Fertility Flashcards
Where does the pituitary sit
Pituitary fossa in the sella turica
What is the pituitary gland derived from
Outward pouching of oral ectderm
What is the anterior pituitary derived from
Roof of mouth
What is posterior pituitary derived from
Notochord
What nerves passes through the Cavernous sinus
III, IV, VI, V1, V2
What is beneath the pitutiary fossa
Sphenoid air sinus
What is a microadenoma pituitary tumour
Less than 10mm
What a is macroadenoma pituitary tumour
Over 10mm, more likely to cause compression
What are macroadenomas caused by
NFPA, acromegaly (GH), Cushing’s (overproduction of ACTH), prolactinoma (prolactin producing tumours), TSHoma (thyrotoxicosis)
What does a lesion at the optic chiasm cause
Bitemporal hemanopia
How is pituitary hypofunction tested
PRL - lactation
TSH - T4, T3
LH - testosterone/estradiol
FSH - spermatogenesis/folliculogenesis
GH - IGF1-1 through insulin tolerance test (causes hypoglycaemia, which body should automatically correct by producing GH, cortisol, adrenaline and glucagon)
ACTH - cortisol through synacthen (synthetic ACTH) or ITT
What if too much ACTH is suspected
give dexamethasone as test to see if pituitary gland reacts
What is the treatment for pituitary tumours
Conservative, surgery, medical (dopamine agonist therapy in prolactin producing tumours or acromegaly with somatostatin analogues), radiotherapy
When does cortisol peak
7am, falls throughout the day. Cortisol to be given in 3 courses in a day.
What is the antrafollicle
First follicles seen on US. One antrafollicle is selected to progress to Graafian follicle
What are the 3 stages of the Ovarian cycle
Follicular
Ovulatory
Luteal
What is the follicular phase
- At the start of the cycle levels of FSH rise causing stimulation of a few ovarian follicles.
- As follicles mature they compete with each other for dominance.
- The 1st follicle to become fully mature will produce large amounts of oestrogen.
- This inhibits the growth of the other competing follicles.
- The 1 follicle reaching full maturity is called the Graafian follicle (oocyte develops within this).
- The Graafian follicle continues to secrete increasing amounts of oestrogen.
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- Oestrogen causes:
Endometrial thickening
Thinning of cervical mucous to allow easier passage of sperm
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- Oestrogen also initially inhibits LH production from the pituitary gland.
What is the ovulatory phase
When the ovum is mature, oestrogen reaches a threshold level which conversely causes a sudden spike in LH around day 12.
The high amounts of LH cause the membrane of the Graafian follicle to become thinner.
Within 24-48 hours of the LH surge, the follicle ruptures releasing a secondary oocyte.
The secondary oocyte quickly matures into an ootid and then into a mature ovum.
The ovum is then released into the peritoneal space and is taken into the fallopian tube via fimbriae
What is the luteal phase
- Once ovulation has occurred the hormones LH and FSH cause the remaining graafian follicle to develop into the corpus luteum.
- The corpus luteum then begins to produce the hormone progesterone.
- Increased levels of progesterone result in:
Endometrium becoming receptive to implantation of the blastocyst
Increased production of oestrogen by the adrenal glands
Negative feedback causing decreased LH and FSH (both needed to maintain the corpus luteum)
Increase in the woman’s basal body temperature
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17. As the levels of FSH and LH fall, the corpus luteum degenerates.
- This results in progesterone no longer being produced.
- The falling level of progesterone triggers menstruation and the entire cycle starts again.
- However if an ovum is fertilised it produces hCG which is similar in function to LH.
- This prevents degeneration of the corpus luteum (continued production of progesterone).
- Continued production of progesterone prevents menstruation.
- The placenta eventually takes over the role of the corpus luteum (from 8 weeks).
