Fertilisation And Pregnancy Flashcards
1
Q
How long can sperm last
A
4-6 days
2
Q
How long can egg survive
A
1-2 days
3
Q
When can sperm be introduced for successful fertilisation
A
5 days before to 1 day after ovulation
4
Q
Egg transport
A
Extruded from ovary as digestive enzymes break the surface membrane
Carried out in antral fluid
Smooth muscle and Fimbriae move egg to fallopian tube
Cilia present in fallopian tube which carry egg to uterus
5
Q
What wafts egg down fallopian tube
A
Cilia
6
Q
What helps to transport sperm
A
Fluid pressure of ejaculation
7
Q
Sperm transport
A
Sperm move themselves using tail
Vagina is acidic and high in nutrients which sperm utilises
Glucose comes from presence of oestrogen
8
Q
Glucose in uterus
A
Comes from presence of oestrogen
Higher oestrogen level —>more glucose—> longer sperm can survive
9
Q
What is the viscosity of uterine mucus dependant on
A
Woman’s hormone levels
10
Q
Capacitation
A
Maturation process of spermatozoon
Tails become stronger
Plasma membrane develops allowing fusion with egg to occur
11
Q
Where does fusion of sperm and egg normally occur
A
Ampulla of fallopian tube
12
Q
When does fusion of egg and sperm occur
A
Within hours of ovulafion
13
Q
Glycoproteins on Zona pellucida
A
ZP3 receptors
14
Q
Binding
A
Acrosome reaction- enzymes exposed to the Zona pellucida causing it to be digested
15
Q
Formation of zygote
A
Head of sperm passes into the cytosol and fertilisation occurs
16
Q
How is polyspermy prevented
A
Fertilisation causes a reaction which changes the membrane potential of the cell- preventing entry of other sperm
Done by exocytosis of vesicles containing enzymes to inactivate ZP3, hardening the Zona pellucida
17
Q
How long after gamete fusion is meiosis II completed
A
4-7 hours
18
Q
what happens to the 2nd polar body
A
Degenrated
19
Q
Pronuclei
A
2 sets of haploid chromosomes are present
23 sperm and 23 egg
Equal in size and contain nucleoli
20
Q
What happens after fusion of sperm and egg
A
Nucleoli migrate to centre of cell and haploid chromosomes fuse
DNA replication occurs in preparation for Meiotic divisions
Mitosis then occurs
21
Q
What happens on days 2/3
A
Cleavage
22
Q
Where does cleavage of zygote take place
A
Fallopian tube
23
Q
What maintains contraction within tubes
A
Oestrogen
24
Q
What allows zygote to pass through fallopian tube
A
Increase in progesterone causes smooth muscle relaxation
25
What happens during cleavage stage
No cell growth but cleavage occurs increasing the number of cells present
Each cell is totipotent so can develop into an entire individual
26
What happens day 4
Compaction
27
Compaction
Cells flatten and maximise space
Tight junctions form between cells
Polarisation of outer cells
Conditions allow for rapid differentiation
28
What happens day 5
Cavitation and differentiation
29
Cavitation and differentiation
Fluid filled cavity expands and forms blastocysts
>80 cells
Lost totipotency
30
Blastocyst
>80 cells
Lost totipotency
Trophoblast = outer cell layer
Inner cell mass
Fluid filled cavity in middle
31
Trophoblast
Outer cell layer of blastocyst
32
What happens day 5-6
Expansion
33
Expansion
Cavity expands
Zona pellucida thins
34
What happens day 6+
Hatching
35
Hatching
Blastocyst expansion and enzymes
Embryo out of Zona pellucida- essential for implantation
36
Stages after fertilisation day 1 —> day 8/9
Fertilisation
2 cell stage
4 cell stage
8 cell- uncompacted morula
8 cell- compacted morula
Early blastocyst
Late stage blastocyst (hatching)
Implantation
37
Morula
Solid ball of cells
38
Morula —> blastocyst
through the segregation of an inner cell mass from an external trophoblastic cell layer
39
When does implantation occur
7 days after fertilisation
On 21st day of menstrual cycke
40
Upon implantation
Endometrial cells provide metabolic fuel for early growth
Occurs for first 5 weeks until fetal heart is fully functioning
41
When does Apposition occur
9 days post-fertilisation
42
Apposition
Hatched blastocyst orientates via embryonic pole
Synchronises with endometrium
43
Attachment stage
Integrins between endometrial endothelium and trophoblast cells
44
What 2 layers does the trophoblast split into
Cytotrophoblast
Syncytiotrophoblast
45
Invasion stage
Synctiotrophoblast erodes blood vessels by using enzymes to digest the basal lamina
46
Decidual reaction
Differentiation of stromal cells adjacent to blastocyst
47
Maternal recognition
Secretion of IL-2 prevents rejection
