Lecture 7: Early pregnancy, background and recurrent miscarriage.

Question 1

What is gestational age?

Answer 1

Determined relative to the last menstrual period (LMP)

Question 2

Define conception:

Answer 2

Conception is at approx day 14 so an embryo at five weeks post conception (Used by developmental biologist/embryologist)

Question 3

When is it considered embryo vs fetus:

Answer 3

Embryo <11 weeks gestation

Fetus >10 weeks gestation

Question 4

What is trophectoderm:

Answer 4

Epithelium surrounding the preimplantation blastocyst

Question 5

What does the trophoblast epithelium of the placenta consist of?

Answer 5

• Syncytiotrophoblast

- Extravillous trophoblast

Question 6

What are the essential functions of the placenta?

Answer 6

• Exchange/transport/transfer
• Separation
• Protection from maternal infections
• Protection from the maternal immune system
• A large endocrine organ

Question 7

Why do we care about the placenta?

Answer 7

Because you are what you eat and so does the placenta.

Unhealthy placenta gives a poor pregnancy.

Blood does not mix but comes into close contact

Question 8

How is placenta important in early gestation:

Answer 8

Early gestation

• Ectopic implantation
• Failed implantation
• Spontaneous miscarriage
• Recurrent miscarriage -3 or more miscarriages with the same partner

Question 9

How is placenta important in mid-late gestation:

Answer 9

• Fetal hypoxia / brain damage
• pre-eclampsia
• Intrauterine growth restriction

Question 10

Describe the earliest stages of the placenta:

Answer 10

During the implantation (lacunar) stage days 8-12 (post fertilisation)

• The embryo burrows into the decidua
• Digests the decidua forming gaps in the maternal tissue
• The trophectoderm is now called trophoblast protrusions of which extend into the gaps in the uterine tissue

[Meanwhile amniotic and mesodermal + other cell layers are forming]

Question 11

Why does one care about the early placenta?

Answer 11

The ‘real placenta’ exists from day 12…. yet 70% of conceptions of lost, therefore issues with palcental formation are worth thinking about

Question 12

Describe the early placenta and its structure:

Answer 12

A three dimensional ball of villi

Villi initially surround the implanted embryo

• Those villi to the sides and towards the uterine lumen regress to form the smooth chorion ‘chorion Laeve’
• Those villi at the base of the implantation site form the definitive placenta ‘Chorion frondosum’

Question 13

Describe the regression of villi on a 7.5 week old placenta:

Answer 13

• The placenta forms essentially as a sphere surrounding the embryo but as gestation progressess
• > Villi to the sides and luminal aspect regress to form the smooth chorion
• > Only villi basal to the implantation site remain as the definitive placenta

Question 14

What are the placental villi?

Answer 14

The structural unit of the placenta

Question 15

What are floating villi:

Answer 15

Floating Villi

• Most villi do not have contact with the maternal tissues but are suspended in the intervillous space these are called floating villi
• Floating villi are responsible for the exchange and barrier functions of the placenta

Question 16

At term syncitotrophoblast covers what?

Answer 16

Entire placenta, one cell thick? Fact check this bad boy

Question 17

What are anchoring villi:

Answer 17

Anchoring Villi

• In a few villi, cytotrophoblasts break through the syncytiotrophoblast
• Columns of extravillous trophoblasts continue to stream out of these anchoring villi to invade the decidua and spiral arteries during the first and second trimesters “The physiological changes of pregnancy”

Question 18

Insert slide 20

Answer 18

now

Question 19

What happens to the spiral arteries with the placental tissues:

Answer 19

Endovascular trophoblast invades radial arteries and destroys endothelial cells and replaces them. (SM and elastin destroyed therefore widen lumen, replaces therefore increase blood flow) mid gestation

Question 20

Describe how the spiral arteries are plugged:

Answer 20

Trophoblast plugs in the spiral arteries break down around 10 weeks allowing full perfusion of the placenta by 13 weeks (Dont respond to maternal stimuli once these vessels change)

Therefore the embryo develops in low oxygen environment

Question 21

Discuss premature blood flow and miscarriage:

Answer 21

• Doppler ultrasound demonstrated an increased flow of maternal blood to the placenta in missed miscarriages. (before 11 weeks)
• The premature maternal blood flow was distributed centrally and across the placenta, whereas, in normal pregnancies, the maternal blood flow was more likely to be observed at the periphery of the placenta.

Take home: Premature maternal blood-flow to the placentae is BAD and may cause miscarriages.

Question 22

Define recurrent miscarriage:

Answer 22

2 or more miscarriages with the same partner

Question 23

Are there any antibodies associates with recurrent miscarriages:

Answer 23

- Antiphospholipid antibodies
3 key examples
-> Lupus anticoagulant
-> Anticardiolipin AB
-> Anti-B2-glycoprotein 1 AB

These activities may one antibody or three seperate ABs - differs between patients (triple most at risk)

Question 24

Describe anti-phospholipid antibodies in treatment of pregnancy:

Answer 24

• Mainstay of treatment is heparin plus aspirin
• (historically based on association of aPL systemic thrombosis)
• BUT THROMBOSIS is not a likely cause of obstetric complications because physiologically we know are clamped off anyways early on)

Question 25

What do aPL autoantibodies damage?

Answer 25

Damage mitochondria in the syncytiotrophoblast (apparently)

Question 26

What did the cochrane systematic review of anticoagulant drugs in the prevention of recurrent miscarriage in women with aPL autoantibodies:

Answer 26

• Very uncertain if aspirin has any effect on live births
• Heparin plus aspirin MAY increase the number of live births and MAY reduce the risk of pregnancy loss.
• We are uncertain about the SAFETY of heparin and aspirin for mothers and infants because of the LACK of reporting of adverse events.

Question 27

Describe the similarity of hCG to other hormones:

Answer 27

hCG

• Two chain hormone
• Shares its alpha chain with TSH, LH and FSH
• Unique beta chain, but very similar to LH and has LH like actions

Question 28

What produces Beta hCG:

Answer 28

Produced exclusively by the trophectoderm of the preimplantation blastocyst and syncytiotrophoblast of the placenta.

Detectable in the maternal blood/urine within days of implantation used to detect pregnancy.

Question 29

Describe the hCG time profile:

Answer 29

• Secretion of beta hCG increases
• Peaks around 10 weeks
• Abnormal/slow pregnancy in hCG may indicate a failing pregnancy
• Women with multiple pregnancies have increased levels hCG. (increased syncytiotrophoblast)
• High levels of hCG are also found in trophoblastic tumours (choriocarcinoma and hydatidiform mole, also some testicular tumors)

Question 30

What are the functions of hCG:

Answer 30

• hCG binds to the LH/hCG receptor and thus transmits similar signals to LH.
• Luteal support: hCG has strong leutotrophic properties and is important in stimulating the production of progesterone and oestrogen by the ovary during the first 6-8 weeks of pregnancy.
• Stops regression of corpus luteum
• The CL doubles in size about a month into pregnancy under the influence of hCG.