MRCOG Part 1 · Pathology · Pregnancy-Related Pathology

Disorders of Early Pregnancy: MRCOG Part 1 questions and key facts

Disorders of early pregnancy in the examination focus on the cytogenetics of molar pregnancy, the histology of gestational trophoblastic tumours, and the benign Arias-Stella reaction. The syllabus contrasts diploid androgenetic complete moles (46,XX commonest, usually no fetal tissue, markedly raised hCG, snowstorm ultrasound appearance) with triploid partial moles (one maternal and two paternal sets, fetal tissue often present, lower hCG). Complete moles arise when an anucleate ovum is fertilised by paternal sperm, producing androgenetic diploidy, whereas most partial moles result from dispermy. Malignant trophoblastic tumours require precise histological differentiation, particularly choriocarcinoma which lacks chorionic villi. Finally, high sex steroid levels in intrauterine or ectopic gestation induce the Arias-Stella reaction, an exuberant but benign endometrial glandular atypia that must not be mistaken for adenocarcinoma.

The Uterio bank has 11 questions on this topic. 2 arebelow in full; the syllabus detail is in the Pathology study guide.

How the exam tests Disorders of Early Pregnancy

  • Differentiating the genetic mechanisms, ploidy, and parental origins of complete and partial hydatidiform moles.
  • Identifying histological characteristics of choriocarcinoma, particularly malignant trophoblastic proliferation in the complete absence of chorionic villi.
  • Recognising the Arias-Stella reaction as a benign endometrial glandular response to high oestrogen and progesterone levels in pregnancy.
  • Linking a snowstorm ultrasound appearance and markedly raised hCG with the genetics of a complete mole.
  • Distinguishing complete mole, partial mole, invasive mole, choriocarcinoma and placental site trophoblastic tumour by villi, ploidy and cell type.

High-yield facts

  1. Complete hydatidiform moles are androgenetic diploid, nuclear DNA entirely paternal, typically arising from monospermic fertilisation of an empty ovum followed by duplication.
  2. The most common karyotype in a complete mole is 46,XX, although 46,XY can arise through dispermic fertilisation of an anucleated ovum.
  3. Partial hydatidiform moles possess a triploid karyotype, most frequently 69,XXY or 69,XXX, and less commonly 69,XYY.
  4. A partial mole arises from the fertilisation of a normal haploid ovum by two spermatozoa or by a single diploid spermatozoon.
  5. Partial moles contain one maternal and two paternal chromosome sets, usually exhibiting embryonic or fetal tissue, less trophoblastic proliferation, and lower hCG than complete moles.
  6. Complete moles feature trophoblastic hyperproliferation, markedly elevated human chorionic gonadotrophin levels, and a snowstorm ultrasound appearance without fetal tissue.
  7. The Arias-Stella reaction is a benign endometrial change driven by high oestrogen and progesterone levels seen in intrauterine pregnancy, ectopic pregnancy, or trophoblastic disease.
  8. Arias-Stella exhibits enlarged, hyperchromatic nuclei and vacuolation, whereas chronic endometritis features plasma cells and carcinoma shows gland crowding, stromal invasion, and mitoses.
  9. An invasive mole is molar tissue with chorionic villi invading the myometrium, so villi are present, unlike in choriocarcinoma.
  10. Placental site trophoblastic tumour is composed of cells resembling intermediate trophoblast.
  11. Choriocarcinoma consists of intimately related malignant syncytiotrophoblasts and cytotrophoblasts in a biphasic pattern completely lacking chorionic villi.

Common pitfalls

  • Confusing the Arias-Stella reaction with endometrial adenocarcinoma due to glandular nuclear atypia and hyperchromasia.
  • Assuming complete moles cannot be 46,XY; dispermic fertilisation of an anucleated ovum can produce a diploid 46,XY complete mole.
  • Believing choriocarcinoma contains hydropic villi; the total absence of chorionic villi is its hallmark histological feature.
  • Assuming a partial mole has no fetal tissue: embryonic or fetal tissue is often present in a partial mole, whereas a complete mole has none.