Completed by day 11 post fertilisation
48
Placenta
Interlocking fetal and maternal tissues
Organ of exchange between mother and fetus
49
Function of placenta
Nutrition
Gas exchange
Waste removal
Endocrine and immune support
50
What is the first stage of placental development
Implantation- outer layer of trophoblastic cell mass invades endometrium
51
Chorion structure
Outermost layer of trophoblast cells
High/vast capillary network
52
Chorion function
Supply embryonic portion of placenta
Extends chorionic villi into endometrium
Releases digestive enzymes which break endometrial vessels so become surrounded by pool of maternal blood
53
How does placental blood enter the chorion
Uterine vein
54
How does placental blood leave the chorion
Decidual (maternal chorion)
55
Barriers to transport
Fetal endothelial cells
Fetal connective tissue
Chorionic epithelial cells
Endometrial epithelial cells
Maternal connective tissue
Maternal epithelial cells
56
Where does the amniotic cavity form
Between inner cell mass and chorion
57
What does the fluid inside the amniotic cavity resemble
ECF
58
Function of amniotic fluid
Buffers mechanical disturbances and temperature changes
59
Amniotic sac
Epithelial cells lining amniotic cavity
Fuses with chorion so there is only a single combined membrane around the fetus
60
Which cells produce hCG
Trophoblast
61
When do trophoblasts produce hCG
When they begin endometrial invasion
62
Effects of hCG
Maintenance of corpus luteum
Stimulation of oestrogen and progesterone production - preventing menstruation
63
What does hCG stand for
Human chorionic gonadotropin
64
When does hCG secretion peak
60-80 days after last menstruation
65
Clinical use of hCG
Hormone detected in pregnancy tests
66
Levels of hCG during pregnancy
Peaks at 60-80 days after last menstruation
Rapidly decreases which is maintained until end of pregnancy
67
As hCG decreases
The placenta increases secretion of oestrogen and progesterone
68
Where is prolactin released from
Anterior pituitary
69
Function of prolactin
Involved in milk production
Prevention of ovulation
70
What control release of prolactin
Suckling
71
Levels of prolactin
Increases at end of pregnancy when oestrogen and progesterone decrease
72
Where is relaxin produced
Ovaries and placenta
73
Function of relaxin
Limits uterine activity
Softens cervix
Ripens cervix
74
Levels of relaxin
Increases early in pregnancy
75
Where produces oxytocin
Posterior pituitary
76
Function of oxytocin
Stimulates uterine contractions
Triggers caring behaviour
77
Levels of oxytocin
Secreted throughout pregnancy
Levels increase towards end of pregnancy
78
Function of prostaglandin
Initiates labour
79
Where are prostaglandins produced
Uterine tissue
80
2 types of prostaglandin
PGF2a
PGE2
81
Which is the most abundant prostaglandin
PGF2a
82
Which prostaglandin is 10x stronger
PGE2
83
When does the corpus luteum regress
After 3 months
84
Which cells continue to produce oestrogen and progesterone after the corpus luteum regresses
Trophoblast cells
85
Where do the androgens for oestrogen come from
Maternal ovaries
Maternal adrenal medulla
Fetal adrenal medulla
Placenta
86
Aromatase
Found in placenta
Converts androgens into oestrogen
87
What inhibits GnRH release
Increased progesterone
88
Maternal adaptations: cardiovascular changes
Increased cardiac output
Decreased systemic BP
Decreased total peripheral resistance
Increased uterine blood flow
Increased blood volume
Increased plasma and blood cell mass
Tachycardia
89
Maternal adaptations: respiratory changes
Increased alveolar ventilation
90
Maternal adaptations: GI changes
Increased acid reflux
Delayed gastric emptying -gastroparesis
91
What causes maternal GI changes
Fetus pressing on stomach
92
Maternal adaptations: skin changes
Linea nigra
Striae gravidae
Darkened areola on breasts
93
Linea nigra
Dark line down central abdomen
94
Striae gravidae
Stretch marks on lower abdomen
95
Maternal adaptations: biochemical changes
Weight gain
Increased protein and lipid synthesis
Insulin resistance
96
Why don’t obese women gain as much weight as underweight women when pregnant
Already have fat stores
97
Length of pregnancy
40 weeks from day of last menstrual cycle
38 weeks from ovulation/conception
98
What stops contractions occurring during pregnancy
Smooth muscle cells of myometrium are disconnected from each other
Maintained by progesterone
99
What allows for coordinated contractions
