR Study Group. Preimplantation genetic testing for aneuploidy versus morphology as selection criteria for single frozen-thawed embryo transfer in good-prognosis patients: a multicenter randomized clinical trial. Fertil Steril. 2019 Dec;112(6):1071-1079.e7. doi: 10.1016/j.fertnstert.2019.07.1346. Epub 2019 Sep 21.

  PMID: 31551155 BACKGROUND

• Cheng HYH, Chow JFC, Lam KKW, Lai SF, Yeung WSB, Ng EHY. Randomised double-blind controlled trial of non-invasive preimplantation genetic testing for aneuploidy in in vitro fertilisation: a protocol paper. BMJ Open. 2023 Jul 27;13(7):e072557. doi: 10.1136/bmjopen-2023-072557.

  PMID: 37500277 DERIVED

Study Officials

• Ernest HY Ng, MD

  The University of Hong Kong

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: SCREENING
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 6, 2020
• First Posted: July 16, 2020
• Study Start: July 1, 2021
• Primary Completion: May 30, 2023
• Study Completion: March 24, 2025
• Last Updated: March 28, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)