P-362 The association between pregnancy-test day serum progesterone in IVF pregnancies and obstetrical complications
Authors: Wertheimer A , Zlatkin R , Sapir O , Hochberg A , Krispin E , Ben-Haroush A , Altman E , Shochat T , Shufaro Y 
Published: June 2022

Abstract

Study question
Is there an association between pregnancy-test day serum progesterone level in IVF pregnancies and late gestational complications?

Summary answer
Low serum progesterone on pregnancy diagnosis day is independently associated with a higher prevalence of preeclampsia.

What is known already
Low first trimester arbitrary serum progesterone is associated with early pregnancy complications such as ectopic pregnancies and miscarriages. IVF pregnancies are associated with higher prevalence of obstetrical complications such as preterm birth, preeclampsia and small for gestational age. Different patient and treatment parameters such as age, diagnosis, peak blood Estradiol level, endometrial thickness, fresh or frozen embryo transfer are associated with obstetrical complications. Progesterone is a potent immunomodulator that can affect the inflammatory pathway and trophoblast invasion. Little is known about the association between early pregnancy progesterone level and obstetrical complications, with conflicting results.

Study design, size, duration
A cohort study reviewing fertility and delivery files of all singleton live births from successfully treated infertile patients, who underwent ovarian stimulation, IVF and fresh embryo transfer in a tertiary medical center between 2008 and 2018.

Participants/materials, setting, methods
Serum progesterone concentration was measured with the first serum hCG on 4 + 0 gestational week (14 days after oocyte retrieval) under luteal support with vaginal progesterone. Pregnancy-test day serum progesterone was categorized in quartiles. The prevalence of obstetrical complications including gestational diabetes mellitus, preterm birth, preeclamsia, small for gestational age, post-partum hemorrhage and neonatal ICU hospitalization was compared between the four groups. Confounders were adjusted for by multivariate analysis.

Main results and the role of chance
719 singleton live births were included. The four serum progesterone quartiles were: Q1:3-44 nmol/L(n = 180); Q2:45-107 nmol/L(n = 180); Q3:108-223 nmol/L(n = 178); Q4:225-808nmol/L(n = 181). Patients with lower progesterone levels (Q1) had significantly more IVF treatments, lower peak estradiol level, fewer mature follicles and frozen embryos. The incidence of preterm labor, gestational diabetes mellitus, small-for-gestational-age, post-partum hemorrhage, placental abruption or neonatal ICU administration did not differ between the groups. Patients with lower serum progesterone had higher incidence of preeclampsia (9.44% in Q1, 2.78% in Q2, 2.81% in Q3 and 3.31% in Q4, P = 0.0046). On multivariate analysis, controlling for age, gravidity, treatment number, number of oocytes, peak follicular estradiol and progesterone, Q1 progesterone level was independently associated with an increased risk of preeclampsia (estimated OR = 3.27 95% CI 1.455-7.299).

Limitations, reasons for caution
Retrospective design, vaginal progesterone luteal support administration.

Wider implications of the findings
Low serum progesterone on pregnancy diagnosis day in gestations resulting from fresh ET is associated with a significantly higher prevalence of preeclampsia, possibly because of aberrant placentation and vascular development. This association is important for the obstetrical management, preeclampsia risk assessment, and administration of preventive therapy.

Trial registration number
not applicable