Study Comparing Outcomes Between Conventional IVF and a "Freeze-all"-Strategy in Assisted Reproductive Technology

NCT ID: NCT02746562

Last Updated: 2019-04-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

424 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-05-31

Study Completion Date

2019-09-30

Brief Summary

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The purpose of this study is to compare conventional fresh embryo transfer with a "freeze all and transfer later strategy" in assisted reproductive technology in terms of ongoing pregnancy rates, live birth rates as well as perinatal outcomes.

Detailed Description

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The study is a multicentre randomized controlled double-blinded trial with the purpose to investigate if pregnancy- and live birth rates can be improved by a "freeze all and transfer later"-strategy with transfer of the best quality, frozen, thawed embryo in a subsequent natural cycle compared with conventional fresh embryo transfer with transfer of the embryo in the stimulated cycle.

In total 5 clinics in Denmark and Sweden will be participating in the recruitment of patients for the study.

The patients will be screened and randomized computerized on cycle day 2 or 3 and allocated to one of the two study arms:

I: hCG (human chorion gonadotrophin) arm with traditional hCG triggering and fresh blastocyst transfer II: GnRH (gonadotropin-releasing hormone)- agonist triggering arm with blastocyst cryopreservation and subsequent transfer in a subsequent natural cycle.

The randomization will be done after the decision of gonadotrophin (rFSH/hMG) starting dose, and both doctor and patient will be blinded to the randomization until the day of hCG/agonist trigger. Both groups will be stimulated in a short GnRH antagonist protocol. The ovarian stimulation The gonadotrophin stimulation is performed according to the general standards in each of the clinics and can be altered according to the ovarian response with a maximum of 300 IU.

Blood samples are collected at baseline before the first gonadotrophin injection and at day of hCG injection and further blood samples in the luteal phase will be collected for a small subgroup of patients. All blood samples will be kept at the Biobank for the study at Hvidovre Hospital.

Women in both arms will furthermore be requested to fill out a physical discomfort and a quality of life questionnaire at two different visits. Additionally the men will be asked to fill out quality of life questionnaires.

Comprehensive sonography will be performed at the start of ovulation with details on each ovary. Ultrasound examination is performed on cycle day 2-3, at stimulation day 6 and thereafter every 2-3 days until ovulation is inducted.

On the day of oocyte retrieval the randomization is unblinded. The oocytes are fertilized by either IVF or ICSI and cultured individually according to the normal procedures in the clinics.

If the patient is allocated to the "Fresh embryo transfer"-group the best quality blastocyst will be transferred on day five after oocyte pick-up, if a blastocyst is developed. Surplus good quality blastocysts are vitrified on day five or six.

For patients in the "Freeze all" group all embryos of good quality are vitrified at the blastocyst stage day 5 in the stimulated cycle according to the criteria for freezing blastocysts in each clinic. The highest quality embryo is selected and marked and will be the first one to be thawed after at least one mentrual cycle that is considered as a wash out period. Embryo transfer is performed 6-7 days after hCG injection in the blastocyst transfer cycle in this group.

A serum beta-hCG test is performed 11 days after blastocyst transfer, and clinical pregnancy is confirmed by transvaginal ultrasound 3 to 4 weeks after a positive serum-hCG test.

A follow-up of all pregnancies will be performed within three months after delivery or termination of pregnancy on predefined information sheets. All pregnancies resulting from blastocysts retrieved and thawed according to this study protocol will be followed from study inclusion and one year onwards.

All data will be collected in a single database and all participants will be anonymized by way of an identificationcode. The biobank will be closed and all samples destroyed after 5 years of the conclusion of the study at the latest.

The study is a superiority study with 424 (212 in each arm) patients required to have an 80 % chance of detecting, as significant at the 5 % level, a decrease in the primary outcome measure from 30 % in the control group to 43 % in the experimental group.

Conditions

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Infertility

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Freeze all

Transfer of a frozen, thawed blastocyst in a subsequent natural menstrual cycle

Group Type EXPERIMENTAL

Freeze all

Intervention Type PROCEDURE

Freezing of all blastocyst stage embryos with thawing and transfer in a subsequent natural cycle

Fresh embryo transfer

Standard procedure

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Freeze all

Freezing of all blastocyst stage embryos with thawing and transfer in a subsequent natural cycle

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* AMH (Anti-Müllerian hormone) \> 6.28 pmol/L (Roche Elecsys assay)
* Female age 18 years to less than 40 years
* 1, 2 or 3 IVF/ICSI cycle with oocyte aspiration
* Regular menstrual cycle between 24 and 35 days
* BMI between 18 and 35
* Two ovaries
* Can and will sign informed consent

