2 - Pregnancy Flashcards
How long does human pregnancy last approximately?
9 months
How many cases of pregnancy have complications per year?
What is a trimester and how many are there in pregnancy?
Trimester = three month period
Pregnancy is typically divided into three trimesters
In what trimester of pregnancy is spontaneous loss of pregnancy most common?
The first trimester
- 1/3 of all conceptions do not complete the first trimester
When is the end of the second trimester?
26-27 weeks
What is the absolute limit of infant survival in the absence of modern neonatal intensive care?
the end of the second trimester = 26-27 weeks
(in the absence of modern neonatal intensive care)
What is the absolute limit of infant survival with modern neonatal intensive care?
The absolute limit is about 22 weeks of pregnancy and 50% survival is at about 25 weeks
What is ‘term’?
Normally stated as 280 days since the beginning of the last menstrual period (40 weeks)
The word ‘term’ covers gestational ages from 37-41 weeks of gestation, with deliveries either side of this being ‘pre-term’ or ‘post-term’.
When do abdominal changes become more apparent during pregnancy?
Abdominal changes become more apparent during the second trimester, and the major changes are during the third trimester
Summarise the main maternal changes of pregnancy
Increased weight
Increased hormone levels / altered endocrine system
Increased blood clotting tendency
Decreased blood pressure
Increased basal body temperature
Increased breast size
Increased vaginal mucus production
Increased nausea and vomiting (‘morning sickness’)
Altered brain function
Altered appetite
Altered fluid balance and urination frequency
Altered emotional state
Altered joints
Altered immune system
The first eight items in the list show clear directionality of change (increase or decrease), whereas the others are all affected as pregnancy progresses, but vary between individuals.
Generically summarise the first weeks of pregnancy, concentrating on ovarian and uterine events
This summary of the earliest events of pregnancy reflects an average of the timings
Variability in length of the menstrual cycle makes it difficult to identify (in a normal pregnancy) the exact timings of ovulation and fertilisation.
What is the convention when counting the start of pregnancy for O&G doctors?
The convention is that pregnancy is counted from the first day of the last menstrual period (LMP)
Other events are then dated from this time
When would an embryologist consider the start of pregnancy?
An embryologist would start the count from fertilisation
How big of a difference would there be between gestational age derived from LMP and gestational age in an IVF pregnancy?
2-2.5 week difference
GA from LMP
Counted from first day of last menstrual period
GA in IVF Pregnancy
Could be counted from:
- addition of sperm to oocyte (fertilisation)
- insertion of ferilised oocyte into mother, 3-5 days after fertilisation (embryo transfer)
What GA should be used when making decisions as to whether to treat pre-term infants?
GA from fertilisation
What GA is conventionally used when discussing maternal changes?
GA - LMP (first day of Last Menstrual Period)
How much weight is gained by the mother during pregnancy?
Overall weight gain in pregnancy is variable
Average: 10-15 kg
What does weight gain in pregnancy include?
- weight of fetus
- amniotic fluid
- placenta
- increased fluid retention
- increased nutritional stores (to feed the baby after delivery)
When does most of the weight gain occur during pregnancy?
Weight changes are concentrated into the second and particularly, the third trimester
Outline how the levels of the main hormones of human pregnancy change throughout the duration of pregnancy
Human Chorionic Gonadotrophin (hCG)
- peak levels in maternal plasma in first trimester
- declines thereafter
- hCG is also produced by the placenta like the other hormones, but the regulation of its production is different
Placental Lactogen
- increases as pregnancy progresses
- parallels the increased size of the placenta
- produced by the placenta
Oestrogens (mainly oestriol)
- increases as pregnancy progresses
- parallels the increased size of the placenta
- produced by the placenta
- level can go up to 20nM (greatly exceeds level during normal menstrual cycle)
Progesterone
- increases as pregnanacy progresses
- parallels the increased size of the placenta
- produced by the placenta
- level can go up to 1µM (greatly exceeds level during normal menstrual cycle)
- key hormone in allowing pregnancy to continue
Administration of what hormone antagonist will lead to loss of pregnancy at all gestational ages?
Low progesterone levels or administration of a progesterone antagonist will lead to loss of pregnancy at all gestational ages
Why are there very low levels of FSH and LH throughout pregnancy?
High levels of steroids suppress the HPG (hypothalamic-pituitary-gonadal) axis
This leads to very low levels of LH and FSH
This is important as this results in no cyclic ovarian and uterine functions
What are the sources of progesterone during pregnancy?