When does implantation occur
begins by day 6-7 after ovulation (day 21 of menstrual cycle) - occurs in the uterus
What happens when oocyte is in fallopian tube
It’s propelled by cilia and fallopian tube contractions
What are the 3 stages of the uterine cycle
Menstrual phase (days 1-5) Proliferative phase (D6-14) Secretory phase (D15-22):
What happens in the menstrual phase
At the end of the luteal phase, the corpus luteum degenerates (if no implantation occurs).
The loss of the corpus luteum results in decreased progesterone production.
The decreasing levels of progesterone cause the spiral arteries in the functional endometrium to contract.
The loss of blood supply causes the functional endometrium to become ischaemic and necrotic.
As a result, the functional endometrium is shed and exits out through the vagina.
This is seen as the 3-5 day period of menstruation a woman experiences each month.
What happens in the proliferative phase
During the proliferative phase, the endometrium is exposed to an increase in oestrogen levels caused by FSH and LH stimulating the ovaries. This oestrogen causes repair and growth of the functional endometrial layer allowing recovery from the recent menstruation and further proliferation of the endometrium.
What happens in the secretory phase
The secretory phase begins once ovulation has occurred.
This phase is driven by progesterone produced by the corpus luteum.
It results in the endometrial glands beginning to secrete various substances.
These secretions make the uterus a more welcoming environment for an embryo to implant.
What happens when GnRH analogues are given in a pulsatile manner
Increase production of FSH and LH (and vice versa for continuous)
What does clomid do
oestrogen receptive blockers. Disruption of negative feedback of GnRH
What does combined oral contraceptive pill do
negative feedback to ant pituitary and GnRH
What causes insensitivity of follicles
PCOS
What are the causes of anovulation
Hypothalamic dysfunction (10%) - GnRH production is low or not in pulsatile manner. Pituitary dysfunction (10% with hyperprolactinemia) Thyroid dysfunction PCOS - 70% Ovarian failure
What effect does obesity have on fertility
less fertile, have higher rates of miscarriage, require higher doses of ovulation-inducing agents. Causes insulin resistance, hyperinsulinaemia and hyperandrogenaemia
Weight loss restores ovulation, achieves spontaneous pregnancy
What is clomiphene citrate
stimulate endogenous FSH production. Frist line of treatment for those with absent or irregular ovulation but who have normal basal endogenous estradiol
How is PCOS diagnosed
12 or more peripheral follicles or increase ovarian volume (greater than 10cm^3)
Oligo-ovulation or anovulation
Clinical and or biochemical signs of hyperandrogenism. Testosterone normal or slightly raised. LH:FSH ratio increased with FSH normal. Free androgen index is usually normal or elevated.
What happens in premature ovarian insufficiency
depleted eggs and increased FSH levels below age of 40.
Inhibin B production by small follicles decreases with age, the inhibin suppression of FSH secretion decreases and pituitary glands secretion of FSH increases
An elevated day-3 FHS level in women with menses is highly sensitive and specific for identifying women with a depleted ovarian pool
How is ovarian reserve measured
Antral follicle count, measuring AMH
What are the main causes of hyperprolactinemia
prolactin secreting pituitary gland tumour and use of psychiatric mediations. Test for hypothyroidism and pregnancy
How is hyperprolactinemia treated
Bromocriptine and cabergoline are also used to treat hyperprolactinemia with no known cause
What are the causes of hypogonadotropic hypogonadism
low BMI under 20, high intensity exercise, certain dietary patterns including high-fibre, low fat, excessive stress.
What is hypogondotropic hypogonadism
Hypogonadism due to impaired secretion of gonadotropin secretion
What is the treatment for hypogonadotropic hypogonadism and what are the complications of this
Months treatment with hMG (FSH and LH)
Ovarian hyper stimulation syndrome and multiple pregnancies
What temperature is best for testes
35
Describe the anatomy of a testicle
Each testicle is divided by fibrous tissue into 200 lobules. Each lobule will contain 4 or 5 seminiferous tubules, containing germinal epithelium producing sperm. Between seminiferous tubules, there are Leydig cells.
