DISORDERS OF EARLY DEVELOPMENT

Question 1

What is the definition of miscarriage?

Answer 1

Loss of pregnancy prior to 23 weeks gestation

• Early clinical pregnancy loss < 12 weeks
• Late clinical pregnancy loss > 24 weeks

Question 2

What classifies recurrent miscarriage/recurrent pregnancy loss in the UK?

Answer 2

3 or more pregnancy losses (can be non-consecutive)

Question 3

What is the major cause behind early pregnancy loss?

Answer 3

Aneuploidy in embryo
- exponential increase in risk of trisomy with increasing
maternal age

Question 4

Why does aneuploidy increase with maternal age?

Answer 4

During meiotic arrest, the chromatids of homologous chromosomes are held together by cohesin proteins.

As age of oocyte increases, cohesin proteins are lost as they aren’t replaced. This can cause chromatids to separate and drift during meiotic division, rather than being segregated accurately by spindle

Question 5

What signalling patterns underpin recurrent pregnancy loss/recurrent miscarriage?

Answer 5

Leukaemia inhibitory factor (LIF)

LIF promotes decidualisation of human endometrial stromal cells in culture

Failed implantation in LIF deficient mouse models + reduced levels in uterine secretions of subfertile women

Question 6

What are gestational trophoblastic diseases (GTD) and what forms does it have?

Answer 6

Collection of disorders characterised by overgrowth of trophoblastic tissue

Benign: Molar pregnancy/hydatidiform moles
Malignant: Gestational trophoblastic neoplasias

Question 7

What are the 2 forms of hydatidiform moles?

Answer 7

Complete hydatidiform moles:
- fetal tissue absent

Partial hydatidiform moles:
- fetal tissue present

Question 8

What are some examples of malignant gestational trophoblastic neoplasias?

Answer 8

Rare:

• Invasive mole
• Choriocarcinoma

Very rare:

• Placental site trophoblastic tumour (PSTTs)
• Epithelioid trophoblastic tumour

Question 9

How does a complete hydatidiform mole arise?

Answer 9

Empty egg fertilised by:

• 1 sperm and genome duplicated
• 2 sperm with no duplication

Question 10

How does a partial hydatidiform mole arise?

Answer 10

Normal egg fertilised by:

• 1 sperm and genome duplicated
• 2 sperm with no duplication

Question 11

What mutations may underpin recurrent hydatidiform moles?

Answer 11

NLRP7 mutations - failure to recognise and clear failed pregnancy

Question 12

What can be seen on a molar pregnancy placenta?

Answer 12

Grape like villi

Question 13

What is ectopic pregnancy?

Answer 13

Extra-uterine implantation

- Mostly occur in fallopian tube but also ovary, cervix…

Question 14

What is the treatment for ectopic pregnancy?

Answer 14

Expectant management
Chemotherapy - methotrexate
Surgery to remove trophoblast and/or tube

Question 15

What is the impact of smoking on the fallopian tube?

Answer 15

Continine in cigarette smoke:
- Regulates expression of PROKR1 - regulates fallopian
tube smooth muscle contractility
- Induces pro-apoptosis protein expression

Tobacco smoke inhibits ciliary function –> reduces tubal transit of embryo

Question 16

What is the impact of cannabis on the fallopian tube?

Answer 16

Cannabinoid receptors CB1 displayed in fallopian tubes

THC ect. may:
- Act directly on fallopian tube and preturb embryo transit
- Alter balance of endocannabinoids leading to disrupted
embryo environment

Question 17

What are the risk factors for ectopic pregnancy?

Answer 17

Prior ectopic pregnancy
Poor fallopian tube surgery
STIs
Pelvic inflammatory diseases
Endometriosis
Smoking
Cannabis use?
Age > 35
Infertility history
Assisted reproductive technology e.g. IVF