Elevated Progesterone Impacts Embryo Development During IVF

Introduction: Elevated progesterone (P4) levels during IVF leads to poor endometrial receptivity. Controversy exists as to whether it may also impact embryo development. Because of the lowered implantation rate, IVF cycles with elevated P4 levels often do not have fresh embryo transfers; the embryos are frozen with a subsequent frozen embryo transfer. If embryonic development is impacted, cryopreservation may not be the best strategy. This research utilized morphometric parameters to determine if elevated P4 has an impact on embryonic development during IVF. Methods: Retrospective cohort study of patients undergoing IVF with low P4 (LP) (< 1.0ng/mL) and high P4 (HP) (≥1.8ng/mL) on the day of hcg. Inclusion criteria included cycles performed at a university-based IVF center between 1/1/2016 and 9/1/2016. All embryos were cultured in a time-lapse incubator from fertilization to embryo transfer/freeze. Data included age, protocol type, amount of FSH used, # oocytes/mature oocytes retrieved, fertilization rate, # reaching blastocyst stage, and morphometric parameters including time to PN appearance/fade, time to 2-5 cell development. Statics included student's t-test and chi-square. Results: There were 105 patients in the LP group and 17 patients in the HP group. There were no differences in regard to age, type of stimulation, or total units of gonadotropin. HP patients had a greater level of estrogen on day of hCG trigger (1664 pg/mL vs 2483pg/mL, p=0.005) and a greater number of eggs retrieved (7.7 v 11.7, p=0.01). Although no difference was noted in time to PN appearance, the time from fertilization to 5-cell embryo was 43.6h in the LP group vs 36.7h in the HP group, p=0.04. Blastulation rates (defined as # blasts/#fertilized embryos) were significantly higher for the HP group (43.4% for LP vs 65.3%for HP, p < 0.001). Conclusions: Patients with high P4 had higher levels of estrogen and more eggs retrieved. Embryos from the HP group exhibited quicker development from fertilization through cleavage and were more likely to become blastocysts. Although aggressive stimulation protocols may impact the endometrium and lower rates of implantation during fresh IVF, our data suggest that there is no adverse impact on embryonic development. In fact, cycles with elevated P4 exhibited enhanced embryo development. Therefore, aggressive stimulation with FET may be an optimal IVF protocol. Further, these data may explain the improved pregnancy rate some authors report with frozen embryos transfer.