Different Strategies in Frozen IVF/ICSI Cycles

Study Overview
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Brief Summary
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In the absence of robust contemporary data, investigators decided to perform a multicenter cohort study of various IVF centers, to compare the different modalities used for pregnancy rates following frozen-thawed embryo transfer (FET) treatment cycles in normoovulatory patients undergoing IVF/ICSI.

Detailed Description
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In general, the type of FET protocol for each patient is selected by the attending physicians at their own discretion. In all centers, patients with ovulatory cycles are typically prescribed an NC-FET or mNC-FET, whereas patients with oligomenorrhoea or amenorrhoea are prescribed an artificial cycle to prepare the endometrium for FET. Ovarian stimulation protocol The antagonist protocol The long 21 /2 agonist protocol Laboratory technique a. IVF or b. ICSI Embryo freezing using only vitrification will be performed in days 3 or 5/6. Embryo transfer will be conducted at days 3 or 5/6. The maximum number of embryos transferred will be two, as in accordance to the Hellenic legislation. The following modalities will be analyzed, patients with: Natural cycle, spontaneous ovulation or ovulation triggering by exogenous hCG without luteal support (Group 1) Natural cycle, spontaneous ovulation or ovulation triggering by exogenous hCG with luteal support (progesterone) (Group 2) Hormone Replacement cycle (cyclacur) plus GnRHa suppression with luteal support (progesterone) (Group 3) Hormone Replacement cycle (cyclacur) without GnRHa suppression with luteal support (progesterone) (Group 4) Of note, the conversion between different supplementation methods may be testimated as follows: 0.75 mg of micronised estradiol (oral administration) = 1.25 g of estradiol gel (transdermal administration) = 1 mg of estradiol valerate (oral or vaginal adminstration).

Official Title
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Impact of Different Strategies in Frozen Cycles Using HRT in Normo Responding Patients Undergoing IVF/ICSI Cycles: a Multicenter Cohort Study

Conditions
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Pregnancy Rates

Intervention / Treatment
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* Drug: Hormone Replacement cycle 1
* Drug: Hormone Replacement cycle 2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age 25-39 years, BMI ≤ 35 and ≥ 19, normo-ovulatory patients and basal FSH ≤11 mIU/mL. Definition of expected normal ovarian response will be based primarily on antral follicle count (AFC) between 6-14. Exclusion Criteria: history of more than three previous unsuccessful IVF/ICSI cycles, FSH > 12 mIU/mL, BMI >35 or <19, poor ovarian response according to the 2011 Bologna criteria, PCOS patients according to the Rotterdam criteria, history of untreated autoimmune, endocrine or metabolic disorders, history of pathology affecting the endometrial cavity and/or receptivity and clinical and/or laboratory markers of hereditary or acquired thrombophilia that complied to the standard protocols of each Unit and patients without embryo after thawing.

Ages Eligible for Study
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Minimum Age: 25 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 |
| --- | --- |
| Group 1<br>Natural cycle, spontaneous ovulation or ovulation triggering by exogenous hCG without luteal support | Drug: Hormone Replacement cycle 1<br>* Hormone Replacement cycle (cyclacur) without GnRHa suppression with luteal support (progesterone)<br>|
| Group 2<br>Natural cycle, spontaneous ovulation or ovulation triggering by exogenous hCG with luteal support (progesterone) | Drug: Hormone Replacement cycle 1<br>* Hormone Replacement cycle (cyclacur) without GnRHa suppression with luteal support (progesterone)<br>|
| Group 3<br>Hormone Replacement cycle (cyclacur) plus GnRHa suppression with luteal support (progesterone) | Drug: Hormone Replacement cycle 2<br>* Hormone Replacement cycle with GnRHa suppression<br>|
| Group 4<br>Hormone Replacement cycle (cyclacur) without GnRHa suppression with luteal support (progesterone) | Drug: Hormone Replacement cycle 2<br>* Hormone Replacement cycle with GnRHa suppression<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| live birth | birth after 20 weeks of gestation | 1 year | 
| ongoing pregnancy | positive heart rate after 12 weeks | 3 months | 
| miscarriage | pregnancy loss up to 20 weeks of gestation | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| biochemical pregnancy (positive β-hCG), multiple, ectopic and clinical pregnancy rates | positive β-hCG, multiple, ectopic and clinical pregnancy rates | 3 months |