O-147 Role of serum progesterone levels and subcutaneous progesterone supplementation in endometriosis patients undergoing artificial cycle frozen embryo transfer
Authors: Sachs Guedj N , Coroleu B , Álvarez M , García S , Polyzos N P 
Published: July 2024

Abstract

Study question
Is there any impact of serum progesterone levels and subcutaneous progesterone supplementation on live birth rate in endometriosis patients undergoing Artificial Cycle-Frozen Embryo Transfer (AC-FET)?

Summary answer
Endometriosis patients have comparable progesterone levels before transfer to those without endometriosis. Progesterone supplementation results in similar live birth rate (LBR) to the general population.

What is known already
Progesterone (P4) resistance is a hallmark of uterine alterations in endometriosis. This disease could disrupt balance between progesterone and estrogen signaling pathways, resulting in estrogen dominance and progesterone resistance at the receptor level, which warrants a deeper exploration for adjusting dosages when performing AC-FET. A recent retrospective study highlights the potential significance of a progesterone threshold when using vaginal and intramuscular progesterone systematically in AC-FET, correlating with a significantly higher LBR for endometriosis-patients. However, no current studies have compared LBR according to P4 the day before blastocyst-transfer and progesterone supplementation in endometriosis versus non-endometriosis-patients undergoing AC-FET with standard vaginal treatment.

Study design, size, duration
This is a retrospective cohort study including 985 cycles undergoing autologous AC-FET with standard vaginal progesterone treatment (600 mg/day) at a university-affiliated fertility center from January 2019 to December 2022. 168 cycles were from patients with confirmed endometriosis. LBR was evaluated in both groups based on P4 levels the day before transfer. Progesterone supplementation via SC injection (25 mg/day) was administered when levels were deemed low (&lt;10.6 ng/mL based on our previously published research).

Participants/materials, setting, methods
Endometrial preparation involved oral estrogens at 6 mg daily from the begging of menstrual cycle. Micronized vaginal progesterone (600 mg/day) was added when thickness reached 7 mm. P4 was measured before embryo transfer; supplementation (25 mg SC injection) was added if &lt; 10.6 ng/mL. FET occurred 6 days after initiating luteal phase support. Treatment continued until the pregnancy test. If pregnant, treatment ceased at 10 weeks of amenorrhea.

Main results and the role of chance
Comparisons between endometriosis and non-endometriosis groups revealed similar baseline characteristics regarding age, BMI, parity, number of embryos transferred, and embryo quality.
The number of cycles with levels ≥10.6 ng/mL before transfer were comparable between patients with and without endometriosis (aOR 0.98, 95% CI 0.65-1.47) according to a multivariable logistic regression analysis adjusting for age, BMI, and prior progesterone levels &lt;10.6ng/mL the day before transfer.
Unadjusted findings demonstrated equivalent clinical pregnancy, miscarriage, and live birth rates in endometriosis compared to non-endometriosis patients.
A subsequent multivariable logistic regression analysis to analyze LBR was conducted, considering four groups:
Group 1: Endometriosis with progesterone &lt;10.6ng/mL and SC supplementation (51 patients)
Group 2: Endometriosis with progesterone ≥10.6ng/mL (117 patients)
Group 3: Non-endometriosis with progesterone &lt;10.6ng/mL and SC supplementation (274 patients)
Group 4: Non-endometriosis with progesterone ≥10.6ng/mL (543 patients)
Adjusted for age, BMI, and embryo quality, Group 1 was considered as the reference. Results showed comparable live birth rates between the reference group and Group 2 (aOR 0.79, 95% CI 0.36-1.74), Group 3 (aOR 0.91, 95% CI 0.45-1.8), and Group 4 (aOR 1.9, 95% CI 0.71-2.74). Subcutaneous supplementation for endometriosis patients with P4&lt;10.6ng/mL the day before embryo transfer led to similar LBR compared to the other groups.

Limitations, reasons for caution
The main limitation of this study is the single-center retrospective approach. While the total number of endometriosis patients is 168, the representation of endometriosis patients in group 1 may be a study limitation. Furthermore, all endometriosis stages were analyzed together although this may be clinically distinct entities.

Wider implications of the findings
Endometriosis patients have the same risk to have P4&lt;10.6ng/mL the day before FET as non-endometriosis patients. Vaginal progesterone, with subcutaneous supplementation if necessary, appears user-friendly, leading to a comparable live birth rate to that of patients with normal progesterone levels before transfer, regardless of endometriosis status.

Trial registration number
not applicable