reproduction Flashcards
(181 cards)
1
Q
What is the testis?
A
gonad (sexual gland) in male or female
2
Q
When does testicular descent occur?
A
during gestational development
3
Q
What are the testis and epididymis (duct) anteriorly anchored by?
A
the diaphragmatic (cranial) ligaments
4
Q
What are the testis and epididymis (duct) posteriorly anchored by?
A
the Gubernaculum testis
5
Q
What happens to the testis as the body grows?
Hint - GDT through the tunnel
A
- gubernaculum shrinks
- diaphragmatic ligament and gubernaculum degenerate
- testes descend through inguinal canal
6
Q
How often do positional defects in the testes occur and what can they include?
(Hint - crypto something)
A
- around 2%
- cryptorchidism (absence of 1-2 testes from scrotum)
7
Q
What can positional defects cause?
Hint - obvious, the big C and clinical anatomy
A
- reduced fertility
- increased risk of testes related tumours
- increased susceptibility to inguinal hernias
8
Q
What is the penis composed of?
A
- root
- shaft
- head and neck
9
Q
Where in the penis does the urethra run?
A
throughout
opens into ducts via accessory organs
10
Q
Where is the base/root of the penis attached?
Hint - which hip bone?
A
below pubic symphysis
11
Q
How is the the crura of corpora attached to the penis?
A
via ligament to bone
12
Q
What are the corpus cavernosum and corpus spongiosum and what do they surround?
A
erectile tissues – both surround the urethra
13
Q
What do the bulbourethral (Cowper’s) glands secrete?
Hint - gallbladder of reproductive system and promoting smoothness
A
alkaline mucus to lubricate and neutralise urinary acids
14
Q
What do preputial glands produce?
Hint - PREPUtial glands
A
a waxy secretion (smegma) between prepuce (foreskin) and glans pubis
15
Q
Which 3 components make up the head of the penis?
Hint - PEG
A
- prepuce (foreskin)
- glans penis
- external meatus
16
Q
State the 3 stages of the erection process.
Hint - vasodilator compound, increase then decrease
A
- NO causes vasodilation in deep penile arteries
- increased blood flow into corpora cavernosa (blood filling erectile tissue)
- compression of veins so reduced venous blood flow by constriction
17
Q
What type of process is erection?
Hint - the less common one like oxytocin
A
+VE feedback mechanism
18
Q
What are the testes?
hint - shape and number
A
paired, oval structures
19
Q
What is the tunica albuginea?
A
thick wall which encloses cavity divided by septa
20
Q
What does each cavity dividing the septa in the tunica albuginea contain?
(Hint - Septa and Tunica albuginea)
A
seminiferous tubules (s. tubules)
21
Q
Describe the movement of the sperm starting from the s. tubules.
(Hint - SREE and no. 3 is something external)
A
S. tubules into chamber →rete testis (anastomosing network of tubules) → efferent ducts → epididymis.
22
Q
Within the epididymis through which different sections does sperm travel?
(Hint - 3 Cs of sperm traveling, no. 1 sounds like Cahoot)
A
caput → corpus → cauda
23
Q
Which structure binds the epididymis to the testis and what is it involved in?
(Hint - gonad in males and females)
A
- the tunica vaginalis
- involved in sperm maturation
24
Q
Via which structure do sperm leave the urethra?
Hint - the one which comes before in the alphabet
A
ductus deferens
25
What do the prostate gland and seminal vesicles empty into?
the urethra
26
Why is hormonal-based therapy given for prostate cancer?
prostate gland is androgen-dependent
27
What are the extra-tubular histological features of the testis?
(Hint - LIMB)
- interstitial cells
- leydig cells
- macrophages
- blood vessels
28
What are the tubular histological features of the testis?
| Hint - SPF
- peritubular cells
- fibroblasts
- SM cells (peristalsis of tubule)
29
What are the intra-tubular histological features of the testis?
(Hint - 5 variations of S; Brinkworth lectures)
- spermatogonia (outside blood-testis barrier)
- sertoli cells (somatic)
- spermatocytes
- spermatids
- spermatozoa
30
Which part of the tubule are sertoli cells attached to?
| Hint - like nurses in NHS
base of tubule
31
Where in the tubule of the testis do spermatogonia lie?
| Hint - not in it and not above it
beneath the tubule
32
Which structures between sertoli cells make up the blood-testis barrier?
