FertilityPhase 4PROMICOFETNCT07818278
Cycle-to-cycle Variability of Progesterone in the Endometrium in Patients Undergoing an Euploid Blastocyst Transfer in a Hormone Replacement Therapy (HRT) Cycle (PROMICOFET)
A Phase 4 study testing Oestrogel® 0.75 mg (estradiol transdermal gel), Progesterone 200 mg vaginal capsules and Endometrial biopsy in people with Fertility and Implantation, Embryo, run by University Hospital, Ghent at 1 site in Belgium.
Trial summary
This study looks at progesterone, a hormone that prepares the womb lining (endometrium) for pregnancy, in women having a frozen embryo transfer after IVF. Before an embryo is transferred, women take estrogen and progesterone medication to prepare the endometrium. Read more about this study
- Who is it for?
- Ages 18 to 40 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Fertility, Implantation, Embryo
- What is being tested?
- Oestrogel® 0.75 mg (estradiol transdermal gel), Progesterone 200 mg vaginal capsules and Endometrial biopsy
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- 1 siteBelgium
- Study dates
- Oct 2026to 31 Aug 2029
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
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
- Healthy volunteers accepted
- Adult
Who may be able to join
- Age ≥18 and ≤40 years old.
- BMI ≥ 18 kg/m² and < 35 kg/m².
- Current pregnancy wish.
- PGT-A tested patients, undergoing a euploid blastocyst transfer in an artificial cycle.
- Dutch, French and/or English speakers, as informed consent forms (ICFs) are made in those three languages.
Who cannot join
- Known reasons for impaired implantation (specifically: presence of a hydrosalpinx; presence of a type I, II or III fibroid; Asherman's syndrome; uterine malformations; intrauterine adhesions; ≥ grade 3 endometriosis according to the ASRM classification, endometrial tuberculosis, adenomyosis).
- Abnormal (not menstrual) vaginal bleeding without a known/diagnosed cause.
- Tumours of the ovary, breast, uterus, pituitary or hypothalamus.
- Untreated and uncontrolled thyroid dysfunction.
- Personal history of a thromboembolic event.
- Use of carbamazepine, rifampicin, phenytoin.
- Subjects unable to comprehend the investigational nature of the proposed study.
- Patients with a history of known thin endometrium (< 5 mm).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Belgium1 site
Ghent University Hospital
Ghent, 9000
Paula Iglesias Moreno, MSc, 93325631 ext. +32, paula.iglesiasmoreno@ugent.be
Kathleen Wijnant, PhD, 93324903 ext. +32, arg.studies@uzgent.be
About this study
This study looks at progesterone, a hormone that prepares the womb lining (endometrium) for pregnancy, in women having a frozen embryo transfer after IVF. Before an embryo is transferred, women take estrogen and progesterone medication to prepare the endometrium. Doctors currently check progesterone levels in the blood, but blood levels do not always match what is happening in the endometrium itself, and it is not yet known whether progesterone levels in the womb tissue stay the same from one treatment cycle to the next.
The study also looks at whether hormone levels relate to how the uterus contracts, to the bacteria naturally present in the vagina, cervix, uterus and gut, and to tiny particles released by cells (called extracellular vesicles) that may help the embryo and the womb "communicate" during implantation.
Read more
Participants are women who are already waiting for genetic test results on their embryos, a wait that typically lasts around 8 weeks. During this time, they go through two practice ("mock") treatment cycles using the same hormone medications as a real embryo transfer, but without an actual embryo. During these cycles, researchers collect blood and urine samples, a small tissue sample from the womb lining, swabs from the vagina, cervix and rectum, and a short ultrasound recording of womb movement. Afterwards, participants proceed with their real embryo transfer cycle, with similar (though fewer) measurements taken, and are followed to see whether they become pregnant.
The findings from this study may help doctors better understand how to personalize hormone treatment for future frozen embryo transfers, with the aim of improving pregnancy outcomes.
