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

NCT ID: NCT05511272

Last Updated: 2023-12-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-08-15
• Study Completion Date: 2023-12-01

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.

Conditions

Fertility Disorders

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Frozen embryo transfer cycle

Patients who will undergo a frozen embryo transfer in the modified natural cycle and in an artificially prepared cycle will be included

Group Type: EXPERIMENTAL

blood test

Intervention Type: BIOLOGICAL

four blood samples will be withdrawn from the participants during the day of their frozen embryo transfer cycle

Interventions

blood test

four blood samples will be withdrawn from the participants during the day of their frozen embryo transfer cycle

Intervention Type: BIOLOGICAL

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Universitair Ziekenhuis Brussel

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christophe Blockeel, MD

Role: PRINCIPAL_INVESTIGATOR

Universitair Ziekenhuis Brussel

Locations

Brussels IVF

Brussels, Jette, Belgium

Countries

Belgium

References

Mackens S, Santos-Ribeiro S, van de Vijver A, Racca A, Van Landuyt L, Tournaye H, Blockeel C. Frozen embryo transfer: a review on the optimal endometrial preparation and timing. Hum Reprod. 2017 Nov 1;32(11):2234-2242. doi: 10.1093/humrep/dex285.

Reference Type: BACKGROUND

PMID: 29025055 (View on PubMed)

Melo P, Chung Y, Pickering O, Price MJ, Fishel S, Khairy M, Kingsland C, Lowe P, Petsas G, Rajkhowa M, Sephton V, Tozer A, Wood S, Labarta E, Wilcox M, Devall A, Gallos I, Coomarasamy A. Serum luteal phase progesterone in women undergoing frozen embryo transfer in assisted conception: a systematic review and meta-analysis. Fertil Steril. 2021 Dec;116(6):1534-1556. doi: 10.1016/j.fertnstert.2021.07.002. Epub 2021 Aug 10.

Reference Type: BACKGROUND

PMID: 34384594 (View on PubMed)

Labarta E, Mariani G, Rodriguez-Varela C, Bosch E. Individualized luteal phase support normalizes live birth rate in women with low progesterone levels on the day of embryo transfer in artificial endometrial preparation cycles. Fertil Steril. 2022 Jan;117(1):96-103. doi: 10.1016/j.fertnstert.2021.08.040. Epub 2021 Sep 20.

Reference Type: BACKGROUND

PMID: 34548167 (View on PubMed)

Wang Z, Liu H, Song H, Li X, Jiang J, Sheng Y, Shi Y. Increased Risk of Pre-eclampsia After Frozen-Thawed Embryo Transfer in Programming Cycles. Front Med (Lausanne). 2020 Apr 8;7:104. doi: 10.3389/fmed.2020.00104. eCollection 2020.

Reference Type: BACKGROUND

PMID: 32322584 (View on PubMed)

Labarta E, Rodriguez-Varela C, Mariani G, Bosch E. Serum Progesterone Profile Across the Mid and Late Luteal Phase in Artificial Cycles Is Associated With Pregnancy Outcome. Front Endocrinol (Lausanne). 2021 Jun 10;12:665717. doi: 10.3389/fendo.2021.665717. eCollection 2021.

Reference Type: BACKGROUND

PMID: 34177806 (View on PubMed)

Loreti S, Roelens C, Aktoz F, Niero M, De Munck N, Tournaye H, Mackens S, Blockeel C. Circadian serum progesterone variations on the day of frozen embryo transfer in a modified natural cycle protocol. Hum Reprod. 2024 May 22:deae101. doi: 10.1093/humrep/deae101. Online ahead of print.

Reference Type: DERIVED

PMID: 38775072 (View on PubMed)

Other Identifiers

1432022000124

Identifier Type: -

Identifier Source: org_study_id