The Circadian Variability of Serum Progesterone During the Day of a Frozen Embryo Transfer

Not Applicable

Completed

• Conditions: Fertility Disorders
• Interventions: Biological: blood test

• Registration Number: NCT05511272
• Lead Sponsor: Universitair Ziekenhuis Brussel

Brief Summary

Serum progesterone levels will be evaluated at four different time points during the day of an artificially prepared frozen embryo transfer cycle (HRT FET cycle) and a modified natural cycle frozen embryo transfer cycle (mNC FET cycle) (at 08:00, 12:00, 16:00 and 20:00).The pairwise percentage differences in serum progesterone levels for each patient will be calculated. The intra-day variability of progesterone will be analyzed using mixed models. Pregnancy outcomes will also be assessed. The sample size calculated consisted of 22 patients for the HRT-FET study and 22 patients for the mNC FET study.

Detailed Description

In the HRT FET, estradiol valerate (Progynova) will be administered for endometrial preparation. If the endometrial thickness will be ≥ 6,5 mm during an ultrasound scan planned following an initial period of estrogen priming, micronized vaginal progesterone will be started (Utrogestan 800 mg/d). The transfer of a single blastocyst will be performed on the 6th day of progesterone administration. In a modified NC FET, there is no intake of medication but endocrine and ultrasound monitoring during the proliferative phase. Ovulation trigger with hCG will be considered when a dominant follicle between 16 and 20 mm will be observed and when the endometrial thickness will be ≥ 6,5 mm. The transfer of a single blastocyst will take place on the 7th day after hCG injection.

Serum progesterone levels will be evaluated at four different time points during the day of an artificially prepared frozen embryo transfer cycle (HRT FET cycle) and a modified natural cycle frozen embryo transfer cycle (mNC FET cycle) (at 08:00, 12:00, 16:00 and 20:00). Pairwise percentage differences in serum progesterone levels for each patient will be calculated. The intra-day variability of progesterone will be analyzed using mixed models. Pregnancy outcomes will also be assessed.

Study Timeline

• Status Verified: 2022-07
• Study Start: 2022-08-15
• Study First Submitted: 2022-08-16
• Study First Submitted QC: 2022-08-19
• Study First Posted: 2022-08-22
• Primary Completion: 2023-12-01
• Study Completion: 2023-12-01
• Last Update Submitted: 2023-12-18
• Last Update Posted: 2023-12-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 44

Inclusion Criteria

• Age ≥ 18 and ≤ 40 years old
• BMI ≥ 18.5 and ≤ 25,9 kg/m2
• The patient will undergo a hormone replacement therapy frozen embryo transfer cycle (HRT FET) or a modified natural cycle frozen embryo transfer cycle (mNC FET) according to the standard clinical practice in Brussels IVF
• In the HRT FET cycle the patient will be administered estradiol valerate and 6 days of micronized vaginal progesterone before the embryo transfer
• Adequate endometrial pattern (triple layer) and thickness (>6.5 mm) at the moment of planning of the transfer
• Single blastocyst embryo transfer
• Signed informed consent
• Non-smokers

Exclusion Criteria

• Age > 40 (women > 40 years old demonstrated an enhanced rate of absorption of progesterone using vaginal tablets compared to younger patients)
• BMI ≥ 26 (serum progesterone levels on the day of embryo transfer are lower in overweight and obese women compared to those with normal weight)
• Patients who need to take vaginal estradiol valerate during the HRT FET cycle
• Intake of any experimental drug or any participation in any other clinical trial within 30 days prior to study start
• Mental disability or any other lack of fitness, in the investigator's opinion, to preclude subjects in or to complete the study.
• Current or recent substance abuse, including alcohol and tobacco (patients who stopped tobacco usage at least 3 months prior to screening visit would be allowed)
• Refusal or inability to comply with the requirements of the study protocol for any reason, including scheduled clinic visits and laboratory tests.
• Embryo transfer after IVM cycle, PGT or oocyte acceptance
• Uterine pathologies (fibroids, polyps, chronic endometritis), uterine malformations (septum, Mullerian malformation) and hydrosalpinx

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Frozen embryo transfer cycle	blood test	Patients who will undergo a frozen embryo transfer in the modified natural cycle and in an artificially prepared cycle will be included

Primary Outcome Measures

Name	Time	Method
The existence of circadian variability of serum progesterone during the day of a frozen embryo transfer	the day of the embryo transfer (from 8 am to 8 pm)	To evaluate if there is significant variability in circadian level of serum progesterone on the day of an artificially prepared frozen embryo transfer cycle and during the day of a modified natural frozen embryo transfer cycle

Secondary Outcome Measures

Name	Time	Method
The critical progesterone threshold to optimize pregnancy outcomes	from the day of the embryo transfer to 12 weeks of pregnancy	To evaluate the critical threshold of serum progesterone on the day of the FET below which pregnancy rates are significantly lower
The assessment of serum progesterone on the day of frozen embryo transfer	the day of the embryo transfer (from 8 am to 8 pm)	To study when is the best moment to measure serum progesterone on the day of FET
Pregnancy outcomes after the frozen embryo transfer	from the day of the embryo transfer to 7 weeks of pregnancy	To evaluate the on going pregnancy rate (OPR) in patients who underwent HRT FET or mNC FET. OPR is defined as a viable pregnancy at the ultrasound taken at 12 weeks of gestation that shows the presence of fetal heartbeat

Trial Locations

Locations (1)

Brussels IVF; 🇧🇪 Brussel, Jette, Belgium