P-130 Progesterone-primed cycles result in slower embryos without compromising the implantation potential, with the advantage of oral administration and potential cost reduction: A time-lapse imaging study
Authors: Carrilho E , Braga D , Setti A , Guilherme P , Iaconelli Junior A , Borges Junior E 
Published: June 2023

Abstract

Study question
Could exogenous progestin replace the use of an antagonist of GnRH (GNRH-antagonist) without any effects on embryo morphokinetics and implantation rate in freeze-all cycles?

Summary answer
Exogenous progestin leads to slower embryo development and increased cyclés cancellation rate, with increased implantation rate when compared to cycles using an GnRH-antagonist.

What is known already
Improvements in cryopreservation techniques associated with the expansion of elective-single embryo transfer have steadily increased the use of deferred embryo transfers. This gives the opportunity to break away from the standard sequence of stimulation–retrieval–transfer, and to consider new strategies for pharmacological control of follicle growth. Usual ovarian stimulation regimens use an analog of the GnRH to prevent the LH surge and premature ovulation. Since progesterone is able to block the LH surge question remains on whether exogenous progesterone may replace the use of an GnRH analogue without compromising embryo development, in cycles followed by embryo cryopreservation.

Study design, size, duration
This cohort study, performed in a private university-affiliated IVF center, from Mar/2019 - Mar/2021, included 288 freeze-all ICSI cycles and its 2,768 respective embryos. Patients were age matched, according to the age, into groups depending on the protocol used to prevent the LH surge: Progestin-Primed-Group (n = 144 cycles and 1,360 embryos) and GnRH-Antagonist-Group (n = 144 cycles and 1,408 embryos). Embryos were cultured in a time-lapse imaging incubation system (TLI) and embryo morphokinetics were compared among the groups

Participants/materials, setting, methods
Evaluated kinetic markers were timing to pronuclei appearance (tPNa) and fading (tPNf), to two, three, four, five, six, seven, and eight cells (t2 - t8), to morulation (tM), start of blastulation (tSB) and blastulation (tB). Durations of the second (t3-t2) and third (t5-t3) cell cycles (cc2 and cc3) and timing to complete synchronous divisions s1 (t2-tPNf), s2 (t4-t3), and s3 (t8-t5) were also calculated. The KID-Score ranking, laboratorial and clinical outcomes were also evaluated.

Main results and the role of chance
Mean maternal and paternal ages were 37.0 ± 3.8 and 39.0 ± 6.4 years old. Slower tPNa (6.2 ± 0.2 vs. 7.0 ± 0.2, p = 0.008), t2 (27.2 ± 0.3 vs. 26.2 ± 0.3, p = 0.045), t7 (56.4 ± vs. 54.7 ± 0.5, p = 0.046), tM (89.3 ± 0.8 vs. 87.1 ± 0.6, p = 0.045), tSB (101.5 ± 0.8 vs. 110.8 ± 0.1, p = 0.012), tB (111.0 ± 0.8 vs. 108.5 ± 0.7, p = 0.034), were observed among embryos derived from Progestin-Primed cycles. Similar tPNf, t3, t4, t5, t6, t8, timing to cc2, cc3, s1, s2, and s3 were observed among the groups. No significant differences were noted in the Kid-score D5, number of aspirated follicles, retrieved oocytes, oocyte yield, mature oocytes, and rates of mature oocytes, fertilization, and blastocyst formation. The cyclés cancelation (15.7% vs. 2.0%, p = 0.004) and implantation rates (63.1% ± 6.1 vs. 44.4% ± 6.3, p = 0.004) were increased in the Progestin-Primed-Group, however no significant differences were noted in the cumulative pregnancy (64.4% vs. 49.0%, p = 0.104) and miscarriage rate (2.6% vs. 8.6%, p = 0.554) for Progestin-Primed and GnRH-Antagonist groups, respectively. The expense for the ovulation prevention using the GnRH-Antagonist was U$318.18, while by using progestins U$ 11.05 was sufficient to inhibit the premature LH surge.

Limitations, reasons for caution
This study has limitations, such as the retrospective design and small sample size.

Wider implications of the findings
Despite the increased implantation rate and potential cost reduction, the high cancellation rate and slower embryo development in the progestin-protocol cannot be ignored. Delayed embryo transfer due to the freeze-only approach may also be inconvenient. Before considering any protocols for LH surge prevention, pros and cons must be carefully evaluated.

Trial registration number
N/A