Read the detailed description
This is a prospective, single-center pilot study conducted at the Department of Reproductive Medicine, Ghent University Hospital, in women undergoing preimplantation genetic testing for aneuploidy (PGT-A) prior to euploid blastocyst transfer in a hormone replacement therapy (HRT)-prepared frozen embryo transfer (FET) cycle. The pilot design was chosen because data on the interaction between endometrial and serum hormonal levels, the reproductive tract and fecal microbiome, uterine peristalsis, and embryo- and maternal-derived extracellular vesicles (EVs) in this setting are currently limited.
Each subject undergoes two mock HRT cycles during the approximately 8-week PGT-A waiting period, followed by one embryo transfer cycle. Endometrial preparation in each cycle consists of transdermal estradiol gel (Oestrogel®) until adequate endometrial thickness is reached, followed by vaginal micronized progesterone (Utrogestan®, 800 mg/day) for 6.5 days. In the mock cycles, no embryo is transferred; instead, study-specific procedures are performed, including endometrial biopsy for tissue hormonal quantification by UPLC-MS/MS, a mock embryo transfer with catheter tip collection for endometrial microbiome analysis, transvaginal ultrasound with speckle-tracking analysis of the uterine junctional zone to characterize contraction frequency, amplitude, and velocity before, during and after the procedure, and collection of vaginal, cervical and rectal swabs, urine, and blood for hormonal and extracellular vesicle profiling. The embryo transfer cycle follows the same sampling scheme (excluding endometrial biopsy) around an actual euploid blastocyst transfer performed under standard of care. Follicular fluid at oocyte pick-up and embryo culture media (collected on days 3 and 6 of embryo culture) are additionally retained for extracellular vesicle analysis, material that would otherwise be discarded during routine IVF laboratory processing.
Beyond the primary focus on intercycle reproducibility of endometrial tissue progesterone, the study explores associations between hormonal levels, uterine contractility, reproductive-tract and fecal microbiome composition, and extracellular vesicle cargo, with the broader aim of identifying candidate biomarkers of endometrial receptivity to inform future optimization of luteal phase support.
Given the established safety profile of the authorized study medications (Utrogestan® and Oestrogel®), adverse event and serious adverse event collection is selective, focused on events not attributable to standard-of-care fertility procedures; a Data Safety Monitoring Board was not deemed necessary.
- Conditions
- Fertility, Implantation, Embryo
- Being tested
- Oestrogel® 0.75 mg (estradiol transdermal gel), Progesterone 200 mg vaginal capsules, Endometrial biopsy, Mock embryo transfer, Transvaginal ultrasound with uterine peristalsis assessment
- Keywords
- progesterone, extracellular vesicles, embryo implantation, microbiome, female tract microbiome, uterine peristalsis, cycle-to-cycle variability, FET, HRT cycle
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oestrogel® 0.75 mg (estradiol transdermal gel)Drug
Also called estradiol, estradiol gel, transdermal oestradiol, oestrogel
Oestradiol gel for endometrial preparation. Two pumps need to be administered in the morning (between 6 and 8 am) and two pumps in the evening (between 6 and 8 pm). In total, 3mg of estradiol per day.
Progesterone 200 mg vaginal capsulesDrug
Also called utrogestan, progesterone
Utrogestan®, 800 mg/day (in 200mg capsules) for 6.5 days
Endometrial biopsyProcedure or surgery
Also called endometrial sample, endometrial tissue, uterine lining biopsy
Pipelle-based endometrial tissue sampling performed during each of the two mock HRT cycles (not during the actual transfer cycle), for determination of tissue progesterone, estradiol (and where sufficient tissue remains, estrone and 17-OHP) by UPLC-MS/MS, and for derivation of organoids/cells for in vitro assays.
Mock embryo transferProcedure or surgery
Also called fake embryo transfer, practice embryo transfer
Catheter placement performed identically to a real embryo transfer but without loading an embryo, conducted during each mock cycle. The catheter tip is collected (rather than discarded) for endometrial microbiome analysis.
Transvaginal ultrasound with uterine peristalsis assessmentProcedure or surgery
Also called uterine waves, uterine peristalsis, vaginal ultrasound
Standardized 4-minute transvaginal ultrasound recordings performed before, during and after the (mock) embryo transfer in each of the three cycles, using speckle-tracking analysis of the junctional zone to quantify uterine contraction frequency, amplitude, velocity, coordination and direction.
