A 28-year-old primigravida from rural Tamil Nadu presents at 14 weeks of gestation with vaginal bleeding and passage of grape-like tissue per vaginum. Pelvic ultrasound shows a "snowstorm" appearance with no fetus and bilateral enlarged ovaries. The pathological specimen shows the structure marked **A** — grape-like hydropic vesicles with central cistern formation and circumferential trophoblastic proliferation. Which of the following best explains the pathogenesis of this condition?

Explanation

## Why "Fertilization of an anucleate ovum by a single sperm that duplicates, resulting in diploid androgenetic karyotype (46,XX)" is right The structure marked **A** — grape-like hydropic vesicles with hydropic swelling of chorionic villi — is the pathognomonic gross finding of complete hydatidiform mole (CHM). The pathogenesis of CHM is fertilization of an empty (anucleate) ovum by a single sperm that duplicates (90% of cases) or by two sperms (10%), resulting in a diploid karyotype of purely paternal origin (46,XX or 46,XY — androgenetic). This absence of maternal genetic contribution is why p57 immunohistochemistry is negative in CHM. The hydropic swelling of villi occurs due to abnormal trophoblastic proliferation without fetal development. This is the EXACT pathogenesis described in Williams Obstetrics 26e and Robbins 10e. ## Why each distractor is wrong - **Fertilization of a normal ovum by two sperms resulting in triploidy (69,XXX)**: This describes a partial hydatidiform mole (PHM), not a complete mole. Partial moles have focal (not diffuse) villous edema, often retain fetal parts, and have p57 IHC positive (maternal contribution present). The karyotype is triploid (69,XXX or 69,XXY), not diploid androgenetic. - **Fertilization of a normal ovum by a single sperm with subsequent loss of paternal chromosomes**: This is incorrect and does not match the pathogenesis of either CHM or PHM. Loss of paternal chromosomes would result in a haploid or monosomic state, which is incompatible with the trophoblastic proliferation seen in molar pregnancy. - **Fertilization of an ovum with retention of both maternal and paternal genetic material in equal proportions**: This describes a normal diploid pregnancy (46,XX or 46,XY with biparental contribution), not a molar pregnancy. In CHM, there is complete absence of maternal genetic material — it is purely androgenetic. **High-Yield:** Complete mole = empty ovum + single sperm (duplicates) = 46,XX/XY androgenetic diploid; Partial mole = normal ovum + two sperms = 69,XXX/XXY triploid with fetal parts present. [cite: Williams Obstetrics 26e Ch 20; Robbins 10e Ch 22]