Increase in oestrogen at end of pregnancy signals smooth muscle cells to produce connexins to form gap junctions
100
What is cervical ripening
Growth and remodelling of the cervix
101
What stimulates cervical ripening
Oestrogen
102
What maintains the uterus seal during pregnancy
Progesterone
103
What seals the uterus during pregnancy
Collagen fibres
104
What causes the cervix to become soft and flexible
Breakdown of collagen caused by oestrogen progesterone and relaxin
105
Parturition
Birth process
106
What initiates labour
Increased oxytocin from mother
Oxytocin, vasopressin and cytokines from fetus
107
Pre-labour
Increased prostaglandins—> enhanced oxytocin actions
Increased pressure in cervix as a result of prostaglandins
Contraction of actomyosin in myometrium
108
What hormones have increased levels during labour
PGF2a and oxytocin
109
Result of increased PGF2a and oxytocin during labour
Positive feedback from the pressure on cervix leading to more release thus more contractions
110
Intervals of contraction
10-15 minutes
111
Stages of labour
Latent
Active
Post-partum
112
Latent labour
Little dilation (8hours)
113
Active labour
Organised contractions (5 hours)
Dilation and full expansion
114
Movement of contraction
Top to bottom
115
Maternal embryonic communication regulates
Features of blastocyst morphogenesis
Coordination of implantation
Maternal immunotolerance
116
Developmental plasticity
Selecting the right phenotype to fit the anticipated future environment
117
Potential short-term responses developmental plasticity
Epigenetic modifications
Altered intracellular signalling
Metabolic stress
Gene expression changes
Apoptosis
Cell proliferation disturbances
118
Clinical uses/modifications of fertilisation
Artificial insemination
Embryo transfer
In vitro fertilisation
Intra-cytoplasmic sperm injection
Somatic nuclear transfer (cloning)
Sperm cell therapy
IPS cells
119
What is oocyte activation triggered by
Phospholipase C zeta (PLCz)- a sperm protein
120
Function of phopholipase C zeta
Activates the egg to release calcium from internal stores - facilitating fertilisation
121
Why is oocyte activation essential
Essential for transformation of the decondensed sperm nucleus in to pronucleus
122
Pronuclei
Fusion of 2 sets of haploid chromosomes
Equal size
Contain nucleoli
123
How long after gamete fusion do the Pronuclei form
4-7 hours
124
Syngamy
Male and female pronucleus migrate to centre
Haploid chromosomes pair and replicate DNA in preparation for first mitotic division
Pronuclear membranes breakdown
Mitotic metaphase spindle forms
46 chromosomes organise at spindle equator
125
How long after fertilisation does the ooplasm divide
24 hours
126
When does activation of the embryonic genome and start of embryonic transcription occur
4-8 cell embryo
127
Totipotent
The nuclei of individual blast omelets are each capable of forming an entire fetus
128
Size of morula
16 cells
129
Trophectoderm
Tight junctions between outer single epithelial layer
130
Inner cell mas
Pluripotent
131
Why does the fluid filled cavity expand
Sodium pumped in which pulls water in by osmosis
132
Which part of the blastocyst is extraembryonic
Trophectoderm
133
Which part of the blastocyst is embryonic
Inner cell mass
134
Energy metabolism of early preimplantation embryo
low ATP turnover
ATP/ADP ratio is high
Energy metabolism is characterised by oxidative phosphorylation of pyruvate
Glucose uptake and utilisation is low
135
Energy metabolism of blastocyst stage
Metabolic activity rises sharply
ATP/ADP ratio falls reflecting an increase demand for energy eg protein biosynthesis and ion pumping associated with blastocoel cavity
Glucose is predominant exogenous energy substrate
136
Genetic control of early cleavage
Maternal RNA
137
Genetic control of blastocyst
Embryonic
138
Metabolic and biosynthetic activity of early cleavage
Low
139
Metabolic and biosynthetic activity of blastocyst
High
140
Exogenous nutrient requirements of early cleavage
Simple
Low glucose
Non essential amino acids
141
Exogenous nutrient requirements of blastocyst
Complex
High glucose
Essential and non essential amino acids
Vitamins
142
What supplies exogenous nutrients in vivo
Cumulus cells
Fallopian tube secretions eg calcium, sodium, chloride, glucose, protein
Uterine secretions eg iron, fat soluble vitamins, glucose
143
Insulin-like growth factor
IGF-I
IGF-II
Increase cell numbers in blastocyst