Biological sample collection (blood, urine, vaginal/cervical/rectal swabs, follicular fluid, embryo culture media)Procedure or surgery
Also called blood sample, blood, urine, urine sample
Study-specific collection of: blood samples for hormonal profiling (estradiol, estrone, progesterone, 17α-hydroxyprogesterone) and extracellular vesicle (EV) analysis; urine samples for EV isolation; vaginal, cervical, and rectal swabs for microbiome analysis; follicular fluid collected at oocyte pick-up (otherwise discarded in routine care); and embryo culture media collected on days 3 and 6 of culture - all for EV composition and cargo analysis.
Embryo transfer catheter tip collection for bacterial DNA analysisProcedure or surgery
Also called embryo transfer catheter tip collection, ET catheter collection
Collection of catheter tips following embryo transfer (study cycle) and, separately, from 30 routine clinical embryo transfers in non-enrolled patients, for protocol optimization of bacterial DNA extraction and endometrial microbiome analysis.
Questionnaires and pain assessment (VAS)Other
Also called questionnaire, questions, vas score, pain assessment
Patient-completed questionnaires on dietary habits and lifestyle (to support microbiome data interpretation) and a Visual Analogue Scale (VAS) pain-scoring questionnaire completed at the time of each (mock) embryo transfer.
| Study group | Role | What they receive |
|---|---|---|
| HRT-Prepared FET with Endometrial and Biofluid Sampling | Experimental | All enrolled participants undergo HRT endometrial preparation - transdermal estradiol gel (Oestrogel®) followed by vaginal micronized progesterone (Utrogestan®, 800 mg/day for 6.5 days) - across three consecutive artificial cycles: two mock cycles and one embryo transfer cycle, conducted during the standard-of-care waiting period for PGT-A results.
In each mock cycle, participants undergo: endometrial biopsy, a mock embryo transfer (with catheter tip collection for microbiome analysis), transvaginal ultrasound (uterine peristalsis), and collection of vaginal, cervical and rectal swabs, urine, and blood samples for hormonal profiling and extracellular vesicle analysis.
In the embryo transfer cycle, an actual euploid blastocyst is transferred under standard clinical care, with the same non-invasive study-specific sampling performed (excluding endometrial biopsy). Participants are followed for pregnancy outcomes. Receives: Drug: Oestrogel® 0.75 mg (estradiol transdermal gel); Drug: Progesterone 200 mg vaginal capsules; Procedure: Endometrial biopsy; Procedure: Mock embryo transfer; Procedure: Transvaginal ultrasound with uterine peristalsis assessment; Procedure: Biological sample collection (blood, urine, vaginal/cervical/rectal swabs, follicular fluid, embryo culture media); Procedure: Embryo transfer catheter tip collection for bacterial DNA analysis; Other: Questionnaires and pain assessment (VAS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Endometrial hormonal concentrations
Endometrial biopsies will be taken in mock embryo transfer cycles 1 and 2, on the day of mock transfer (day 6 after progesterone administration). This tissue will be sent to the clinical biology department in the hospital UZ Gent, to perform UPLC-MS/MS and obtain the concentration of progesterone, estradiol, estrone, 17α-hydroxyprogesterone in the tissue. This will later be correlated with the other outcome measurements: hormonal levels in blood, microbiome composition, uterine peristalsis, EV composition, etc. The concentrations will be obtained in ng/ml or μg/ml.
Measured: For an individual patient: mock embryo transfer cycles 1 and 2. Approximately 8 weeks. For the whole study: through the study completion, approximately 2 years since start of recruitment.
Secondary outcomes (14)
Hormonal levels in blood
Analysis of progesterone, oestradiol, oestrone and 17-alphahydroxyprogesterone concentration in blood and correlation with endometrial levels.
Measured: From OPU (oocyte pick-up day) until pregnancy follow-up visit (between 6 and 8 weeks of gestation)
Microbiome composition
Microbiome composition in the vagina, cervix, uterus and rectum; via swabs and embryo transfer catherter tip. The samples will be collected on the day of (mock) embryo transfer through the three identically prepared HRT cycles.
Measured: On the day of (mock) embryo transfer through the three identically prepared HRT cycles. Approximately 3 months per patient.
