Early dev disorders Flashcards
What is a miscarriage and what is the timespan for early and late clinical pregnancy loss
Miscarriage: loss of a pregnancy prior to ~22 weeks gestation
Early clinical pregnancy loss (<12 weeks gestation)
Late clinical pregnancy loss (12-22 weeks gestation)
Give the 3 general causes for loss of a pregnancy
Errors in embryo-fetal development
Failure of the embryo to implant in the uterine lining
Inability to sustain development of an implanted embryo/fetus
What is the difference between a biochemical pregnancy and a clinical pregnancy
Clinical: Detectable through ultrasound
Biochemical: Only detectable through hCG
What is the definition of Recurrent Miscarriage (RM) / Recurrent Pregnancy Loss (RPL) and in what percentage of pregnancies does this occur?
UK: three or more pregnancy losses (consecutive or non-consecutive)
USA/Europe: two or more pregnancy losses (consecutive or non-consecutive)
0.8-1.4% pregnancies
What % of lost pregnancies are prior to implantation?
30%
What % of lost pregnancies are lost post implantation but before the missed menstrual cycle(3-4wks)
30%
What percentage of conceptions are lost in the clinical stage and what percentage specifically in 20-24yrolds and 40-44yrolds?
15% generally
10% 20-24yrolds
51% in 40-44yrolds
What is the leading cause of pregnancy loss?
Aneuploidy
What percentage of IVF donor eggs are aneuploid?
53%
What percentage of early lost pregnancies show chromosomal errors
50%
How (mathematically) does risk of trisomic pregnancy increase with maternal age?
Exponentially
When do oocytes undergo meiosis and then how long can they remain in arrest?
During fetal life-Then can remain arrested for up to 50yrs
Why does aneuploidy increase with maternal age?
Throughout meiotic arrest, the chromatids of homologous chromosomes are held together by cohesin proteins
These cohesin proteins are not replaced, leading to loss of cohesion between chromatids with increasing age of the oocyte
If cohesion has been lost, chromatids can separate and drift during meiotic division, rather than being segregated accurately by the spindle.
REC8 and SMC2 are cohesin proteins involved in maintaining cohesion between chromatids within chromosomes
What is an ectopic pregnancy?
Implantation of the embryo of somewhere other than the endometrium lining - 98% occur in fallopian tube
What is the incidence rate of ectopic pregnancy and how can it be treated?
1-1.5%
Treatment ranges from expectant management, through chemotherapy (methotrexate) to surgery to remove the trophoblast and/or tube.
How does tobacco smoking cause increased rates of ectopic pregnancy?
Tobacco smoke inhibits cilia function»_space; reduce fluid movements in the fallopian tube and thus transit of the embryo along the tube
PROK1 and PROK2 growth factor proteins signal through the PROKR1 and PROKR2 receptor proteins to regulate contractility of the smooth muscle layer contractions of the fallopian tube (oviduct).
Continine, a component of cigarette smoke, changes the levels of PROKR1 in fallopian tubes»_space; disruption of normal contractility/fallopian tube function?
In support of this - PROKR1 and PROKR2 receptor levels are reduced in tubes from ecoptic pregnancies vs normal pregnancies.
Cotinine also alters the balance of pro- and anti-apoptosis (cell death) proteins in fallopian tube explants in vitro
How does cannabis affect the fallopian tubes
Fallopian tube expresses cannabinoid receptors CB1 and
CB1 levels are reduced in ectopic pregnancy patients,
CB1 knockout mice display embryo retention in the fallopian tubes.
Endocannabinoid levels are elevated in ectopic pregnancy fallopian tubes
Components such as THC in cannabis may act directly on the fallopian tube to peturb embryo transit,
or
alter the balance of endocannabinoids the ‘endocannabinoid tone’) in the tube leading to a disrupted embryo environment
Give 5 risk factors for ectopic pregnancy
Prior ectopic pregnancy
Prior fallopian tube surgery
Certain sexually transmitted infections (STIs)
Pelvic inflammatory disease
Endometriosis
Cigarette smoking
Cannabis use?
Age older than 35 years
History of infertility
Use ofassisted reproductive technology, such asin vitro fertilization (IVF)