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

Preimplantation Diagnosis Clinical Trial

Official title:

A Randomized Double Blind Controlled Trial of Non-invasive Preimplantation Genetic Testing for Aneuploidy and Morphology Compared With Morphology Alone in in Vitro Fertilisation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04474522
• Other study ID #: UW 20-248
• Status: Recruiting
• Phase: N/A
• Start date: July 1, 2021
• Est. completion date: September 1, 2024

Study information

• Verified date: August 2023
• Source: The University of Hong Kong
• Contact: Heidi Cheng, MBBS
• Phone: 852-22553657
• Email: chy610a[@]ha.org.hk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 500
• Est. completion date: September 1, 2024
• Est. primary completion date: May 30, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 43 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Aneuploidy
• Preimplantation Diagnosis

Intervention

Genetic:
• Non-invasive Preimplantation genetic testing for aneuploidy status
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.

Locations

Country	Name	City	State
China	Department of Obstetrics and Gynaecology	Hong Kong	Hong Kong

Sponsors (1)

Lead Sponsor	Collaborator
The University of Hong Kong

Country where clinical trial is conducted

China, 

References & Publications (11)

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. — View Citation

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):137 — View Citation

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. Ep — View Citation

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. — View Citation

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. — View Citation

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. Erratum In: Hum Reprod Update. — View Citation

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 select — View Citation

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. — View Citation

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 randomize — View Citation

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. — View Citation

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 pil — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Live birth	Birth beyond 22 weeks of gestation per the first FET	Number of live births beyond 22 weeks of gestation
Secondary	Cumulative live birth rate	Number of pregnancies leading to live birth within 6 months of randomization	Number of pregnancies leading to live birth within 6 months of randomization
Secondary	Time to pregnancy	between time of IVF and pregnancy	1 year
Secondary	Positive urine pregnancy test	Urine pregnancy test positive	Positive urine pregnancy test 14 days after embryo transfer
Secondary	Clinical pregnancy	Presence of intrauterine gestational sac on scanning at gestational week 6	6 weeks
Secondary	Ongoing pregnancy	Presence of a fetal pole with pulsation at 8-10 weeks of gestation	10 weeks
Secondary	Miscarriage defined	Clinically recognized pregnancy loss before the 22 weeks of pregnancy and whose denominator is the clinical pregnancy.	Pregnancy loss up to 22 weeks
Secondary	Multiple pregnancy	presence of more than one intrauterine sac at 6 weeks of gestation	more than one intrauterine sac at 6 weeks
Secondary	Ectopic pregnancy	Pregnancy not in the uterus	12 weeks
Secondary	Birth weight	Pregnancy outcome	1 year
Secondary	Apgar score	Pregnancy outcome	1 year