Early Pregnancy

Front 1

Hormonal control of ovulation

Back 1

Front 2

Follicular Phase

Back 2

1. FSH stimulates follicle growth (15-20 grow one matures fully)
2. FSH drops due to inhibin secetion

Front 3

Luteal Phase

Back 3

PG drops of as the corpus leutum dies and then the -ve feedback is released allowing the FSH to rise again

Front 4

Terminology

Back 4

Front 5

Completion of meiosis & fertilisation

Back 5

Front 6

Pre-implantation stages (Days 0-6)

Back 6

the inc. in PG relaxes the sphincter allowing passage to the blastocyst (into uterus)

Front 7

Compaction - the start of differentiation

Back 7

COMPACT: formation of tight junction proteins

Front 8

Compact 8 cell

Back 8

totipotent

Front 9

Morula

Back 9

- apolar cells are pluripotent
- polar cells form trophoblasts

Front 10

Function of the zona pellucida during early pregnancy

Back 10

- surrounds conceptus from fertilisation to blastocyst stage
1. Prevents polyspermy
2. Prevents premature implantation
3. Prevents two zygotes from sticking together
4. Keeps blastomeres together until compaction

Front 11

Formation of Monozygotic Twins

Back 11

Front 12

Receptivity of uterus to conceptus implantation

Back 12

1. Pre-receptive phase
-epithelium has long apical microvilli, thick glycocalyx, -ve charge
 impairs attachment
2. Receptive phase
- apical protrusions absorb uterine fluid
 decrease volume of uterine cavity
- loss of -ve charge
- microvilli shorten
- glycocalyx thins
 close apposition of blastocyst to uterus  attachment
3. Refractory phase
- resists attachment

Front 13

Why is implantation necessary?

Back 13

•Blastocyst - bathed in uterine secretions
»Provides O2 and metabolites required for growth and survival
•Size limited
•Critical for conceptus to develop its own blood supply for exchange of substances
•Implantation failure - major cause of infertility due to inadequate uterine receptivity
•Implantation = 1) Attachment 2) Invasion

Front 14

Attachment - day 6

Back 14

- close apposition and adherence of trophoblast cells to endometrium

Front 15

Attachment

Back 15

•Zona broken down by proteases
•In a few hours 
»increases vascular permeability in stroma underlying contact point
»Changes in stromal morphology - sprouting and ingrowth of new capillaries = primary decidua
•A few days after initial attachment
»Formation of new capillaries in stroma spreads to larger area

Front 16

Attachment TO invasion

Back 16

Still within a few hours of attachment
- surface epithelium under the blastocyst becomes eroded
- trophoblast processes invade between epithelial cells
- isolating and digesting them

Front 17

Implantation (completed by day 9)

Back 17

- some trophoblasts fuse to form syncytium (syncytiotrophoblast)
- others remain proliferative (cytotrophoblasts)
- uterine glandular and decidual tissue is destroyed
-> release of metabolic substances which can be taken
up by conceptus (functions as a yolk)

Front 18

Hormones/cytokines involved in attachment
1. oestrogen: on uterus

Back 18

Front 19

Hormones/cytokines and attachment
Oestrogen (2) acts on blastocyst

Back 19

Front 20

Hormones/cytokines and attachment
Corticotrophin releasing hormone (CRH)

Back 20

During implantation the endometrial response to the invading blastocyst has characteristics of an acute aseptic inflammatory response
But - once implanted the embryo suppresses this and prevents rejection
Trophoblast and decidual cells produce CRH and express Fas ligand -> kills activated T cells
-> prevents embryo rejection

Front 21

Maternal recognition of pregnancy

Back 21

After ovulation the collapsed follicle transforms into corpus luteum consisting of:
Granulosa cells - secrete progesterone and oestrogen
Thecal cells - secrete progesterone and androgens
In non-pregnant woman
- life of corpus luteum 12 -15 days
- low LH level -> fall in progesterone secretion -> luteolysis

Front 22

Pregnant:
requires prolongation of luteal phase of ovarian cycle

Back 22

In pregnant woman
- hCG secreted by trophoblasts from 6-7 days post-fertilisation
- secreted by syncytiotrophoblasts
- passes into maternal circulation (measureable at 8-12 days)
- binds to LH receptors on luteal cells (thecal)
-> prevents luteolysis
-> progesterone production maintained

