Deferred Versus Fresh Embryo Transfers (DEFETOSE)

March 26, 2026 updated by: Assistance Publique - Hôpitaux de Paris

A Randomized Trial of Deferred Versus Fresh Embryo Transfers in Infertile Women Undergoing IVF-ICSI

Controlled ovarian stimulation (COS) enhances the efficacy of ART (Assisted reproductive technology) by permitting multiple-oocyte yields, but also alters endometrial receptivity (ER) by an advancement of endometrial development which contributes to diminished pregnancy chances. Previous reports suggest that pregnancy rates are increased following deferred frozen embryo transfers. In addition as compared to fresh embryo transfers, frozen embryo transfers seem to be associated with less affected perinatal outcomes, in particular lower risk of preterm birth, small for gestational age and caesarean section. Unfortunately, most of the current evidence is based only on preliminary reports, needing further scientific evidence. Thus, whether differing embryo transfers could restore optimal ER leading to higher live birth rate (LBR) and better obstetrical outcomes as compared to fresh embryo transfers, is actually still under investigation.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Controlled ovarian stimulation (COS) enhances the efficacy of ART (Assisted reproductive technology) by permitting multiple-oocyte yields, but also alters endometrial receptivity (ER) by an advancement of endometrial development which contributes to diminished pregnancy chances. Recently, technical improvements in vitrification make frozen embryo transfers (FETs) a safe and feasible alternative to fresh embryo transfer (Evans et al., 2014). In case of FET the absence of COS avoid the alteration of endometrial receptivity. Previous reports suggest that pregnancy rates are increased and perinatal outcomes are less affected following FET (Evans et al., 2014). In fact previous studies plead for increased risk of preterm birth, small for gestational age, caesarean section after fresh embryo transfer as compared to frozen embryo transfer (Maheshwari et al., 2012). Unfortunately, most of the current evidence is based only on preliminary reports, needing further scientific evidence. Thus, one of the main questions, in the management of infertile women, is to know whether differing embryo transfers could restore optimal endometrial receptivity leading to higher live birth rate (LBR) and better obstetrical outcomes as compared to fresh embryo transfer. This question is actually debated in the literature in many different reviews (Blockeel et al., 2016; Cedars, 2016; Engmann et al., 2016; Evans et al., 2014; Roque, 2015). However even if the scientific rationale is in favour of increased pregnancy rates after differed FET, compelling clinical evidence is still lacking and most of the current evidence is based on retrospective and uncontrolled studies. Currently the best evidence come from a very recent randomized control trial of fresh versus frozen embryo transfers in a specific population of polycystic ovary syndrome affected women (Chen et al., 2016). The authors failed to show any difference in pregnancy rate after fresh versus frozen embryo transfers but they found higher rate of miscarriages after fresh embryo transfers and in consequence a slight but significant decrease in live birth after fresh as compared to frozen embryo transfers (Chen et al., 2016). However whether these results, coming from a specific population of polycystic ovary syndrome affected women, may be generalizable is actually still unknown. Furthermore some evidence come from a meta-analysis, including 3 randomized studies. The conclusions of this meta-analysis are that IVF outcomes may be improved by performing FET compared with fresh embryo transfer probably through an improvement of endometrial receptivity (Roque et al., 2013). Nevertheless, this meta-analysis should be interpreted with caution. One of the included studies had been retracted from literature because of methodological problem (Aflatoonian et al., 2010). Therefore, this meta-analysis banking on a retracted study seems no more valid and therefore its conclusions remained uncertain. Even in absence of solid clinical studies and even in absence of valid recommendations, some authors conclude that IVF outcomes can be improved using the freeze-all policy with differed FET (Roque et al., 2015). In addition they recommend that further randomized clinical trials are needed to confirm the advantage of this strategy and determine the population for which it would be most beneficial. This last point seems crucial as ART procedures (IVF-ICSI) encompass a mixture of different fertility problem more or less sensible to the effects of COS on endometrial receptivity. Among the different causes of infertility, endometriosis is quite common and up to 20 % of women undergoing ART have associated endometriosis (Kawwass et al., 2015; Kuivasaari-Pirinen et al., 2012; Senapati et al., 2016). In addition endometriosis is characterized by impaired endometrial receptivity, contributing to the mechanisms by which endometriosis interfere with fecundity (de Ziegler et al., 2010). Estimated prevalence of endometriosis range from 2 to 10% of women of reproductive age, to 50% of infertile women (Eskenazi and Warner, 1997; Meuleman et al., 2009). Reverting to ART in case of endometriosis related infertility remain a solid option. However recent meta-analysis evocates decreased live birth rate in case of severe endometriosis as compared to disease free women (Hamdan et al., 2015). In addition endometriosis may be associated to adverse obstetrical outcomes (Leone Roberti Maggiore et al., 2016). Thus, given the existence of altered endometrial receptivity in endometriosis, and diminished ART outcomes, it is actually also debated whether deferring embryo transfers could restore optimal endometrial receptivity leading to higher live birth rate and reduced obstetrical risk in endometriosis affected women.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
237

