Different Strategies in Frozen IVF/ICSI Cycles

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

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.

Study Overview

• Status: Completed
• Conditions: Pregnancy Rates
• Intervention / Treatment: Drug: Hormone Replacement cycle 1; Drug: Hormone Replacement cycle 2

Detailed Description

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

1. The antagonist protocol
2. 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:

1. Natural cycle, spontaneous ovulation or ovulation triggering by exogenous hCG without luteal support (Group 1)
2. Natural cycle, spontaneous ovulation or ovulation triggering by exogenous hCG with luteal support (progesterone) (Group 2)
3. Hormone Replacement cycle (cyclacur) plus GnRHa suppression with luteal support (progesterone) (Group 3)
4. 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).

• Study Type: Observational
• Enrollment (Actual): 311

Contacts and Locations

Study Locations

• Greece
  • Chaidari
    • Athens, Chaidari, Greece, 12462
      • Attikon University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 42 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Probability Sample

Study Population

Following clinical evaluation along with previous medical and reproductive history, participants will be categorized according to the subfertility factor and further demographic parameters (age, Body Mass Index (BMI), smoking status, basal FSH levels, parity, antral follicle count (AFC) in the fresh cycle, type (primary/secondary) and duration of subfertility and number of unsuccessful IVF/ICSI attempts (fresh and/or frozen) will be recorded along with the respective hormonal profiles.

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Group 1; Natural cycle, spontaneous ovulation or ovulation triggering by exogenous hCG without luteal support	Drug: Hormone Replacement cycle 1; Hormone Replacement cycle (cyclacur) without GnRHa suppression with luteal support (progesterone)
Group 2; Natural cycle, spontaneous ovulation or ovulation triggering by exogenous hCG with luteal support (progesterone)	Drug: Hormone Replacement cycle 1; Hormone Replacement cycle (cyclacur) without GnRHa suppression with luteal support (progesterone)
Group 3; Hormone Replacement cycle (cyclacur) plus GnRHa suppression with luteal support (progesterone)	Drug: Hormone Replacement cycle 2; Hormone Replacement cycle with GnRHa suppression
Group 4; Hormone Replacement cycle (cyclacur) without GnRHa suppression with luteal support (progesterone)	Drug: Hormone Replacement cycle 2; Hormone Replacement cycle with GnRHa suppression

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: National and Kapodistrian University of Athens
• Collaborators: Democritus University of Thrace

Study record dates

Study Major Dates

• Study Start (Actual): June 6, 2019
• Primary Completion (Actual): December 2, 2019
• Study Completion (Actual): December 2, 2019

Study Registration Dates

• First Submitted: May 24, 2019
• First Submitted That Met QC Criteria: May 24, 2019
• First Posted (Actual): May 29, 2019

Study Record Updates

• Last Update Posted (Actual): September 9, 2020
• Last Update Submitted That Met QC Criteria: September 4, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormones
• Other Study ID Numbers: HRT001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: Will discuss it with other authors

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No