What is a seminiferous tuble
Lined by spermatogonial stem cells (starts production at puberty
What is in between spermatogonial stem cells
Sertoli cells: provide support, nutrition, protection( Forms a barrier from immune system due to the production of new antigens)
How is sperm produced from spermatogonial stem cells
two types, dark and pale: undergo mitosis and then meiosis due to haploid nature of sperm. Meiosis I is primary spermatocyte and meiosis II is secondary spermatocyte í spermatid (early and late) í mature sperm (when it reaches the luminal end, it passes into the fluid produced by the Sertoli cells, propelling sperm outside
What is spermiogenesis
elongation of spermatid into mature sperm, creating a sac full of proteolytic enzymes that can penetrate the egg (acrosome) and a tail piece. Cytoplasm not needed except for mitochondria.
How many sperm are produced each day
120 million - whole cycle takes 72 days
What do sertoli cells do
Provide structural support. Create 2 compartments. Provide nutrients for mature sperm. Eliminate degenerate germ cells. Secretes Inhibin, ABP (enhances the function of testosterone), AMH and growth factors
What do Leydig cell do
surrounds seminiferous tubules. Secrete androgens (C19), mainly testosterone. Mainly molecule is cholesterol. 95% produced in the testicles, 5% in adrenal gland.
What are the effects of tesosterone
Anabolic male hormone (increase bone and muscle mass)
Primary and secondary sexual characters
Libido and sexual behaviour
Stimulates Sertoli cells and spermatogenesis
What produces GnRH
Paraventricular and perioptic nuclei in the hypothalamus
What does GnRH do
reach the pituitary gland to produce FSH and LH
What does FSH do in the testes
FSH stimulate spermatogonial stem cells by stimulating Sertoli cells to produce ABP, which binds to testosterone to stimulate spermatogenesis, with feedback provided by inhibin produced by Sertoli
What does LH do in the testes
produce testosterone, which provides feedback to the pituitary.
Where does fertilisation take place
Ampullary portion of the tube
What is sperm capacitation
Switching on of sperm - hyperactive
Takes about 4 hours after ejaculation
Cholesterol loss and calcium and bicarbonate influx from vaginal secretions, increasing ATP production.
What is the acrosome reaction
Triggered by contact with oocyte. Interaction with ZP3 protein on oocyte membrane. Leads to exposure of hyaluronidase and acrosin enzymes. Facilitates oocyte penetration.
What occurs in oocyte activation
Release of cortical granules - block polyspermic penetration. Resumption of meiosis. Formation of the male and female pronuclei (fertilisation)
What happens with too much testosterone
suppression of LH and FSH. Spermatogenesis is interrupted.
What occurs in Kallman’s syndrome
affects development of nuclei of hypothalamus producing GnRH. Less stimulation of the pituitary. Hypogonadotropic hypogonadism
What occurs in androgen insensitivity syndrome
end organ receptor deficiency - end up with female external features. Testicles remain intraabdominal.
What does vasectomy stop spermatogenesis
Block vas on both sides so sperm cannot leave testicles. Pressure inside testicles goes up, which creates cracks in the BTB. Immune system produces anti-sperm antibodies. High pressure can lead to seminiferous tubule atrophy.
What stage are oocytes arrest at birth
P1 of meiosis, Majority of primordial follicles will undergo atresia from birth to menopause
What stage do secondary oocytes arrest at
metaphase II of Meiosis II
When is meiosis II complete
Meiosis II only completes when the egg is fertilised at which point the second polar body is extruded to prevent triploidy
What do theca cells do
LH and produce androgens. Androgens go across to granulosa cells, and are turned to oestrogens under the influence of FSH.
How is menopause defined
Defined as LMP over 45. Retrospective after one year of amenorrhoea (or based on symptoms for women without a uterus). No laboratory tests over 45.