144
Leukaemia inhibitory factor
Enhances embryo-endo interaction
145
Length of cellular differentiation
10 days
146
Histogenesis
3 germ layers of embryo form - gastrulation after implantation
147
3 germ layers
Ectoderm
Mesoderm
Endoderm
148
Implantation window
4 days (6-10 days post ovulation)
149
Changes to uterus for implantation
Endometrial cell changes to help absorption of uterine fluid- bring the blastocyst nearer to the endometrium and immobilise it
Change in thickness of endometrium and its blood supply development
Formation of decidua
150
What mediates embryo implantation
Hormones - sex steroids
Cell adhesion molecules
Proteases
Cytokines
Growth factors
5 genes upregulated during implantation window
151
3 phases of embryo implantation
Apposition
Attachment
Invasion
152
Apposition
Unstable adhesion of blastocyst to uterine lining
Synchronisation of embryo and endometrium (decidua)
Hatched blastocyst orientates via embryonic pole (always attached at the area above the inner cell mass)
Receptive endometrium
153
When is the implantation window
Day 19-22
154
Attachment stage of implantation
Stable/stronger adhesion
Penetrate with protrusions of the trophoblast cells (microvilli)
Massive communication between the blastocyst and endometrium conveyed by receptor-ligand interactions
Apical surfaces of the endometrial epithelial cells express variety of adhesion molecules (integrin subunits)
Trophoblastic cells also express integrins
Attachment occurs through the mediation of bridging ligands that connect with integrins on their surfaces
155
How does the blastocyst and endometrium communicate
Receptor-ligand interactions
156
How does attachment occur
Bridging of ligands that connect with integrins on their surfaces
157
Invasion
Trophoblast protrusions continue to proliferate and penetrate the endometrium
•cells differentiate to become syncytiotrophoblast
•The trophoblast surrounding the ICM = cytotrophoblasts.
•Highly invasive - trophoblast quickly expands and erodes into endometrial stroma.
•Invasion is enzymatically mediated
•Syncytiotrophoblast erodes endometrial blood vessels
•Eventually syncytiotrophoblast comes into contact with maternal blood and form chorionic villi – in initiation of the formation of the placenta
•Blood filled lacunae form (spaces filled with maternal blood). Exchange nutrients and waste products.
158
Cytotrophoblasts
Trophoblast surrounding inner cell mass
159
Initiation of formation of placenta
Syncytiotrophoblast erodes endometrial blood vessels
•Eventually syncytiotrophoblast comes into contact with maternal blood and form chorionic villi – in initiation of the formation of the placenta
•Blood filled lacunae form (spaces filled with maternal blood). Exchange nutrients and waste products.
160
Function of Decidual reaction
Promotes placental formation
161
Decidual reaction
stromal cells adjacent to the blastocyst differentiate into metabolically active, secretory cells or Decidual Cells (under influence of progesterone)
•Secretions include growth factors/proteins to support growth of implanting blastocyst in the initial stages before the placenta is fully developed.
•Endometrial glands enlarge and local uterine wall becomes highly vascularised.
•The decidual reaction is not required for implantation e.g. ectopic implantation can occur anywhere in the abdominal cavity.
162
Decidual cells
Metabolically active, secretory cells
Secretions include growth factors/proteins to support growth of implanting blastocyst in the initial stages before the placenta is fully developed
163
Role of progesterone
Modifies the distribution of oestrogen receptors
•Stimulates secretory activity
•Stimulates stromal oedema
•Increases volume of blood vessels
•Primes decidual cells
•Stabilises lysosomes
•Might be an immunosuppresent
•May stimulate growth factors and binding proteins
•May regulate the formation of reactive oxygen species (reducing oxidative stress)
164
Maternal recognition
Embryo is antigenically different from the mother
•At the same time as the decidual reaction, leukocytes in the endometrial stroma secrete interleukin-2 which prevents maternal recognition of the embryo as a foreign body during the early stages of implantation
•uterine natural killer cells
165
Role of hCG
Essential to sustain early pregnancy
•ensures the corpus luteum continues to produce progesterone throughout the first trimester of pregnancy (prevents menstruation).
