Assissted Reproduction + pcos Flashcards
What is the criteria to receive ivf on the nhs?
Defined infertile: for at least 2 years though
Under 23-42: get 3 rounds
40-42? : get 1 round
What are conception rates in normal/fertile couples?
20% chance of conception in each menstrual cycle.
85% conceive in 1 year
When counselling patients seeking IVF, what are some details you should tell them?
Lots of needles
6 weeks where you will require lots of appointments, you and your partner need to be available for these so must be able to take time off work or do it in a holiday.
Success rates higher for younger patients, reduces with age.
Success rates reduce with each subsequent round.
What is the process involved in IVF?
- Initial tests and ultrasound
- GnRH agonist or antagonist (start at day 21 for 2-3 weeks)
- suppress menstrual cycle via stopping FSH and LH
- FSH given - ovarian stimulation
- LH/hCG injections - stimulate/triggers ovulation -> oocyte collection. 34-38h post injection. hCG preferred
- Fertilisation and culture - can use ICSI (wait 2-3/5-6 days before implantation in uterus).
- woman goes home and takes progesterone/ injections - Embryo transfer to uterus;
- max 2 eembryos implanted
- give progesterone for luteal phase support
What are the Complications of Assisted Conception?
Multiple pregnancy - biggest risk. women usually hAve more than 1 embryo transferred to increase success rate
Ovarian hyperstimulation syndrome
Egg collection: intraperitoneal haemorrhage and pelvic infection (<1% risk)
Pregnancy complications: risk multiple and ectopic pregnancy
what is used for Luteal Phase Support in IVF?
this is required post egg collection:
- Progesterone
- (vaginally/rectally/IM/sc — oral = unreliable)
- to induce secretory changes within endometrium
- most used. usally given alone - hCG – increased risk of OHSS
o not widely used
- Oestrogen?
o No real data to support oestrogen in luteal phase
during egg colleciton in ivf?
granulosa cell / follicular cell
during IVF, when looking to trigger/induce ovulation, when could it be appropriate to use GNRH agonist as a trigger?
only if used GNRH antagonist to downregulate pituitary/ shut off menstrual cycle.
what is the mutliple pregnancy rate in ivf?
18%
at what stage is the embryo implanted back into uterus?
at the blastocyst stage
day 2 after collection (this is early)
days 2-5 depends
what type of FSH is given during IVF?
Urinary or synthetic/recombinant
whats the risk of urinary fsh?
cjd/prion disease - if donor is a carrier
what is used in the Prevention of Ovulation in ivf? when are the given
GNRH agonist
- follicular phase. have to give 2 weeks b4 to be able to block lh surge
- due to excess stimulation, leads to reduced receptor
expression
- injection, nasal spray
GNRH antagonist
- luteal phase
- compete for binding with endogenous
benefit of long protocol over short?
Associated with an increase in the no. of eggs
Higher clinical pregnancy rates compared to short protocols (not live birth rate)
Long protocol; involves GNRH use to switch off period and then conduct ovarian stimulation.
Short protocol; different types but injection 5-9 days before collection or no injections and collect base on natural menses cycle
benefit of using antagonists over agonists?
reduction in OHSS
list the methods of assisted conception?
IUI,
IVF + ICSI,
frozen embryo replacement,
oocyte donation
PGD - preimplantation genetic diagnosis
list causes of infertility by prevalence?
Male factors-30%
Ovulatory-25%
Tubal damage-20%
Uterine-10%
Endometriosis-5-15%
Unexplained-25%
Both male and female factors-40%
what is the protocol for IUI? indication?
Select & wash sperm with best motility and concentrate it
Put sperm into uterus via transvaginal catheter usually 24h before ovulation is meant to occur or TRiggered to occur
Eggs: 1. Allow natural release stimulated: 2. Give Clomid: inc FSH = nice big follicles 3. Give FSH: superovulation can then trigger release
indication: unexplained infertility, Cervical factors
Sexual factors, Male Factors
risks of IUI?
multiple pregnancy
what are the indications of PGD?
Couples at risk of having children with serious genetic diseases can have
unaffected embryos transferred to the uterus, eliminating the need for prenatal diagnosis and termination of
pregnancy
Applicable if they are carriers or have risk of certain conditions;
BRCA, sickle cell, thalassaemia, x-linked etc
some contraindications for IUI?
Requires regular ovulatory cycles (…PCOS…)
Still requires patent tubes (hydroslapinx etc)
what are some requirements for ivf?
need normal ovarian reserve;
AMH (anti-mullerian hormone)
TVUS - Antral follicle count
FSH-early follicular
Dfference between long and short protocol?
long started in luteal phase
short started in follicular phase
what are the indications for ICSI?
Insufficient motile sperm
indications for oocyte donation?
Ovarian failure
Older age
Genetic disease
what method would you suggest for this woman with:
Uterine abnormality or absence
Poor health e.g. renal failure
Use of teratogenic drugs
surrogacy
list some causees of infertility?
Tubal damage:
PID, Endometriosis, surgery/sterilisation -> adhesions
Cervical:
infectoin -> reduced mucus for sperm travel
cone biopsy
if diagnosed male factor infertility what method to recommedn them to use?
IVF + ICSI
How is a woman/couple investigated for cause of infertility?
