Study protocol: E-freeze-freezing of embryos in assisted conception: A randomised controlled trial evaluating the clinical and cost effectiveness of a policy of freezing embryos followed by thawed frozen embryo transfer compared with a policy of fresh embryo transfer, in women undergoing in vitro fertilisation

Abha Maheshwari*, Siladitya Bhattacharya, Ursula Bowler, Daniel Brison, Tim Child, Christina Cole, Arri Coomarasamy, Rachel Cutting, Stephen Harbottle, Pollyanna Hardy, Edmund Juszczak, Yacoub Khalaf, Jennifer J. Kurinczuk, Stuart Lavery, Clare Lewis-Jones, Nick Macklon, Nick J. Raine-Fenning, Madhurima Rajkohwa, Graham Scotland, Stephen Troup

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Background: Infertility affects one in seven couples; many of these need in vitro fertilisation (IVF). IVF involves external hormones to stimulate a woman's ovaries to produce eggs which are harvested surgically. Embryos, created in the laboratory by mixing eggs with sperm, are grown in culture for a few days before being replaced within the uterus (fresh embryo transfer). Spare embryos are usually frozen with a view to transfer at a later point in time-especially if the initial fresh transfer does not result in a pregnancy. Despite improvements in technology, IVF success rates remain low with an overall live birth rate of 25-30% per treatment. Additionally, there are concerns about health outcomes for mothers and babies conceived through IVF, particularly after fresh embryo transfer, including maternal ovarian hyperstimulation syndrome (OHSS) and preterm delivery. It is believed that high levels of hormones during ovarian stimulation could create a relatively hostile environment for embryo implantation whilst increasing the risk of OHSS. It has been suggested that freezing all embryos with the intention of thawing and replacing them within the uterus at a later stage (thawed frozen embryo transfer) instead of fresh embryo transfer, may lead to improved pregnancy rates and fewer complications. We aim to compare the clinical and cost effectiveness of fresh and thawed frozen embryo transfer, with the primary aim of identifying any difference in the chance of having a healthy baby. Methods: E-Freeze is a pragmatic, multicentre two-arm parallel group randomised controlled trial where women aged ≥18 and < 42 years, with at least three good quality embryos are randomly allocated to receive either a fresh or thawed frozen embryo transfer. The primary outcome is a healthy baby, defined as a term, singleton, live birth with appropriate weight for gestation. Cost effectiveness will be calculated from a healthcare and societal perspective. Discussion: E-Freeze will determine the relative benefits of fresh and thawed frozen embryo transfer in terms of improving the chance of having a healthy baby. The results of this pragmatic study have the potential to be directly transferred to clinical practice.

Original languageEnglish
Article number81
Number of pages11
JournalReproductive Health
Volume16
DOIs
Publication statusPublished - 13 Jun 2019

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Embryo Transfer
Fertilization in Vitro
Freezing
Cost-Benefit Analysis
Embryonic Structures
Randomized Controlled Trials
Ovarian Hyperstimulation Syndrome
Live Birth
Eggs
Uterus
Mothers
Hormones
Pregnancy
Ovulation Induction
Birth Rate
Pregnancy Rate
Infertility
Spermatozoa
Ovary
Technology

Keywords

  • Assisted conception
  • Elective freezing
  • Fertility
  • Fresh embryo transfer
  • Frozen thawed embryo transfer
  • IVF
  • OHSS
  • Receptivity
  • Ovarian Hyperstimulation Syndrome/epidemiology
  • Ovulation Induction
  • Embryo, Mammalian
  • Humans
  • Infertility, Female/therapy
  • Freezing
  • Young Adult
  • Fertilization in Vitro/legislation & jurisprudence
  • Pregnancy Complications/epidemiology
  • Adult
  • Female
  • Pregnancy Rate
  • Embryo Transfer/methods
  • Live Birth/epidemiology
  • Embryo Implantation
  • Pregnancy
  • Cost-Benefit Analysis
  • Cryopreservation/economics
  • Adolescent
  • Pregnancy Outcome