•Interacts with the endometrium via specific receptors
•Immunosuppressive – has highly negative charge, may repel the immune cells of the mother & protect the foetus.
166
Slow rate of increase in hCG indicates
Slow rate of increase might indicate
–Early abortion
–Ectopic pregnancy
–Delayed implantation
–Inadequate trophoblast
167
Rate of increase in hCG in first 10-12 days of pregnancy
Doubles every 1.3 days
168
In vitro culture systems
Use a sequential culture medium – different composition at different stages
169
Day 1-3 in vitro culture systems
Water, salts &ions
Pyruvate, lactate, protein
and
No/low Glucose
Non essential amino acids
170
Day 3+ in vitro culture systems
Water, salts &ions
Pyruvate, lactate, protein
and
Glucose
Essential and non essential amino acids
Vitamins
171
One-step in vitro culture systems
Culture day 1-6 in same media one media
–Let the embryo choose principal
–useful in uninterrupted systems like time lapse
–Why? Reduce stress, less disturbance, Increase embryo viability
172
Maternal factors affecting embryo growth in vitro
Follicle environment
Oocyte maturity (hCG trigger 36 hours before egg collection)
173
Embryonic factors affecting embryo growth in vitro
Cleavage rate, size of blastomeres, degree of fragmentation
Gross chromosome imbalance
Variations in embryo metabolism
Failure or abnormal formation of the blastocoel cavity
174
Laboratory conditions affecting embryo growth in vitro
Exposure to light
Exposure to high oxygen concentrations
Changes in pH or osmolarity
Culture medium
Volatile organic compounds
175
Embryo transfer
Select morphologically best embryo(s) to transfer on day 5.
•If any remaining embryos - cryopreserve.
•Need to be of good quality and correct stage
176
Causes of failed implantation
Problem with the embryo - high proportion of embryos fail to implant
–Aneuploidy (40% IVF fertilised eggs abnormal)
•Interaction between embryo and uterus - insufficient trophoblast invasion
– miscarriage
•Insufficient invasion of maternal blood vessels
-Pre-eclampsia, poor foetal growth, hypertension
•Sperm problem – DNA fragmentation (abnormal genetic material). Increase miscarriage. Nutrition & lifestyle.
177
Recurrent implantation failure
Failure to achieve a clinical pregnancy after transfer of at least 4 good quality embryos in at least 3 cycles
•Under the age of 40
178
Causes of recurrent implantation failure
Poor ovarian function
•Increased sperm DNA fragmentation
•Uterine pathologies
–Polyps/fibroids
–Congenital anomalies
–Intrauterine adhesions
•Hydrosalpinges shown to significantly reduce implantation and preg rates - fluid toxic to embryos and affects endometrial receptivity.
•Immunological factor (NK cells)
179
Management of recurrent implantation failure
Lifestyle changes (smoking, BMI)
•Sperm DNA fragmentation test
•Improve embryo selection e.g. PGT-A
•Hysteroscopy – remove anomalies
•Fibroid / Polyps /Hydrosalpinges removal
•Immunotherapy (intravenous immunoglobulin) – maybe only subgroup of women benefit.
180
After fertilization, male and female pronucleuses are unified. What this process is called?
Syngamy
181
What happens in the embryo after embryonic genome activation and before blastocyst formation?
Compaction
182
Implantation happens after blastocyst has hatched through
Zona pellucida
183
What is the best choice of treatment for:“A 36 year old man with 47XXY karyotype that is consistently azoospermic at semen analysis but has a small number of sperm recovered by testicular biopsy. His 31 year old partner is of normal biology with patent Fallopian tubes and has responded well to superovulation”
Intra-cytoplasmic sperm injection
184
What promotes myometrial contraction
Prostaglandins in seminal fluid
185
3 outcomes of cortical reaction
1 Slow polyspermy block
2 Completion of meiosis II
3 Zygote formation.
186
Completion of meiosis II
The Ca2+ released during the cortical reaction acts at the nucleus of the secondary oocyte to stimulate the completion of meiosis II. As a result, there is a definitive ovum and a polar body; the latter is later degraded.
187
Zygote formation and implantation
Finally, the pronucleus of the definitive ovum (n) is now able to fuse with the pronucleus of the sperm cell (n). This produces the zygote (2n).