Clinical pregnancy outcomes: biochemical pregnancy
Clinical pregnancy outcomes will be measured with percentage of patients that reach:
- Biochemical pregnancy: if no gestational sac was seen in the ultrasound during the follow-up pregnancy visit (6-8 weeks of gestation), but there is a positive blood or urine test measuring human chorionic gonadotropin (hCG).
Measured: Follow-up pregnancy visit (6-8 weeks of gestation)
Clinical pregnancy outcomes: live birth
Clinical pregnancy outcomes will be measured with percentage of patients that reach:
- Live Birth Rate: The delivery of a live infant after 24 to 28 weeks of gestation, considered the gold-standard endpoint in fertility trials.
Measured: Follow-up pregnancy (6-8 weeks of gestation) until live birth (up to approximately 40 weeks after embryo transfer)
Clinical pregnancy outcome: miscarriage
Clinical pregnancy outcomes will be measured with percentage of patients that reach:
- Miscarriage Rate: The spontaneous loss of a verified clinical pregnancy before 22 completed weeks of gestational age
Measured: From the follow-up pregnancy (6-8 weeks of gestation) visit until miscarriage happens (before 22 completed weeks of gestational age).
Clinical pregnancy outcome: clinical pregnancy
Clinical pregnancy outcomes will be measured with percentage of patients that reach:
- Clinical Pregnancy: Confirmed by ultrasound at 6-8 weeks showing a heartbeat or gestational sac, distinguishing it from a purely chemical (biochemical) pregnancy detected only by blood or urine hormone tests.
Measured: Follow-up pregnancy visit (6-8 weeks of gestation)
Questionnaire about lifestyle and dietary habits for better analysis of microbiome composition
This questionnaire mostly has questions that can be answered with YES/NO, being the remaining questions a multiple choice questions, or a fill in question (mostly if they check "yes" and we need more information, for example if they said they used antibiotics in the last 30 days, to ask which product, dose and duration of the treatment, and until when). The data will be expressed as percentage of patients answering "yes", or percentage of patients selecting each option (in multiple choice questions).
Measured: On the day of (mock) embryo transfer through the three identically prepared HRT cycles. Approximately 3 months per patient.
Visual Analogue Scale (VAS) for (mock) embryo transfer
Visual Analogue Scale (VAS) for pain assessment during (mock) embryo transfer procedures. The VAS score goes from 0 to 10, being 0 no pain, and being 10 the worst pain.
Measured: On the day of (mock) embryo transfer through the three identically prepared HRT cycles. Approximately 3 months per patient.
Uterine waves/peristalsis analysis - contraction coordination
One of the uterine waves parameters we will obtain is the contraction coordination, which represents if anterior and posterior walls move synchronously or asynchronously to each other. A higher value shows decreased coordination. It does not have units but it is expressed in mean squared error. This will be assessed before, during and after embryo transfer by 4-minute TVUS video recording.
Measured: On the day of (mock) embryo transfer through the three identically prepared HRT cycles. Approximately 3 months per patient.
Uterine waves/peristalsis analysis - contraction velocity
One of the uterine waves parameters we will obtain is the contraction velocity, which analyses at which speed do the waves propagate in a certain direction (F2C or C2F). This is obtained by first analysing the radial strain signal in the spatiotemporal frequency domain (20 seconds) and then averaging the velocities over time in the corresponding direction (C2F or F2C). A high value represents increased velocity in that direction. It is expressed in mm/s.
This will be assessed before, during and after embryo transfer by 4-minute TVUS video recording.
Measured: On the day of (mock) embryo transfer through the three identically prepared HRT cycles. Approximately 3 months per patient.
Uterine waves/peristalsis analysis - contraction direction
One of the uterine waves parameters we will obtain is the contraction direction, which explains whether the wave propagates fondus to cervix (F2C) or cervix to fondus (C2F). It has no units. Positive value is F2C, negative value is C2F and a value of 0 is a movement without predominant direction (opposing contractions). This will be assessed before, during and after embryo transfer by 4-minute TVUS video recording.
Measured: On the day of (mock) embryo transfer through the three identically prepared HRT cycles. Approximately 3 months per patient.