ASJC Scopus subject areas

  • Obstetrics and Gynaecology
  • Reproductive Medicine

Cite this

Study protocol : E-freeze-freezing of embryos in assisted conception: A randomised controlled trial evaluating the clinical and cost effectiveness of a policy of freezing embryos followed by thawed frozen embryo transfer compared with a policy of fresh embryo transfer, in women undergoing in vitro fertilisation. / Maheshwari, Abha; Bhattacharya, Siladitya; Bowler, Ursula; Brison, Daniel; Child, Tim; Cole, Christina; Coomarasamy, Arri; Cutting, Rachel; Harbottle, Stephen; Hardy, Pollyanna; Juszczak, Edmund; Khalaf, Yacoub; Kurinczuk, Jennifer J.; Lavery, Stuart; Lewis-Jones, Clare; Macklon, Nick; Raine-Fenning, Nick J.; Rajkohwa, Madhurima; Scotland, Graham; Troup, Stephen.

In: Reproductive Health, Vol. 16, 81, 13.06.2019.

Research output: Contribution to journalArticle

Maheshwari, Abha ; Bhattacharya, Siladitya ; Bowler, Ursula ; Brison, Daniel ; Child, Tim ; Cole, Christina ; Coomarasamy, Arri ; Cutting, Rachel ; Harbottle, Stephen ; Hardy, Pollyanna ; Juszczak, Edmund ; Khalaf, Yacoub ; Kurinczuk, Jennifer J. ; Lavery, Stuart ; Lewis-Jones, Clare ; Macklon, Nick ; Raine-Fenning, Nick J. ; Rajkohwa, Madhurima ; Scotland, Graham ; Troup, Stephen. / Study protocol : E-freeze-freezing of embryos in assisted conception: A randomised controlled trial evaluating the clinical and cost effectiveness of a policy of freezing embryos followed by thawed frozen embryo transfer compared with a policy of fresh embryo transfer, in women undergoing in vitro fertilisation. In: Reproductive Health. 2019 ; Vol. 16.
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abstract = "Background: Infertility affects one in seven couples; many of these need in vitro fertilisation (IVF). IVF involves external hormones to stimulate a woman's ovaries to produce eggs which are harvested surgically. Embryos, created in the laboratory by mixing eggs with sperm, are grown in culture for a few days before being replaced within the uterus (fresh embryo transfer). Spare embryos are usually frozen with a view to transfer at a later point in time-especially if the initial fresh transfer does not result in a pregnancy. Despite improvements in technology, IVF success rates remain low with an overall live birth rate of 25-30{\%} per treatment. Additionally, there are concerns about health outcomes for mothers and babies conceived through IVF, particularly after fresh embryo transfer, including maternal ovarian hyperstimulation syndrome (OHSS) and preterm delivery. It is believed that high levels of hormones during ovarian stimulation could create a relatively hostile environment for embryo implantation whilst increasing the risk of OHSS. It has been suggested that freezing all embryos with the intention of thawing and replacing them within the uterus at a later stage (thawed frozen embryo transfer) instead of fresh embryo transfer, may lead to improved pregnancy rates and fewer complications. We aim to compare the clinical and cost effectiveness of fresh and thawed frozen embryo transfer, with the primary aim of identifying any difference in the chance of having a healthy baby. Methods: E-Freeze is a pragmatic, multicentre two-arm parallel group randomised controlled trial where women aged ≥18 and < 42 years, with at least three good quality embryos are randomly allocated to receive either a fresh or thawed frozen embryo transfer. The primary outcome is a healthy baby, defined as a term, singleton, live birth with appropriate weight for gestation. Cost effectiveness will be calculated from a healthcare and societal perspective. Discussion: E-Freeze will determine the relative benefits of fresh and thawed frozen embryo transfer in terms of improving the chance of having a healthy baby. The results of this pragmatic study have the potential to be directly transferred to clinical practice.",
keywords = "Assisted conception, Elective freezing, Fertility, Fresh embryo transfer, Frozen thawed embryo transfer, IVF, OHSS, Receptivity, Ovarian Hyperstimulation Syndrome/epidemiology, Ovulation Induction, Embryo, Mammalian, Humans, Infertility, Female/therapy, Freezing, Young Adult, Fertilization in Vitro/legislation & jurisprudence, Pregnancy Complications/epidemiology, Adult, Female, Pregnancy Rate, Embryo Transfer/methods, Live Birth/epidemiology, Embryo Implantation, Pregnancy, Cost-Benefit Analysis, Cryopreservation/economics, Adolescent, Pregnancy Outcome",
author = "Abha Maheshwari and Siladitya Bhattacharya and Ursula Bowler and Daniel Brison and Tim Child and Christina Cole and Arri Coomarasamy and Rachel Cutting and Stephen Harbottle and Pollyanna Hardy and Edmund Juszczak and Yacoub Khalaf and Kurinczuk, {Jennifer J.} and Stuart Lavery and Clare Lewis-Jones and Nick Macklon and Raine-Fenning, {Nick J.} and Madhurima Rajkohwa and Graham Scotland and Stephen Troup",
note = "Acknowledgements The E-Freeze Collaborators Group contributed to the overall design of the E-Freeze trial. Funding The trial is approved and funded by the National Institute of Health Research (NIHR) Health Technology Assessment (HTA) programme. Availability of data and materials Applications for data sharing should be made to the NPEU CTU, using ctu@npeu.ox.ac.uk, with an accompanying protocol for the intended use of the data. This will be reviewed by the Trial Steering Committee if still operational or Data Sharing Committee/Data Controller. If approved, a Data Sharing Agreement will be compiled laying out the conditions to which the requestor must abide. Protocol E-Freeze Protocol, Version 2.0 (18/01/2017). Author notes All authors contributed equally to this work.",
year = "2019",
month = "6",
day = "13",
doi = "10.1186/s12978-019-0737-2",
language = "English",
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journal = "Reproductive Health",
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TY - JOUR

