Optimal Timing of Euploid Day 6 Blastocyst Transfer in Frozen HRT Cycles, Day 6 or Day 7 of Progesterone Administration.

NCT ID: NCT05980091

Last Updated: 2025-02-21

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

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

316 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-09-22

Study Completion Date

2025-12-30

Brief Summary

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The goal of this study is to compare the difference in clinical pregnancy, miscarriage and livebirth rate between day 6 euploid blastocyst transfer on the 6th and the 7th day of progesterone exposure in Hormonal Replacement Therapy (HRT) FET cycles. This prospective \& randomized study will only include euploid day 6 blastocysts. This will be the first prospective study of euploid day 6 blastocysts thereby excluding aneuploidy as a cause of miscarriage and implantation failure. The point of randomization will occur on the day of progesterone commencement.

Detailed Description

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Traditionally the duration of progesterone exposure before embryo transfer has been considered equal for day 5 and day 6 embryos but this may not be the case and warrants further study. The optimal preparation of the endometrium in frozen embryo transfer (FET) cycles is yet to be determined. Synchronization between the embryonic stage and the endometrial window of implantation (WOI) is crucial and progesterone plays a critical role in the WOI (1). Data on the optimal route of administration, the dose and duration of progesterone supplementation before blastocyst transfer are inconsistent (2,3). In view of the current lack of evidence, this study will be of importance.

Conditions

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Infertility Fertility Issues Infertility, Female

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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Group A

Embryo transfer is scheduled on the 6th full day of progesterone administration, following the initial commencement of progesterone (120 hours)

Group Type OTHER

Transvaginal ultrasound

Intervention Type DIAGNOSTIC_TEST

Transvaginal ultrasound throughout the HRT cycle to not only monitor endometrial development but to also exclude the presence of an ovarian dominant follicle

Serum LH, E2, P4

Intervention Type DIAGNOSTIC_TEST

In conjunction with ultrasound monitoring, participants will undergo serial measurements of serum Luteinizing Hormone (LH), Estradiol (E2) and Progesterone (P4) levels

Estradiol Valerate 2 MG

Intervention Type DRUG

Participants will commence estradiol valerate 4 mg ( 2 x 2 mg) on day 2 / day 3 of menses.

Estradiol will be increased to 6 mg on day 2 of estrogen treatment, and continued at a daily dose of 6 mg (3 tablets daily)

Progesterone 100 Mg Vaginal Insert

Intervention Type DRUG

The initial progesterone dose of 100 mg will be commenced at 13hrs and repeated at 21hrs considered day 1 (vaginal suppository) when an optimal endometrial thickness for each participant has been achieved with a trilaminar appearance. The following day (day 2) progesterone administration will be increased to 100 mg vaginally three times daily

Serum P4 day of ET

Intervention Type DIAGNOSTIC_TEST

On the day of embryo transfer (ET), a blood test is taken to measure serum P4

Embryo transfer

Intervention Type PROCEDURE

Procedure in which embryo is transferred into the uterus

Group B

Embryo Transfer is scheduled on the 7th full day of progesterone administration, following the initial commencement of progesterone (144 hours)

Group Type OTHER

Transvaginal ultrasound

Intervention Type DIAGNOSTIC_TEST

Transvaginal ultrasound throughout the HRT cycle to not only monitor endometrial development but to also exclude the presence of an ovarian dominant follicle

Serum LH, E2, P4

Intervention Type DIAGNOSTIC_TEST

In conjunction with ultrasound monitoring, participants will undergo serial measurements of serum Luteinizing Hormone (LH), Estradiol (E2) and Progesterone (P4) levels

Estradiol Valerate 2 MG

Intervention Type DRUG

Participants will commence estradiol valerate 4 mg ( 2 x 2 mg) on day 2 / day 3 of menses.

Estradiol will be increased to 6 mg on day 2 of estrogen treatment, and continued at a daily dose of 6 mg (3 tablets daily)

Progesterone 100 Mg Vaginal Insert

Intervention Type DRUG

The initial progesterone dose of 100 mg will be commenced at 13hrs and repeated at 21hrs considered day 1 (vaginal suppository) when an optimal endometrial thickness for each participant has been achieved with a trilaminar appearance. The following day (day 2) progesterone administration will be increased to 100 mg vaginally three times daily

Serum P4 day of ET

Intervention Type DIAGNOSTIC_TEST

On the day of embryo transfer (ET), a blood test is taken to measure serum P4

Embryo transfer

Intervention Type PROCEDURE

Procedure in which embryo is transferred into the uterus

Interventions

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Transvaginal ultrasound

Transvaginal ultrasound throughout the HRT cycle to not only monitor endometrial development but to also exclude the presence of an ovarian dominant follicle

Intervention Type DIAGNOSTIC_TEST

Serum LH, E2, P4

In conjunction with ultrasound monitoring, participants will undergo serial measurements of serum Luteinizing Hormone (LH), Estradiol (E2) and Progesterone (P4) levels

Intervention Type DIAGNOSTIC_TEST

Estradiol Valerate 2 MG

Participants will commence estradiol valerate 4 mg ( 2 x 2 mg) on day 2 / day 3 of menses.

