What is the Optimal Cycle Regimen for Frozen- Thawed Embryo Transfer Cycles

Study Overview
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Brief Summary
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Investigators will be comparing artificial (HRT) frozen-thawed embryo transfer cycles to correctly conducted spontaneous natural cycles after the transfer of a chromosomally normal embryo.

Detailed Description
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The most common treatment protocols for frozen embryo transfers include natural cycles with or without human chorionic gonadotrophin (HCG) trigger or endometrial preparation with hormonal treatment (artificial cycles), with or without Gonadotrophin - releasing hormone agonist suppression. Recent studies comparing artificial and natural cycles concluded that the optimal means of endometrial preparation for frozen- thawed cycle remains unclear and both options may be offered to women with regular ovulatory cycles. Correctly identified spontaneous natural cycles are the preferred option for frozen-thawed embryo transfer in women with regular menstrual cycles. Investigators will be comparing artificial (HRT) frozen-thawed embryo transfer cycles to correctly conducted spontaneous natural cycles after the transfer of a chromosomally normal embryo.

Official Title
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What is the Optimal Cycle Regimen for Frozen- Thawed Embryo Transfer Cycles: Spontaneous Natural Cycles Versus Hormonal Replacement Treatment (HRT) Cycles

Conditions
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Infertility, Female Infertility, Pregnancy Early

Participation Criteria
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Eligibility Criteria
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Inclusion criteria include the following: Women aged 18 years to 42 years with regular menses (26-34 days) Having 1 or 2 chromosomally normal cryopreserved blastocysts available for transfer. First frozen-thawed transfer cycle Progesterone level < 1.5 ng/mL day of trigger injection in stimulation cycle from which embryos to be transferred were created. Exclusion criteria include the following: Polycystic ovarian syndrome Poor ovarian responder in accordance with Bologna criteria Uterine abnormality US / saline infusion sonohysterogram Previous dilatation & curettage (D&C) Hydrosalpinx Asherman syndrome History of endometriosis ICSI due to severe male factor with testicular sperm Any known contraindications or allergy to oral estradiol or progesterone. Discontinuation of HRT medication ( medication error in research HRT cycle ) Failure to detect ovulation in the research natural cycle Duration of estradiol exposure ≥ 17 days and endometrium < 6mm Spontaneous ovulation in HRT artificial cycle

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 42 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Artificial (HRT) Cycles<br>Commence estradiol valerate (E2) 4mg from day 2 or 3 of period for 3 days Increase E2 to 6mg on day 4 of E2 treatment, according to clinician discretion based on endometrial thickness. Transvaginal scan throughout the HRT cycle to not only monitor endometrial development but to also exclude the presence of a dominant follicle on the ovaries. Serial measurements of serum LH (luteinizing hormone), estradiol and progesterone levels. Initial progesterone dose of 100mg at 22hrs (vaginal suppository) after ≥ 7 days and ≤ 16 days of estradiol administration when the minimal endometrial thickness achieved is 6mm with a trilaminar appearance. Subsequently increase progesterone administration to 100mg vaginally three times daily. Continue E2 administration 6mg (3 tablets daily). Embryo transfer is scheduled on the 5th full day of progesterone administration. | |
| Spontaneous natural cycles:<br>Day 2 of menses and throughout patients' natural cycle scans to monitor follicular growth. Measurements of serum LH, estradiol and progesterone levels to determine ovulation. The LH surge will be considered to have begun when the concentration rises by 180% above the most recent serum value and continues to rise thereafter (Irani et al. 2017, Fatemi et al., 2010). Day 1 after the LH rise, a decrease in estradiol concentration is identified. Twenty four hours later progesterone concentrations rise with a level of greater than or equal to 1.5ng/mL confirming ovulation (day 0) (Irani et al., 2017; Speroff et al.). This is considered as day 0 with initiation of vaginal progesterone 100mg at 22hrs that night. The following day (day 1) the patient increases progesterone administration to 100mg vaginally 8 hourly and continues until 7 weeks gestation as per clinic protocol. Embryo transfer is scheduled 5 days (day 5) following confirmation of ovulation (day 0). | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ongoing pregnancy rate to 8 weeks gestation | viable pregnancy to 8 gestational weeks | 8 weeks | 
| Pregnancy rate beta human chorionic gonadotropin (ß-hCG) > 5 IU | Number of patients with a hCG > 5 IU out of the number of patients who underwent an embryo transfer with one or two euploid embryos | 12 days | 
| Biochemical pregnancy rate | Positive ß-hCG, but at 5 gestational weeks no ultrasonographic visible gestational sac seen | 5 weeks | 
| Clinical implantation rate | Number of gestational sacs observed by ultrasound at 6 weeks of gestation divided by the number of embryos transferred | 6 weeks | 
| Clinical pregnancy rate | Ultrasonographic visible sac at 5 gestational weeks | 5 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hormone replacement therapy, Frozen thawed embryos, Frozen embryo cycle