Placental villitis of unclear etiology during ovum donor in vitro fertilization pregnancy Aaron K. Styer, MD, a Hannah J. Parker, MD, b Drucilla J. Roberts, MD, c Darryl Palmer-Toy, MD, PhD, c Thomas L. Toth, MD, d and Jeffrey L. Ecker, MD e Boston, Mass OBJECTIVE: Preliminary observations by a single pathologist at our institution revealed a 75% incidence of villitis of unexplained etiology in ovum donor in vitro fertilization pregnancies. Because the incidence of villitis of unexplained etiology in the general population is approximately 10%, we conducted a controlled study to compare the incidence of villitis of unexplained etiology in ovum donor in vitro fertilization pregnancies to that in in vitro fertilization pregnancies that do not use donated ova. STUDY DESIGN: Placental specimens of ovum donor in vitro fertilization pregnancies were matched randomly with pregnancies that resulted from both fresh and frozen/thawed native oocyte in vitro fertilization from March 5, 1995, to October 10, 2001, and examined in a blinded fashion by a single pathologist (D. J. R.) for villitis of unexplained cause. The incidence of villitis of unexplained etiology was analyzed in 27 patients who underwent ovum donor in vitro fertilization versus 37 patients who underwent native oocyte in vitro fertilization. RESULTS: Villitis of unexplained cause occurred in 22.2% of ovum donor in vitro fertilization pregnancies, 10.8% of native oocyte in vitro fertilization pregnancies (fresh and frozen/thawed combined), and 14.3% of frozen/thawed cycles (P = .21). CONCLUSION: Although the incidence was not statistically different than in in vitro fertilization that used native maternal oocytes, there was a 2-fold increase in villitis of unexplained cause in the ovum donor in vitro fertilization placentas, which suggests that immune-related disorders may be increased in ovum donor pregnancies. (Am J Obstet Gynecol 2003;189:1184-6.) Key words: Ova donation, in vitro fertilization, villitis of unclear etiology, VUE During mammalian pregnancy, inherited maternal and paternal genes govern embryo development. Remarkably, the maternal immune system tolerates the conceptus and does not reject products of paternal genes, which may be incompatible with the maternal immune system. Although several aspects of pregnancy immunobiology condition have been elucidated, many key components remain poorly understood. Maternal intolerance possibly due to zygotic expression of foreign antigens has been documented in the case of pathologic findings such as maternal floor infarct, massive chronic intervillositis, and villitis of unknown etiology (VUE). 1-5 In these cases, a maternal immune response is present in the absence of infection and may recur in subsequent pregnancies. 6-8 Pregnancies that are conceived after ova donation are an interesting model to study the interactions of em- bryonic antigens with the maternal immune system. These pregnancies occur after in vitro fertilization (IVF) with ova donated by a relative, or more commonly an unrelated donor. As such, neither embryonic haplotype matches that of the gestational carrier. To date, there are no published studies that outline perinatal outcomes in this circumstance. One of us (D. J. R) examined 17 placental pathologic specimens that were identified as ovum donor sent for routine review between January 1, 1995, and December 31, 1998. A 75% incidence of chronic VUE was noted. This was higher than the reported 10% incidence of VUE in the general population. 9 We hypothesized that the placental findings of an ovum donor pregnancy may show an increased incidence of immune-related findings, as manifested in placental disease. We organized a cohort to further investigate our preliminary finding. Material and methods Study population. The Partners Healthcare Institu- tional Board of Review for Human Subjects Research approved this study. To ensure similarity of preconcep- From the Department of Obstetrics and Gynecology, Vincent Center for Reproductive Biology, a the Department of Pathology, c the Divisions of Reproductive Endocrinology and Infertility d and Maternal Fetal Medicine, e the Department of Obstetrics and Gynecology, Massachusetts General Hospital; and the Department of Obstetrics and Gynecology, Brigham and Women’s Hospital. b Received for publication January 14, 2003; revised March 25, 2003; accepted May 2, 2003. Reprint requests: Jeffrey L. Ecker, MD, Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, Massachusetts General Hospital, 55 Fruit St, Boston, MA, 02114. E-mail: jecker@partners.org Ó 2003, Mosby, Inc. All rights reserved. 0002-9378/2003 $30.00 + 0 doi:10.1067/S0002-9378(03)00577-5 1184