Uterine waves/peristalsis analysis - contraction amplitude
One of the uterine waves parameters we will obtain is the contraction amplitude, which reflects the strength of uterine contraction. It is obtained by calculating SD of the strain signal in the longitudinal and radial directions from its frequency spectrum. It has no units. This will be assessed before, during and after embryo transfer by 4-minute TVUS video recording.
Measured: On the day of (mock) embryo transfer through the three identically prepared HRT cycles. Approximately 3 months per patient.
Uterine waves/peristalsis analysis - contraction frequency
One of the uterine waves parameters we will obtain is the contraction frequency, which is the amount of contractions per minute (unit of measurement contractions/minute). This will be assessed before, during and after embryo transfer by 4-minute TVUS video recording.
Measured: On the day of (mock) embryo transfer through the three identically prepared HRT cycles. Approximately 3 months per patient.
EVs composition in blood, follicular fluid and urine (maternal), and embryo culture media
EVs cargo and composition analysis and RNA sequencing
Measured: From OPU (oocyte pick-up day) until pregnancy follow-up (between 6 and 8 weeks of gestation)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2026
- Study startOct 2026 (estimated)
- Primary completion31 Aug 2029 (estimated)
- Study completion31 Aug 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for FertilityStudies of the same condition, open and under way.
- More trials run by University Hospital, GhentThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Identical hormone replacement therapy (HRT) cycles: endometrial preparation with transdermal estradiol gel (Oestrogel®, 3 mg/day), followed by vaginal micronized progesterone (Utrogestan®, 800 mg/day for 6.5 days)
- Masking
- None (open label)
- Enrolment
- 70 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Ghent
- Sponsor type
- University, hospital or other
- Collaborators
- Besins Healthcare
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07818278
- Sponsor's protocol ID
- ONZ-2023-0403
- Other IDs
- B6702024000267
- Acronym
- PROMICOFET
- Status last verified
- Sep 2026
- First submitted
- 24 Aug 2026
- Last updated
- 14 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cycle-to-cycle Variability of Progesterone in the Endometrium in Patients Undergoing an Euploid Blastocyst Transfer in a Hormone Replacement Therapy (HRT) Cycle (PROMICOFET)
- ClinicalTrials.gov ID
- NCT07818278
- Acronym / sponsor ID
- PROMICOFET / ONZ-2023-0403
- Conditions
- Fertility, Implantation, Embryo
- Keywords
- progesterone, extracellular vesicles, embryo implantation, microbiome, female tract microbiome, uterine peristalsis, cycle-to-cycle variability, FET
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 70 participants (estimated)
- Lead sponsor
- University Hospital, GhentUniversity, hospital or other
- Collaborators
- Besins Healthcare
- Study start
- Oct 2026 (estimated)
- Primary completion
- 31 Aug 2029 (estimated)
- Study completion
- 31 Aug 2029 (estimated)
- First posted
- 14 Sep 2026 (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.
This study looks at progesterone, a hormone that prepares the womb lining (endometrium) for pregnancy, in women having a frozen embryo transfer after IVF. Before an embryo is transferred, women take estrogen and progesterone medication to prepare the endometrium. Doctors currently check progesterone levels in the blood, but blood levels do not always match what is happening in the endometrium itself, and it is not yet known whether progesterone levels in the womb tissue stay the same from one treatment cycle to the next.
The study also looks at whether hormone levels relate to how the uterus contracts, to the bacteria naturally present in the vagina, cervix, uterus and gut, and to tiny particles released by cells (called extracellular vesicles) that may help the embryo and the womb "communicate" during implantation.
Participants are women who are already waiting for genetic test results on their embryos, a wait that typically lasts around 8 weeks. During this time, they go through two practice ("mock") treatment cycles using the same hormone medications as a real embryo transfer, but without an actual embryo. During these cycles, researchers collect blood and urine samples, a small tissue sample from the womb lining, swabs from the vagina, cervix and rectum, and a short ultrasound recording of womb movement. Afterwards, participants proceed with their real embryo transfer cycle, with similar (though fewer) measurements taken, and are followed to see whether they become pregnant.
