Preimplantation Genetic Screening in IVF Treatment

Study Overview
=================
Brief Summary
-----------------
This is the pilot phase of a randomised controlled trial. The purpose of the pilot study is to assess the ability to recruit, randomise, adherence to the study protocol and plan for a full study. The purpose of the full study will be to determine if a policy of embryo selection and transfer based on morphological evaluation and preimplantation genetic testing for aneuploidy (PGT-A) is a more clinically effective, safer, cost-effective and acceptable way to provide in vitro fertilisation (IVF) treatment in women of advanced reproductive age compared to the routine practice of embryo selection and transfer based on morphological evaluation alone.

Detailed Description
-----------------
The target population for the trial are women aged 35 - 42 years undergoing IVF±ICSI treatment. Intervention The experimental strategy will be to perform PGT-A (also referred as preimplantation genetic screening - PGS) involving trophectoderm biopsy on embryos reaching the blastocyst stage on day 5/6/7 following egg collection. All embryos will be frozen after the biopsy procedure. Comprehensive chromosome screening (CCS) of all chromosomes will be performed using next generation sequencing (NGS). Embryos will be categorised as euploid, mosaic euploid and aneuploid embryos and embryos will be ranked based on the degree of euploidy. Only euploid embryos or mosaic euploid embryos deemed suitable to be replaced will be transferred in subsequent frozen-thawed embryo transfer cycles. Comparison Women in the control arm will have the fresh embryo transfer procedure on day 5 following egg collection or a frozen-thawed embryo transfer as first line if clinically indicated in keeping with current routine practice. Embryo selection for transfer will be based on morphological criteria alone.

Official Title
-----------------
Preimplantation Genetic Testing for Aneuploidy (PGT-A) in in Vitro Fertilisation (IVF) Treatment: Pilot Phase of a Randomised Controlled Trial

Conditions
-----------------
Infertility

Intervention / Treatment
-----------------
* Procedure: PGT-A Strategy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Inclusion criteria for the study would be women aged 35 - 42 years undergoing IVF ± ICSI for treatment of infertility Patients with 3 or more good quality embryos (assessed according to the embryo scoring system of the Association of Clinical Embryologists, UK) on day 3 following egg collection Ability to provide informed written consent Exclusion Criteria: Women undergoing preimplantation genetic testing for inherited genetic disorders Gamete donation cycles Untreated hydrosalpinges Untreated uterine pathology (eg: endometrial polyps, submucous fibroids, intramural fibroids > 5 centimetres in maximum diameter, intrauterine adhesions, uterine septa)

Ages Eligible for Study
-----------------
Minimum Age: 35 Years
Maximum Age: 42 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Pilot phase of a prospective, allocation concealed two arm parallel RCT
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>The intervention will be PGT-A strategy involving trophectoderm biopsy and comprehensive chromosome screening (CCS) using Next Generation Sequencing (NGS). All embryos will be frozen after the biopsy procedure and transferred in a subsequent frozen-thawed embryo transfer. Embryo selection for transfer will be based on morphological criteria and the genetic screening result. Only euploid embryos or mosaic euploid embryos deemed suitable to be transferred will be replaced into the uterus in a subsequent frozen-thawed embryo transfer cycles. | Procedure: PGT-A Strategy<br>* PGT-A strategy involves trophectoderm biopsy, comprehensive chromosome screening (CCS) using Next Generation Screening (NGS), freezing of embryos and replacement in a frozen-thawed embryo transfer cycle.<br>* Other names: PGS Strategy;|
| No Intervention: Control arm<br>Women in the control arm will have the fresh embryo transfer procedure on day 5 following egg collection, or a frozen-thawed embryo transfer as first line over a fresh embryo transfer, if clinically indicated. Embryo selection for transfer will be based on morphological criteria. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recruitment rate | Pilot phase RCT with an aim to progress to a multi-centre RCT | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical pregnancy rate | Clinical pregnancy is defined as presence of an intrauterine gestational sac with a foetal pole and heart beat identified by ultrasound scan. | 21 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Preimplantation Genetic Testing, IVF, RCT, Pilot Study