(Hint - a secure type of junction)
tight junctions
33
What do post-spermatogonia stages develop within and then progress towards through maturation?
- within sertoli cells
| - towards lumen of tubule
34
What do immature spermatozoa shed into?
the lumen
35
Which action moves sperm into the rete testis?
peristaltic action (waves)
36
Which 5 parts does the adult female reproductive system consist of?
(Hint - VUCOV)
- vulva (labia minora and majora and clitoris)
- uterus
- cervix (internal os and external os)
- oviducts/fallopian tubes (fimbriae, ampulla, isthmus)
- vagina (inc. hymen)
37
Define folliculogenesis.
maturation of the ovarian follicle
38
State the 4 main regions of the ovary.
| Hint - GOOTuntaag
- germinal epithelium
- tunica albuginea
- ovarian cortex
- ovarian medulla
39
For each stage of oogenesis, state the meiotic events which occur:
a) no follicle (fetal period)
b) primordial follicle (before birth after birth)
c) primary follicle (after puberty)
d) antral follicle
e) ovulated ovum
f) fertilised ovum
a) oogonium (mitosis)
b) primary oocyte (meiosis I started - arrested in diplotene)
c) primary oocyte (meiosis II started)
d) secondary oocyte (polar body 1 - ovulation)
e) secondary oocyte (polar body 1 - arrested at metaphase I and fertilisation)
f) fertilised ovum - polar body 2 + sperm
(note that primary oocytes are always FSH and LH-dependent)
40
Define oogenesis.
creation of eggs
41
State the 4 stages of oogenesis.
| Hint - 1) division, 2) maturation, 3) half meiosis and 4) release and mess cleaned up
1. oogonia mitosis in foetal life
2. oogonia mature → primary oocytes (50-60 days)
3. undergo meiosis but arrested at diplotene (chromatids cannot separate) - cells in dictyate stage
4. oocytes destined to mature released by ovary - remaining dictyate germ cells apoptose in last trimester
42
When does puberty occur in females and what happens at this point?
- by 1st ovulation (release of an egg)
| - first menses/menarche occurs (menstruation)
43
For each secondary sexual characteristic state the hormone that causes it and the location of release:
a) breasts and genitilia
b) pubic and axillary hair
a) oestrogen, from the ovary
| b) androgens, from ovary and adrenal gland
44
What is the age on onset of puberty dictated by?
genes, environmental and nutritional factors
45
What is primordial germ cells?
earliest germ cells
46
Where do primordial germ cells originate (week 3 post-conception)?
embryonic epiblast, close to yolk sac
47
After primordial germ cells originate where do they migrate and through which structure (day 24 p.c.)?
- through hind-gut
- to genital ridge
(mechanism disputed)
48
What do primordial germ cells enter and where do they first settle on during spermatogenesis?
- enter presumptive seminiferous tubes (hoops) with pro-Sertoli cells
- settle on tubule wall first
49
Where is spermatogonia (spermatozoa precursor) formed during spermatogenesis?
(Hint - outside a wall)
outside blood-testis-barrier
50
State the stages of spermatogenesis starting from primordial germ cells denoting them using an arrow (→).
(Hint - r g in every single cell type; one begins with g)
PGC’s (proliferate by mitosis) → gonocytes → pro-spermatogonia → spermatogonia (end of the foetal stage)
51
What do some spermatagonia become during the prepubertal phase and what do they acquire?
(Hint - to do with growth and differentiation)
- become stem cells
| - acquire self-renewal capacity
52
What does peri-natal spermatogonial division produce?
| Hint - the next stage from spermatogonia
spermatocytes
53
When do spermatocytes arrest?
in prophase of 1st meiotic division
54
What is spermatocytic arrest?
| Hint - germs and sperms
- interruption of germinal cells
| - which elicits altered spermatozoa formation
55
What is all post-stem-cell development before sperm release classified as?
syncitia (multinucleated cell from multiple fusions)
56
In rodents what are A0 cells considered?
stem cells that give rise to generations of A spermatogonia
57
State the stages of stem cell development in rodents using arrows (→).
(Apaired, Aaligned, A1-4) → intermediate → B
58
What does stem cell development in rodents allow?
dramatic expansion of small stem cell pool
59
What are considered stem cells in primate (i.e. humans)?
Adark cells
60
State the stages of stem cell development in primates (i.e. humans) using arrows (→).
