P-330 Is 17 alpha hydroxyprogesterone caproate an adequate alternative to improve reproductive outcomes in artificially prepared frozen embryo transfer cycles (FET)?
Authors: Zappacosta Villarroel M P , Garcia Ojeda M B , Viglierchio M I , Young E , Isa L , Valcarcel A 
Published: June 2023

Abstract

Study question
Is 17 alpha-hydroxyprogesterone caproate an adequate option to improve reproductive outcomes in patients with low serum progesterone (P4) level the day of frozen embryo transfer?

Summary answer
Patients with serum P4&lt;10ng/ml may benefit with the addition of intramuscular 17alpha-hydroxyprogesterone caproate injections, and have similar ongoing pregnancy rates than patients with serum P4≥10ng/ml.

What is known already
Indications of embryo cryopreservation have expanded in the last years. Recently published papers highlight that low serum progesterone levels before frozen embryo transfers decrease pregnancy and live birth rates and increase miscarriage rates, even in cases of euploid embryos transfers. Other studies have published a beneficial effect with the addition of daily subcutaneous progesterone injections in patients with low serum progesterone levels around the time of embryo transfers. In Argentina subcutaneous progesterone has been available since October 2022, not before. 17alpha-hydroxyprogesterone caproate is a synthetic progestin used for luteal phase support and approved for the prevention of preterm birth.

Study design, size, duration
This prospective cohort study was performed between May 2021 and August 2022 in 114 patients undergoing 138 FET cycles after an artificial endometrial preparation with estradiol valerate 4mg daily and micronized vaginal progesterone 200mg, three times daily.

Participants/materials, setting, methods
Patients &lt;50 years old with triple-layer endometrium ≥7mm underwent frozen embryo transfer. Progesterone was measured immediately before the embryo transfer. Group 1 (N = 47): P4&gt;10ng/ml; Group 2 (N = 46): P4&lt;10ng/ml with addition of 17 alpha-hydroxyprogesterone caproate after embryo transfer; Group 3 (N = 46): P4&lt;10ng/ml without addition of 17 alpha-hydroxyprogesterone. Primary endpoint was to compare ongoing pregnancy rate beyond week 12 between the three groups. Secondary endpoints were pregnancy rate and miscarriage rate.

Main results and the role of chance
Parameters were comparable between the groups in terms of age, body mass index, estradiol, P4 levels at the beginning of endometrial preparation and number of embryos transferred. Ongoing pregnancy rate was: Group 1 = 38.3% (18/47); Group 2 = 39.1% (18/46); Group 3 = 28.3% (13/46) (p = 0,337). Pregnancy rate was: Group 1 = 48,9% (23/47); Group 2 = 50% (23/46); Group 3 = 50% (23/46) (p&gt;0,05). Miscarriage rate was: Group 1 = 21.73% (5/23), Group 2 = 26.1% (6/23) and Group 3 = 43.47% (10/23) (p =  0,208). Although there were no significant differences between the groups, both, Group 1 and Group 2, had higher ongoing pregnancy rates and lower miscarriage rates than group 3. This is probably due to the limited sample size.

Limitations, reasons for caution
The main limitation of our study is the sample size and the fact that most of the embryos were not genetically evaluated before being transferred, which would eliminate a variable that could interfere with the results obtained.
Only micronized progesterone and 17alpha-hydroxyprogesterone caproate were studied.

Wider implications of the findings
The addition of exogenous 17alpha-hydroxyprogesterone caproate on the embryo transfer day may improve ongoing pregnancy rates in cases of low serum progesterone levels, being a simple and safe strategy to individualize luteal phase support when no other form of progesterone administration is available.

Trial registration number
NOT APPLICABLE