Cycle-to-cycle Variability of Progesterone in the Endometrium in Patients Undergoing an Euploid Blastocyst Transfer in a Hormone Replacement Therapy (HRT) Cycle (PROMICOFET)

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.

Inclusion Criteria: * 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. Exclusion Criteria: * 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).