(Hint - like getting a tan skin gets darker)
Apale (proliferative) → intermediate → B
61
What does stem cell development in primates allow?
large reserve of stem cells w/ relatively few proliferative divisions
62
For each type of spermatocyte, stage of division and the role taken within the cell:
a) preleptotene spermatocytes →
b) leptotene s'cytes →
c) zygotene s'cytes →
d) pachytene s'cytes →
e) diplotene s'cytes →
f) 1st meiotic division →
g) secondary s'cytes →
h) 2nd meiotic division (N/A)
a) S-phase
b) chromatin remodelling
c) chromatin remodelling
d) transcription, translation; increase in size
e-f) enter meiosis
g) NB: haploid - homologous chromatids have separated
h) N/A
63
What is spermatogenesis?
development of spermatids
64
What is a round spermatid?
| Hint - TN and less DNA
- the transition proteins of spermatid are replaced with nuclear proteins
- they have no DNA and so no transcriptional ability
65
Round spermatids are present at the onset of which cellular structures?
onset of flagellum and acrosome development
66
What is an elongating spermatid?
| Hint - PT
- protamines replace transition histones
| - transcriptionally inactive
67
What changes are made to form an elongating spermatid?
| Hint - when you lose excess weight you are taller and move faster
- reduction in nuclear size
- flagellum fully-developed (motility)
- cytoplasm shrinks away (forms droplet)
68
What is a maturation phase spermatid?
| Hint - graduated sperm and then cleaned up by nurses
- structure of a mature spermatozoa
| - cytoplasmic droplet phagocytosed by sertoli cell
69
During spermination, where is a maturation phase spermatid shed into?
lumen of tubule
70
What is a sertoli cell?
nurse cell of testacles
71
State phases of spermiogenesis to form a sperm (mature, haploid male gametes)?
(Hint - preparation and then two sets of division)
- growth
- meiosis I and cytoplasmic division
- meiosis II and cytoplasmic division
72
What does formation of polar bodies allows oocytes to do?
reduce genome so fertilisation can occur
73
What is an oogonium?
female primordial germ cell
74
State the main stages of gametogenesis in females to get to the ovulatory follicles.
- multiple divisions, → 1° oocyte
- puberty = a few 1° follicles recruited to re-commence gamete level
- after that, daily:
1º follicle → 2º follicle → pre-ovulatory follicles
75
Describe the structure of a primary oocyte.
| Hint - membrane, granny cells, nucleus type and its stage in the cell cycle
- bounded by BM
- surrounded by (spindle) granulosa cells
- distinctive nucleus - germinal vesicle
- primordial follicle - enters cell-cycle arrest
76
How is a primary/pre-antral follicle formed?
| Hint - grow, secrete to form ZP, cells joined a new way, more cells around follicle
- growth (follicle and oocyte)
- glycoprotein secretion forms zona pellucida.
- granulocyte cells divide
- cytoplasmic processes to oocyte
- gap junctions form + become avascular
- ovarian stromal cells theca around follicle (interna + externa)
77
What is a theca?
group of endocrine cells in ovary (CT surrounding a follicle)
78
Label the diagram of a pre-antral follicle.
A - zona pellucida
B - oocyte
C - follicular cells = zona granulosa
79
How is a secondary/antral (graafian) follicle formed?
| Hint - bigger, fluid, mRNA, hormone stuff
- proliferates increasing follicular size
- follicular fluid secreted (mucopolysaccharides + serum) from antrum
- oocyte continues mRNA storing
- now hormone-dependent (gonadotrophin) otherwise atresia occurs
- can synthesise steroids
80
What is the cumulus oophorous?
| Hint - 'cumulus' means heap, 'oo' means egg and 'phorus' means carrying
thick granular egg cell layer that connects oocyte to stalk
81
How is a pre-ovulatory follicle formed?
| Hint - L hormone, DNA disappears, sisters are separated, pb1, met plate, meiosis start and stop
- transient peak of LH-stimulated ovulation
- nuclear membrane breakdown
- chromosome separation
- unequal cytoplasmic division - 1st polar body leaves
- chromatid separation → metaphase plate → 2nd meiotic arrest (stop)
82
Label the diagram of a pre-ovulatory follicle.
| Hint - GP
```
A - zona granulosa
B - zona pellucida
C - antrum
D - corona radiata
E - oocyte
```
83
How does the pre-ovulatory follicle change just before ovulation?