Practice questions: Disorders of Early Pregnancy

Single best answer, exactly as the exam asks. Commit to an option before opening the explanation.

Question 1

Pathology

A 22-year-old woman presents with vaginal bleeding and significantly elevated serum hCG levels, much higher than expected for gestational age. Ultrasound reveals a 'snowstorm' appearance with no fetal parts. What is the genetic origin of this pathology?

  1. ADiploid, entirely maternal
  2. BDiploid, entirely paternal
  3. CTriploid, two maternal sets, one paternal set
  4. DTriploid, one maternal set, two paternal sets
  5. ETetraploid, equal maternal and paternal contribution
Show answer and explanation

Correct answer: B. Diploid, entirely paternal

Key takeaway

A complete hydatidiform mole ('snowstorm' ultrasound, very high hCG, no fetus) results from fertilisation of an empty ovum, leading to a diploid, entirely paternal genetic origin.

A complete hydatidiform mole, a form of gestational trophoblastic disease, arises from the fertilisation of an ovum that has lost its own chromosomes (an 'empty' ovum) by one sperm (which then duplicates its chromosomes) or, less commonly, by two separate sperm. This results in a conceptus with a diploid karyotype (typically 46,XX or 46,XY) where all chromosomes are of paternal origin. This abnormal genetic makeup leads to hyperproliferation of trophoblastic tissue (causing markedly elevated hCG levels and the characteristic 'snowstorm' appearance on ultrasound) and the absence of fetal development.

Partial hydatidiform moles, in contrast, usually arise from the fertilisation of a normal ovum by two sperm (dispermy) or by a diploid sperm. This results in a triploid karyotype (e.g., 69,XXY or 69,XXX), typically with one maternal and two paternal sets of chromosomes. Partial moles are associated with the presence of fetal tissue (often abnormal), less marked trophoblastic proliferation, and lower hCG levels compared to complete moles. Diploid, entirely maternal origin would result in a parthenogenote, which is not viable. Triploid with two maternal sets is less common and associated with different developmental abnormalities or early loss. Tetraploidy is very rare and usually results in spontaneous abortion.

Question 2

Pathology

What is the typical chromosomal makeup (karyotype) of a partial mole?

  1. ADiploid (46,XX or 46,XY), entirely paternal
  2. BDiploid (46,XX), entirely maternal
  3. CTriploid (69,XXX, 69,XXY, or 69,XYY)
  4. DTetraploid (92 chromosomes)
  5. EAneuploid (e.g., 45,X or 47,XXY)
Show answer and explanation

Correct answer: C. Triploid (69,XXX, 69,XXY, or 69,XYY)

Key takeaway

A partial hydatidiform mole typically has a triploid karyotype (69,XXX, 69,XXY, or 69,XYY) containing both maternal and paternal chromosomes; 69,XXY and 69,XXX are the most frequent.

A partial hydatidiform mole arises typically from the fertilisation of a normal haploid ovum (23,X) by two separate spermatozoa (dispermy) or by a single diploid spermatozoon that failed meiosis II. This results in a conceptus with three sets of chromosomes, making it triploid. The most common karyotypes are 69,XXY or 69,XXX, though 69,XYY can also occur. Importantly, partial moles contain both maternal and paternal genetic material.

A complete mole, in contrast, is typically diploid (46,XX or less commonly 46,XY) but contains only paternal genetic material. This usually occurs when an 'empty' ovum (lacking maternal chromosomes) is fertilised by a single spermatozoon that duplicates its chromosomes (46,XX) or by two separate spermatozoa (46,XX or 46,XY). Entirely maternal diploid cells are not characteristic of molar pregnancy. Tetraploidy (92 chromosomes) and aneuploidy (abnormal number of chromosomes, e.g., 45 or 47) are not the typical karyotypes associated with partial moles.

9 more disorders of early pregnancy questions in the bank

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What the syllabus covers under disorders of early pregnancy

  • Molar Pregnancy
  • Ectopic Pregnancy

Read the full section in the Pathology guide, or check the next exam dates.