The findings from this study may help doctors better understand how to personalize hormone treatment for future frozen embryo transfers, with the aim of improving pregnancy outcomes.
Detailed description
This is a prospective, single-center pilot study conducted at the Department of Reproductive Medicine, Ghent University Hospital, in women undergoing preimplantation genetic testing for aneuploidy (PGT-A) prior to euploid blastocyst transfer in a hormone replacement therapy (HRT)-prepared frozen embryo transfer (FET) cycle. The pilot design was chosen because data on the interaction between endometrial and serum hormonal levels, the reproductive tract and fecal microbiome, uterine peristalsis, and embryo- and maternal-derived extracellular vesicles (EVs) in this setting are currently limited.
Each subject undergoes two mock HRT cycles during the approximately 8-week PGT-A waiting period, followed by one embryo transfer cycle. Endometrial preparation in each cycle consists of transdermal estradiol gel (Oestrogel®) until adequate endometrial thickness is reached, followed by vaginal micronized progesterone (Utrogestan®, 800 mg/day) for 6.5 days. In the mock cycles, no embryo is transferred; instead, study-specific procedures are performed, including endometrial biopsy for tissue hormonal quantification by UPLC-MS/MS, a mock embryo transfer with catheter tip collection for endometrial microbiome analysis, transvaginal ultrasound with speckle-tracking analysis of the uterine junctional zone to characterize contraction frequency, amplitude, and velocity before, during and after the procedure, and collection of vaginal, cervical and rectal swabs, urine, and blood for hormonal and extracellular vesicle profiling. The embryo transfer cycle follows the same sampling scheme (excluding endometrial biopsy) around an actual euploid blastocyst transfer performed under standard of care. Follicular fluid at oocyte pick-up and embryo culture media (collected on days 3 and 6 of embryo culture) are additionally retained for extracellular vesicle analysis, material that would otherwise be discarded during routine IVF laboratory processing.
Beyond the primary focus on intercycle reproducibility of endometrial tissue progesterone, the study explores associations between hormonal levels, uterine contractility, reproductive-tract and fecal microbiome composition, and extracellular vesicle cargo, with the broader aim of identifying candidate biomarkers of endometrial receptivity to inform future optimization of luteal phase support.
Given the established safety profile of the authorized study medications (Utrogestan® and Oestrogel®), adverse event and serious adverse event collection is selective, focused on events not attributable to standard-of-care fertility procedures; a Data Safety Monitoring Board was not deemed necessary.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Identical hormone replacement therapy (HRT) cycles: endometrial preparation with transdermal estradiol gel (Oestrogel®, 3 mg/day), followed by vaginal micronized progesterone (Utrogestan®, 800 mg/day for 6.5 days)
| Arm | Type | Receives |
|---|---|---|
| HRT-Prepared FET with Endometrial and Biofluid Sampling | Experimental | Drug: Oestrogel® 0.75 mg (estradiol transdermal gel), Drug: Progesterone 200 mg vaginal capsules, Procedure: Endometrial biopsy, Procedure: Mock embryo transfer, Procedure: Transvaginal ultrasound with uterine peristalsis assessment, Procedure: Biological sample collection (blood, urine, vaginal/cervical/rectal swabs, follicular fluid, embryo culture media), Procedure: Embryo transfer catheter tip collection for bacterial DNA analysis, Other: Questionnaires and pain assessment (VAS)All enrolled participants undergo HRT endometrial preparation - transdermal estradiol gel (Oestrogel®) followed by vaginal micronized progesterone (Utrogestan®, 800 mg/day for 6.5 days) - across three consecutive artificial cycles: two mock cycles and one embryo transfer cycle, conducted during the standard-of-care waiting period for PGT-A results. In each mock cycle, participants undergo: endometrial biopsy, a mock embryo transfer (with catheter tip collection for microbiome analysis), transvaginal ultrasound (uterine peristalsis), and collection of vaginal, cervical and rectal swabs, urine, and blood samples for hormonal profiling and extracellular vesicle analysis. In the embryo transfer cycle, an actual euploid blastocyst is transferred under standard clinical care, with the same non-invasive study-specific sampling performed (excluding endometrial biopsy). Participants are followed for pregnancy outcomes. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Age ≥18 and ≤40 years old.