(Hint - extensions leave, synthesis, growth, loosen, vascularise, change to sickness hormone, bubble, thinning)
- cytoplasmic processes disappear
- cortical granules + new proteins synthesised
- follicle size increases (more fluid)
- outer granular cell layers loosen
- follicular blood supply increases
- steroid synthesis switches to progesterone
- bulge in ovary wall
- thinning at stigma/macula pellicuda (due to lasminogen activator collagenase)
84
Describe the rupture of the pre-ovulatory follicle during ovulation.
(Hint - to do with the floor sweep of the ovaries and a duct)
- cilia on fimbriae sweep oocyte + cumulus cells
| - through oviduct
85
What is the corpus luteum?
| Hint - 'corpus' means body and 'luteum' means yellow or messed-up
collapsed (post-ovulatory) follicle
86
What happens to the ovary follicle after ovulation?
| Hint - cells and hormones - GOP including a +VE feedback hormone and TAP and lysis
- luteinisation of granular cells: synthesis of progestagens (i.e. progesterone) + oxytocin
- thecal cells (smaller lutein cells): synthesise androgens + progesterone
- both synthesise inhibin
- luteolysis (regression of corpus luteum)
87
Describe endocrine regulation in males by hormone GnRH.
| Hint - all about the H hormones, and two brain structures
- produced by: median eminence of hypothalamus
- acts on: pituitary
- effects: the release of gonadotropins (i.e. LH and FSH)
88
Describe endocrine regulation in males by hormone FSH.
| Hint - nurse cells and transport of the most male hormone there ever was, and germ cells
• acts on: sertoli cells
• effects:
- ABP-production for testosterone transport around blood
- direct effect on germ cells via sertoli cells
89
Describe endocrine regulation in males by hormone LH.
| Hint - L for LH and production of the most male hormone there ever was
- acts on: leydig cells
| - effects: produces testosterone
90
What does hormone testosterone act on in males?
| Hint - PGCs, downstairs, acne, 'i can feel it in my...' and hairiness
• acts on:
- germ cells
- bone
- skin
- hair
- accessory sexual organs (post-puberty)
91
Describe endocrine regulation in males by hormone dihydrotestosterone (DHT).
- produced by: testosterone
- acts on: prostate
- effects: on prostate
92
Describe endocrine regulation in males by hormone oestradiol.
(Hint - all about the body of bones and produced by the most male hormones)
- produced by: testosterone
- acts on: reproductive system
- effects: epiphysial closure
93
How does the hypathalamus release GnRH?
by pulsatile secretion
94
When are gonadotropin reserves replenished during GnRH secretion?
between pulses of GnRH
95
What does overstimulation with GnRH lead to?
gonadotropin depletion and deficiency
96
What does understimulation with GnRH lead to?
inadequate gonadotropin production and deficiency
97
Which hormones is FSH positively regulated by?
| Hint - F for FSH and another which allows ACTIVIty
activin and follistatin
98
What is FSH negatively regulated by?
| Hint - this hormone INHIBIts its activity
inhibin (s.cells of pituitary)
99
What is LH negatively regulated by?
| Hint - the most male hormone of them all
testosterone (pituitary and hypothalamus)
100
State the 7 principal hormone involved in endocrine regulation of females.
(Hint - HOLP FIG - one of which is used to detect pregnancy)
- GnRH (LHRH)
- LH
- FSH
- inhibin
- oestradiol
- progesterone
- human Chorionic Gonadotrophin (hCG)
101
Which 2 systems is the ovarian cycle controlled by?
| Hint - the brain one and then just the female one
1. gonadotrophin system:
- hypothalamic control: LHRH (LH-releasing hormone)
- LH and FSH; pulsatile release
2. ovarian hormones; oestrogens (oestradiol) and progestogens (progesterone); cyclical production
102
Describe the follicular phase of the menstrual cycle (10-16 days).
(Hint - growth, OI hormones come out, create a negative system which affects levels of F hormone)
FSH acts on primary and secondary follicles → follicular growth
- promotes oestradiol (follicles) and inhibin secretion
- both hormones cause -VE feedback (FSH levels decreases as oestradiol rises)
103
Describe the ovulatory phase of the menstrual cycle (36 hours on day 12)
(Hint - back to being +VE, the ratio of H hormones changes, leads to the short hormone surge, and what is ovulation?)
