Multi-center, parallel-group, randomized controlled trial of modified natural versus programmed cycles for frozen embryo transfers and their association with preeclampsia and live births (NatPro)

The primary objective is to determine the proportion of preeclampsia in pregnant women assigned to a modified natural cycle FET (corpus luteum present) protocol compared to a programmed FET (corpus luteum absent) protocol. The secondary objective is to determine the cumulative proportion of live births in the modified natural cycle FET (corpus luteum present) compared to the programmed FET (corpus luteum absent).

Potential participant plans to undergo frozen embryo transfer with an embryo created with autologous oocytes with planned transfer to participant’s uterus. Planned embryo transfer with embryos created using donor oocytes, embryo transfer to a gestational carrier, embryos created using frozen oocytes, donor embryo cycles and reciprocal IVF cycles (one female partner carrying pregnancy, other female is source of eggs) are not eligible.

• At least one vitrified blastocyst of fair quality is available for transfer. If pre-implantation genetic testing was performed, at least one euploid embryo of any quality is available.

• Age 18-39 years at the time that embryos were created if no PGT testing was performed. If PGT testing was performed and indicates that an embryo is euploid, the patient can be included if she was age 18-41 years at the time that the embryo was created.

In addition: Inclusion: – Body mass index ≤ 40 – Uterine cavity screen normal within one year of enrollment – Menstrual cycle length usual approximately 24-35 days – Blood tests within past year if performed: Normal TSH and hemoglobin A1C (according to local standards)

Exclusion: – Medical contraindication to pregnancy – Recurrent implantation failure defined as no clinical pregnancy with ≥2 prior consecutive embryo transfers unless patient also had successful live birth between or after the failed embryo transfers Anti-phospholipid antibody syndrome or rheumatologic disease requiring chronic systemic medications – Uncontrolled diabetes mellitus – History of >1 pregnancy loss in the second or third trimester – Uncontrolled hypertension – Untreated hydrosalpinx – Contraindication to any medication which is required in preparation for a frozen embryo transfer (i.e., estradiol, progesterone, human chorionic gonadotropin (hCG))