Disorders of early development Flashcards
What fraction of fertilised eggs are estimated to spontaneously miscarry in the early stages of pregnancy?
very wide range
- Before implantation 30-50%
- Before 6 weeks: 50%, 70%, 80%
- Before 8 weeks: 75%
- First trimester: 70%
- Between fertilisation and birth: 46%- 90%
human fecundity (monthly probability of conception) is low so high loss if unlikely
What proportion of those are lost after a pregnancy has been biochemically confirmed?
10% of all clinically pregnancies lost
- 80% of these losses occur in the first trimester
when do most miscarriages occur?
first trimester
What is a major contributor to pregnancy loss before 12 weeks’ gestation?
maternal age
How does maternal age affect the chance of miscarriage?
risk lowest 25-29 (10%)
it increases with maternal age (50% at >45)
risk of miscarriage mirrors increase in aneuploidy (eg. trisomy)
Risk is also slightly high if you get pregnant before your 20s
Why does increasing maternal age increase risk of miscarriage?
Cohesins start to degrade as you get older and are not replaces.
increase likelihood of chromosomal abnormalities
There is also increased chance of mitochondrial dysfunction
What are recurrent miscarriage and recurrent implantation failure and what is the major difference between them?
Recurrent miscarriage (RM) = loss of 3 or more consecutive pregnancies, affects 1% of couples
Recurrent implantation failure (RIF) = 3 failed IVF attempts with good quality embryos
Key difference:
• failure to implant/sustain pregnancy by natural conception vs failure of transferred embryo to implant/sustain
What are some possible overlapping (physiological) causes of recurrent miscarriage and RIF?
Check uterine anatomical defects or presence of fibroids/polyps that may disrupt implantation.
Determine presence of auto-immune antibodies anti-nuclear, anti-phospholipid antibodies)
Test for paternal DNA sperm integrity/fragmentation
What signalling pathways might underpin RM/RIF?
LIF: leukaemia inhibitory factor (cytokine)
LIF promotes decidualisation of human endometrial stromal cells in culture
reduced LIF in uterine secretions of subfertile women
What is endometrial scratching and how might it help a patient experiencing RIF?
Use of a pipette or hysteroscope to damage endometrial mucosa before embryo transfer in IVF.
It is thought to stimulate immune cell infiltration and wound healing cytokine production
evidence in support is variable - possible benefit in selected groups (RIF)
Histologically, how is the fallopian tube adapted to support transit of the fertilised embryo to the uterus?
smooth muscle - contractions drive embryo along the fallopian tube
Epithelium coated in cilia (microvilli) to promote fluid movement.
Fimbrea- to capture relased ovum
What is an ectopic pregnancy? what risk does this increase?
When a fertilised egg develops outside the uterus (usually in the fallopian tube)
high risk for rupture and death
Explain the impact and physiology of smoking on the fallopian tube
Continine, component of cigarette smoke, has been shown to regulate expression of PROKR1
- PROKR1 regulates fallopian tube smooth muscle contractility
Continine also increases expression of pro-apoptotic proteins in fallopian tube
- tobacco smoke also likely to inhibit ciliary function.
This can lead to an ectopic pregnancy
What is the impact of cannabis on the fallopian tube?
Fallopian tube expresses CB1 and CB2 cannabinoid receptors
CB1 reduced in ectopic pregnancy patients.
levels of endocannabinoids and anandamine elevated in ectopic pregnancy tubes
components (eg THC) in cannabis may act directly on fallopian tubes (tone) to perturb transit, or alter the balance of endocannabinoids in the tube leading to disrupted embryo environment