- oestradiol achieves the threshold to switch to +VE feedback
- LH : FSH from pituitary rises so LH surge
- oocyte matures → ovum released by the end
104
Describe the luteal phase of the menstrual cycle (14 days)
| Hint - follicle, granulosa cells, short hormones suppressed, long PO hormones secreted and endometrium origin
- empty tertiary follicle collapse
- residual granulosa cells luteinise/invade corpus luteum
• secretes oestradiol and progesterone
• suppresses LH/FSH (prog.)
• maintains endometrium
105
Describe the late luteal phase/menstruation (4-5 days)
(Hint - immune crash, less PO hormones, uterus wall falls, system changed, results in F hormone being introduced and then repeat)
- corpus luteum involutes (macrophages)
- oestradiol and progesterone fall
- endometrium not maintained (menstruation)
- loss of -VE feedback
- FSH rises
- new cycle begins
106
Identify the stage of the ovarian cycle shown by each diagram/graph.
(Hint - F-O-LL)
(top to bottom) follicular, ovulatory and late luteal phase
107
If fertilisation occurs, what happens at the start of a new menstrual cycle?
(Hint - ovum role, hormone in a pregnancy test and its role, CL and PO hormones it releases, period, what is established?)
- ovum implants
- uterus secretes hCG which maintains corpus luteum
- corpus luteum secretes oestradiol and progesterone
- endometrium maintained
- no menstruation
- pregnancy established
108
What role does the hormone oestrogen have on just males or just females?
(Hint - oil burning, body fat, diabetic stuff, platelets)
- on lipid metabolism
- on fat distribution
- promote insulin secretion
- effects on blood clotting (thrombosis)
109
What role does the hormone oestrogen have in both sexes?
| Hint - BCV
- maintenance of bone mass
- on CNS
- on vasculature
110
What is menopause caused by?
- decline in ovarian follicle numbers and reduced gonadotrophin responsiveness
- oestrogen loss increases LH + FSH
- vasomotor changes
111
How does menopause affect women?
- reproductive outcome compromised from 35+
- 40’s–50’s: climacteric (last period, mood changes, loss of libido, hot flushes, rarer in oriental women)
- increased risk of coronary thrombosis
- reduction in vaginal lubrication - rise in pH (discomfort)
- increased risk of osteoporosis
112
What is the rationale for hormone replacement therapy (HRT) in treating menopause?
risk vs benefit discussion needed
113
Summarise the embryogenesis process using arrows (→).
| Hint - FZCMBG(germ layers)OF
fertilisation → zygote → cleavage → morula → blastocyst → gastrulation → ectoderm, mesoderm, endoderm → organogenesis → foetal development (mammals)
114
What is a morula?
a ball of cells ('mulberry')
115
Why are there 3 germ cell layers?
to allow more diversity of cells
116
What is organogenesis?
organ formation (after embryonic period)
117
What is a morula called after implantation?
blastocyst
118
Label the female reproductive system.
```
A - uterus
B - morula
C - 2-cell stage
D - zona pelludica
E - ampulla region
F - fertilisation
G - fimbriae
H - ovulation
I - ovary
J - blastocyst
K - early stage of implantation
L - final cleavage
M - oviduct
```
119
What occurs during fertilisation?
| Hint - structure formed, distribution of products, signalling, something is contained within
- zygote formed
- already has unequal distribution of some cellular products (e.g. leptin)
- autocrine signalling taking place w/in cell
- cell contains TFs
120
What occurs during cleavage?
- cells divide into but there no growth
- after each cell splits, called a 'blastomere'
- 32 cells →
zygote now called morula (containing blastomeres)
- split cells, now possess TFs
121
State the number of cells on each day:
a) day 2
b) day 3
c) day 4
d) day 5
e) day 6
a) 1-2
b) 9
c) 16 (morula)
d) 58 (blastocyst)
e) 107 (blastocyst)
122
What is rotational cleavage and what does it allow?
- plane of cleavage rotates
| - allows a ball of cells to be created
123
What occurs during the start of blastulation (compaction)?
| Hint - compaction, junctions and dividing
- blastomeres in morula get closer, flatter and more compact
- tight junctions formed
- blastomeres start to differentiate slightly (due to possessing TFs)
124
What occurs during differentiation in embryogenesis?
| Hint - EmbTro formed, and cells become P/NP
- formation of embryoblasts and trophoblasts (trophectoderm)
- internal cells non-polar
- external cells polarised
125
What occurs when embryo-blasts cramp together into one part of cell (inner cell mass)?
