SHorter Treatment of Replacement Therapy for Frozen Embryo Transfer (FET)

Study Overview
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Brief Summary
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This is a Single-centre pilot study, randomized, controlled open-label trial with the aim to assess the clinical pregnancy rate and the early pregnancy loss rate between two different schemas for frozen embryo transfer cycles stimulated with HRT. Furthermore, the investigators would like to evaluate the predictivity of pregnancy and early miscarriage by looking at the endocrinological profile (estradiol and progesterone levels) within the endometrial preparation and the day of embryo transfer (ET).

Detailed Description
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Women planned for a FET-HRT will be asked to do a blood test day 1 of their cycle in order to evaluate the endocrine profile; those with basal hormonal values will receive 6 mg oral estradiol daily beginning from day 1 of their cycle. On day 7 of the treatment a blood test for the serum hormone evaluation and an ultrasound will be planned in order to evaluate the endometrium thickness; those who will meet the criteria (endometrium thickness ≥7mm) will be randomized. In the 7 days estradiol (E2) arm (A) the study coordinator will plan the FET after 6 days of progesterone supplementation (13 days of E2 intake). In the 14 days E2 arm (B) the team will plan on day 14 of treatment with E2 the serum hormone evaluation and an ultrasound in order to evaluate the endometrium thickness, consequently the FET will be planned after 6 days of progesterone supplementation (after 14 days of E2 intake). Furthermore, all the patients included in the study will undergo a blood test on the day of the transfer for the evaluation of the hormones level. For the assessment of the pregnancy a first blood test will take place 12 days after the ET and a blood test with an ultrasound will take place at 7 weeks for the evaluation of the clinical pregnancy.

Official Title
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Clinical Pregnancy Rate for Frozen Embryo Transfer With Hormonal Replacement Therapy (HRT): a Pilot Study Comparing 1 Versus 2 Weeks of Treatment

Conditions
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Infertility

Intervention / Treatment
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* Other: Longer administration of estradiol (Progynova®)


Participation Criteria
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Eligibility Criteria
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Women aged ≥18 and < 40 years Unexplained infertility Normal uterine cavity IVF/ICSI IVF cycle with GnRH agonist or antagonist Single day 5 blastocyst transfer Top quality embryo (at least Bl 3BA) at the moment of ET Signed informed consent Participants can be included only once in the trial Informed consent documents signed prior to screening evalua-tions.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>Group A will include all the patient that will start with progesterone ((P), Utrogestan®) supplementation after 7 days of E2 (Progynova®) intake and that will perform the FET (after 13 days of E2 and 6 days of P). | Other: Longer administration of estradiol (Progynova®)<br>* All women included will take exogenous hormone with daily administration of Estradiol Valerate (Progynova®), the standard dose used will be 6 mg/day (Cobo et al., n.d.). On day 7 of endometrial preparation patients will be examined with vaginal ultrasound and blood test, to evaluate the endometrial thickness and the hormones levels. In both arms the FET will take place after 6 days of Progesterone supplementation (600 mg per day, vaginal administration of Utrogestan®) According to embryo quality after warming, embryo transfer to the uterine cavity will be performed on day 5 of development under ultrasound guidance whenever possible. Following embryo transfer, luteal support will be continued with vaginally administered P (Utrogestan®). All patients 12 days after the FET will undergo the pregnancy test (blood test to evaluate hCG).<br>* Other names: comparing 7 vs 14 days of administration of estradiol (Progynova®) for artificially prepared endometrium in frozen embryo transfer;|
| Active Comparator: Group B<br>Group B will include the patients that will perform 14 days of E2 intake (Progynova®, 6 mg per day (2 mg every 8 hours) those patients will be asked to perform a supplementary blood test and ultrasound on day 14 of E2 intake, afterwards, they will start with P supplementation (Utrogestan®, 800 mg per day, 400 mg every 12 hours) from day 15 of E2 for 6 days and they will get their FET day 20 of the cycle (after 14 days of E2 and 6 days of P) | Other: Longer administration of estradiol (Progynova®)<br>* All women included will take exogenous hormone with daily administration of Estradiol Valerate (Progynova®), the standard dose used will be 6 mg/day (Cobo et al., n.d.). On day 7 of endometrial preparation patients will be examined with vaginal ultrasound and blood test, to evaluate the endometrial thickness and the hormones levels. In both arms the FET will take place after 6 days of Progesterone supplementation (600 mg per day, vaginal administration of Utrogestan®) According to embryo quality after warming, embryo transfer to the uterine cavity will be performed on day 5 of development under ultrasound guidance whenever possible. Following embryo transfer, luteal support will be continued with vaginally administered P (Utrogestan®). All patients 12 days after the FET will undergo the pregnancy test (blood test to evaluate hCG).<br>* Other names: comparing 7 vs 14 days of administration of estradiol (Progynova®) for artificially prepared endometrium in frozen embryo transfer;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Pregnancy Rate | The number of clinical pregnancies expressed per 100 initiated cycles, aspiration cycles or embryo transfer cycles. When clinical pregnancy rates are recorded, the denominator (initiated, aspirated or embryo transfer cycles) must be specified. | 2 years | 
| Live Birth Rate | The number of deliveries that resulted in at least one live birth, expressed per 100 cycle attempts. In the case of assisted reproductive technologies (ART) interventions, they can be initiated cycles, insemination, aspiration cycles or embryo transfer cycles. When delivery rates are given, the denominator (initiated, inseminated, aspirated or embryo transfer cycles) must be specified. | 4 years | 
| Miscarriage rate | The spontaneous loss of an intra-uterine pregnancy prior to 22 completed weeks of gestational age, over the number of transferred embryos. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| positive hCG tests | the number of participants with positive hCG measured on a blood sample 12 days after ET | 2 years | 
| biochemical pregnancy | the number of patients with positive hCG but no embryo development assessed | 2 years | 
| early pregnancy loss | the number of participants who had a pregnancy loss before 8 weeks of pregnancy | 2 years |