Disorders of Early Pregnancy Flashcards
What is the range of estimates for loss before implantation/pregnancy detection?
- Probably ~40% but uncertain
2. Estimates range 30% - 75% loss before implantation
What is the total loss between fertilisation and birth estimated?
between 46% - 90%
What are the monthly probability of conception?
- 15-25%
- So very high estimates (>80%) of loss are unlikely
What are the number of loss after clinically determined pregnancy?
- 10% of all clinically-recognized pregnancies lost
2. 80% of those losses occur in the first trimester
What is the cause of maternal age increasing risk of of miscarriage?
- loss of cohesion between homologous chromosomes in oocyte with increasing age
- loss of proteins (cohesins) holding homologues together
What is a recurrent miscarriage?
loss of three or more consecutive pregnancies, affects 1% of couples trying to conceive
What is recurrent implantation failure?
cases in which women have had three failed in vitro fertilization (IVF) attempts with good quality embryos
What is the key difference between recurrent implantation failure and recurrent miscarriage?
Failure to implant or sustain pregnancy by natural conception (recurrent miscarriage) vs failure of transferred embryo to implant/sustain pregnancy (RIF)
What are the initial diagnostic approaches for recurrent implantation failure and recurrent miscarriage?
-same (possible common/overlapping causes):
1,. check for uterine anatomical defects or presence of fibroids/polyps that might disrupt implantation
2. Determine presence of auto-immune antibodies (anti-nuclear, anti-phospholipid antibodies)
3. Test for paternal DNA sperm integrity/fragmentation?
What is LIF?
leukemia inhibitory factor (cytokine)
What signalling pathways may underpin RM/RIF?
- Normal embryo development but failed implantation in Lif-deficient mouse models
- LIF promotes decidulaisation of human endometrial stromal cells in culture
- Reduced LIF in the uterine secretions of subfertile women
What is endometrial scratching?
use of pipette or hysteroscope to damage endometrial mucosa before embryo transfer in IVF
What is the mechanism of endometrial scratching?
mechanism unknown but thought to stimulate immune cell infiltration and wound healing cytokine production
When is endometrial scratching beneficial?
- Evidence in support variable – possible benefit in selected groups (eg RIF)
- Large NZ study suggests no benefit in any group
What are the smooth muscle adaptations in fallopian tubes?
contractions drive embryo along the fallopian tube
What are the epithelial fallopian tube adaptations?
Epthilium coated in cilia (microvilli) to promote fluid movement
What is continine?
- component of cigarette smoke
2. shown to regulate the expression of PROKR1 a regulator of fallopian tube smooth muscle contractility
How else does continine affect fallopian tubes?
increases expression of pro-apopotic proteins in fallopian tube explants
How does tobacco smoke affect fallopian tubes?
- likely to inhibit ciliary function
- reducing transit of the embryo through the tube.
- Epidemiological studies: OR: 1.7-4 for tubal pregnancy in smokers
What receptors are expressed in fallopian tube?
expresses CB1 and CB2 cannabinoid receptors
How does CB1 affect pregnancies?
- CB1 reduced in ectopic pregnancy patients
- CB1 KO in mice causes embryo retention in the fallopian tubes.
Levels of what are elevated in ectopic pregnancy fallopian tubes?
endocannabinoids
How does components such as THC in cannibas affect fallopian tubes?
may act directly on the fallopian tube to peturb transit, or alter the balance of endocannabinoids (the ‘endocannabinoid tone’) in the tube leading to a disrupted embryo environment
