A 24-year-old woman, gravida 1 para 0, presents to her physician with persistent nausea, vaginal bleeding, and passage of grape-like tissue at 11 weeks' gestation. Her uterus is larger than expected for gestational age. Serum β-hCG concentration is markedly elevated. Transvaginal ultrasonography demonstrates a heterogeneous intrauterine mass with numerous cystic spaces and no identifiable fetus. Cytogenetic analysis demonstrates a 46,XX karyotype in which all nuclear DNA is of paternal origin.
Which of the following fertilization events most likely produced this pregnancy?
The correct answer is:
C) Fertilization of an empty ovum by one sperm followed by duplication of the paternal genome
A complete hydatidiform mole most commonly develops when a sperm fertilizes an enucleate (empty) ovum and subsequently duplicates its chromosomes, producing a 46,XX androgenetic diploid conceptus. Less commonly, two sperm fertilize an empty ovum, resulting in a 46,XX or 46,XY conceptus that is also entirely paternal in origin. Because no maternal nuclear genome is present, embryonic development does not occur. Instead, there is diffuse hydropic swelling of chorionic villi, diffuse trophoblastic hyperplasia, markedly elevated β-hCG levels, and an increased risk of progression to gestational trophoblastic neoplasia.
Answer choice A: Fertilization of a normal ovum by one sperm followed by paternal genome duplication, is incorrect. A normal ovum contributes a maternal haploid genome. Duplication of the paternal genome in this setting would produce an abnormal chromosomal complement rather than the androgenetic diploid genome characteristic of a complete mole.
Answer choice B: Fertilization of a normal ovum by two sperm, is incorrect. Dispermic fertilization of a normal ovum typically results in a triploid partial hydatidiform mole (69,XXY is most common). Partial moles often contain fetal tissue or identifiable embryonic structures.
Answer choice D: Fertilization of an empty ovum by two sperm producing a triploid conceptus, is incorrect. Fertilization of an empty ovum by two sperm produces an androgenetic diploid, not triploid, genome because no maternal chromosomes are present. Triploidy requires a normal maternal haploid genome plus two paternal haploid genomes.
Answer choice E: Failure of the maternal second meiotic division after fertilization, is incorrect. Failure of meiosis can produce aneuploid conceptuses but does not result in the entirely paternal genome that defines a complete hydatidiform mole.
Key Learning Point
A complete hydatidiform mole is usually caused by fertilization of an empty ovum by a single sperm that duplicates its genome, producing a 46,XX androgenetic diploid conceptus with no fetal tissue, diffuse trophoblastic proliferation, and markedly elevated β-hCG. In contrast, a partial mole most commonly results from dispermic fertilization of a normal ovum, producing a triploid conceptus with some fetal development.