T1 - Study protocol

T2 - E-freeze-freezing of embryos in assisted conception: A randomised controlled trial evaluating the clinical and cost effectiveness of a policy of freezing embryos followed by thawed frozen embryo transfer compared with a policy of fresh embryo transfer, in women undergoing in vitro fertilisation

AU - Maheshwari, Abha

AU - Bhattacharya, Siladitya

AU - Bowler, Ursula

AU - Brison, Daniel

AU - Child, Tim

AU - Cole, Christina

AU - Coomarasamy, Arri

AU - Cutting, Rachel

AU - Harbottle, Stephen

AU - Hardy, Pollyanna

AU - Juszczak, Edmund

AU - Khalaf, Yacoub

AU - Kurinczuk, Jennifer J.

AU - Lavery, Stuart

AU - Lewis-Jones, Clare

AU - Macklon, Nick

AU - Raine-Fenning, Nick J.

AU - Rajkohwa, Madhurima

AU - Scotland, Graham

AU - Troup, Stephen

N1 - Acknowledgements The E-Freeze Collaborators Group contributed to the overall design of the E-Freeze trial. Funding The trial is approved and funded by the National Institute of Health Research (NIHR) Health Technology Assessment (HTA) programme. Availability of data and materials Applications for data sharing should be made to the NPEU CTU, using ctu@npeu.ox.ac.uk, with an accompanying protocol for the intended use of the data. This will be reviewed by the Trial Steering Committee if still operational or Data Sharing Committee/Data Controller. If approved, a Data Sharing Agreement will be compiled laying out the conditions to which the requestor must abide. Protocol E-Freeze Protocol, Version 2.0 (18/01/2017). Author notes All authors contributed equally to this work.

