Clinical Effectiveness of Frozen Thawed Embryo Transfer Compared to Fresh Embryo Transfer

A Randomized Controlled Trial of Clinical Effectiveness of Freezing All Embryos Followed by Frozen Thawed Embryo Transfer Compared to Fresh Embryo Transfer, in Women Undergoing In-vitro Fertilization Treatment

The objective of the present randomized controlled study is to compare clinical effectiveness and safety of freezing all embryos followed by frozen-thawed embryo transfer (FET) compared to fresh embryo transfer, in women undergoing IVF treatment.

Study Overview

• Status: Terminated
• Conditions: Subfertility
• Intervention / Treatment: Procedure: Fresh embryo transfer; Procedure: Frozen embryo transfer

Detailed Description

A total of 800 infertile women undergoing IVF treatment will be randomized into one of the following two groups by computer-generated random numbers:

Fresh embryo transfer group: a single fresh embryo transfer FET group: a single FET following freezing of all embryos in the stimulated IVF cycle

All techniques of IVF including ovarian stimulation, harvesting of oocytes, insemination with specially prepared sperm and embryo culture in the laboratory will be according to local protocols. Once the embryos have been cultured up to day 2 or 3, women with 3 or more suitable quality embryos will be randomized to either fresh embryo transfer (control arm) or FET (Intervention arm).

Control arm Women allocated to the control arm will either undergo embryo transfer at cleavage stage or extended culture and transfer at blastocyst stage according to local policy. A maximum of 2 embryos or blastocysts will be replaced according to the standard protocol under transabdominal ultrasound guidance. Luteal phase support is given according to local protocols.

Intervention arm For those allocated to the intervention arm fresh embryo transfer will not be undertaken. Embryos will be frozen by vitrification or slow freezing at cleavage or blastocyst stage according to standard agreed local protocols. Women will be contacted after 4 weeks and arrangements made for frozen embryo transfer.

After at least 4 weeks women will attend the IVF clinic for the transfer of thawed frozen embryos, either in a natural cycle (in ovulatory women who have regular menstrual cycles) or in a hormonally supported cycle using physiological doses of estrogen and progestogens to mimic normal cyclical changes within the endometrium. The choice between replacing frozen-thawed embryos in a natural or hormonally mediated cycle will be a decision driven by the clinical circumstances.

Embryos or blastocysts will be thawed according to local protocols. The transfer is performed by the team clinician with a maximum of 2 embryos or blastocysts being replaced according to the standard protocol under transabdominal ultrasound guidance. Luteal phase support is given at the discretion of the physician.

Follow up strategy:

A pregnancy test will be carried out 2 weeks after embryo transfer in both arms. All women who have a positive pregnancy test 2 weeks after embryo transfer will undergo a transvaginal ultrasound scan to identify the presence and number of a gestation sac with a fetal heart signifying an ongoing pregnancy. Pelvic scan will be repeated at 8 weeks, 12 weeks, 24 weeks and 36 gestation for fetal growth.

Data on all pregnancy outcomes including early pregnancy losses such as miscarriage or ectopic pregnancy will be collected.

In order to achieve consistency with respect to the collection of outcome, standardised case report forms (CRF) will be completed for each woman at each centre. These CRFs will include details on treatment received, pregnancy outcomes, complications in pregnancy, mode of delivery and birth outcomes.

• Study Type: Interventional
• Enrollment (Actual): 138
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Hong Kong
    • Hong Kong, Hong Kong, China
      • Department of Obstetrics and Gynaecology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 42 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Women under 42 years of age
• Presence of at least 3 embryos suitable to freeze on day 2 or 3 following fertilisation based on the centre's criteria
• Written informed consent

Exclusion Criteria:

• Women using donor eggs/donor sperm
• Women undergoing preimplantation genetic diagnosis
• Women with abnormal uterine cavity shown on hysterosalpingogram or saline infusion sonogram
• Women with hydrosalpinges shown on scanning and not corrected treated
• Women with excessive ovarian response at risk of ovarian hyperstimulation where elective freeze is already planned
• Women with serum progesterone level on day of human chorionic gonadotrophin>1.5ng/ml or 5 nmol/L
• Women whose embryos have not survived freeze-thawing in the past
• Fresh transfer is planned e.g. patients with endometriosis or adenomyosis who have received prolonged downregulation
• Only frozen transfer is planned e.g. patients receiving ovarian stimulation regimens which may have adverse impacts on the endometrium

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control arm; Women allocated to the control arm will either undergo fresh embryo transfer at cleavage stage or extended culture and transfer at blastocyst stage according to local policy. A maximum of 2 embryos or blastocysts will be replaced according to the standard protocol under transabdominal ultrasound guidance. Luteal phase support is given according to local protocols.	Procedure: Fresh embryo transfer; Women allocated to the control arm will either undergo embryo transfer at cleavage stage or extended culture and transfer at blastocyst stage according to local policy. A maximum of 2 embryos or blastocysts will be replaced according to the standard protocol under transabdominal ultrasound guidance. Luteal phase support is given according to local protocols.
Active Comparator: Intervention arm; Fresh embryo transfer will not be undertaken in this group. Embryos will be frozen by vitrification or slow freezing at cleavage or blastocyst stage according to standard agreed local protocols. Women will be contacted after 4 weeks and arrangements made for frozen embryo transfer.	Procedure: Frozen embryo transfer; Fresh embryo transfer will not be undertaken. Embryos will be frozen by vitrification or slow freezing at cleavage or blastocyst stage according to standard agreed local protocols. Women will be contacted after 4 weeks and arrangements made for frozen embryo transfer.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Live birth rate	A baby born alive after 20 weeks gestation	up to 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Miscarriage rate	Miscarriage before 20 weeks gestation	up to 24 weeks
Clinical pregnancy rates	Presence of at least one gestational sac on ultrasound at 6 weeks	up to 24 weeks
Ovarian hyperstimulation rate	Ovarian hyperstimulation rate classified according to Royal College of Obstetrics and Gynaecology in the United Kingdom	about 1 month
Failure of embryos to survive after thawing (per embryo thawed)	More than 50% of cells lysed on thawing	around 6 months
Cumulative live birth within 6 months of ovarian stimulation	Live birth from the fresh and frozen thawed embryo transfer	up to 24 weeks
Complications of pregnancy	Complications of pregnancy	around 1 years

Collaborators and Investigators

• Sponsor: The University of Hong Kong
• Collaborators: Peking University Third Hospital; Nanfang Hospital of Southern Medical University; Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Publications and helpful links

General Publications

• Zaat T, Zagers M, Mol F, Goddijn M, van Wely M, Mastenbroek S. Fresh versus frozen embryo transfers in assisted reproduction. Cochrane Database Syst Rev. 2021 Feb 4;2(2):CD011184. doi: 10.1002/14651858.CD011184.pub3.

Study record dates

Study Major Dates

• Study Start: October 1, 2015
• Primary Completion (Actual): December 1, 2018
• Study Completion (Actual): December 1, 2018

Study Registration Dates

• First Submitted: September 29, 2015
• First Submitted That Met QC Criteria: October 5, 2015
• First Posted (Estimate): October 7, 2015

Study Record Updates

• Last Update Posted (Actual): April 18, 2019
• Last Update Submitted That Met QC Criteria: April 16, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: In-vitro fertilization; fresh embryo transfer; frozen thawed embryo transfer
• Additional Relevant MeSH Terms: Infertility
• Other Study ID Numbers: UW 15-001