Disorders of Early Development

Question 1

How common is miscarriage after pregnancy is confirmed?

Answer 1

10%

Question 2

How common is miscarriage before pregnancy is confirmed?

Answer 2

40%

Question 3

What is major contributor to pregnancy loss before 12 weeks’ gestation?

Answer 3

Chromosomal abnormalities- aneuploidy

Question 4

What happens to risk of miscarriage as people get old? Why?

Answer 4

Oocytes are held in meiotic arrest which resumes just before ovulation
Through meiotic arrest chromatids are held together by cohesin (e.g. REC8 and SMC2)
Cohesin can be lost over time which can cause chromatids to separate during meiotic division
This can lead to chromosomal abnormalities

Question 5

Define recurrent miscarriage

Answer 5

3 or more consecutive pregnancy losses

Question 6

Define recurrent implantation failure

Answer 6

Failure to achieve a clinical pregnancy after transfer of at least three good-quality embryos in IVF

Question 7

What is the key difference between recurrent miscarriage and recurrent implantation failure?

Answer 7

Failure to implant or sustain pregnancy by natural conception vs failure of transferred embryo to implant/sustain pregnancy

Question 8

What are some common causes of recurrent miscarriage and recurrent implantation failure?

Answer 8

Uterine anatomical defects or presence of fibroids/polyps that might disrupt implantation
Autoimmune antibodies e.g. anti-nuclear, anti-phospholipid
Also test for paternal DNA sperm integrity/fragmentation

Question 9

What signalling pathway is associated with miscarriage?

Answer 9

LIF (leukemia inhibitory factor) pathway

Question 10

What does LIF deficiency do?

Answer 10

Causes failure in implantation

Question 11

What LIF promote?

Answer 11

Decidualization of human endometrial stromal cells

Question 12

Whats endometrial scratching?

Answer 12

A technique used to improve the ability of an embryo to implant in the uterus after in-vitro fertilization

Question 13

How is endometrial scratching carried out?

Answer 13

It involves superficially wounding the endometrial mucosa of the womb using a pipette or hysteroscope

Question 14

What is endometrial scratching though to stimulate?

Answer 14

Immune cell infiltration and wound healing cytokine production

Question 15

What are some adaptations the fallopian tube has to promote transition into the uterus?

Answer 15

Smooth muscle contracts to move the embryo along the tube

Epithelium is coated in cilia (microvilli) to promote fluid movement

Question 16

What is the name of the component that affects pregnancy in smokers? What does it do?

Answer 16

Continine is a component of cigarette smoke and regulates expression of PROKR1, a regulator of fallopian tube smooth muscle contractility

Question 17

What does continine increase expression of in the fallopian tube?

Answer 17

Pro-apoptotic proteins

Question 18

What does tobacco smoke inhibit?

Answer 18

Ciliary function

Question 19

What cannabinoid receptors do fallopian tubes express?

Answer 19

CB1 and CB2

Question 20

What does THC in cannabis do to fallopian tubes?

Answer 20

Acts on it directly to peturb transit or alter balance of endocannabinoids in the tube leading to disrupted embryo environment