PY - 2019/6/13

Y1 - 2019/6/13

N2 - Background: Infertility affects one in seven couples; many of these need in vitro fertilisation (IVF). IVF involves external hormones to stimulate a woman's ovaries to produce eggs which are harvested surgically. Embryos, created in the laboratory by mixing eggs with sperm, are grown in culture for a few days before being replaced within the uterus (fresh embryo transfer). Spare embryos are usually frozen with a view to transfer at a later point in time-especially if the initial fresh transfer does not result in a pregnancy. Despite improvements in technology, IVF success rates remain low with an overall live birth rate of 25-30% per treatment. Additionally, there are concerns about health outcomes for mothers and babies conceived through IVF, particularly after fresh embryo transfer, including maternal ovarian hyperstimulation syndrome (OHSS) and preterm delivery. It is believed that high levels of hormones during ovarian stimulation could create a relatively hostile environment for embryo implantation whilst increasing the risk of OHSS. It has been suggested that freezing all embryos with the intention of thawing and replacing them within the uterus at a later stage (thawed frozen embryo transfer) instead of fresh embryo transfer, may lead to improved pregnancy rates and fewer complications. We aim to compare the clinical and cost effectiveness of fresh and thawed frozen embryo transfer, with the primary aim of identifying any difference in the chance of having a healthy baby. Methods: E-Freeze is a pragmatic, multicentre two-arm parallel group randomised controlled trial where women aged ≥18 and < 42 years, with at least three good quality embryos are randomly allocated to receive either a fresh or thawed frozen embryo transfer. The primary outcome is a healthy baby, defined as a term, singleton, live birth with appropriate weight for gestation. Cost effectiveness will be calculated from a healthcare and societal perspective. Discussion: E-Freeze will determine the relative benefits of fresh and thawed frozen embryo transfer in terms of improving the chance of having a healthy baby. The results of this pragmatic study have the potential to be directly transferred to clinical practice.

AB - Background: Infertility affects one in seven couples; many of these need in vitro fertilisation (IVF). IVF involves external hormones to stimulate a woman's ovaries to produce eggs which are harvested surgically. Embryos, created in the laboratory by mixing eggs with sperm, are grown in culture for a few days before being replaced within the uterus (fresh embryo transfer). Spare embryos are usually frozen with a view to transfer at a later point in time-especially if the initial fresh transfer does not result in a pregnancy. Despite improvements in technology, IVF success rates remain low with an overall live birth rate of 25-30% per treatment. Additionally, there are concerns about health outcomes for mothers and babies conceived through IVF, particularly after fresh embryo transfer, including maternal ovarian hyperstimulation syndrome (OHSS) and preterm delivery. It is believed that high levels of hormones during ovarian stimulation could create a relatively hostile environment for embryo implantation whilst increasing the risk of OHSS. It has been suggested that freezing all embryos with the intention of thawing and replacing them within the uterus at a later stage (thawed frozen embryo transfer) instead of fresh embryo transfer, may lead to improved pregnancy rates and fewer complications. We aim to compare the clinical and cost effectiveness of fresh and thawed frozen embryo transfer, with the primary aim of identifying any difference in the chance of having a healthy baby. Methods: E-Freeze is a pragmatic, multicentre two-arm parallel group randomised controlled trial where women aged ≥18 and < 42 years, with at least three good quality embryos are randomly allocated to receive either a fresh or thawed frozen embryo transfer. The primary outcome is a healthy baby, defined as a term, singleton, live birth with appropriate weight for gestation. Cost effectiveness will be calculated from a healthcare and societal perspective. Discussion: E-Freeze will determine the relative benefits of fresh and thawed frozen embryo transfer in terms of improving the chance of having a healthy baby. The results of this pragmatic study have the potential to be directly transferred to clinical practice.

KW - Assisted conception

KW - Elective freezing

KW - Fertility

KW - Fresh embryo transfer

KW - Frozen thawed embryo transfer

KW - IVF

KW - OHSS

KW - Receptivity

KW - Ovarian Hyperstimulation Syndrome/epidemiology

KW - Ovulation Induction

KW - Embryo, Mammalian

KW - Humans

KW - Infertility, Female/therapy

KW - Freezing

KW - Young Adult

KW - Fertilization in Vitro/legislation & jurisprudence

KW - Pregnancy Complications/epidemiology

KW - Adult

KW - Female

KW - Pregnancy Rate

KW - Embryo Transfer/methods

KW - Live Birth/epidemiology

KW - Embryo Implantation

KW - Pregnancy

KW - Cost-Benefit Analysis

KW - Cryopreservation/economics

KW - Adolescent

KW - Pregnancy Outcome

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DO - 10.1186/s12978-019-0737-2

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