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.
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.
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.
Single group
Oestrogel® 0.75 mg (estradiol transdermal gel)
DrugOestradiol 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 capsules
DrugUtrogestan®, 800 mg/day (in 200mg capsules) for 6.5 days
Endometrial biopsy
Procedure/SurgeryPipelle-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 transfer
Procedure/SurgeryCatheter 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 assessment
Procedure/SurgeryStandardized 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/SurgeryStudy-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 analysis
Procedure/SurgeryCollection 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 interventionPatient-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.
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.
Hormonal levels in blood
Analysis of progesterone, oestradiol, oestrone and 17-alphahydroxyprogesterone concentration in blood and correlation with endometrial levels.
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.
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).
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.
Click on the lead sponsor to view all of their trials.
University Hospital, Ghent
Lead sponsor
Besins Healthcare
Collaborator
This trial is not recruiting at the moment. You can still explore other options:
