OBSTETRICS Triploid pregnancies: genetic and clinical features of 158 cases Mette W. Joergensen, MD; Isa Niemann, PhD; Anders A. Rasmussen, PhD; Johnny Hindkjaer, MSc; Inge Agerholm, PhD; Lars Bolund, DMSc, MD; Lone Sunde, PhD OBJECTIVE: The purpose of this study was to analyze the correlation between the genetic constitution and the phenotype in triploid pregnancies. STUDY DESIGN: One hundred fifty-eight triploid pregnancies were identified in hospitals in Western Denmark from April 1986 to April 2010. Clinical data and karyotypes were collected retrospectively, and archived samples were retrieved. The parental origin of the genome, either double paternal contribution (PPM) or double maternal contribution (MMP) was determined by an analysis of methylation levels at imprinted sites. RESULTS: There were significantly more PPM than MMP cases (P < .01). In MMP cases, the possible karyotypes had similar frequencies, whereas, in PPM cases, 43% had the karyotype 69,XXX, 51% had the karyotype 69,XXY, and 6% had the karyotype 69,XYY. Molar phenotype was seen only in PPM cases. However, PPM cases with a nonmolar phenotype were also seen. For both parental genotypes, various fetal phenotypes were seen at autopsy. Levels of human chorionic gonadotropin in maternal serum were low in MMP cases and varying in PPM cases, some being as low as in the MMP cases. CONCLUSION: In a triploid pregnancy, suspicion of hydatidiform mole at ultrasound scanning, by macroscopic inspection of the evacuated tissue, at histology, or because of a high human chorionic gonado- tropin in maternal serum level each predict the parental type PPM with a very high specificity. In contrast, the sensitivity of these observations was <100%. Key words: diagnosis, genomic, human chorionic gonadotropin, hydatidiform mole, triploidy Cite this article as: Joergensen MW, Niemann I, Rasmussen AA, et al. Triploid pregnancies: genetic and clinical features of 158 cases. Am J Obstet Gynecol 2014;210:. T riploidy, which is one of the most common chromosome aberra- tions, is estimated to occur in 1-2% of all human conceptions. 1 Triploid pregnancies can be classified according to the genetic constitution. The genome in a triploid pregnancy is either digynic, which consists of 2 maternal and 1 paternal set of chromo- somes (MMP), or diandric, which con- sists of 2 paternal and 1 maternal set of chromosomes (PPM). 1 Extremely vary- ing frequencies of the 2 parental types have been reported (the frequency of PPM cases ranges from 20e73%). 1-9 Triploid pregnancies can also be classified according to their phenotype. By the use of ultrasound scanning (US), it has been found that the placenta can appear normal, small, or enlarged and with or without vesicular changes. If a fetus is present, it can exhibit malformations but can also appear normal. Growth restriction appears to be a common, but not a consistent, phe- nomenon. 10 In studies that have been focused on levels of serum maternal human chorionic gonadotropin (MS- hCG), low, normal, and high levels have been reported. 11-13 In some studies that involved postmortem examinations of triploid pregnancies, 2 distinctive phe- notypes have been suggested: type 1, relatively well-grown fetuses with pro- portionately sized body parts and large placentas with the morphologic condi- tion of a partial hydatidiform mole; type 2, fetuses with severe growth retardation, an uneven development of various body parts that typically results in a relative macrocephaly and small, noncystic placentas. 4,14 However, a systematic description and classification of a large cohort of triploid pregnancies has not been pub- lished. We correlate the parental origin of the genome with karyotype and phe- notype of the triploid pregnancy and with the concentration of MS-hCG in a series of 158 triploid pregnancies. From the Department of Clinical Genetics, Vejle Hospital, Vejle (Drs Joergensen and Rasmussen); Institute of Regional Health Research, University of Southern Denmark, Odense (Dr Joergensen); Department of Gynecology and Obstetrics, Aarhus University Hospital (Dr Niemann); Department of Biomedicine, Aarhus University (Drs Bolund and Sunde); Department of Clinical Genetics, Aarhus University Hospital (Dr Sunde); the Fertility Clinic and Center for Preimplantation Genetic Diagnosis (Mr Hindkjaer), Aarhus University Hospital, Aarhus; and the Fertility Clinic, Horsens Hospital, Horsens (Dr Agerholm), Denmark. Received Nov. 25, 2013; revised Feb. 10, 2014; accepted March 14, 2014. Supported by Vejle Hospital, University of Southern Denmark, Aase and Einar Danielsen Foundation, the Augustinus Foundation, the Medical Research Foundation of Central Region Denmark, and the A. P. Moeller and Chastine McKinney Moeller Foundation. The authors report no conflict of interest. Reprints: Mette W. Joergensen, MD, Department of Clinical Genetics, Vejle Hospital, Kabbeltoft 25, 7100 Vejle, Denmark. mette.warming.joergensen@rsyd.dk. 0002-9378/$36.00  ª 2014 Mosby, Inc. All rights reserved.  http://dx.doi.org/10.1016/j.ajog.2014.03.039 MONTH 2014 American Journal of Obstetrics & Gynecology 1.e1 Research www. AJOG.org