P-690 Time to bust some myths about progesterone supplementation in the luteal phase. Role of the route of administration and usefulness (or uselessness) of plasma determination
Authors: Barrenetxea Ziarrusta G , Celis García R , Martínez Sanz E , De Las Heras Martínez M , Gómez Picado O , Aguirre Landaluce O , Arambarri Beldarrain J.I , Da Silva Tabuyo A , Barrenetxea Arrinda J 
Published: June 2022

Abstract

Study question
Is it worth measuring plasma progesterone levels after FET?
Is there any difference in results depending on the route of progesterone administration?

Summary answer
The administration route of progesterone supplementation after FET entails different plasmatic levels (whose determination is useless) but without any correlation with ongoing pregnancy.

What is known already
Embryonic aneuploidy is likely to be the major contributor to human implantation failure, but not all failures are due to embryonic defects.
The need for progesterone supplementation in ART frozen-thawed cycles is well accepted. Several studies have demonstrated an increase in live birth rate with progesterone luteal support although there is a discussion on the association of Progesterone levels on day of embryo transfer and birth or pregnancy loss rates.
Moreover, although the effect of route of administration of progesterone on serum levels and pregnancy rates have been thoroughly studied, there is no consensus on the optimal endometrial preparation protocol.

Study design, size, duration
Prospective, randomized study performed during the 2020-21.
A total of 201 genetically screened blastocyst (after PGT-A) transfers were performed after endometrial preparation, performed with exogenous estrogen administration followed by progesterone administration before embryo transfer (ET) .
After embryo transfer, two different Progesterone regimens were randomly administered. Group I and Group II (see “Participants”)

Participants/materials, setting, methods
Group I patients (n = 100): 800 mg of micronized Progesterone was administered vaginally (Cyclogest® 1-0-1).
Group II patients (n = 101): vaginal administration of 400 mg of micronized progesterone was combined with the subcutaneous administration of 25 mg of Progesterone (Prolutex 25®)
Plasmatic progesterone (PP) levels on day of B-HCG determination (pregnancy test) (10 days after ET) and ultrasound confirmation of pregnancy (3 weeks after ET) were determined.
The relationship between progesterone levels and ongoing pregnancy rates was amalyzed.

Main results and the role of chance
The rate of positive pregnancy test among the 201 FET was 71,64%. The overall ongoing pregnancy was 58,71%.
PP on day of pregnancy test was 24,92±1,27 ng/ml (mean±SEM). The corresponding figures por positive (n = 144) and negative (n = 57) HCG were 27,65±1,09 and 20,33±2,13 respectively (t = 2,68; p = 0,008).
The PP levels on day of HCG determination were 23,12±1,48 among ongoing pregnancies whereas the levels among non-evolutive gestations were 48,78±3,55 (t = 7,19; p = 0,000).
PP levels were significantly higher among group II patients (combined treatment) both, on day of B-HCG determination (28,25±1,22 ng/ml) and on day of ultrasound confirmation of a gestational sac (33,61±2,39) than among group I patients (vaginal treatment) (15,12±1,60 and 19,77±1,50 ng/ml) (t = 0651, p = 0,000 and t = 5,38, p = 0,000 respectively). But these differences do not correlate with ongoing pregnancy rates: 59 out of 101 (58,42%) in group I patients and 59 out of 100 (59%) in group II patients.

Limitations, reasons for caution
Even though only euploid embryos have been transferred, ee must be cautious when drawing conclusions from the present study taking into account the limited number of cases evaluated.

Wider implications of the findings
Since only euploid embryos have been transferred in the present study, results in terms of successful ongoing pregnancies may be influenced by endometrial factors.
Although the need of progesterone supplementation among frozen-thawed cycles is accepted, some debate exists on the route of administration and the need of progesterone serum determinations

Trial registration number
NOT applicable