Placental pathology in live births conceived with in vitro fertilization after fresh and frozen embryo transfer

• Published in: American journal of obstetrics and gynecology Vol. 222; no. 4; pp. 360.e1 - 360.e16
• Main Authors: Sacha, Caitlin R., Harris, Amy L., James, Kaitlyn, Basnet, Kristen, Freret, Taylor S., Yeh, John, Kaimal, Anjali, Souter, Irene, Roberts, Drucilla J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-04-2020
• Subjects: Adult; assisted reproduction; Birth Weight; Cryopreservation; embryo; Embryo Transfer - methods; Embryo, Mammalian; Female; Fertilization in Vitro - methods; fresh transfer; frozen transfer; Humans; Infant, Newborn; IVF; Live Birth; pathology; placenta; Placenta - abnormalities; Placenta Diseases - epidemiology; Placenta Diseases - pathology; Pregnancy; Retrospective Studies; Thrombosis - epidemiology; assisted reproduction; frozen transfer; pathology; IVF; embryo; placenta; fresh transfer
• ISSN: 0002-9378; 1097-6868
• DOI: 10.1016/j.ajog.2019.09.047

The availability and use of frozen embryos after ovarian hyperstimulation for assisted reproduction has increased with improvement in vitrification techniques and the rise of preimplantation genetic testing. However, there are conflicting data regarding whether obstetric outcomes differ between fresh and frozen embryo transfer cycles.
To compare placental pathology from live births arising from fresh and frozen embryo transfer cycles.
A cohort of 1140 live births with placental pathology arising from autologous in vitro fertilization cycles with fresh or frozen programmed transfer performed at MGH Fertility Center between 2004 and 2017 was retrospectively reviewed. An experienced placental pathologist categorized the reported placental pathology as anatomic, infectious, inflammatory, or vascular/thrombotic. Our primary outcomes were differences in these placental pathologies between the 2 groups. Patient demographic, cycle, and birth outcomes were compared with the use of χ2 tests, Student t test, or nonparametric tests, as appropriate. Multivariate logistic regression models were used to compare placental pathology between the fresh and frozen transfer groups.
Of the 1140 cycles included in our analysis, 929 arose from fresh embryo transfers (81.3%) and 211 arose from programmed frozen embryo transfers (18.5%). For both transfer types, the average age of the women at time of treatment was 35 years; mean body mass indices were within the normal range (23.6 kg/m2 for fresh transfers and 23.2 kg/m2 for frozen transfers, P = .26), and mean day 3 follicle-stimulating hormone values were 7.1 and 7.0 IU/L (P = .44), respectively. Deliveries occurred on average at 37.5 and 38.0 weeks’ gestational age (P = .04) in the fresh versus frozen transfer group, with similar rates of obstetric complications. However, frozen transfers were more likely to be associated with marginal cord insertion (adjusted odds ratio, 1.87; confidence interval, 1.21, 2.91; P = .01), accessory lobe formation (adjusted odds ratio, 2.96; confidence interval, 1.12, 7.79; P = 0.03), subchorionic thrombi (adjusted odds ratio, 3.72; confidence interval, 1.80, 7.71; P < .001), and fetal vascular malperfusion characteristics with cord anomalies (adjusted odds ratio, 2.34; confidence interval, 1.22, 4.46; P = .01). These trends persisted when we analyzed day 5 transfers alone, and single frozen embryo transfers remained associated with increased rates of subchorionic thrombi compared to single fresh embryo transfers.
Pregnancies arising from frozen embryo transfers demonstrated more anatomic and vascular placental pathology than those from fresh transfers in our cohort of patients, despite similar maternal outcomes. More research is needed to explore how these differences in pathology may influence obstetric and perinatal outcomes.