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Paris, France, 75014
        • Hôpital Cochin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 40 years (Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Women [18 - 40[years of age (according to date of birth at time of informed consent) who are eligible for ovarian stimulation and ART treatment, including intracytoplasmic sperm injection (ICSI)
  • Absence of anatomical abnormalities of the reproductive tract that would interfere with implantation or pregnancy
  • Absence of any medical condition in which pregnancy is contraindicated
  • Motile, ejaculatory sperm must be available (donated and/or cryopreserved sperm is allowed). Intracytoplasmic sperm injection (ICSI) will be allowed during this trial
  • Body mass index 18 to 35 kg/m2, inclusive
  • Able to understand the study
  • Affiliation with a social security scheme
  • Dated and signed inform consent

Exclusion Criteria:

  • Altered ovarian reserve (Day3: FSH >12 UI/l; AMH<1,0 ng/ml; AFC<8)
  • History or presence of tumours of the hypothalamus or pituitary gland
  • Presence of non isolated uni- or bilateral hydrosalpinx
  • Abnormal gynaecological bleeding of undetermined origin
  • Contraindication to being pregnant and/or carrying a pregnancy to term
  • Known infection with human immunodeficiency virus, active hepatitis B or C virus in the female or male partner
  • History or presence of ovarian, uterine or mammary cancer
  • Known allergy or hypersensitivity to human gonadotropin preparations or to compounds that are structurally similar to any of the other medications administered during the trial
  • Substance abuse that would interfere with trial conduct, as determined by the investigator
  • Use of testicular or epididymal sperm
  • Pregnant patient, nursing patient
  • Participation in another ART clinical trial within the past 30 days
  • Women who have risk to develop severe ovarian hyperstimulation syndrome (OHSS) during controlled ovarian stimulation (COS) defined as ≥ 18 follicles measuring 10 - 14 mm on the day of triggering
  • Women with less than 3 follicles ≥ 15 mm on the triggering day or the day before the triggering
  • Women with premature progesterone elevation during COS ( ≥1.5 ng/ml)
  • Women with uterine polyps diagnosed during COS
  • Participation with another interventional study involving human subjects

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Fresh transfer

Women randomized in the non experimental group will have:

  • Antagonist stimulation protocol
  • Ovarian triggering using a single injection of rhCG (Ovitrelle®; Serono, France)
  • All of their embryo kept in prolonged culture
  • A fresh single embryo transfer at blastocyst stage (on day 5 or 6 according to blastocyst stage)
  • Supernumerary blastocysts cryopreserved
Procedure: fresh transfer

Women randomized in the non experimental group will have:

  • Antagonist stimulation protocol
  • Ovarian triggering using a single injection of rhCG (Ovitrelle®; Serono, France)
  • All of their embryo kept in prolonged culture
  • A fresh single embryo transfer at blastocyst stage (on day 5 or 6 according to blastocyst stage)
  • Supernumerary blastocysts cryopreserved
Experimental: Deferred-frozen embryo transfer