From fertilisation (at about 8 weeks):
- corpus luteum is main source of progesterone
- this production is sustained by the rapidly increasing hCG levels
- placenta also makes progesterone
- placenta is small at this stage of pregnancy and so its contribution to maternal progesterone is limited
About 6 weeks of gestational age:
- corpus luteum gradually starts to produce less progesterone, despite very high hCG levels
6-9 weeks of gestational age:
- placenta increases in size
- gradually contributes more to maternal progesterone
About 9 weeks:
- corpus luteum ceases to make steroids
About 10 weeks of gestational age:
- placenta is source of all progesterone
The placenta produces progesterone constitutively at increasing levels for the rest of pregnancy
What is the ‘luteo-placental shift’?
The change is source of progesterone (from the corpus luteum to the placenta) in order to sustain pregnancy
Summarise the production of steroids during human pregnancy
Early Weeks of Pregnancy:
- corpus luteum produces progesterone
- corpus luteum produces oestrogens (mainly 17β-oestradiol
Luteo-Placental Shift:
- production of oestrogens changes as outline in the figure attached
- complex interaction between the placenta and the fetal adrenal glands
What complex interaction regarding production of oestrogens in pregnancy occurs following the luteo-placental shift?
PRODUCTION OF OESTROGENS IN HUMAN PREGNANCY, FOLLOWING THE LUTEO-PLACENTAL SHIFT
COMPLEX INTERACTION BETWEEN THE PLACENTA AND FETAL ADRENAL GLANDS
Human placenta does not express the enzyme CYP450 17A1 (also known as CYP 17 or CYP450 17,20-lyase)
- this enzyme converts pregnenolone to androgens
Therefore, conversion of prenenolone to androgens takes place in the fetal adrenal glands
- fetal adrenal glands are large and well-developed even in the first trimester
The weak androgen produced is dehydroepiandrosterone, DHEA
DHEA is sulphated as well to give DHEA-S, which is inactive
Hence, a female fetus is not exposed to an androgen during development
DHEA-S circulates to the placenta, where it is converted to 17beta-oestradiol as shown
In human pregnancy, very high levels of oestriol are found, which are produced by a parallel mechanism (Figure 3.5), which includes hydroxylation of DHEA-S in the fetal liver to produce the precursor 16OH-DHEA-S.
Outline the increased blood clotting frequency associated with pregnancy
The maternal blood tends to clot more readily; this starts early in pregnancy, and is greatest at term.
It is thought that this is protective against losing too much blood at delivery, but may also be important in view of the interactions between the placenta and maternal blood throughout pregnancy.
Outline the decreased blood pressure associated with pregnancy
We are very used to the concept that increased blood clotting and increased blood pressure are parallel changes, as it is well established that hypertension is strongly linked to an increase in stroke and heart attacks.
Human pregnancy shows one of its atypical features, in that these two parameters change in opposite directions. Maternal blood pressure is lowest during the second trimester, and increases the risk of maternal fainting – so pregnant women should not stand for prolonged periods of time! Blood pressure tends to increase during the third trimester, but should still remain below a level that would be considered as hypertension; 120/70 mmHg would be considered normal.
Outline the increased basal body temperature associated with pregnancy
Basal body temperature increases by ~0.5°C in the second half of the menstrual cycle after ovulation. This reverses during menstruation, and is sustained into the first trimester of pregnancy, probably by the thermogenic roles of progesterone.
As the fetus increases in size, it contributes to maternal temperature, and normal maternal temperatures may exceed 38°C.
Outline the increased breast size associated with pregnancy
Breast changes are dependent on increased hormone levels in the maternal circulation
The changes (including an increase in size) start in the first trimester and continue through the rest of pregnancy, so the changes are generally greatest by the time of delivery.
Outline the increased vaginal mucus production
A common and normal change in pregnancy, clear mucus is produced throughout most of pregnancy. If the mucus is not clear (bloodstained, coloured or has an offensive odour), medical advice should be sought.
What is early development of the human embryo vulnerable to?
TERATOGENS
Factors that can affect the details of development, although the primary structures will be present
Summarise the stages in development of a fertilised human oocyte to an embryo, then to a fetus
Outline the preimplantation development of a human embryo
The cells of the embryo are undergoing mitotic (cleavage) division, deriving their nutrients from the secretions of the Fallopian tube.
Outline the normal trajectory of growth of a fetus during human pregnancy
Summarise embryonic development during the first trimester of human pregnancy
All of this takes place in a low oxygen environment (~3%)
Week 8 of embryonic development = Week 10 of gestation
Describe the main structural features of the placenta
The primary subunit is the placental villus, which have the complex branched structure shown. This provides a very large surface area (estimated to be 11 square metres) for exchange between the maternal and fetal vascular systems, thus meeting a primary requirement for exchange functions (point 1).