The zygote continues to divide via mitosis within the fallopian tubes. At the 16-cell stage (3-4 days after fertilisation), the embryo is called a morula. All 16 cells of the morula are totipotent, and not specified to a particular fate. At day 5, the embryo becomes a blastocyst, characterised by the development of a distinct inner cell mass and blastocoele (fluid filled cavity), and surrounded by trophoblast cells. Implantation occurs on day 7-8, at the late blastocyst stage
188
Polyspermy block
To prevent multiple sperm from binding to the cell membrane, there are two mechanisms of polyspermy block.
Fast Block: Na+ dependent, rapid onset, short duration
Binding of sperm to the cell membrane activates Na+ ion channels which allow for Na+ influx into the egg. This causes depolarisation, making the oocyte more positive and thus repelling further sperm and inhibiting them from binding. A fast block has a rapid onset, but short duration.
Slow Block: Ca2+ dependent (occurs secondary to the cortical reaction), slow onset, long duration
Fusion of the sperm and oocyte cell membrane activates the smooth endoplasmic reticulum (smooth ER), causing it to release large amounts of Ca2+. This stimulates intracellular lysosomes to release hydrolytic enzymes to further degrade the ZP, and stimulates exocytosis of cortical granules to harden the oocyte cell membrane, making it impenetrable to further sperm.
The slow block has a slower onset but is longer in duration.
189
Polyspermmy fast block
Na+ dependent, rapid onset, short duration
Binding of sperm to the cell membrane activates Na+ ion channels which allow for Na+ influx into the egg. This causes depolarisation, making the oocyte more positive and thus repelling further sperm and inhibiting them from binding. A fast block has a rapid onset, but short duration.
190
Polyspermy slow block
Ca2+ dependent (occurs secondary to the cortical reaction), slow onset, long duration
Fusion of the sperm and oocyte cell membrane activates the smooth endoplasmic reticulum (smooth ER), causing it to release large amounts of Ca2+. This stimulates intracellular lysosomes to release hydrolytic enzymes to further degrade the ZP, and stimulates exocytosis of cortical granules to harden the oocyte cell membrane, making it impenetrable to further sperm.
The slow block has a slower onset but is longer in duration.
191
Cortical reaction
After the ZP is digested, a single sperm fuses with the cell membrane of the oocyte. This causes the smooth endoplasmic reticulum of the oocyte to release Ca2+, raising intracellular Ca2+ levels
192
Sperm capacitation
Firstly, it prepares the sperm’s head for the acrosomal reaction. Secondly, the motility of the sperm is hyperactivated by the changes to the strength and speed of flagellum’s movements.
193
Binding of sperm and egg
Once the capacitated sperm reach the secondary oocyte in the fallopian tube, there are multiple sperm-oocyte interactions that must occur before the sperm can fertilise the egg. The capacitated sperm first encounters the cumulus-oocyte complex surrounding the secondary oocyte, and a much high concentration of follicular fluid. Hyaluronidase present on the surface of the capacitated sperm head dissolves the hyaluronic acid cementing the cells of the COC together, enabling the capacitated sperm to penetrate the COC. The sperm then reach a layer of glycoproteins surrounding the oocyte, known as the zona pellucida (ZP). Binding to ZP3 causes the sperm’s plasma membrane to fuse with its acrosomal membrane, leading to the release of hydrolytic and proteolytic enzymes from the sperm’s acrosome. These enzymes digest the zona pellucida, enabling the sperm to reach the cell membrane.
Multiple sperm are involved in the above three processes. However, only one of these sperm will fuse and fertilise the oocyte.
194
Sperm travelling to egg
After ejaculation, the semen immediately coagulates to form a loose gel, which holds the sperm at the cervical os and protects against the acidic pH and immunological response of the vagina.`At the cervix, the sperm encounters cervical mucus. High levels of oestrogen around the time of ovulation reduce its viscosity and alter its microstructure to allow for easier passage of the sperm through the cervix and into the uterus. Additionally, components of the seminal fluid assist the sperm to penetrate the mucus barrier.
Once the sperm enters the uterus, pro-ovarian contractions of the uterine myometrium help to propel the sperm towards the fallopian tube. Prostaglandins present in the seminal fluid promote these myometrial contractions.
The first sperm enter the fallopian tubes only minutes after ejaculation, however may survive in the female reproductive tract for up to five days.