Women randomized in the experimental group will have:

  • Antagonist stimulation protocol
  • Ovarian triggering using a single injection of 0.2 mg of GnRH agonist triptorelin (Decapeptyl® Ipsen France)
  • All of their embryo cryopreserved at the blastocyst stage after prolonged embryo culture.
  • A frozen-thawed single embryo transfer at blastocyst stage, is planned 3-11 weeks after cryopreservation
Procedure: Deferred-frozen embryo transfer

Women randomized in the experimental group will have:

  • Antagonist stimulation protocol
  • Ovarian triggering using a single injection of 0.2 mg of GnRH agonist triptorelin (Decapeptyl® Ipsen France)
  • All of their embryo cryopreserved at the blastocyst stage after prolonged embryo culture.
  • A frozen-thawed single embryo transfer at blastocyst stage, is planned 3-11 weeks after cryopreservation

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Live birth rates
Time Frame: ≥ 35 weeks of gestation after the first single blastocyst embryo transfer according to fresh or deferred-frozen transfer.
The cut-off of 35 weeks postmenstrual age is to ensure the health and well being of the newborns babies.
≥ 35 weeks of gestation after the first single blastocyst embryo transfer according to fresh or deferred-frozen transfer.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Miscarriage
Time Frame: ≥ 35 weeks of gestation after the first single blastocyst embryo transfer a
Miscarriage is defined as an intrauterine clinical pregnancy that occurs before 20 completed weeks postmenstrual age (18 weeks post fertilization). Clinical pregnancy is defined as a pregnancy diagnosed by ultrasonographic visualization of one or more gestational sacs or definitive clinical signs of pregnancy. It includes ectopic pregnancy
≥ 35 weeks of gestation after the first single blastocyst embryo transfer a
Preterm birth
Time Frame: ≥ 35 weeks of gestation after the first single blastocyst embryo transfer a
Preterm birth is defined as a live birth or stillbirth that takes place after at least 20 but before 37 completed weeks of postmenstrual age.
≥ 35 weeks of gestation after the first single blastocyst embryo transfer a
Preterm rupture of membranes
Time Frame: ≥ 35 weeks of gestation after the first single blastocyst embryo transfer a
s defined as rupture of the foetal membranes occurring before labour and prior to 37 weeks of postmenstrual age.
≥ 35 weeks of gestation after the first single blastocyst embryo transfer a
Pre-eclampsia
Time Frame: ≥ 35 weeks of gestation after the first single blastocyst embryo transfer a
is defined as gestational hypertension (Blood pressure ≥ 14 mm Hg systolic or ≥ 9 mm Hg diastolic, measured on two occasions at least four hours apart) associated with proteinuria ≥ 0.3 grams (300 mg) or more of protein in a 24-hour urine sample.
≥ 35 weeks of gestation after the first single blastocyst embryo transfer a
Placenta praevia
Time Frame: ≥ 35 weeks of gestation after the first single blastocyst embryo transfer a
is defined by the presence of lower edge of the placenta < 50 mm behind the internal cervical os as diagnosed during the obstetrical ultrasound during the third trimester of the pregnancy. We also defined as placenta praevia when placenta partially or completely covers the internal cervical.
≥ 35 weeks of gestation after the first single blastocyst embryo transfer a
Live birth rates in Endometriosis related infertility
Time Frame: ≥ 35 weeks of gestation after the first single blastocyst embryo transfer a
Analysis of live birth among women with endometriosis related infertility
≥ 35 weeks of gestation after the first single blastocyst embryo transfer a
Number of oocytes retrieved
Time Frame: ≥ 35 weeks of gestation after the first single blastocyst embryo transfer according to fresh or deferred-frozen transfer.
≥ 35 weeks of gestation after the first single blastocyst embryo transfer according to fresh or deferred-frozen transfer.
Number of MII oocytes
Time Frame: ≥ 35 weeks of gestation after the first single blastocyst embryo transfer according to fresh or deferred-frozen transfer.
≥ 35 weeks of gestation after the first single blastocyst embryo transfer according to fresh or deferred-frozen transfer.
Number of embryo
Time Frame: ≥ 35 weeks of gestation after the first single blastocyst embryo transfer according to fresh or deferred-frozen transfer.
