Lecture 7: Early pregnancy background and recurrent miscarriage

Question 1

What is the number of weeks gestation of fetus vs embryo

Answer 1

embryo: less than 10 wks gestation
fetus: more than 10 wks gestation

Question 2

What is the syncytiotrophoblast

Answer 2

Single cell that covers the whole placenta.

Question 3

What makes hCG, what is its structure, function and factors that effect the level of hCG

Answer 3

hCG made from trophectoderm of pre implantation blastocyst and syncitiotrophoblast of the placenta once implantation has taken place

hCG has two chains and is almost identical to LH except having longer half life- helps to keep up progesterone and oestrogen production by the ovary in the first 6-8 wks of pregnancy and also stops regression of the corpus luteum-> doubles in size.

hCG should exponentially increase in implanted woman until 10wks.

If drop/ slow increase of hCG may indicate failing pregnancy

Increased levels of hCG may be

• multiple pregnancies due to increased syncitiotrophs for each placenta
• Trophoblastic tumour: choriocarcinoma, hydatidiform mole, testicular tumour - so hCG helps to monitor if treatment is working

Question 4

What is the function of the placenta. Does fetal and maternal blood mix in the placenta?

Answer 4

Functions

• Exchange of O2, nutrients and waste
• Separation of mum and bb immune systems
• Protection against some maternal infections
• A large endocrine organ

Maternal and fetal blood do not mix- separate circulations that are brought to close apposition by the placenta

Question 5

What are the steps of embryo during implantation/lacunar phase - 8-12 days post fertilisation

Answer 5

1. Embryo burrows into decidua
2. placenta enzymes digesting decidua to form gaps in the maternal tissue
3. Trophectoderm is now called trophoblasts of the placenta and have protrusions which extend into the gaps.

Question 6

How does the early placenta develop from a ball of villi containing the embryo to the disk on 7.5 wk placenta

Answer 6

The villi on side sand towards the uterine lumen regress to form the smooth chorion: chorion laeve

the villi at the base of the implantation site remain to form the Definitive placenta: chorion frondosum

Question 7

What are the two types of villi - structural unit- that make up the early placenta : structure and function

Answer 7

1. Floating villi: (99%) for barrier and exchange functions of placenta
   - suspended in the intervillous space (maternal blood lake)
2. Anchoring villi: - made of cytotrophoblasts that break through the syncitiotrophoblast, they physically attaching to the placenta to uterine wall.
   This allows columns of extravillous trophoblasts to get out and invade the decidua and spiral arteries

Question 8

What are the normal physiological changes to spiral arteries in trim 1 and 2- mid gestation and why is this important

Answer 8

1. After invading the decidua, extra villous trophoblasts digest the muscular wall of spiral arteries
2. they replace the endothelium- becoming endovascular trophoblasts– they can invade into up to 2/3 of myometrium.

This is important because it destroys the ability of the spiral arteries to be tonically active so avoids symp triggered vaso-constriction=> reduced blood flow for bb brain

Question 9

What are the changes to the spiral arteries up to 12 weeks and how does this impact the fetus- how is this compensated

Answer 9

Trophoblasts migrate down the spiral arteries, plugging the lumen as an endovascular trophoblast plug.
This stops RBCs going through so fetus is in a low O2 environment which is normal.

however the lack of nutrients is compensated by uterine glandular secretions which fill the intervillous space (before the blood lake).

by 10 weeks the plugs start breaking down and full perfusion of placenta starts at 13wks +

Question 10

What is the relationship between maternal blood flow and miscarriage

Answer 10

• Premature maternal blood flow before 12-13wks can be damaging to embryo due to ROS.
• central maternal blood flow was seen in missed miscarriage compared to peripheral maternal blood flow around placenta in normal pregnancy

Question 11

What may be a cause of poor pregnancy in early (failed implantation, miscarriage), and mid-late gestation (eg. fetal hypoxia, pre eclampsia)

Answer 11

Unhealthy placenta

Question 12

What is definition of recurrent miscarriage

Answer 12

3 or more miscarriages with the same partner (2 is quite common)

Question 13

What is one condition that can cause recurrent miscarriage and what is the mechanism

Answer 13

Antiphospholipid antibody syndrome:
having autoantibodies against lipid binding protein.

Against 3 types is most risk

• against lupus anticoagulant
• anticardiolipin
• antiBeta2glycoprotein 1

3 types done by one antibody or 3 separate. Miscarriage generally in 1st trim

Question 14

What is the prevalence of antiphospholipid antibody syndrome and what is treatment. Is this even helpful in pregnancy setting?

Answer 14

General population is 1-3% but makes 15-40% of recurrent miscarriage population

Treatment is with low Mwt Heparin plus low dose aspirin (because of increased risk of coagulation)

Not very helpful as thrombosis is not likely cause of obstetric complications as in 1st trimester there is no perfusion due to trophoblast plug and miscarriages are more likely in 1st trimester