(Hint - the bubble bursts to release fluid, you get menstrual pains and its now a b)
- cells release fluid which creates a cavity named the = blastocoel
- fluid also causes cells to cramp
- cell now called a blastocyst
126
What occurs during hatching?
cell membrane ‘hatches’ out of zona pellucida (outer layer)
127
What occurs during formation of amniotic cavity (inner cell mass)? Use the diagram to help you.
(Hint - hypo + epi formed, amnio stuff, more hypo and blastoc. and egg yolk)
- cells start to differentiate again creating hypoblasts and epiblasts
- amnioblasts/cytes line amniotic cavity which secrete amniotic fluid
- hypoblasts line blastocoel which makes up yolk sac
128
What are the 3 germ layers?
ectoderm
endoderm
mesoderm
129
Which cells does the ectoderm give rise to?
| Hint - skin, electrical signals and tan cells
- epidermis
- nervous system
- pigment cells
130
Which cells does the mesoderm give rise to?
| Hint - main systems - KGB MHB
- kidneys
- gonads
- bones
- muscle
- heart
- blood cells
(most internal organs)
131
Which cells does the endoderm give rise to?
| Hint - tubes
- lining of gut
| - respiratory system
132
What is pattern formation in embryonic development?
| Hint - spatial and temporal and organization
the process by which a spatial and temporal pattern of cell activities is organised within the embryo
133
What does pattern formation in embryonic development involve?
(Hint - lots of different signalling)
the co-ordination of a variety of mechanisms of cellular communication
134
What is induction in embryology?
| Hint - cell 1 → cell 2
- where one cell type causes another cell type to change their fate
- cells produce signals to cause response in target cells
135
Define morphogenesis.
developing diversity by formation of different structures from the same initial structure (gastrulation, neurulation)
136
In morphogenesis what does juxtracrine/paracrine signalling lead to?
a yes/no response
137
Why can there sometimes be a variable response to juxtracrine/paracrine signalling in morphogenesis?
(Hint - other factors too)
as a result of modulation by interplay and other (threshold) signals
138
What is a morphogen?
a signalling molecule that forms an extracellular concentration gradient (more active near source of secretion)
139
# Define gastrulation.
(Hint - the 3 Gs)
process by which the 3 germ layers are formed
140
What initiates gastrulation?
the ‘organiser’- sends signals
141
In future where is the organiser located?
on dorsal, posterior region
142
State the 8 stages of gastrulation.
1. bilaminar/embryonic disk formed
2. primitive streak formed (virtual sectioning of the bilaminar disc into 2 halves)
3. primitive streak posterior extensions
4. expands to form primitive node (slight depression)
5. primitive groove formation (depression continues w/in the primitive streak)
6. migration of epiblasts through node/groove to endoderm
7. migration of epiblast cells through streak to V+L mesoderm
8. trilaminar disk formation - migrated cells differentiate further into 3 germ layers
9. notochord formation for functions in neurulation (regression of streak and further differentiation of cells in mesoderm)
143
Define neurulation
neural tube formation (forms CNS - brain & spinal cord)
144
# Define somites
(Hint - a ball)
- balls of cells formed
- when neural tube forms from paraxial mesoderm
(differentiate into tissues/cells)
145
State the 5 stages of neurulation.
(Hint -
1. n. plate
2. n. fold
3. n. tube starts from n. fold fusion
4. outer ecto. aroun meso. and endo. and fusing
5. n.c. cells step in)
1. notochord induces a change in ectoderm so neural plate forms
2. lateral edges of ectoderm elevated and form neural fold (neural groove is depressed area)
3. neural tube formation starts as neural folds fuse together
4. outer ectoderm moves down and surrounds mesoderm and endoderm - fusing proceeds cranially and caudally
5. neural tube breaks off from endoderm where fusion occurs, neural crest cells arise (basis of tissues) and differentiation (future nerve and tissue cells)
146
What is spina bifida anencephaly?
- tube fusion doesn’t occur
- fails to close in the cervical region and caudally to it
- most of the brain fails to form
- children with this disorder lose neurological function
147
Define infertility?
a continuous period of 12 months+ without conceiving despite regular, unprotected intercourse
148
What may male factor infertility result from?
poor seminal characteristics
149
What is an “infertile” male?