Anchorage to the maternal decidualised endometrium is also shown (point 2). Within each villus there is a complex blood supply, including arterial and venous vessels, connected to smaller capillaries in the terminal portions of each villus. Note that the arterial system contains de-oxygenated blood, and the venous blood is oxygenated – because the placenta has a parallel function to the lungs for the fetus during pregnancy.
This figure also shows that the maternal and fetal blood supplies are separated from each other, despite being in close proximity.
What are cotyledons?
The maternal surface of a placenta is sub-divided into cotyledons (30-60 per placenta). Each cotyledon contains one or more villi, with larger cotyledons containing more villi. The variability in the shape and size of cotyledons does not affect placenta function.
By how many days after fertilisation is the conceptus almost completely implanted?
Approximately day 9 post-fertilisation (Figure 3.13), the conceptus is almost completely implanted within the maternal decidualising endometrium.
What happens to the structure of the conceptus following implantation, with regards to the placenta?
Following implantation, the cytotrophoblast proliferate into the syncytium; first a columnar structure is formed (cytotrophoblast column), which then undergoes branching (villous sprouts).
At the centre of each villus are mesenchymal (extra-embryonic mesoderm) cells, from which the villus vascular system develops.
The branching process continues through out pregnancy, giving rise to the complex branched villi shown in Figure 3.14.
What happens to the overall structure of the placental villi during pregnancy?
The overall structure of a placental villus does not change throughout pregnancy (Figure 3.15), but there are modifications.
In brief, there are fewer cytotrophoblast present at term, so that there can be a closer apposition between the syncytium and the placental capillaries.
This will maximise the efficacy of nutrient transfer into the fetal blood, and enhance fetal growth in later pregnancy.
Outline the different stages of contact between the conceptus and maternal throughout pregnancy
At the earliest stages of pregnancy, the conceptus is in contact with maternal endometrial cells (Figure 3.13).
As it grows, it makes transient contact with the maternal capillaries (Figure 3.14), but the rapidly proliferating cytotrophoblast cells form a shell around the conceptus (Figure 3.16), isolating it from maternal blood by about 4 weeks post fertilisation.
Why happens to the decidual glands in the first trimester of human pregnancy?
The decidual glands hypertrophy during the first trimester of human pregnancy (Figure 3.17), and these provide the nutrients for the placenta and developing baby.
It must be emphasised that the placenta functions normally at this time, it is the source of the nutrients (glands: histotrophic nutrition) rather than maternal blood (haemotrophic nutrition) that is different.
Outline the remodelling of uterine spiral arteries during human pregnancy
The cytotrophoblast shell (Figure 3.18, labelled as CT) remains in place until about 8 weeks post-fertilisation, which is 10 weeks gestational age.
The spiral arteries are blocked by cytotrophoblast plugs.
During weeks 10-12 (GA), the cytotrophoblast plugs gradually break down, beginning with those at the periphery of the placenta, and ending with those near the centre. The result is the structure shown in Figure 3.19, with spiral arteries providing maternal blood to the placenta, and hence forming the main supply of nutrients to the developing placenta and fetus. Note that this is one of the risky time-frames of pregnancy; if the placenta is not fully anchored to maternal decidua, the increase in pressure as it is exposed to the maternal arterial supply can detach the placenta and lead to miscarriage (late first trimester).
The placenta is about 5cm in diameter at the stage of pregnancy; during the second and third trimesters it grows to ~20cm in diameter, but the key structural components do not change. Most of the growth is due to increased size and branching of the villi.
A further point to note from Figure 3.19 is the remodelling of the spiral arteries by cytotrophoblast cells (points E and F), during which the vascular endothelium, and underlying smooth muscle cells are lost, and replaced by cytotrophoblast. This remodelling process begins during the first trimester, and continues until weeks 16-18 of gestation.
This remodelling is critical for later growth of the fetus, as it converts the narrow, vasoactive spiral arteries to wide-bore vessels that can transport very large volumes of maternal blood to the placenta, and hence provide the quantities of nutrients needed. The lack of smooth muscle cells in these remodelled vessels is important, as this means that the blood flow remains high as these arteries cannot respond to vasoconstrictors.
The placenta has no nervous system, so it is not regulated by such systems at any stage of pregnancy. This means that it can feel no pain during delivery, and the umbilical cord can be cut after delivery without any impact on the infant.