195
Combined hormonal contraception
uses oestrogen and progesterone
• Act primarily to inhibit ovulation due to negative feedback effect of the oestrogen and progesterone on the hypothalamo-pituitary axis- prevents LH surge thus preventing ovulation
• Progesterone also inhibits proliferation of the endometrium , creating unfavourable conditions for implantation and increases the thickness of the cervical mucus, preventing passage of sperm
196
Progesterone only contraception
thickens cervical mucus preventing the entry of sperm
• Thins endometrium which inhibits implantation
197
Causes of female factor infertility
1 Disorders of ovulation – most common cause of infertility in women
2 Tubal causes
3 Uterine/peritoneal causes
4 Other causes
198
Disorders of ovulation
WHO has classified ovulation disorders into 3 categories:
Group I: hypothalamic pituitary failure (10%)
Hypothalamic amenorrhoea – can be due to low body weight/excessive exercise
Hypogonadotrophic hypogonadism e.g. due to Kallmann syndrome
Group II: hypothalamic-pituitary-ovarian (85%)
Predominately PCOS
Group III: ovarian failure (4-5%)
Hypergonadotropic hypogonadism
199
Tubal causes of infertility
Pelvic inflammatory disease (PID) – see our article on PID for more information
Endometriosis
Previous sterilisation
200
Uterine and peritoneal causes of infertility
Endometriosis
Previous pelvic surgery (formation of adhesions, including intrauterine)
Uterine fibroids
Uterine anomalies
Cervical factors
201
Other causes of female infertility
Unexplained
Genetic factors
Immune factors and systemic illnesses
Medications: chemotherapy and cytotoxic agents
Lifestyle factors: smoking, excessive alcohol, obesity
202
Endocrine and biochemical maternal adaptation to pregnancy
Weight gain
Protein synthesis
Lipid synthesis
Insulin resistance
203
Pregnancy hormones
Human chorionic gonadotrophin
Oestrogen
Progesterone
Prolactin
Relaxin
Oxytocin
Prostaglandins
204
Human chorionic gonadotrophin hormone function
Stimulates oestrogen/progesterone production in ovary
205
Human chorionic gonadotrophin hormone diminishes when
Placenta is mature enough to take over oestrogen.progesterone production
206
Oestrogen function
Regulates levels of progesterone
Prepares uterus for baby and breasts for lactation
207
Progesterone function
Prevents miscarriage
Builds up endometrium for support of placenta
Prevents uterine contractions
208
Prolactin function
Increases cells that produce milk
Prevents ovulation
After birht- stimulates production of milk and also controlled by suckling
209
Relaxin levels
High in early pregnancy
210
Relaxin function
Limits uterine activity
Softens the cervix- cervical ripening in preparation for delivery
211
Oxytocin function
Triggers caring reproductive behaviour
Responsible for uterine contractions during pregnancy and labour
212
Prostaglandins function
Tissue hormones
Initiation of labour
213
Which drugs are used to induce labour
Oxytocin
Synthetic Prostaglandins
214
Maternal cardiovascular changes
Increasing cardiac output
Reduced systemic blood pressure
Reduced total peripheral resistance
Increased uterine blood flow
Increased red cell mass
215
Common maternal problems affecting pregnancy
Poor weight gain/undernutrition
Extremes of maternal age
Medical conditions
Drug misuse: cigarettes, heroin
Haemorrhage
216
Common fetal problems
Miscarriage
Abnormal development
Disordered fetal growth
Premature birth
217
What allows uterine growth
Cell division and hypertrophy of individual myometrial cells
218
Uterine cervix
Protects fetus during development
Mainly collagen and ground substance with glycosaminoglycans
Collagen has cross-links which increase tensile strength
219
Cervical ripening
Growth and remodelling of the cervix prior to labour
Occurs under influence of placental hormones and relaxin through gestation
Process accelerates in last 3 months due to oestrogens and dehydroepiandrosterone
Promoted by release of PGE from cervical mucosa- relaxin and placental oestrogens
Effacement and dilation due to muscular action of cervix and uterus
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Which hormone promote cervical ripening
PGE from cervical mucosa
Relaxin
Placental oestrogens
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PGE
Prostaglandins E
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The process of cervical ripening accelerates when
Last 3 months of pregnancy
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Cervical ripening increases in last 3 months due to
Oestrogens
Dehydroepiandrosterone
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What is the main prostaglandin released during labour
PGF2(Alpha)
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Which prostaglandin is more potent
PGE2 X10 more than PGF2(alpha)
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Events of pre labour
Enhanced prostaglandin production
Initiation of labour: maternal signal (oxytocin), fetal signals (oxytocin, vasopressin and cytokines)
PGF2(alpha) enchanted action of oxytocin
With increased pressure on cervix , increased release of PG from decidua and chorioamnion
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Fetal signals that initiate labour
Oxytocin
Vasopressin
Cytokines
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Components of labour
Passenger - th baby
Passages - the pelvis
Powers- the uterus
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The powers- the uterus
Braxton-Hicks contraction
Co-ordinate
Into-ordinate
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Labour action
