Pregnancy

Question 1

First trimester: define the features and risks of the first trimester (0-13 weeks) of normal human pregnancy.

Answer 1

Pregnancy

Start of Pregnancy

• Pregnancy is counted from the first day of the last menstrual period (LMP), with other events dated from this time.
  gestastional age = LMP + 2 weeks
• This is important as an embryologist and an obstetrician would use different time-scales.
• IVF pregnancy timing – fertilisation occurs 2-3 days before:
• There will be a difference in time of 2-2.5w from the gestational age (GA, derived from LMP) and the GA in an IVF pregnancy – this can make a large difference when determining viability (22 vs 24 weeks for example).
• Pregnancy is divided into 3 trimesters.
• Spontaneous loss of pregnancy in the first trimester is very common (1/3rd of all) but after that, loss is minimal.
• The end of the 2nd trimester marks the limit of infant survival (after this, the child is viable).
  
  • Modern care can push this back to 22 weeks.
• Term (39-40 weeks) is expected delivery time and is stated as ~280 days (40 weeks) since LMP.

26 weeks - baby born at 26 weeks can survive without modern neo-natal ICU

miscarriage - more often before week 13 - something about vessels?

Question 2

Maternal physiological changes: recognise the maternal anatomical and physiological changes associated with pregnancy.

Answer 2

Maternal Changes

• General changes – abdominal changes in the mother only become apparent during the 2nd trimester +.

Main maternal changes:

• Increased weight. (3rd)
• Increased hormone levels. (1st +)
• Increased body temperature.
• Increased blood clotting. (2+)
• Decreased BP. (WTF) (2+)
• Increased breast size.
• Increased vaginal mucus.
• “Morning sickness”
• Altered brain function (1st +)
• Altered appetite. (1+)
• Altered fluid balance. (2nd +)
• Altered emotional state. (1st +)
• Altered joints. (3rd)
• Altered immune system. (1st +)

These all are either obvious ± or they vary between individuals (“altered”) and the extent to which they change varies throughout pregnancy.

hepertension proteinurea before week 22 and after week 22 preeclampsia

Question 3

Outline endocrine

learn this

Answer 3

Increased hormone levels:

• hCG
  
  • peaks 1st trimester and decreases thereafter
  • HCG peaks during the first trimester - it keeps menstruation form happening
  • Morning sickness has been correlated
• All other hormones (progesterone, oestrogens, lactogen) – slowly increase as the pregnancy progresses.Progesterone is key to maintaining the pregnancy – progesterone antagonists à loss of pregnancy at ALL gestational ages.
  
  • Progesterone source:
    
    • Fertilisation -> 8 weeks’ gestation – corpus luteum source via hCG.
    • 8+ weeks – placenta supplies progesterone.
      
      • The change-over = “Luteo-placental shift”.
• Oestrogen source:
  
  • Fertilisation à Luteo-placental shift – corpus luteum.
  • 8+ weeks – complex interplay between foetal/maternal adrenals and placenta.
    
    • Human placenta – does not express the enzymes needed to convert pregnenolone à androgens so this occurs in foetal adrenals.
      
      • The weak androgen produced (DHEA) is sulphated to give DHEA-S which is inactive (so female foetus is not exposed to androgens).
      • DHEA-S goes to the placenta to be converted to 17b-oestradiol.
    • High levels of oestriol are produced by a parallel mechanism including hydroxylation of DHEA-S in foetal liver to give 16OH-DHEA-S.
• High steroid levels supress HPG-axis à low FSH and LH throughout

Question 4

Foetal Perspectives:

Answer 4

Foetal Changes – much seems to be a repeat of known information (Embryology), I will cover what is new or needed:

• Blastocyst - 9 days
• Embryo: 5-6 weeks
• Fetus: 2 months

Definitions:

• Conceptus – everything resulting from the fertilised egg.
• Embryo – the baby up to week 8 of development.
• Foetus – the baby for the rest of pregnancy.
• Infant – applied after delivery typically.

Again, remember that timings used to discuss embryology are usually from point of fertilisation, 2 weeks after LMP timings used in timings of pregnancy – the embryology timings are PF – Post-Fertilisation.

Weights:

• First trimester – 50g.
• Second trimester – 1050g – viable at 500-820g stage (21-24 weeks).
• Third trimester – 2100g.

Early in development embryos of different species look very similar.

Question 5

Second trimester: define the features and risks of the second trimester (14-26 weeks) of normal human pregnancy, list the main purpose of this phase and recognise the point of viability.

Question 6

Third trimester: define the features and risks of the second trimester (27-39 weeks) of normal human pregnancy, list the main purpose of this phase.

Question 7

Steroidogenesis: recognise pregnancy as a three-way interaction between mother, foetus and placenta with steroidogenesis as an example of this.

Question 8

Placental functions: list the main placental functions including separation, exchange, biosynthesis, immunoregulation and connection.