- BMI ≥ 18 kg/m² and < 35 kg/m².
- Current pregnancy wish.
- PGT-A tested patients, undergoing a euploid blastocyst transfer in an artificial cycle.
- Dutch, French and/or English speakers, as informed consent forms (ICFs) are made in those three languages.
Key exclusion criteria (8 listed)
- Known reasons for impaired implantation (specifically: presence of a hydrosalpinx; presence of a type I, II or III fibroid; Asherman's syndrome; uterine malformations; intrauterine adhesions; ≥ grade 3 endometriosis according to the ASRM classification, endometrial tuberculosis, adenomyosis).
- Abnormal (not menstrual) vaginal bleeding without a known/diagnosed cause.
- Tumours of the ovary, breast, uterus, pituitary or hypothalamus.
- Untreated and uncontrolled thyroid dysfunction.
- Personal history of a thromboembolic event.
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 |
|---|---|---|
| Oestrogel® 0.75 mg (estradiol transdermal gel)Also: estradiol, estradiol gel, transdermal oestradiol, oestrogelOestradiol gel for endometrial preparation. Two pumps need to be administered in the morning (between 6 and 8 am) and two pumps in the evening (between 6 and 8 pm). In total, 3mg of estradiol per day. | Drug | HRT-Prepared FET with Endometrial and Biofluid Sampling |
| Progesterone 200 mg vaginal capsulesAlso: utrogestan, progesteroneUtrogestan®, 800 mg/day (in 200mg capsules) for 6.5 days | Drug | HRT-Prepared FET with Endometrial and Biofluid Sampling |
| Endometrial biopsyAlso: endometrial sample, endometrial tissue, uterine lining biopsyPipelle-based endometrial tissue sampling performed during each of the two mock HRT cycles (not during the actual transfer cycle), for determination of tissue progesterone, estradiol (and where sufficient tissue remains, estrone and 17-OHP) by UPLC-MS/MS, and for derivation of organoids/cells for in vitro assays. | Procedure or surgery | HRT-Prepared FET with Endometrial and Biofluid Sampling |
| Mock embryo transferAlso: fake embryo transfer, practice embryo transferCatheter placement performed identically to a real embryo transfer but without loading an embryo, conducted during each mock cycle. The catheter tip is collected (rather than discarded) for endometrial microbiome analysis. | Procedure or surgery | HRT-Prepared FET with Endometrial and Biofluid Sampling |
| Transvaginal ultrasound with uterine peristalsis assessmentAlso: uterine waves, uterine peristalsis, vaginal ultrasoundStandardized 4-minute transvaginal ultrasound recordings performed before, during and after the (mock) embryo transfer in each of the three cycles, using speckle-tracking analysis of the junctional zone to quantify uterine contraction frequency, amplitude, velocity, coordination and direction. | Procedure or surgery | HRT-Prepared FET with Endometrial and Biofluid Sampling |
| Biological sample collection (blood, urine, vaginal/cervical/rectal swabs, follicular fluid, embryo culture media)Also: blood sample, blood, urine, urine sampleStudy-specific collection of: blood samples for hormonal profiling (estradiol, estrone, progesterone, 17α-hydroxyprogesterone) and extracellular vesicle (EV) analysis; urine samples for EV isolation; vaginal, cervical, and rectal swabs for microbiome analysis; follicular fluid collected at oocyte pick-up (otherwise discarded in routine care); and embryo culture media collected on days 3 and 6 of culture - all for EV composition and cargo analysis. | Procedure or surgery | HRT-Prepared FET with Endometrial and Biofluid Sampling |
| Embryo transfer catheter tip collection for bacterial DNA analysisAlso: embryo transfer catheter tip collection, ET catheter collectionCollection of catheter tips following embryo transfer (study cycle) and, separately, from 30 routine clinical embryo transfers in non-enrolled patients, for protocol optimization of bacterial DNA extraction and endometrial microbiome analysis. | Procedure or surgery | HRT-Prepared FET with Endometrial and Biofluid Sampling |
| Questionnaires and pain assessment (VAS)Also: questionnaire, questions, vas score, pain assessmentPatient-completed questionnaires on dietary habits and lifestyle (to support microbiome data interpretation) and a Visual Analogue Scale (VAS) pain-scoring questionnaire completed at the time of each (mock) embryo transfer. | Other | HRT-Prepared FET with Endometrial and Biofluid Sampling |
Primary outcome
Endometrial hormonal concentrations
Time frame: For an individual patient: mock embryo transfer cycles 1 and 2. Approximately 8 weeks. For the whole study: through the study completion, approximately 2 years since start of recruitment.