- History
In no particular order:
Male: semen analysis (WHO criteria)
Female:
Ovarian reserve testing; AMH, AFC etc
Menstrual cycle regularity - day 21 progesterone
Hysterosalpingography (HSG) +- contrast -> if no established cause. screens tubal occlusion
Laparoscopy and dye - if established cause, will look for tubal occlusion as well as established issue
if a woman has an ovulatory disorder, what hormone should you measure?
Prolactin
list some causes of absent or abnormal sperm?
Smoking & drugs eg steroids
Varicocele - 25%
Antisperm antibody 5% - after vasectomy reversal
Infection: epididymitis
Mumps orchitis
Testicular abnormalities e.g. Klinefelter’s
(XXY)
Kallmann’s syndrome
Hyperprolactinaemia
Congenital absence of vas deferens
what is the role of lh and fsh in the male?
LH Leydig cells testosterone production
o FSH + testosterone sertoli cells synthesis and transport of sperm
what are the symptoms of OHSS?
Hypovolaemia Electrolyte disturbances Ascites Thromboembolism Pulmonary oedema Death
SO theyre wet but extravascularly rather than intravascular
management of OHSS?
Hospitalisation required for Restoration of intravascular volume Electrolyte monitoring Analgesia Thromboprophylaxis Drainage of ascetic fluid
What are some signs of ovulation in a normal menstrual cycle?
Vaginal spotting, Vaginal Discharge or pelvic pain (‘mittelschmertz’)
body temperature increases by 0.5C in luteal phase - due to prog
Only real proof though is : Conception
TVUS appearance of multiple (12 or more) small (2-8mm) follicles in an enlarged (>10ml vol) ovary is indicative of?
PCOS
what is the GREATEST cause of anovulatory infertility?
PCOS
list the 3 criteria for PCOS?
PCO on USS
Irregular periods (>35 days apart)
Hirsuitism - clinical or biochemical features
Diagnosis using Rotterdam Criteria for PCOS (at least 2 of the following)
o Oligo/anovulation (> 2 years)
o Clinical or biochemical features of hyperandrogenism
o Polycystic ovaries on ultrasound (> 12 in one ovary measuring 2-9 mm in diameter)
aetiiology of pcos?
Disordered LH production and peripheral insulin resistance with compensatory raised insulin levels
LH and insulin ovarian androgen production
insulin adrenal androgen production and reduce sex hormone binding globulin free androgen
levels
intraovarian androgens excess small ovarian follicles + irregular/absent ovulation
peripheral androgens acne / excess hair growth
body weight insulin androgen levels
what ivx would you do for PCOS?
Bloods o FSH increased in POF reduced in Hypothalamic disease o Prolactin o TSH o Serum testosterone - high o LH - high high LH:FSH ratio (3:1 - fsh itself may be normal)
TVUS - >12 follicles, increased stroma /size of ovary. See past card
Other
o DM screening
complications of PCOS?
50% develop T2DM in later life
30% develop GDM
sub fertility
what is the management of pcos?
Diet and exercise
Normalisation of weight
COCP - if amenorrhoea/dysfunctional uterine bleeding.
good if planning pregnancy. low dose
Metformin
Co-cyprindol (dianette) - for acne + hirsutism +
contraceptive
Eflornithine = topical antiandrogen for facial hirsutism
Subfertility:
Weight loss
Clomifine - SERM. Anti estrogen blocks receptors in hypothal and pituitary
Surgery:
Laparoscopic ovarian drilling - if undesponsive to medical rx
list causes of anovulation?
Hypothalamic hypogonadism
- anoxeria, excess exercise
- can cause pcos
Kallmans syndrome
- gnrh releasing hormones dont develop
Pituitary :
A. Hyperprolactinaemia - suppresses gnrh
- cabergoline (dopamine agonists)
B. Sheehans
Ovarian Premature ovarian failure Gonadal dysgenesis Luteinised unruptured follicle syndrome PCOS
what is gonadal dysgenesis in the female? biological presentation?
46XX
Streak ovaries are present with non-functional tissues unable to produce the required sex steroid oestrogen
Low levels of oestrogen
FSH/LH high
this is NOT turners
chracterise progesterone levels in oligo/amenorrhoeic cycles.
for women with symptoms of oligo-amenorrhoea, progesterone will remain low throughout the menstrual cycle
so not much of a fuss whether it is day 21 or not
what does laparoscopic ovarian dirlling involve ?
Under general anaesthetic, your doctor will make a small cut in your lower tummy and pass a long, thin microscope called a laparoscope through into your abdomen.
The ovaries will then be surgically treated using heat or a laser to destroy the tissue that’s producing androgens.
helps to restore hormonal imbalance and improve ovulation
how does metformin help in PCOS?
usually used if BMI >25
not licenced for pcos but used off label
improves insulin sensitivity - hence reduces circulating androgen levels, and improves weight
reduced circulating androgen levels menas LH surge can occur to allow ovulation
why does pcos cause anovulation?
Despite the high levels of LH, the increased circulating androgens suppress the LH surge (which is required for ovulation to occur).
Follicles develop within the ovary, but are arrested at an early stage (due to the disturbed ovarian function) – and they remain visible as “cysts” within the ovary.
how does clomiphene work?
it blocks hypothalamic estrogen receptors
this blocks negatve feedback of oestrogen
this increases GnRH hence FSH,LH production
so clomiphene given between day 2-6 (5 day course) of cycle =
more FSH allows follicle maturation
LH surge can then stimulate ovulation