Myosin can only react with actin when phosphorylated by MLCK
MLCK functionally dependent on Ca2+ ions and calmodulin but inactivated by its own phosphorylation
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What is MLCK functionally dependent on
Ca2+ ions
Calmodulin
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What is MLCK inhibited by
Its own phosphorylation
233
Problems with contractions
Too strong/weak
Disorganised
Cervix too rigid
Cervix weak
Postpartum bleeding
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Problems with the stages of labour
Prolonged latent phase
Failure to progress in labour
Delayed 2nd stage - instrumental delivery
Delayed 3rd stage - manual removal of the placenta
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When does the placenta begin to develop
At blastocyst implantation
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Fetal surface of placenta
Umbilical cord attachment
Covered with amnion attached to chorionic plate
Umbilical vessels branch into anastomosing chorionic vessels
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Maternal surface of placenta
Cotyledons
Cobblestone appearance
Covered with maternal decidua basalis
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Implantation- placental development
1st stage
Adhesion/attachment of embryo trophoblast and endometrial epithelial cells
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3 main functions of placenta
Metabolism
Transport
Endocrine
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Placental metabolism
Synthesised glycogen, cholesterol and fatty acids
Provided nutrient and energy
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Placental transport
Gases and nutrition
Water, glucose and vitamins
Hormones - mainly steroid
Electrolytes
Maternal antibodies _IgG
Waste products
Drugs and their metabolites
Infectious agents
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Maternal antibodies cross placenta
IgG
Not IgM
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Placental hormones
Human chorionic gonadotrophin (hCG)
Human chorionic somatommotropin (hCS)
Human chorionic thyrotropin (hCT)
Human chorionic corticotropin (hCACTH)
Progesterone and oestrogen
Relaxin
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Function of human chorionic somatommotropin
Stimulates mammary development
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Haemolytic disease of the newborn
Fetus Rh+
Maternal Rh-
Fetal causes anti Rh antibodies
Dangerous for 2nd child
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Placenta accreta
Abnormal adherence with absence of decidua basalis
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Placenta percreta
Villi penetrate myometrium
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Placenta praevia
Placenta overlies internal os of uterus
Abnormal bleeding
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When does labour usually occur
37-42 weeks
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Patruition
Pregnancy
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Dilation of cervix - latent
<4 cm
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Active dilation of cervix
4-10cm
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3rd stage of labour
Delivery of placenta
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Stage 1 of labour
Dilatation of cervix
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Stage 2 of labour
Birth of fetus
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The human embryo develops in a number of discrete stages.
The Morula stage of embryonic development happens before which of the following?
Blastocyst formation
257
The ovarian follicle is a collection of cells which surround a single oocyte.
Which one of these forms the inner most layer of an ovarian follicle?
Zona pellucida
258
24-year-old woman presents with a two month history of heavy periods.
What is the name given to the part of the uterus that lies above the entrance of the Fallopian tubes?
Fundus
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23 year old women presents to her GP for advice on getting pregnant as she is experiencing difficulty conceiving.
Which of these events induces ovulation?
Increasing plasma oestrogen triggers a surge of Luteinising Hormone
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Pregnancy tests rely on the detection of hCG (human chorionic gonadotrphin).
Which of the following best describes the role of chorionic gonadotropin (hCG)?
stimulates the corpus luteum to produce progesterone beyond the 14 days after ovulation when the corpus luteum would normally regress.
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Where is hCG produced
Placenta
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When are hCG levels highest
First trimester but production is throughout pregnancy
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24-year old presents to her GP as they are having difficulty conceiving.
Where in vivo in the female reproductive tract does fertilisation normally take place?
Fallopian tubes
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The corpus luteum is the remains of an ovarian follicle after ovulation.
Which hormone is produced by the corpus luteum?
Progesterone
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Portal system is where the blood from the capillaries of one organ is transported to the capillaries of another organ via a connecting vein(s)
Which of these hormones is secreted directly into a portal system?
Gonadotropin-releasing hormone
