P-417 Intravaginal progesterone dose and subcutaneous supplementation in luteal support protocols for frozen embryo transfers: a practical preliminary study
Authors: Mignini Renzini M.R , Brienza L , Gippone S , Brigante C , De Ponti E , Dal Canto M , Buratini J 
Published: June 2022

Abstract

Study question
Can the outcomes of frozen transfers be improved by increasing daily intravaginal progesterone dose from 600 to 800mg or by adding 25mg sc supplementation?

Summary answer
Yes, both modifications can increase post frozen embryo transfer outcomes, but supplementation with 25mg progesterone appears more effective.

What is known already
Recent studies indicate that luteal support should ideally be based on circulating progesterone levels, which are variable in artificial cycles (AC) for endometrial preparation. Since the comparative efficacy of AC in relation to natural or modified natural cycles is a controversial topic, the AC strategy is often chosen for frozen transfers due to its logistical convenience. In the face of the possible absence of a functional corpus luteum, the AC strategy usually utilizes fairly high progesterone support. However, no consensus has been achieved regarding the ideal progesterone support regimen.

Study design, size, duration
Retrospective study including 1547 patients younger than 40 years undergoing ICSI/IVF cycles reaching a frozen single blastocyst transfer (FSET) from January 2016 to October 2021. Patients were subjected to three different daily progesterone supplementation treatments, as decided by the gynecologist, aiming for endometrial preparation: A- 600mg intravaginally (iv; n = 847), B- 800mg iv (n = 242), and C- 600mg iv + 25mg subcutaneously (sc; n = 458). Patient profiles and FET outcomes were compared among these three treatment-groups.

Participants/materials, setting, methods
Patients received estradiol (6-8mg/day) from cycle day 2/3. Progesterone was started on the day after endometrial thickness was ≥7mm, and FET was performed six days later. Outcomes were compared using Fisher’s and Wilcoxon sum rank tests. Multivariate analysis was performed to assess the relationship between treatment and pregnancy achievement, controlling for potential interferences of age, BMI and endometriosis. Statistical differences were considered when p &lt; 0.05, while p values &gt;0.05 and ≤0.1 indicated a tendency of difference.

Main results and the role of chance
Patient age and BMI tended to differ among treatment groups. Mean maternal age was 33.9 ± 3.6, 33.4± 3.3 and 33.6 ± 3.4 (p = 0.06), and mean BMI was 22.1 ± 3.3, 22.5± 3.4 and 22.6 ± 3.5 (p = 0.06), for group-treatments A, B and C, respectively. The incidence of endometriosis did not vary among groups and was 6.1%, 7.4% and 8.1%, (p = 0.37), for group-treatments A, B and C, respectively. Clinical outcomes significantly varied among treatment groups. Implantation rates were 37.7%, 44.2% and 48.7%, (p &lt; 0.0001), and pregnancy rates were 38.6%, 45.0% and 49.6%, (p = 0.001), for group-treatments A, B and C, respectively. The multivariate analyses indicate that treatment C is associated with higher pregnancy achievement in relation to treatment A, independently of maternal age, BMI and endometriosis [OR = 1.56 (1.24-1.96); p &lt; 0.0001], while treatment B tends to favor pregnancy achievement in relation to treatment A [OR = 1.28 (0.96-1.71); p = 0.096]. No significant differences were observed when outcomes from treatments B and C were compared.

Limitations, reasons for caution
Our study is limited by its retrospective and preliminary nature. Larger sample size, particularly for treatment B, may be needed to determine its comparative efficacy. Our data must be interpreted with caution as treatment efficacy may vary among different clinics with different patient profiles.

Wider implications of the findings
Our findings suggest that, when progesterone levels to guide luteal support are unavailable, daily administration of 600mg progesterone iv combined with 25mg sc appears to provide optimal post-FET outcomes. Our data may serve as a valuable reference for the definition of the luteal support strategy accompanying FET.

Trial registration number
not applicable