Answer 8

Placental Functions

1. Separation – despite the close contact, the foetus and the maternal vascular system must remain separated.
2. Exchange of nutrients and waste products.
3. Biosynthesis – second only to the liver in the biosynthesis functions.
4. Immunoregulation –
   
   • only allows ensures no rejection of conceptus. This cannot be the function of the uterus as ectopic pregnancies outside of the uterus can still proceed.
5. Connection/Anchorage – the foetus is bound to the mother’s arterial blood supply.

Question 9

Placental structures: identify the main placental structures and explain how the placenta develops.

Answer 9

Anatomy of the Placenta

Very effective for transport of molecules between maternal and fetal circulations.

Also anchors the placenta (and hence the baby) securely for 9 months.

Intimate contact between maternal and placenta tissues – interesting immunology!

• Primary subunit is the placental villus that has the branches.
• This provides a large surface area for exchange between the maternal and foetal vascular systems.
  
  • Very highly branched structure, provides a large surface area (~11m2).
• Note that the veins contain oxygenated blood and the arteries contain deoxygenated blood as the placenta carries out a parallel function to the lungs during pregnancy.
• Note the separation of the maternal and foetal systems despite being near.
• Cotyledons – the maternal surface of the placenta is sub-divided into cotyledons (30-60/placenta). Each contains one or more villi.- it is a BASIC PLACENTAL STRUCTURE

Cotyledon: central stem from where vessels pass and then it branches to increase SA

Carries both maternal and fetal blood supplies, maternal blood supply carries oxygen and nutrients and transports them to the foetal ones

Artery: carrries blood away from the heart and is usually oxygenated

Vein: carries blood to the heart and is usually deoxygenated

In this case, artery goes from heart to placenta: deoxygenated blood

Question 10

Overview placental development

Answer 10

(1) Development of the Placenta

• Approx. 9 days PF, the conceptus is completely implanted in the maternal endometrium.
• Placenta originates from the cytotrophoblasts layer.

(2) Development of the Placenta

• Cytotrophoblasts proliferate into the syncytium to form a columnar structure which becomes a villous structure.
• Formation of placental villus tree
• At 8 weeks gestation placenta: contact
• There is a lot of angiogenesis going on in the placenta during 2nd and 3rd trimester because the baby grows significantly
• The embryo is not exposed to many oxygen free radicals and is likely to be damaged REWATCH EDW LIGO KOLLITI GIATI XANOMASTE

(3) Development of the Placenta

• The overall structure then does not change but it is modified.
  
  • There are fewer cytotrophoblasts present at term so that there can be a closer apposition between the syncytium and placental capillaries

1. ST on the outside - first comes into contact with moms
2. CT - when ct grows into st is called primary villus
3. mesoderm line these villi - secondary chorionic villi
4. blood vessels form in the mesoderm - tertiary
5. CTB from villi grow towards the decidua and form a CTB shell
6. 6 week - spiral artery remodeling
7. 10-12 week - CTP plugs breakdown and placental exposed to full maternal blood flow
   
   • Cytotrophoblast shell: protects the embryo/fetus from receiving too many oxygen radicals because they are dangerous
   • First trimester: low oxygen environment

Histotrophic nutrition - decidual glands -> heterotrophic nutrition

Question 11

Outline the placenta’s content with maternal tissues

Answer 11

• During weeks 10-12 GA, the Cytotrophoblast plugs break down (from the periphery directed centrally) and the spiral arteries form to supply the foetus with blood normally.
  
  • This is a risk-time in the pregnancy – if the placenta is not anchored properly, the increased pressure as it is exposed to the maternal blood supply can lead to a detach and a miscarriage.
• During the 1^st trimester, the placenta is ~5cm diameter but this increases to ~20cm during 2^nd and 3^rd.
• The cytotrophoblast (ctb) cells remodel the spiral arteries during the 1^st trimester from 4-5-6 until ~16-18w GA.
• The remodelling converts the narrow bore spiral vessels into wide-bore vessels to transport more volumes of blood.
  
  • The ctb cells replace the vascular endothelium and VSMCs which is important as it means the vessels here cannot respond to vasoconstrictors.
• The placenta has no nerves so can be cut without harm.

Regulation of Growth/Development

• Placenta regulates its own growth/development through autocrine functions.
• The maternal decidua mainly seems to restrain (modulate) placental growth/development so the placenta is optimal both for the baby and mother.

Question 12

Maternal Risks

Answer 12

Placental mal-development

• Miscarriage (late first trimester)
• Miscarriage (second trimester)
• Pre-eclampsia (early delivery)
• Fetal growth restriction (small infant)

Maternal Risks

• Most risks to the mother lie in delivery and labour.

Risks:

Remodelling of the spiral arteries means that vessels can lose relatively large amounts of blood after delivery – this should be limited by contractions of the uterus after the placenta has been delivered.

Placenta must be checked carefully to make sure all has been delivered as it is quite inflexible and any left in the uterus may lead to ineffective uterine contractions.

Question 13

Miscarriage and stillbirth: explain the difference between miscarriage and stillbirth and recognise how US imaging and foetal dopplers and used in foetal assessment.