Pathologies of Pregnancy

Question 1

Describe the levels of oestrogen and progesterone in a normal menstual cycle

Answer 1

Oestrogen:

Rises up until day 14 of the cycle, which neg. feedbacks to FSH so that only one follicle survives. Decreases to Day 28 (other than another surge)

Progesterone:

Puts negative feedback on the HPG axis. This, together with inhibin (inhibits FSH) stalls the cycle in anticipation of fertilisation.

Without fertilisation, corpus luteum regresses and hormone levels fall, releasing neg feedback on HPG axis

Question 2

What has happens to the hormonal cycle to allow fertilisation?

Answer 2

Progesterone keeps rising

Question 3

What does progesterone do to the endometrium?

Answer 3

Progesterone turns endometrium into decidua

• Increases vascularity
• Between glands and vessels the stromal cells enlarge and become procoagulant ⇒ stops bleeding

Question 4

What do the trophoblast cells (found on the outer edge of a chorion) produce?

Answer 4

B-hCG or Beta-human Chorionic Gonadotrophin

Question 5

What is the action of Beta-human Chorionic Gonadotrophin (B-hCG)?

Answer 5

Targets the corpus luteum in the ovary

Function is to stimulate corpus luteum to produce progestogen, which stops decidua from shedding to maintain the pregnancy

Question 6

How is B-hCG used clinically?

Answer 6

Pregnancy tests

Question 7

What is the fate of the trophoblasts of the chorion and how does it occur?

Answer 7

Helps to form the placenta

1. Fertilised egg burrows in to decidua
2. Trophoblast cells stream off to invade mother’s blood vessels and (eventually) link these vessels up with those of the fetus
3. Projections of chorion (chorionic villi), covered in trophoblast cells, start to move into the decidua
4. Eventually the chorionic villi, covered by trophoblast cells, are bathed in the mother’s blood, forming the forerunner of the placenta

Question 8

What are decidual stromal cells?

Answer 8

The decidual cells are procoagulant and help stop bleeding when the trophoblast cells invade mother’s blood vessels

Question 9

Case 1:

• Woman, 26 yrs
• Misses period
• Pregnancy test positive
• Vaginal bleeding 7 weeks after missed period
• What has probably happened?

Answer 9

• US scan: No fetuspresent but membranes and decidua lining uterus still there = miscarriage
• Removal of remaining tissue by obstetrician

Follow up:

• No problems afterwards
• B-hCGreturns to normal (ie zero)

Question 10

What are causes miscarriages?

Answer 10

Causes include: chromosomal abnormality, infection, and maternal issues (such as ill-health, trauma, hormonal problems)

Question 11

Case 2:

• Woman, 32 years old
• Misses period.
• 8 weeks pregnant ⇒ Small amount of bleeding per vagina

Findings:

• BhCG raised
• Ultrasound: Thickened lining of endometrial cavity. Expanded fallopian tube on 1 side.

Diagnosis?

Answer 11

• Diagnosis = ectopic pregnancy
• Considered using methotrexate – but opted foroperative removal of fallopian tube àtissue sent to pathology

Follow up:

• •Woman well 1 week after operation
• •B-hCG returned to zero

Question 12

Case 3:

• Woman 23 years
• Sudden severe abdominal pain. Collapses.
• Admission to A&E àPulse fast. BP low.

Findings:

• Blood given
• Emergency laparotomy
  
  • At operation - several litres of blood in abdomen
  • Blood flowing from fallopian tube area - clamped, removed and sent to pathology
  • Microscopy = blood, fragments of fallopian tube and occasional chorionic villi (part of what will become the placenta and therefore tissue which confirms pregnancy)

Diagnosis?

Answer 12

Ruptured ectopic pregnancy

Follow up:

• B-hCGraised after operation, but returns to normal
• Woman is well 3 weeks later.

Question 13

What is an ectopic pregnancy?

Answer 13

• Pregnancy in the wrong anatomical site
• Most common in fallopian tube
• Lack of proper decidual layer (stops trophoblast cells from causing bleeding when they invade mother’s BV) and small size of tube predispose to haemorrhage and rupture
• If it presents early woman may not even know she is pregnant

Question 14

Case 4:

• 32 year old woman
• +ve pregnancy test
• 7 weeks pregnant – minor bleed
• Ultrasound: uterine cavity shows some placental tissue but no fetus. Fallopian tubes normal.
• B-hCG raised

Diagnosis?

Answer 14

Miscarriage

• Endometrial tissue removed by obstetrician and sent to pathology
• Microscopy = enlarged abnormal chorionic villi with abundant trophoblast

⇒ Molar pregnancy

Question 15

What is a Molar pregnancy?

Answer 15

In normal conception, the fetus is formed from 23 maternal chromosomes and 23 paternal chromosomes. A molar pregnancy arises from an abnormality in chromosomal number during fertilisation.

• They have large choronic villi and overgrowth of trophoblast cells
• A form of precancerof trophoblast cells

Question 16

How does normal fertilisation occur (to understand how molar pregnancies happen)?

Answer 16

In normal gonads of adults:

• Mum switched off certain gene in ova by methylating them (adding methyl groups) ⇒ promotes early baby growth
• Dad switched of different genes in sperm by methylating them ⇒ promotes early placenta growth via trophoblast proliferation

Overall effect is balanced growth of baby and placenta

Question 17

How does molar pregnancies occur?

Answer 17

Various cases but often caused by two sperm fertilising one egg with no chromosomes

This results in imbalance in methylated (switched off) genes ⇒ too many of dad’s methylated genes causes the trophoblast cell proliferation

A problem because in the testis dad has inactivated several genes by adding methyl groups to stretches of DNA ⇒ massive overgrowth of trophoblast cells and therefore overgrowth of placenta ⇒ no or all but non-existent fetalgrowth

Question 18

What can molar pregnancies potentially give rise to?

Answer 18

Can rarely give rise to a malignant tumour called choriocarcinoma, as it’s a form of precancer of trophoblast cells

Question 19

What is the treatment for molar pregnancies?

Answer 19

• If BhCGreturns to normal – no further treatment.
• If BhCGstays high (persistent disease) ⇒ cure by methotrexate