- “infertile” male - can produce sperm and father a child >1 year before
- sub-fertility unless infertility is known to be permanent
150
How is infertility addressed?
- underlying cause should be treated first
| - if unknown/treatment fails, offer alternatives
151
What is intra-uterine insemination (IUI) and when is it used?
- placing sperm inside woman's uterus to facilitate fertilization
indications:
- cryopreserved gametes
- donor sperm
- post-operative scarring of reproductive tract
- mild, male factor infertility (oligozoospermia)
- erectile dysfunction
- problems w/ semen deposition
152
State pros and cons of IUI.
• pros:
- appropriate use cheaper easier option than IVF/ICSI
• cons:
- may require ovarian stimulation
- higher risk of multiple pregnancy (health risks to offspring)
- led to lower success rates/cycle
- controversial as sometimes inappropriately offered
153
What is IVF and when is it used?
- both gametes collected and incubated
- 1 oocyte per 100s of spermatozoa - monitor outcomes
indications:
- cryopreserved gametes
- donor sperm
- post-operative scarring of reproductive tract
- mild, male factor infertility (oligozoospermia)
indications:
- tubule blockage
- oligozoospermia
154
What is intra-cytoplasmic sperm injection (ICSI) and when is it used?
- IVF using 1 sperm per oocyte
Indications:
- tubule blockage
- severe oligozoospermia (very few sperm available)
155
State pros and cons of ICSI.
• pros:
- success rates comparable to IVF but useful in wider range of patients
- higher fertilisation rate
• cons:
- introduced w/o safety & evaluation
- genetic disorders transmitted during spermatogenesis
- a low live birth rate
- men conceived likely to have low inhibin B and high FSH; infertility
156
How do we collect and treat male gametes?
- masturbation or ejaculation into spermicide-free condom (more representative) within ½ - 2 hrs
- liquefaction, sample centrifuged (removes seminal plasma), pellet washed, re-suspended in buffer
157
What is the "swim-up" purification of sperm?
- most motile sperm selected e.g. IUI/IVF
- 2.5 ml pre-warmed Ham's F-10 culture medium
- centrifuged and pellet over-laid w/ medium
- tube sealed, inclined at 45
- 37°C for 60-90 minutes in 5% CO2
- sterile pasteur pipette removes liquid of actively-motile sperm
158
How do we collect female gametes?
- induction of superovulation (drug-induced production of multiple eggs)
- starting dosage tailored to individual
- GnRH analogues used; agonists to reduce exogenous gonadotrophins; antagonists to time LH surge
- hCG stimulates ovulation
(oocytes collected by aspiration under ultrasound guidance)
159
What is ovarian hyperstimulation syndrome?
- condition resulting from excessive follicular development; oestrogen over-production
- causes oedema in abdomen (bloating, nausea) and increased risk of thrombosis
- can persist through first couple of weeks of pregnancy
160
What are the 2 types of gamete transfers for IVF and ICSI?
| Hint - 45BC3
- cleavage stage transfers (3 days)
| - blastocyst stage transfers (4-5 days)
161
Why might someone carry out a blastocyst stage transfer?
to allow selection of “best quality” embryo and maximise chances of success
162
How is an embryo selected/assessed?
| Hint - using which equipment
usually performed under microscope or eeva (incubator-housed camera)
163
What is selection of a day 3 embryo based on?
| Hint - PEN
- evenness of blastomeres
- presence of fragmentation
- number of cells
164
What does each grade (a-d) mean?
- a: even blastomeres; no fragmentation
- b: a little inequality in blastomeres size, <10% cytoplasmic fragments
- c: unequal sized blastomeres; <50% fragments.
- d: unequal blastomeres, severe fragmentation and large black granules
165
What is selection of a day 4-5 embryo based on?
| Hint - BIT
- blastocoel
- inner cell mass
- trophectoderm
166
For each expansion grade (1 - 5+6) of an embryo, state the blastocyst development and stage status.
1 - blastocoel cavity less than half volume of embryo
2 - blastocoel cavity more than half volume of embryo
3 - full blastocyst, cavity completely filling embryo
4 - expanded blastocyst, cavity larger than embryo, w/ thinning of shell
5 + 6 - hatching out of shell
167
For each ICM grade (A-C) of an embryo, state the inner cell mass quality and trophectoderm quality.