Estradiol will be increased to 6 mg on day 2 of estrogen treatment, and continued at a daily dose of 6 mg (3 tablets daily)

Intervention Type DRUG

Progesterone 100 Mg Vaginal Insert

The initial progesterone dose of 100 mg will be commenced at 13hrs and repeated at 21hrs considered day 1 (vaginal suppository) when an optimal endometrial thickness for each participant has been achieved with a trilaminar appearance. The following day (day 2) progesterone administration will be increased to 100 mg vaginally three times daily

Intervention Type DRUG

Serum P4 day of ET

On the day of embryo transfer (ET), a blood test is taken to measure serum P4

Intervention Type DIAGNOSTIC_TEST

Embryo transfer

Procedure in which embryo is transferred into the uterus

Intervention Type PROCEDURE

Other Intervention Names

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Estradiol Valerate Progesterone 100 mg ET

Eligibility Criteria

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Inclusion Criteria

* Women aged 18 years to 43 years.
* Having at least 1 euploid cryopreserved day 6 blastocyst of at least Grade BB quality.
* Endometrial trilaminar appearance on the day of progesterone start

Exclusion Criteria

* Uterine abnormality
* Hydrosalpinx
* Asherman syndrome
* Any known contraindications or allergy to oral estradiol or progesterone.
* Intention to treat : exclusion factors :

1. Spontaneous ovulation HRT cycle
2. Discontinuation of HRT medication
Minimum Eligible Age

18 Years

Maximum Eligible Age

43 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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ART Fertility Clinics LLC

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Carol Coughlan, PhD

Role: PRINCIPAL_INVESTIGATOR

ART Fertility Clinics LLC

Locations

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ART Fertility Clinics LLC

Abu Dhabi, Abu Dhabi Emirate, United Arab Emirates

Site Status RECRUITING

ART Fertility Clinics Dubai

Dubai, , United Arab Emirates

Site Status RECRUITING

Countries

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United Arab Emirates

Central Contacts

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Barbara Lawrenz, PhD

Role: CONTACT

+971 800 337845489

Jonalyn Edades, RN

Role: CONTACT

+971 800 337845489

Facility Contacts

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Barbara Lawrenz, PhD

Role: primary

+971 800 337845489

Carol Coughlan, PhD

Role: primary

+971 800 337845489

References

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Franasiak JM, Ruiz-Alonso M, Scott RT, Simon C. Both slowly developing embryos and a variable pace of luteal endometrial progression may conspire to prevent normal birth in spite of a capable embryo. Fertil Steril. 2016 Apr;105(4):861-6. doi: 10.1016/j.fertnstert.2016.02.030.

Reference Type BACKGROUND
PMID: 26940791 (View on PubMed)

Nawroth F, Ludwig M. What is the 'ideal' duration of progesterone supplementation before the transfer of cryopreserved-thawed embryos in estrogen/progesterone replacement protocols? Hum Reprod. 2005 May;20(5):1127-34. doi: 10.1093/humrep/deh762. Epub 2005 Feb 3.

Reference Type BACKGROUND
PMID: 15695314 (View on PubMed)

van de Vijver A, Drakopoulos P, Polyzos NP, Van Landuyt L, Mackens S, Santos-Ribeiro S, Vloeberghs V, Tournaye H, Blockeel C. Vitrified-warmed blastocyst transfer on the 5th or 7th day of progesterone supplementation in an artificial cycle: a randomised controlled trial. Gynecol Endocrinol. 2017 Oct;33(10):783-786. doi: 10.1080/09513590.2017.1318376. Epub 2017 Apr 26.

Reference Type BACKGROUND
PMID: 28443690 (View on PubMed)

Zegers-Hochschild F, Adamson GD, Dyer S, Racowsky C, de Mouzon J, Sokol R, Rienzi L, Sunde A, Schmidt L, Cooke ID, Simpson JL, van der Poel S. The International Glossary on Infertility and Fertility Care, 2017. Fertil Steril. 2017 Sep;108(3):393-406. doi: 10.1016/j.fertnstert.2017.06.005. Epub 2017 Jul 29.

Reference Type BACKGROUND
PMID: 28760517 (View on PubMed)

Roelens C, Santos-Ribeiro S, Becu L, Mackens S, Van Landuyt L, Racca A, De Vos M, van de Vijver A, Tournaye H, Blockeel C. Frozen-warmed blastocyst transfer after 6 or 7 days of progesterone administration: impact on live birth rate in hormone replacement therapy cycles. Fertil Steril. 2020 Jul;114(1):125-132. doi: 10.1016/j.fertnstert.2020.03.017. Epub 2020 Jun 16.

Reference Type BACKGROUND
PMID: 32553469 (View on PubMed)

Bourdon M, Pocate-Cheriet K, Finet de Bantel A, Grzegorczyk-Martin V, Amar Hoffet A, Arbo E, Poulain M, Santulli P. Day 5 versus Day 6 blastocyst transfers: a systematic review and meta-analysis of clinical outcomes. Hum Reprod. 2019 Oct 2;34(10):1948-1964. doi: 10.1093/humrep/dez163.

Reference Type BACKGROUND
PMID: 31644803 (View on PubMed)

Shapiro BS, Daneshmand ST, Garner FC, Aguirre M, Hudson C. Clinical rationale for cryopreservation of entire embryo cohorts in lieu of fresh transfer. Fertil Steril. 2014 Jul;102(1):3-9. doi: 10.1016/j.fertnstert.2014.04.018. Epub 2014 May 17.

Reference Type BACKGROUND
PMID: 24842675 (View on PubMed)

Other Identifiers

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2306-ABU-013-CC

Identifier Type: -

Identifier Source: org_study_id

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