Optimal Timing of Euploid Day 6 Blastocyst Transfer in Frozen HRT Cycles, Day 6 or Day 7 of Progesterone Administration.
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Other: Group A Embryo transfer is scheduled on the 6th full day of progesterone administration, following the initial commencement of progesterone (120 hours) |
Diagnostic Test: 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
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
Drug: 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)
Other Names:
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
Other Names:
Diagnostic Test: Serum P4 day of ET
On the day of embryo transfer (ET), a blood test is taken to measure serum P4
Procedure: Embryo transfer
Procedure in which embryo is transferred into the uterus
Other Names:
|
| Other: Group B Embryo Transfer is scheduled on the 7th full day of progesterone administration, following the initial commencement of progesterone (144 hours) |
Diagnostic Test: 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
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
Drug: 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)
Other Names:
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
Other Names:
Diagnostic Test: Serum P4 day of ET
On the day of embryo transfer (ET), a blood test is taken to measure serum P4
Procedure: Embryo transfer
Procedure in which embryo is transferred into the uterus
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Livebirth rate (LBR) [41 weeks]
Defined as the delivery of a live infant born after 24 completed weeks of gestation
Secondary Outcome Measures
- Biochemical pregnancy rate [5 weeks]
Positive hCG, but at 5 gestational weeks no ultrasonographic visible gestational sac seen but without a further development into a clinical pregnancy)
- Clinical pregnancy rate [5 weeks]
Ultrasonographic sac visible at 5 gestational weeks
- Ongoing pregnancy rate after 12 weeks [13 weeks]
Viable pregnancy with a gestational age of more than 12 weeks
- Miscarriage rate [24 weeks]
Spontaneous loss of a clinical pregnancy before 24 completed weeks of gestation
Eligibility Criteria
Criteria
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 :
-
Spontaneous ovulation HRT cycle
-
Discontinuation of HRT medication
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | ART Fertility Clinics LLC | Abu Dhabi | United Arab Emirates | 60202 | |
| 2 | ART Fertility Clinics Dubai | Dubai | United Arab Emirates |
Sponsors and Collaborators
- ART Fertility Clinics LLC
Investigators
- Principal Investigator: Carol Coughlan, PhD, ART Fertility Clinics LLC
Study Documents (Full-Text)
None provided.More Information
Publications
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 2306-ABU-013-CC