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

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

Optimal Timing of Euploid Day 6 Blastocyst (Blastocyst Which Was Biopsied on Day 6 After Fertilization) Transfer in Frozen Hormonal Replacement Therapy Cycles: Day 6 or Day 7 of Progesterone Administration?

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.

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.

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

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

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

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

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)

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

Positive hCG, but at 5 gestational weeks no ultrasonographic visible gestational sac seen but without a further development into a clinical pregnancy)

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

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.

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.

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.

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.

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.