A -
inner cell mass: many cells, tightly packed
trophectoderm: many cells, forming cohesive layer
B -
inner cell mass: several cells, loosely-packed
trophectoderm: several cells, forming epithelium
C -
inner cell mass: very few cells
trophectoderm: very few large cells
168
What is clomiphine and what is it used for?
- medication ‘hypothalamic’ amenorrhoea (lack of periods)
- reset ovarian feedback
- low/normal LH/FSH
- normal weight
- also used in PCOS
- some risk of multiple pregnancy
169
What is gonadotrophins and what are they used for?
- pituitary gonadotrophins (primarily FSH)
- urinary gonadotrophins (LH/FSH mixture) recombinant FSH
- uses: hypothalamic amenorrhoea, pituitary disease, PCOS
- high risk of multiple pregnancy
- careful monitoring essential
- oestrogens, ultrasound
170
What is hyperprolactinaemia?
```
- relatively common
‘Idiopathic’
- prolactinomas
- surgery (outmoded!)
- dopamine agonists (i.e. bromocryptine, cabergolide)
- no increased risk of multiple pregnacy
```
171
What are the current NICE guidelines on IVF?
- suitable patients should have 3 cycles of IVF treatment (50% chance of pregnancy)
- some PCT’s fund none
- some fund 1 cycle
- postcode lottery
- a lot of money for the private sector
172
What is controlled ovarian hyperstimulation and why are its advantages?
- produce multiple eggs
- fertilise and produce multiple embryos
- avoid ovarian hyperstimulation syndrome
- replace 1+ embryos
- freeze spare embryos
- replace as needed later
- achieve higher pregnancy rate
- take control of menstrual cycle
- abolish endogenous gonadotrophins with LHRH agonist
- use exogenous FSH
- obtain multiple follcle growth
- ovulate with excess LH (HCG)
173
Compare IVF controlled ovarian hyperstimulation (COH) and controlled ovarian stimulation (COS).
COH:
- downregulate with LHRH agonist at d21
- when period commences treat with FSH (Day 1)
- review at D5 with oestrogens and ultrasound (modify FSH dose)
- continue to monitor review D8 and D10
- ovulate with HCG
- retrieve eggs at + 36h
COS:
- fertilise in vitro
- replace at D2-5
- maintain endometrium with exogenous progesterone
174
Describe COH cycle outcomes.
• inadequate stimulation (<5 oocytes)
• adequate stimulation (5-20 oocytes), (mean about 12)
• risk of hyperstimulation (>20 oocytes)
- high oestradiol
• if high risk of hyperstimulation syndrome abandon cycle
• if modest risk hyperstimulation syndrome; replace embryos in later cycle
175
Which people need IVF and need it?
- age <24, >40
- smoker - partner smokes (impairs results by 50%)
- BMI <19 or > 30
- FSH > 10 on 3 occasions (ovarian reserve)
- now use single value of AMH (anti-mullerian hormone)
176
What is the trend for fertility with age in IVF based on SET (single embryo transfer)?
- improved embryo selection
| - optimal fertility in young healthy couples 22% per cycle
177
What does the ovarian reserve (AMH) Anti-Mullerian Hormone test tell us about an ovary?
- chronological age of ovary
| - biological age of ovary
178
What is Anti-Mullerian hormone (AMH)?
- protein hormone of TGF beta family
- secreted + acts within the ovary
- secreted by small antral and pre-anteral follicles in the ovary
- menstrual cycle independent
- inhibits follicular recruitment
- regulates late follicular development
- is a good marker of ovarian reserve
- predicts response on IVF cycles
- elevated in PCOS
179
How does AMH affect folliculogenesis?
- inhibits follicular recruitment
| - inhibits the stimulatory growth of FSH on preantral and small antral follicles
180
Describe artificial insemination.
- vaginal Insemination
- intrauterine insemination
- partner insemination
- donor insemination
- fresh sperm
- frozen sperm
- quarantined at least 3 months (infectious diseases)
- monitor LH
- inseminate on day of LH surge
- use intrauterine insemination
- pregnancy rates 21% per inseminated cycle
used less frequently (ICSI)
181
How is each type of male infertility affected:
a) oligospermia?
b) azoospermia?
c) obstructive azoospermia?
a) IVF
b)
- previously donor insemination
- need very few viable sperm - centrifuge ejaculate (ICSI)
c) epidydymal sperm retrieval - testicular biopsy (ICSI)
