Natural Versus Artificial Cycle for Frozen-Thawed Embryo Transfer (NAFT)

• ClinicalTrials.gov Identifier: NCT03642665
• Recruitment Status: Recruiting
• First Posted: August 22, 2018
• Last Update Posted: October 1, 2021
• Sponsor: Universitaire Ziekenhuizen Leuven
• Collaborators: GZA Ziekenhuizen Campus Sint-Augustinus; Imelda Hospital, Bonheiden; Jessa Hospital
• Information provided by (Responsible Party): Universitaire Ziekenhuizen Leuven

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Embryo Transfer	Drug: Natural cycle; Drug: Estradiol Valerate; Drug: Micronized progesterone	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 554 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Multicenter prospective randomized clinical trial
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Frozen-thawed Embryo Transfer in a Natural Versus Artificial Cycle: a Randomized Clinical Trial
• Actual Study Start Date: September 25, 2018
• Estimated Primary Completion Date: September 1, 2022
• Estimated Study Completion Date: June 1, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Natural cycle; no medication	Drug: Natural cycle; no medication
Active Comparator: Artificial cycle; 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.	Drug: 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.; Other Name: Artificial cycle; Drug: Micronized progesterone; 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.; Other Name: Artificial cycle

Outcome Measures

Primary Outcome Measures :

1. Clinical pregnancy rate with fetal heart beat [ Time Frame: 9 weeks ]
   Clinical pregnancy rate with fetal heart beat diagnosed by ultrasound no later than the gestational age of 9 weeks

Secondary Outcome Measures :

1. Biochemical pregnancy rate [ Time Frame: 9 weeks ]
2. Miscarriage rate [ Time Frame: 12 weeks ]
3. Ectopic pregnancy rate [ Time Frame: 9 weeks ]
4. Live birth rate [ Time Frame: 41 weeks ]
5. Multiple pregnancy rate [ Time Frame: 9 weeks ]
6. Adverse events [ Time Frame: 12 weeks ]
   tombo-embolic events, serious side-effects (car leaflet) which require cancellation of treatment
7. Cycle cancellation rate [ Time Frame: 4 weeks ]
8. Endometrial thickness [ Time Frame: 3 weeks ]
9. Endometrial pattern [ Time Frame: 3 weeks ]
   Sonographic aspect of the endometrium (triple-line, no triple-line)
10. number of center visits to monitor FET cycle [ Time Frame: From date of randomization until the date of the embryo transfer or until cancellation (estimated period of time up to 4 weeks) ]
11. cost analysis per treatment cycle [ Time Frame: From date of randomization until the date of the embryo transfer or until cancellation (estimated period of time up to 4 weeks) ]
12. patient satisfaction [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 45 Years (Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

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…)

Contacts and Locations

Locations

Belgium

UZ Leuven; Recruiting

Leuven, Belgium, 3000

Contact: Myriam Welkenhuysen +3216343544 myriam.welkenhuysen@uzleuven.be

Contact: Brecht Geysenbergh, MD +32496125137 brecht.geysenbergh@uzleuven.be

Sponsors and Collaborators

Universitaire Ziekenhuizen Leuven

GZA Ziekenhuizen Campus Sint-Augustinus

Imelda Hospital, Bonheiden

Jessa Hospital

More Information

• Responsible Party: Universitaire Ziekenhuizen Leuven
• ClinicalTrials.gov Identifier: NCT03642665
• Other Study ID Numbers: S61372
• First Posted: August 22, 2018
• Last Update Posted: October 1, 2021
• Last Verified: September 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:

Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Estradiol; Polyestradiol phosphate; Progesterone; Estrogens; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Progestins