Natural Versus Artificial Cycle for Frozen-Thawed Embryo Transfer

Phase 4

Completed

• Conditions: Embryo Transfer
• Interventions: Drug: Natural cycle; Drug: Estradiol Valerate; Drug: Micronized progesterone

• Registration Number: NCT03642665
• Lead Sponsor: Universitaire Ziekenhuizen KU Leuven

Brief Summary

This study evaluates clinical pregnancy rates, obstetrical outcome parameters, costs and patient preferences in natural cycle versus artificial cycle frozen embryo transfers (FET).

Detailed Description

Transfer of cryopreserved embryos can be performed in a natural cycle (NC-FET) or in an artificially prepared cycle (AC-FET). Both cycle regimens have their advantages and disadvantages. So far, most comparative studies have failed to identify the optimal protocol for FET. In this study patients undergoing FET will be randomized between an endometrial preparation by a natural cycle or by an artificial cycle (by oestradiol validate and micronized progesterone).

Study Timeline

• Study First Submitted: 2018-07-17
• Study First Submitted QC: 2018-08-20
• Study First Posted: 2018-08-22
• Study Start: 2018-09-25
• Status Verified: 2024-02
• Primary Completion: 2024-11-01
• Study Completion: 2024-11-01
• Last Update Submitted: 2025-02-25
• Last Update Posted: 2025-02-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 554

Inclusion Criteria

• Women undergoing FET after a first, second or third fresh IVF/ICSI cycle
• Single embryo transfer (SET) or Double embryo transfer (DET)
• Female age between 18-45 year
• Women having a natural ovulatory cycle (24-35 days)
• Normal uterine cavity (fundal indentation at the cavity <10mm)
• Written informed consent

Exclusion Criteria

• Use of donor gametes
• BMI > or equal to 35 kg / m2
• Any contra-indication to estrogen or progesterone supplementation (e.g. history of thrombosis, prior or current hormone-sensitive malignancy...)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Natural cycle	Natural cycle	no medication
Artificial cycle	Estradiol Valerate	Oestradiol valerate (Progynova, Bayer, Germany) 6mg daily will be given from day 2 of the cycle. The dose of Progynova is increased to 8mg daily if the endometrial thickness is less than 7mm after 7-10 days of Progynova use. Progynova will be discontinued the day of the pregnancy test in case of a negative result. In case of a pregnancy, Progynova will be continued until 12 weeks or until diagnosis of a non-viable pregnancy. Micronized progesterone (Utrogestan, Besins, Belgium) 200 mg vaginally three times daily is started as soon as the endometrial thickness is 7 mm. Utrogestan will be discontinued the day of the pregnancy test in case of a negative result. In case of a pregnancy, Utrogestan will be continued until 12 weeks or until diagnosis of a non-viable pregnancy.
Artificial cycle	Micronized progesterone	Oestradiol valerate (Progynova, Bayer, Germany) 6mg daily will be given from day 2 of the cycle. The dose of Progynova is increased to 8mg daily if the endometrial thickness is less than 7mm after 7-10 days of Progynova use. Progynova will be discontinued the day of the pregnancy test in case of a negative result. In case of a pregnancy, Progynova will be continued until 12 weeks or until diagnosis of a non-viable pregnancy. Micronized progesterone (Utrogestan, Besins, Belgium) 200 mg vaginally three times daily is started as soon as the endometrial thickness is 7 mm. Utrogestan will be discontinued the day of the pregnancy test in case of a negative result. In case of a pregnancy, Utrogestan will be continued until 12 weeks or until diagnosis of a non-viable pregnancy.

Primary Outcome Measures

Name	Time	Method
Clinical pregnancy rate with fetal heart beat	9 weeks	Clinical pregnancy rate with fetal heart beat diagnosed by ultrasound no later than the gestational age of 9 weeks

Secondary Outcome Measures

Name	Time	Method
Miscarriage rate	12 weeks
Multiple pregnancy rate	9 weeks
Biochemical pregnancy rate	9 weeks
Ectopic pregnancy rate	9 weeks
Endometrial thickness	3 weeks
Live birth rate	41 weeks
Endometrial pattern	3 weeks	Sonographic aspect of the endometrium (triple-line, no triple-line)
number of center visits to monitor FET cycle	From date of randomization until the date of the embryo transfer or until cancellation (estimated period of time up to 4 weeks)
cost analysis per treatment cycle	From date of randomization until the date of the embryo transfer or until cancellation (estimated period of time up to 4 weeks)
patient satisfaction	12 weeks	To evaluate the effect of the different regimens on patients wellbeing/distress, Patient Reported Experience Measures (PREMS) from validated questionnaires will be used. Twenty-two questions from the Benyamini questionnaire will be used (Benyamini et al. 2005) and 10 questions from the subscales 'environment' (α=0.81) and 'tolerability' (α=0.75) of the FertilQol questionnaire (Pedro et al 2013). On the day of embryo transfer, the treating gynecologist will hand out the questionnaire to the patient. The patient will return the filled-in questionnaire on the day of the pregnancy test, before she knows the result of the pregnancy test.
Adverse events	12 weeks	tombo-embolic events, serious side-effects (car leaflet) which require cancellation of treatment
Cycle cancellation rate	4 weeks

Trial Locations

Locations (1)

UZ Leuven; 🇧🇪 Leuven, Belgium