Identification of a hydatidiform mole in twin pregnancy following assisted reproduction

Abstract

Purpose: The aim of this study was to identify a co-existing hydatidiform mole (HM) in twin pregnancy from the abnormal mixed-genomic products of conception (POC) after assisted reproduction by histopathological review, evaluation of p57^kip2 immunostaining and short tandem repeat genotyping.

Methods: Thirty-seven patients were collected with suspicion for HM by pathological morphology. They had two embryos individually transferred to their uterus after in vitro fertilization and presented two gestational sacs with undeveloped embryos or one sac with an abnormal area by ultrasonography.

Results: Thirty patients were diagnosed as singleton pregnancy, including twenty-two non-molar gestations, six trisomy gestations, one homozygous complete mole and one heterozygous partial mole. Although six patients had ultrasonic imaging of two gestational sacs, the embryonic components in the vacant sac might fade away after transferring. Other seven patients were considered as twin pregnancy by the allelic genotype from two individual conceptions. For the patients with uniform p57^kip2 positivity, excessive paternal alleles indicated the potential partial HM in the twin pregnancy. For the patients demonstrated divergent and/or discordant p57^kip2 immunostaining, twin pregnancy with co-existing complete HM or mosaic conception were confirmed by genotyping of different villi population respectively. These patients were monitored by serum β-HCG, while one twin pregnancy with complete mole suffered invasive mole and received chemotherapy.

Conclusions: A strategy composed of selective clinicopathological screening, immunohistochemical interpretation and accurate genotyping is recommended for diagnostically challenging mixed-genomic POC of potential twin pregnancy with HM, especially to differentiate a non-molar mosaic conception from a partial mole.

Keywords: Assisted; Hydatidiform mole; Reproduction; Short tandem repeat; Twin pregnancy; p57kip2.

Fig. 1

Twin pregnancy with monospermic homozygous complete mole and a co-existent fetus (patient 3 in Table S1). a Large hydropic villi with cistern formation near the fetal components (arrow) (× 40 magnification). b Small fibrotic villi in other areas (× 40 magnification). c Genotyping revealed complete mole with monospermic homozygous paternal allele at 11 STR loci (asterisk) in the hydropic chorionic villus and biparental fetal conception

Fig. 2

Twin pregnancy with non-molar and mosaic hydropic components (patient 4 in Table S1). a Normal villi (angle) and enlarged chorionic villi with cellular stroma (asterisk) (× 100 magnification). b Normal villi were uniform p57^kip2-positive (angle), and enlarged villi were p57^kip2-positive in cytotrophoblast and negative in stromal cells (asterisk) (immunohistochemistry; × 100 magnification). c The normal villi shared the same biparental alleles with the enlarged villi at each locus. The latter didn’t show two paternal alleles at any locus, and the present paternal allele at most loci was in double dose (asterisk), which suggested a possible androgenetic/biparental mosaic

Fig. 3

Twin pregnancy, favoring one co-existing complete mole (patient 18 in Table S1). a Hydropic villi without trophoblastic hyperplasia (angle) and cauliflower-like villi with karyorrhectic nuclear debris and trophoblastic hyperplasia (asterisk) (× 200 magnification). b Hydropic villi were p57^kip2-positive (angle) and cauliflower-like villi were p57^kip2-negative (asterisk) in cytotrophoblast (Immunohistochemistry; × 200 magnification). c Genotyping of the mixed villi suggested polyploid genome fertilized by at least two sperms according to the excessive paternal alleles at four of eleven informative loci (Penta E, D13S317, D7S820 and D16S539) (asterisk)