Endometrial biopsies will be taken in mock embryo transfer cycles 1 and 2, on the day of mock transfer (day 6 after progesterone administration). This tissue will be sent to the clinical biology department in the hospital UZ Gent, to perform UPLC-MS/MS and obtain the concentration of progesterone, estradiol, estrone, 17α-hydroxyprogesterone in the tissue. This will later be correlated with the other outcome measurements: hormonal levels in blood, microbiome composition, uterine peristalsis, EV composition, etc. The concentrations will be obtained in ng/ml or μg/ml.
14 secondary outcomes
Hormonal levels in blood
Time frame: From OPU (oocyte pick-up day) until pregnancy follow-up visit (between 6 and 8 weeks of gestation)
Microbiome composition
Time frame: On the day of (mock) embryo transfer through the three identically prepared HRT cycles. Approximately 3 months per patient.
Clinical pregnancy outcomes: biochemical pregnancy
Time frame: Follow-up pregnancy visit (6-8 weeks of gestation)
Clinical pregnancy outcomes: live birth
Time frame: Follow-up pregnancy (6-8 weeks of gestation) until live birth (up to approximately 40 weeks after embryo transfer)
Clinical pregnancy outcome: miscarriage
Time frame: From the follow-up pregnancy (6-8 weeks of gestation) visit until miscarriage happens (before 22 completed weeks of gestational age).
Clinical pregnancy outcome: clinical pregnancy
Time frame: Follow-up pregnancy visit (6-8 weeks of gestation)
Questionnaire about lifestyle and dietary habits for better analysis of microbiome composition
Time frame: On the day of (mock) embryo transfer through the three identically prepared HRT cycles. Approximately 3 months per patient.
Visual Analogue Scale (VAS) for (mock) embryo transfer
Time frame: On the day of (mock) embryo transfer through the three identically prepared HRT cycles. Approximately 3 months per patient.
Uterine waves/peristalsis analysis - contraction coordination
Time frame: On the day of (mock) embryo transfer through the three identically prepared HRT cycles. Approximately 3 months per patient.
Uterine waves/peristalsis analysis - contraction velocity
Time frame: On the day of (mock) embryo transfer through the three identically prepared HRT cycles. Approximately 3 months per patient.
Uterine waves/peristalsis analysis - contraction direction
Time frame: On the day of (mock) embryo transfer through the three identically prepared HRT cycles. Approximately 3 months per patient.
Uterine waves/peristalsis analysis - contraction amplitude
Time frame: On the day of (mock) embryo transfer through the three identically prepared HRT cycles. Approximately 3 months per patient.
Uterine waves/peristalsis analysis - contraction frequency
Time frame: On the day of (mock) embryo transfer through the three identically prepared HRT cycles. Approximately 3 months per patient.
EVs composition in blood, follicular fluid and urine (maternal), and embryo culture media
Time frame: From OPU (oocyte pick-up day) until pregnancy follow-up (between 6 and 8 weeks of gestation)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Sep 2026.
- Individual participant dataSharing planned: No
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Oestrogel® 0.75 mg (estradiol transdermal gel), Progesterone 200 mg vaginal capsules and Endometrial biopsy in people with Fertility and Implantation, Embryo, run by University Hospital, Ghent 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 5 inclusion and 8 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: opening soon, as of the sponsor's last update on 14 Sep 2026. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Dominic Stoop, Prof. dr. (93321699 ext. +32, arg.studies@uzgent.be), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Endometrial hormonal concentrations (time frame: For an individual patient: mock embryo transfer cycles 1 and 2. Approximately 8 weeks. For the whole study: through the study completion, approximately 2 years since start of recruitment.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 14 Sep 2026.