FSH high >30 due to lack of oestrogen and inhibin from granulosa cells
Oestradiol low <203
Aged 54, over 80% thought to be postmenopausal
What is perimenopause
period around the last menstrual period. Vasomotor symptoms plus irregular bleeding
What happens with limited pool of oocytes
Reduction in oestrogen, FSH increases (lack of inhibitory feedback from oestrogen on hypothalamus)
Leads to -> anovulatory cycles, menstrual irregularities, menorrhagia, physical changes, psychological changes
What are the symptoms of hypo-oestrogenism
hot flush/night sweat, headaches, palpitations, leg cramps, uro-genital symptoms, reduced libido, mood change
Can be measured with Greene climacteric scale
How does menopause cause osteoporosis
Oestrogens are crucial for the maintenance of bone mass in both males and females, acting to suppress bone resorption by osteoclasts and to promote bone formation by osteoblasts. DEXA state for osteopenia and osteoporosis
What are the CV effects of menopause
Coronary artery disease, stroke, venous thromboembolism, pulmonary embolism
What are the HRT options
oral, transdermal, implant or local. Implants can cause tachyphylaxis
What does oestrogen do in HRT
reverse symptoms and effects of low oestrogen (if given alone, can cause endometrial hyperplasia, with risk of developing into carcinoma). Contraindicated for px with history of DVT or breast cancer.
What does progesterone do in HRT
necessary to protect the endometrium if uterus present, not required in women without a uterus (anti-proliferative hormone)
What does testosterone do in HRT
increases overall energy and sexual desire
What are non-hormonal options for menopause
lifestyle, Replens, alpha 2 agonists (clonidine for bad vasomotor symptoms), SSRIs, Gabapentin (joint ache and muscle aches)
What are the causes of idiopathic POI
cytogenetics (50% due to Turner’s), FMR1 premutation screening (trinucleotide repeat CGG in FMR1, X-linked dominant inheritance. Full mutation leads to fragile X metnal retardation), anti-adrenal (need to look for Addison’s - adrenal glands do not produce enough steroid hormones) and anti-thyroid antibodies
What percentage of couples achieve conception within 12 months of trying
84 (49% of remaining will achieve conception within 24 months.
14% of remaining will achieve conception within 36 months)
What is the definition of infertility
A woman of reproductive age who has not conceived after 1 year of unprotected sexual intercourse
What causes subfertility
Male factor, anovulation, tubal factor, subtle factors not detectable on routine (25%)
For secondary infertility, tubal factor is biggest cause (40%)
What is ideal semen volume
Volume >1.5ml
Density >15*10^6
Motility >40% progressively motile
Morphology >4% normal
How is pelvic anatomy and Fallopian tube patency assessed
Laparoscopy and dye: gold standard in tubal patency evaluation
HSG - X-Ray with injection of contrast
Hycosy - US
What is ovarian reserve
measures to assess ovarian reserve used to predict the likelihood of a successful response to ovarian stimulation with assisted reproduction treatment, although seem to have poor correlation with pregnancy outcomes
How many eggs at birth
2 million
How many eggs before birth
7 million
How many eggs at first period
0.4 million
How many eggs at menopause
Less than 1000
What is Group I anovulation
hypothalamic pituitary failure (hypothalamic amenorrhoea or hypogonadotropic hypogonadism)
What is Group II anovulation
hypothalamic-pituitary-ovarian dysfunction (PCOS)
What is Group III anovulation
ovarian failure
What is obstructive azoospermia
normal sized testes and FSH level. Post infection, post vasectomy, congenital absence of vas deferens
What is non-obstructive azoospermia
small testes, raised FSH. Testicular failure
What does ICSI do
Sperm retrival
Local anaesthetic, outpx procedure, samples may be stored for future cycles
Percutaneous epididymal sperm aspiration
Testicular sperm extraction
What are causes of tubal damage
Infection (PID, STI), surgery, ectopic prengnacy, endometriosis
Why and how is AMH measured
Blood test - produced by granulosa cells. Can be measured anytime in the cycle, also accurate in women receiving hormonal contraception.