Front 23

Nausea and vomiting during pregnancy

Back 23

morning sickness !!
most common symptom of pregnancy - 50-90% of women
in 35% have physical and psychosocial implications
begins first trimester
continues to ~12 wks gestation
severe form = hyperemesis gravidarum – in <1% of women
vomiting, weight loss
risk dehydration, electrolyte imbalance
fetal complications – fetal growth retardation

Front 24

N/V Causes

Back 24

underlying pathophysiology - poorly understood
evolutionary adaptation? - also women with nausea during pregnancy are unlikely to miscarriage
combination of factors:
genetic
endocrine – HCG, progesterone, thyroid hormone
gastrointestinal

Front 25

Nausea and vomiting during pregnancy
Treatment:

Back 25

dietary modifications
 dry, bland food !!
adequate hydration
decrease fatty food intake
high protein diet
vitamin B6
antiemetics (dopaminergic antagonists, anti-histamines, anti-cholinergics, 5-HT3 receptor antagonists)
ginger, other herbal remedies

Front 26

Plasma hormones during pregnancy
DAY 40

Back 26

By day 40 - corpus luteum no longer required
- placental trophoblasts produce progesterone
- embryo produces oestrogen

Front 27

Plasma Hormones by week 6-7

Back 27

By 6-7 weeks - hCG levels fall
-> syncytiotrophoblasts start to secrete somatomammatrophins
incl. placental lactogen (placental variant of GH) -> fetal growth

Front 28

Plasma Hormones in Pregnancy

Back 28

Front 29

Dating of pregnancy

Back 29

Front 30

Developmental milestones (embryonic)
2 weeks

Back 30

– sac 2-3mm
– ectoderm, mesoderm, endoderm formed
– yolk sac formed

Front 31

Developmental milestones (embryonic)
week 3

Back 31

– brain, spinal cord and heart begin to develop
– gastrointestinal tract begins to develop

Front 32

Developmental milestones (embryonic)
week 4-5

Back 32

– embryo can be seen on ultrasound
– sac 20-25 mm, embryo 10 mm
– arm and leg buds become visible
– eyes and ear structure begin to form
– formation of tissue that develops into vertebra & some other bones
- further development of heart – now beats at a regular rhythm
- movement of rudimentary blood through the main vessels

Front 33

Foetal heart rate

Back 33

Measurement made from week 4-5 (ultrasound) through to labour (Doppler)
Rate increases with embryo development
- week 4 = 75 beats / min
- week 7-8 = 130 beats / min
Foetal heart rate = 120 – 160 beats / min
Low heart rate at 6-7 weeks (<90 beats / min)
- used as an indicator of developmental failure and predictor of a risk of spontaneous miscarriage

Front 34

Developmental milestones (embryonic)
week 6

Back 34

– sac 30-50 mm, embryo 20 mm
– arms and legs have grown longer
– hands and feet have fingers and toes (digits)
– brain continues to form
- lungs begin to form

Front 35

Causes of spontaneous miscarriage

Back 35

Miscarriage = spontaneous abortion before week 20
1.Maternal causes
•Acute febrile illness
•Septicaemia with infection of the foetus
•Severe hypertension or renal disease
•Diabetes (upto 45% if uncontrolled)
•Hypothyroidism
•Trauma
•Drugs
•Uterine fibroids
•Congenital malformations of uterus
•Hormone deficiency (progesterone) 2. Foetal causes
•Genetic abnormalities
•Congenital malformations
•Faulty implantation

Front 36

Recurrent miscarriage

Back 36

> 3 times consecutively prior to 20 weeks gestation

Front 37

Critical periods of development -preimplantation?

Back 37

30% fail to implant (based on IVF and animal studies)

-environment -> gene expression
-> epigenetic changes
-> genomic imprinting disorders
-> altered metabolism
-> impacts on fetal development
-> impacts on child & adult health

Front 38

Critical periods of development

Back 38

Front 39

Critical periods of development

Back 39