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

Study Overview
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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.

Official Title
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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?

Conditions
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Infertility, Fertility Issues, Infertility, Female

Intervention / Treatment
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* Diagnostic Test: Transvaginal ultrasound
* Diagnostic Test: Serum LH, E2, P4
* Drug: Estradiol Valerate 2 MG
* Drug: Progesterone 100 Mg Vaginal Insert
* Diagnostic Test: Serum P4 day of ET
* Procedure: Embryo transfer


Participation Criteria
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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 : Spontaneous ovulation HRT cycle Discontinuation of HRT medication

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 43 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Group A<br>Embryo transfer is scheduled on the 6th full day of progesterone administration, following the initial commencement of progesterone (120 hours) | Diagnostic Test: Transvaginal ultrasound<br>* Transvaginal ultrasound throughout the HRT cycle to not only monitor endometrial development but to also exclude the presence of an ovarian dominant follicle<br>Diagnostic Test: Serum LH, E2, P4<br>* In conjunction with ultrasound monitoring, participants will undergo serial measurements of serum Luteinizing Hormone (LH), Estradiol (E2) and Progesterone (P4) levels<br>Drug: Estradiol Valerate 2 MG<br>* 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)<br>* Other names: Estradiol Valerate;Drug: Progesterone 100 Mg Vaginal Insert<br>* 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<br>* Other names: Progesterone 100 mg;Diagnostic Test: Serum P4 day of ET<br>* On the day of embryo transfer (ET), a blood test is taken to measure serum P4<br>Procedure: Embryo transfer<br>* Procedure in which embryo is transferred into the uterus<br>* Other names: ET;|
| Other: Group B<br>Embryo Transfer is scheduled on the 7th full day of progesterone administration, following the initial commencement of progesterone (144 hours) | Diagnostic Test: Transvaginal ultrasound<br>* Transvaginal ultrasound throughout the HRT cycle to not only monitor endometrial development but to also exclude the presence of an ovarian dominant follicle<br>Diagnostic Test: Serum LH, E2, P4<br>* In conjunction with ultrasound monitoring, participants will undergo serial measurements of serum Luteinizing Hormone (LH), Estradiol (E2) and Progesterone (P4) levels<br>Drug: Estradiol Valerate 2 MG<br>* 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)<br>* Other names: Estradiol Valerate;Drug: Progesterone 100 Mg Vaginal Insert<br>* 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<br>* Other names: Progesterone 100 mg;Diagnostic Test: Serum P4 day of ET<br>* On the day of embryo transfer (ET), a blood test is taken to measure serum P4<br>Procedure: Embryo transfer<br>* Procedure in which embryo is transferred into the uterus<br>* Other names: ET;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Livebirth rate (LBR) | Defined as the delivery of a live infant born after 24 completed weeks of gestation | 41 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biochemical pregnancy rate | Positive hCG, but at 5 gestational weeks no ultrasonographic visible gestational sac seen but without a further development into a clinical pregnancy) | 5 weeks | 
| Clinical pregnancy rate | Ultrasonographic sac visible at 5 gestational weeks | 5 weeks | 
| Ongoing pregnancy rate after 12 weeks | Viable pregnancy with a gestational age of more than 12 weeks | 13 weeks | 
| Miscarriage rate | Spontaneous loss of a clinical pregnancy before 24 completed weeks of gestation | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Implantation, Infertility, Blastocyst, HRT, Progesterone