Is Assisted Reproduction Associated with Abnormal Placentation?

Abstract

Artificial reproductive technologies (ART) and conception following a period of untreated infertility (>1 year) are independently associated with increased pregnancy complications in both singleton and multiple pregnancies. It is unknown if placental dysfunction associated with macroscopic and/or microscopic histological discrepancies might explain some of these variances. Our aim was to compare the histopathology of placentae from singleton pregnancies belonging to 3 groups, as follows: conception as a result of ART; spontaneous conception (<1 year of trying); and conception following untreated infertility (>1 year). Pathological examination of placentae from singleton pregnancies of nonsmoking, age-matched primiparous women with no significant medical history and no known uterine congenital anomalies was performed by a single pathologist blinded to the groups. Features were compared using analysis of variance and chi-square tests. A total of 89 placental pathology reports were available (control = 39, infertility = 17, ART = 33). The mean placental thickness was significantly higher in the ART group when compared to the spontaneous conception group (P = 0.02). There were significantly more placental hematomas in the ART group (P = 0.04) compared to the other groups. There were no significant differences in rates of abnormal placental shapes or abnormal cord insertions. There were no statistically significant differences in the incidence of microscopic placental lesions, nor were there any statistically significant differences in the incidence of macroscopic and microscopic placental lesions between the infertility group and the other groups. Placentae of ART pregnancies show significantly increased thickness and a higher incidence of hematomas. Increased placental thickness has previously been linked to increased perinatal risk.

Assisted reproductive technologies induce temporally specific placental defects and the preeclampsia risk marker sFLT1 in mouse

“…ART procedures, independent of infertility, induce cellular behavior in late gestation reflective of human placental pathologies associated with ART As noted in previous studies, the late gestational placenta overgrowth phenotype in mouse is relevant to human IVF placentas that also display overgrowth and increased thickness (Choux et al, 2019;Daniel et al, 1999;Haavaldsen et al, 2012;Joy et al, 2012;Zhang et al, 2011). Here, we demonstrate that embryo culture from the 1-cell to blastocyst stage results in the most dramatic increases in placental weight and differences in junctional zone cell composition, suggesting that the embryo culture procedure is the largest driver of placental overgrowth observed in humans.…”

Pregnancy, birth, and infant outcomes by maternal fertility status: the Massachusetts Outcomes Study of Assisted Reproductive Technology

“…These differences have included significantly larger placental weight and higher placental weight/birthweight ratio (51); increased thickness and a higher incidence of hematomas (52, 53), and altered gene expression (54, 55). Nakamura et al (53) reported that the thickness of the Rohr fibrinoid layer and percent loss of decidua were both significantly highest in the hormonal cycles using thawed embryos, with z-scores of both measures positively correlating with the amount of bleeding at delivery.…”

The health outcomes of human offspring conceived by assisted reproductive technologies (ART)

“…141,142,155,156 Increased placental thickness and placental haematomas as well as pathological findings were reported in ART pregnancies. [157][158][159] IVF impairs placental nutrient transport and metabolism in mice. 141,144,156 Placental weight and placental:fetal weight ratio was significantly higher in ART pregnancies than in naturally conceived pregnancies in humans and mouse models.…”