Early dev disorders

Question 1

What is a miscarriage and what is the timespan for early and late clinical pregnancy loss

Answer 1

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)

Question 1

Give the 3 general causes for loss of a pregnancy

Answer 1

Errors in embryo-fetal development

Failure of the embryo to implant in the uterine lining

Inability to sustain development of an implanted embryo/fetus

Question 2

What is the difference between a biochemical pregnancy and a clinical pregnancy

Answer 2

Clinical: Detectable through ultrasound
Biochemical: Only detectable through hCG

Question 3

What is the definition of Recurrent Miscarriage (RM) / Recurrent Pregnancy Loss (RPL) and in what percentage of pregnancies does this occur?

Answer 3

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

Question 4

What % of lost pregnancies are prior to implantation?

Answer 4

30%

Question 5

What % of lost pregnancies are lost post implantation but before the missed menstrual cycle(3-4wks)

Answer 5

30%

Question 5

What percentage of conceptions are lost in the clinical stage and what percentage specifically in 20-24yrolds and 40-44yrolds?

Answer 5

15% generally

10% 20-24yrolds
51% in 40-44yrolds

Question 5

What is the leading cause of pregnancy loss?

Answer 5

Aneuploidy

Question 6

What percentage of IVF donor eggs are aneuploid?

Answer 6

53%

Question 7

What percentage of early lost pregnancies show chromosomal errors

Answer 7

50%

Question 8

How (mathematically) does risk of trisomic pregnancy increase with maternal age?

Answer 8

Exponentially

Question 9

When do oocytes undergo meiosis and then how long can they remain in arrest?

Answer 9

During fetal life-Then can remain arrested for up to 50yrs

Question 10

Why does aneuploidy increase with maternal age?

Answer 10

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

Question 11

What is an ectopic pregnancy?

Answer 11

Implantation of the embryo of somewhere other than the endometrium lining - 98% occur in fallopian tube

Question 12

What is the incidence rate of ectopic pregnancy and how can it be treated?

Answer 12

1-1.5%

Treatment ranges from expectant management, through chemotherapy (methotrexate) to surgery to remove the trophoblast and/or tube.

Question 13

How does tobacco smoking cause increased rates of ectopic pregnancy?

Answer 13

Tobacco smoke inhibits cilia function&raquo_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&raquo_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

Question 14

How does cannabis affect the fallopian tubes

Answer 14

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

Question 15

Give 5 risk factors for ectopic pregnancy

Answer 15

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)