* Endometriosis stage III to IV
* Ovarian cysts with diameter \> 30 mm at day of start of stimulation
* Submucosal fibroids
* Women with severe co-morbidity (IDDM, NIDDM, gastrointestinal, cardiovascular, pulmonary, liver or kidney disease)
* Dysregulation of thyroid disease
* Not danish or English speaking women
* Contraindications or allergies to use of Gonadotrophins or GnRH antagonists
* TESA (testicular sperm aspiration)
* OD (oocyte donation)
* Previous inclusion in the study
Minimum Eligible Age

18 Years

Maximum Eligible Age

39 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Rigshospitalet, Denmark

OTHER

Sponsor Role collaborator

Herlev Hospital

OTHER

Sponsor Role collaborator

Holbaek Sygehus

OTHER

Sponsor Role collaborator

Skane University Hospital

OTHER

Sponsor Role collaborator

Sahlgrenska University Hospital

OTHER

Sponsor Role collaborator

Regional Hospital Skive

UNKNOWN

Sponsor Role collaborator

Dexeus University Hospital Barcelona

UNKNOWN

Sponsor Role collaborator

Anja Bisgaard Pinborg

OTHER

Sponsor Role lead

Responsible Party

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Anja Bisgaard Pinborg

Professor, MD, DMSc

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Anja Bisgaard Pinborg, MD, DMSc

Role: STUDY_DIRECTOR

Fertility Clinic, Obstetrical and Gynecological department, Hvidovre Hospital

Locations

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Rigshospitalet

Copenhagen, , Denmark

Site Status RECRUITING

University Hospital Hvidovre

Hvidovre, , Denmark

Site Status RECRUITING

Countries

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Denmark

Central Contacts

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Sacha Stormlund, MD

Role: CONTACT

Anja Bisgaard Pinborg, MD, DMSc

Role: CONTACT

Facility Contacts

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Sacha Stormlund, MD

Role: primary

Sacha Stormlund, MD

Role: primary

Anja Pinborg, MD, DMSc

Role: backup

References

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Pilegaard SP, Schmidt L, Stormlund S, Koert E, Bogstad JW, Praetorius L, Nielsen HS, la Cour Freiesleben N, Sopa N, Klajnbard A, Humaidan P, Bergh C, Englund ALM, Lossl K, Pinborg A. Psychosocial wellbeing shortly after allocation to a freeze-all strategy compared with a fresh transfer strategy in women and men: a sub-study of a randomized controlled trial. Hum Reprod. 2023 Nov 2;38(11):2175-2186. doi: 10.1093/humrep/dead188.

Reference Type DERIVED
PMID: 37742131 (View on PubMed)

Alexopoulou E, Stormlund S, Lossl K, Praetorius L, Sopa N, Bogstad JW, Mikkelsen AL, Forman J, la Cour Freiesleben N, Vikkelso Jeppesen J, Bergh C, Al Humaidan PSH, Grondahl ML, Zedeler A, Pinborg AB. Embryo Morphokinetics and Blastocyst Development After GnRH Agonist versus hCG Triggering in Normo-ovulatory Women: a Secondary Analysis of a Multicenter Randomized Controlled Trial. Reprod Sci. 2021 Oct;28(10):2972-2981. doi: 10.1007/s43032-021-00564-9. Epub 2021 Apr 13.

Reference Type DERIVED
PMID: 33847977 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33539543 (View on PubMed)

Stormlund S, Sopa N, Zedeler A, Bogstad J, Praetorius L, Nielsen HS, Kitlinski ML, Skouby SO, Mikkelsen AL, Spangmose AL, Jeppesen JV, Khatibi A, la Cour Freiesleben N, Ziebe S, Polyzos NP, Bergh C, Humaidan P, Andersen AN, Lossl K, Pinborg A. Freeze-all versus fresh blastocyst transfer strategy during in vitro fertilisation in women with regular menstrual cycles: multicentre randomised controlled trial. BMJ. 2020 Aug 5;370:m2519. doi: 10.1136/bmj.m2519.

Reference Type DERIVED
PMID: 32759285 (View on PubMed)

Stormlund S, Lossl K, Zedeler A, Bogstad J, Praetorius L, Nielsen HS, Bungum M, Skouby SO, Mikkelsen AL, Andersen AN, Bergh C, Humaidan P, Pinborg A. Comparison of a 'freeze-all' strategy including GnRH agonist trigger versus a 'fresh transfer' strategy including hCG trigger in assisted reproductive technology (ART): a study protocol for a randomised controlled trial. BMJ Open. 2017 Jul 31;7(7):e016106. doi: 10.1136/bmjopen-2017-016106.

Reference Type DERIVED
PMID: 28760794 (View on PubMed)

Other Identifiers

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1600-1116

Identifier Type: -

Identifier Source: org_study_id

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