Fertility DisordersCIRCAPRONCT05511272
The Circadian Variability of Serum Progesterone During the Day of a Frozen Embryo Transfer
A study testing blood test in people with Fertility Disorders, run by Universitair Ziekenhuis Brussel at 1 site in Belgium.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 40 years, women only
- Conditions the study is for
- Fertility Disorders
- What is being tested?
- blood test
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 1 siteBelgium
- Study dates
- 15 Aug 2022to 1 Dec 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 9Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Circadian Variability of Serum Progesterone During the Day of a Frozen Embryo Transfer in an Artificially Prepared Cycle and in a Modified Natural Cycle
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.
Read the 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
- Being tested
- blood test
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
blood testBiological
four blood samples will be withdrawn from the participants during the day of their frozen embryo transfer cycle
| Study group | Role | What they receive |
|---|---|---|
| Frozen embryo transfer cycle | Experimental | Patients who will undergo a frozen embryo transfer in the modified natural cycle and in an artificially prepared cycle will be included Receives: Biological: blood test |
What is being measured
The primary outcome is the main question the study is designed to answer.
The existence of circadian variability of serum progesterone during the day of a frozen embryo transfer
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
Measured: the day of the embryo transfer (from 8 am to 8 pm)
Secondary outcomes (4)
Pregnancy outcomes after the frozen embryo transfer
To evaluate the Clinical pregnancy rate (CPR) in patients who underwent HRT FET or mNC FET. CPR is defined as a pregnancy documented by ultrasound at 6-8 gestational weeks that showed a gestational sac in the uterus
Measured: from the day of the embryo transfer to 12 weeks of pregnancy
The critical progesterone threshold to optimize pregnancy outcomes
To evaluate the critical threshold of serum progesterone on the day of the FET below which pregnancy rates are significantly lower
Measured: from the day of the embryo transfer to 12 weeks of pregnancy
The assessment of serum progesterone on the day of frozen embryo transfer
To study when is the best moment to measure serum progesterone on the day of FET
Measured: the day of the embryo transfer (from 8 am to 8 pm)
Pregnancy outcomes after the frozen embryo transfer
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
Measured: from the day of the embryo transfer to 7 weeks of pregnancy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Aug 2022
- Study start15 Aug 2022
- Primary completion1 Dec 2023
- Study completion1 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Fertility DisordersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universitair Ziekenhuis Brussel
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Christophe Blockeel, MD, Principal investigator, Universitair Ziekenhuis Brussel
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05511272
- Sponsor's protocol ID
- 1432022000124
- Acronym
- CIRCAPRO
- Status last verified
- Jul 2022
- First submitted
- 16 Aug 2022
- Last updated
- 19 Dec 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 29025055Melo 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.
PubMed 34384594Labarta 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.
PubMed 34548167Wang 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.
PubMed 32322584Labarta 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.
PubMed 34177806Loreti 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.
PubMed 38775072
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Circadian Variability of Serum Progesterone During the Day of a Frozen Embryo Transfer in an Artificially Prepared Cycle and in a Modified Natural Cycle
- ClinicalTrials.gov ID
- NCT05511272
- Acronym / sponsor ID
- CIRCAPRO / 1432022000124
- Conditions
- Fertility Disorders
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- Universitair Ziekenhuis BrusselUniversity, hospital or other
- Study start
- 15 Aug 2022 (actual)
- Primary completion
- 1 Dec 2023 (actual)
- Study completion
- 1 Dec 2023 (actual)
- First posted
- 22 Aug 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Frozen embryo transfer cycle | Experimental | Biological: blood testPatients who will undergo a frozen embryo transfer in the modified natural cycle and in an artificially prepared cycle will be included |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| blood testfour blood samples will be withdrawn from the participants during the day of their frozen embryo transfer cycle | Biological | Frozen embryo transfer cycle |
Primary outcome
The existence of circadian variability of serum progesterone during the day of a frozen embryo transfer
Time frame: 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
4 secondary outcomes
Pregnancy outcomes after the frozen embryo transfer
Time frame: from the day of the embryo transfer to 12 weeks of pregnancy
The critical progesterone threshold to optimize pregnancy outcomes
Time frame: from the day of the embryo transfer to 12 weeks of pregnancy
The assessment of serum progesterone on the day of frozen embryo transfer
Time frame: the day of the embryo transfer (from 8 am to 8 pm)
Pregnancy outcomes after the frozen embryo transfer
Time frame: from the day of the embryo transfer to 7 weeks of pregnancy
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2023.
- Background: PubMed 29025055Mackens 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.
- Background: PubMed 34384594Melo 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.
- Background: PubMed 34548167Labarta 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.
- Background: PubMed 32322584Wang 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.
- Background: PubMed 34177806Labarta 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.
- Derived from this study: PubMed 38775072Loreti 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.
- Individual participant dataSharing planned: No
Related trials for Fertility Disorders
Active, not recruiting
Ovarian Tissue Cryopreservation in Children
Cancer
Not yet recruiting
Sperm, Exposure and Endocrine Disruptors
Fertility, Male Fertility
Recruiting
Dietary Intervention to Improve Fertility in Women With Endometriosis Undergoing IVF
Endometriosis
RecruitingObservational study
Gonadal Tissue Freezing for Fertility Preservation in Individuals at Risk for Ovarian Dysfunction, Premature Ovarian Insufficiency and Clinically Indicated Gonadectomy
Turner Syndrome, Post-menarcheal Adolescents
Active, not recruitingObservational study
Factors Influencing Fertility or Pregnancy Health
Menstrual Cycles, Conception
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christophe Blockeel, MD principal investigator
Universitair Ziekenhuis Brussel
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing blood test in people with Fertility Disorders, run by Universitair Ziekenhuis Brussel at 1 site in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The existence of circadian variability of serum progesterone during the day of a frozen embryo transfer (time frame: the day of the embryo transfer (from 8 am to 8 pm)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05511272, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Dec 2023.