Does programmed frozen embryo transfer (FET) with high-dose oestrogen affect obstetric outcomes and placental findings?
A retrospective cohort of live singleton deliveries at a single institution between 2009 and 2017, including deliveries attained by IVF with programmed FET; oocyte recipients were excluded. High-dose oestrogen was defined as a daily dose >6 mg throughout treatment. All placentas were evaluated regardless of complication status and the Amsterdam classification was used to analyse findings.
A total of 57 deliveries in the high-dose oestrogen group were compared with 274 controls. The high-dose oestrogen group displayed significantly longer duration of oestrogen treatment (18.8 ± 4.9 versus 13.3 ± 2.7 days, P < 0.001), total cumulative oestrogen dose (149.7 ± 46.1 versus 80.3 ± 16.8 mg, P < 0.001) and lower endometrial thickness (8.5 ± 1.4 versus 9.8 ± 1.7 mm, P < 0.001). After adjustment for confounders, higher dose oestrogen was found to be associated with a lower average birthweight (coefficient –252.4 g, 95% confidence interval [CI] –483.5 to –21.2), a higher rate of low-birthweight neonates (adjusted odds ratio [aOR] 4.88, 95% CI 1.05 to 22.57), bilobated placentas (aOR 3.36, 95% CI 1.04 to 10.89), accessory lobes (aOR 8.74, 95% CI 1.24 to 61.5), accelerated villous maturation (aOR 2.06, 95% CI 1.09 to 3.87), retroplacental haematoma (aOR 5.39, 95% CI 1.11 to 26.13) and maternal malperfusion lesions (aOR 1.46, 95% CI 1.04 to 2.05).
A higher daily oestrogen dose in programmed FET is associated with low birthweight and placental changes, although this may relate to altered endometrial properties and not to the treatment itself.
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Dr Hadas Ganer Herman is a graduate of Ben Gurion University and completed her OBGYN residency at the Edith Wolfson Medical Center, Israel. She is a senior lecturer at the Tel Aviv University Medical School, Israel, and currently a fellow at the McGill University Reproductive Centre, Montreal, Canada.
A higher daily oestrogen dose in programmed frozen embryo transfers is associated with a lower birthweight, higher rate of low-birthweight neonates and placental changes. As the effect of duration of treatment on outcomes seems more modest, it may be safer to continue treatment at the same dose if needed.
Published online: January 09, 2023
Accepted: January 3, 2023
Received in revised form: November 23, 2022
Received: October 16, 2022
Publication stageIn Press Journal Pre-Proof
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