≥ 35 weeks of gestation after the first single blastocyst embryo transfer according to fresh or deferred-frozen transfer.
Number of blastocyst
Time Frame: ≥ 35 weeks of gestation after the first single blastocyst embryo transfer according to fresh or deferred-frozen transfer.
≥ 35 weeks of gestation after the first single blastocyst embryo transfer according to fresh or deferred-frozen transfer.
Number of transferred blastocyst
Time Frame: ≥ 35 weeks of gestation after the first single blastocyst embryo transfer according to fresh or deferred-frozen transfer.
≥ 35 weeks of gestation after the first single blastocyst embryo transfer according to fresh or deferred-frozen transfer.
The cancellation rate
Time Frame: ≥ 35 weeks of gestation after the first single blastocyst embryo transfer according to fresh or deferred-frozen transfer.
≥ 35 weeks of gestation after the first single blastocyst embryo transfer according to fresh or deferred-frozen transfer.
The rate of started pregnancy
Time Frame: ≥ 35 weeks of gestation after the first single blastocyst embryo transfer according to fresh or deferred-frozen transfer.
≥ 35 weeks of gestation after the first single blastocyst embryo transfer according to fresh or deferred-frozen transfer.
The rate of pregnancy confirmed by the Echography (cardiac activity)
Time Frame: ≥ 35 weeks of gestation after the first single blastocyst embryo transfer according to fresh or deferred-frozen transfer.
≥ 35 weeks of gestation after the first single blastocyst embryo transfer according to fresh or deferred-frozen transfer.
Started pregnancy defined by a rate of HCG>100
Time Frame: ≥ 35 weeks of gestation after the first single blastocyst embryo transfer according to fresh or deferred-frozen transfer.
≥ 35 weeks of gestation after the first single blastocyst embryo transfer according to fresh or deferred-frozen transfer.
Rate of multiple pregnancy
Time Frame: ≥ 35 weeks of gestation after the first single blastocyst embryo transfer according to fresh or deferred-frozen transfer.
≥ 35 weeks of gestation after the first single blastocyst embryo transfer according to fresh or deferred-frozen transfer.
Implantation rate
Time Frame: ≥ 35 weeks of gestation after the first single blastocyst embryo transfer according to fresh or deferred-frozen transfer.
defined as the number of gestational sacs seen via transvaginal ultrasonography 4-5 weeks after embryo transfer, per number of embryos transferred
≥ 35 weeks of gestation after the first single blastocyst embryo transfer according to fresh or deferred-frozen transfer.
Cryopreservation thaw rate
Time Frame: ≥ 35 weeks of gestation after the first single blastocyst embryo transfer according to fresh or deferred-frozen transfer.
defined as percentage of vitrified blastocysts which survive warming.
≥ 35 weeks of gestation after the first single blastocyst embryo transfer according to fresh or deferred-frozen transfer.
The incremental cost effectiveness ratio
Time Frame: ≥ 35 weeks of gestation after the first single blastocyst embryo transfer according to fresh or deferred-frozen transfer.
using live birth rate as the effectiveness endpoint, after 35 weeks
≥ 35 weeks of gestation after the first single blastocyst embryo transfer according to fresh or deferred-frozen transfer.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Assistance Publique - Hôpitaux de Paris

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
URC-CIC Paris Descartes Necker Cochin

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Khaled POCATE, PhD, Assistance Publique - Hôpitaux de Paris

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 24, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 19, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 31, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 17, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 17, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 22, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 31, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 26, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • K160918J
  • AOM160313 (Other Identifier: AOM)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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