Disorders of Early Development Flashcards
What % of fertilised eggs are estimated to spontaneously miscarry in the early stages of pregnancy?
before implantation > 30-75% before 6 wks > 50-80% before 8 wks > 75% first trimester > 70% between fertilisation and birth > 46-90%
What proportion of pregnancies are lost after a pregnancy has been biochemically confirmed?
10% of all clinically recognised pregnancies lost
80% of ^ occur in first trimester
What is likely to be the major contributor to pregnancy loss before 12 weeks’ gestation?
chromosomal abnormalities
How does maternal age affect the chance of miscarriage?
increased maternal age also increases chance of miscarrying
At what maternal age is the risk of miscarriage the lowest?
25-29
What molecular mechanisms underpin miscarriage due to maternal age?
miscarriage risk mirror increase in aneuploidy risk
primary driver of age related miscarriage is aneuploidy
Define recurrent miscarriage.
loss of three or more consecutive pregnancies, affects 1% of couples trying to conceive.
Define recurrent implantation failure.
refers to cases in which women have had three failed in vitro fertilization (IVF) attempts with good quality embryos.
What is the initial diagnostic approach to recurrent miscarriage/recurrent implantation failure.
check for uterine defects or presence of fibroids or polyps, check for presence of autoimmune antibodies, test for paternal DNA sperm integrity or fragmentation
What signalling pathways might underpin recurrent miscarriage/reccurent implantation failure?
LIF promotes decidulaisation of human endometrial stromal cells in culture, Reduced LIF in the uterine secretions of subfertile women
What is LIF?
LIF = leukemia inhibitory factor (cytokine)
What is endometrial scratching?
Use of pipette or hysteroscope to damage endometrial mucosa before embryo transfer in IVF
What is the purpose of endometrial scratching?
Mechanism unknown but thought to stimulate immune cell infiltration and wound healing cytokine production
Histologically, how is the fallopian tube adapted to support transit of the fertilised embryo to the uterus?
smooth muscle for contraction to drive embryo along fallopian tube
epithelium coated in cilia promotes fluid movement
Explain how cigarette smoking increases the risk of ectopic pregnancy.
continine is in cigarette smoke > regulates expression of PROKRI > regulates fallopian tube smooth muscle contractility
continine increases expression of pro-apopotic proteins
also likely to inhibit ciliary function
