Fertility Flashcards
NICE recommended BMI of the female partner before commencing fertility treatment
19-30%
Frozen-thawed embryo replacement increases the overall cumulative pregnancy rate by approximately
11%
Oocyte retrieval is carried out _____ hours after the hCG injection
34-37hours
At the age of 40 years, the woman’s risk of miscarriage per IVF pregnancy
23%
What proportion of pregnancies following transfer of two blastocysts during IVF are twins
35%
Follicular response together with endometrial thickness is monitored by USS commencing on what days of the treatment cycle.
D 6-8
Inseminated oocytes are checked for signs of fertilisation after approximately ____ hours
12-21 (approximately 18)
Optimal endometrial thickness in millimetres for frozen–thawed embryo replacement cycles
7-11 mm
Optimal endometrial thickness in millimetres fresh embryo replacement cycles
10-12 mm
Undertaking eSET in approximately 50% of IVF patients will reduce the multiple twin birth rate to less than
10%
Up to ___ of women with moderate/severe OHSS may require admission to hospital
1%
Normal Semen Volume
1.5 ml (1.4–1.7)
Normal Progressive motility
32% (31–34)
Sperm morphology (normal forms [%])
4% (3.0–4.0)
Sperm concentration (106 per ml)
15 (12–16)
Minimal count of motile sperms per ml is suitable for IUI
5 million/ml
BMI >30 is of high risk to OHSS?
No
In fact, young slim women are at higher risk of developing OHSS
Early follicular phase FSH in determining ovarian reserve
In day 2 to 5
> 8.9 IU/L for a low response
AMH measurement in determining Ovarian Reserve
<5.4 pmol/l for low response
>25 pmol/l for high response
Total antral follicular count in determining of Ovarian reserve
<4 low response
>16 high response
Things don’t ask for when investigating for female infertility
- Post coital Cx mucus
- Prolactin level (unless pitutary tumor, glactorrehea, ovulatory disorder)
- Thyroid function test
- Endometrial Biopsy
Women who undergoing inv. for infertility should be offered serum progesteron in
regular cycles: midluteal phase (day 21)
irregular cycles: day 28-35 & repeated weekly until next menses
In case of suspected tubal occlusion, what inv. shall be taken
If no comorbidities: Hysterosalpingography
If expertise are available: Hysterosalpingo-contrast-ultrasound
If comorbidities: Laproscopy and dye
if the man is HIV positive that the risk of HIV transmission to the female partner is negligible in 3 cases:
- the man is compliant with highly active antiretroviral therapy (HAART)
- the man has had a plasma viral load of less than 50 copies/ml for more than 6 months
- there are no other infections present
- unprotected intercourse is limited to the time of ovulation
if the man is HIV +ve, and the criteria of no transmission are met, do we need to do sperm washing
No
sperm washing may not further reduce the risk of infection and may reduce the likelihood of pregnancy.
If the man is HIV +ve and he isn’t compliat to HAART or viral load >50 copies
offer sperm washing
What is sperm washing
separation of sperms from semen, by removing mucus, non motile sperms and chemicals
Does sperm washing eleminate the risk of HIV transmission
reducesthe risk of HIV transmission, reduces, but does not eliminate it.
if man is HIV +Ve and all criteria is met, does it useful if women take pre exposure prophylaxis
No
no sufficient evidence
For partners of people with hepatitis B, what shall we do before fertility ttt
offer vaccination before starting fertility treatment.
If men with HBV do we offer sperm washing
No
Risk of transmission during intercourse of HCV from a +ve male partner is
LOW
Viral Screening for the female partner before fertility TTT
- HBV
- HCV
- HIV
- Rubella
- Chlamydia Trochomatis
male factor infertility
Men with hypogonadotrophic hypogonadism, offer
gonadotrophin drugs
Men with idiopathic semen abnormalities should not be offered
- anti- oestrogens
- gonadotrophins
- androgens
- bromocriptine
- kinin- enhancing drugs
significance of Anti-sperm anti-bodies in investigating male factor infertility
insgnificant
Where appropriate expertise is available, men with obstructive azoospermia should be offered —-
surgical correction of epididymal blockage because it is likely to restore patency of the duct and improve fertility.
Surgical correction should be considered as an alternative to surgical s
Varicocele surgery as infertility ttt
it does not improve pregnancy rates
Group 1 Ovulatory disorders
hypothalamic pituitary failure (hypothalamic amenorrhoea or hypogonadotrophic hypogonadism)
Group 2 Ovulatory disorders
hypothalamic-pituitary-ovarian dysfunction (predominately polycystic ovary syndrome)
Group 3 Ovulatory disorders
ovarian failure.
First line ttt of group 1 ovulatory disorders (hypogonadotropic hypogonadism)
- increase body weight if BMI <19
- Do less agressive exercise
Medical ttt of Group 1 ovulatory disorders
- pulsatile GnRH
- Gonadotrophin containing LH
to induce ovulation
first line ttt of PCOs (group 2 ovulatory disorder)
Lower body weight if BMI >30
it may restore ovulation, improve response to ovulation induction & have a positive impact on pregnancy outcomes.
Medical ttt of PCOs (group 2 ovulatory disorders)
- Clomifene Citrate
or - Metformin
or - combination of the above
U/S monitoring of women taking clomifene as a stimulant
US during at least the first cycle of treatment to ensure that they are taking a dose that minimises the risk of multiple pregnancy.
How long do you give clomifene for PCOs
no longer than 6 months
metformin side effects
nausea, vomiting and gastrointestinal disturbances
If women has anovulation d.t. hyperprolactinemia what shall we do
Dopamine agonists such as bromocriptine
Risks of ovulation induction with gonadotrophins
- Multiple Pregnancy
- OHSS
What to do for women with proximal tubal obstruction
selective salpingography plus tubal catheterisation
or
hysteroscopic tubal cannulation
Women with hydrosalpingex
Surgical ttt
- Salpingectomy (common)
- Laparoscopic tubal occlusion
- Hysteroscpoic sterilization (lacking evidence)
invstigating for hydrosalpinx
TVS
In case of amneorreah d.t. uterine adhesions
** hysteroscopic adhesiolysis **because this is likely to restore menstruation and improve the chance of pregnancy.
Why we do pituitary downregulation
- Suppress endogenous gonadotropin release
- suppress premature ovulation (so ensuring Oocyte for retrival)
GnRh agonist mode of action
competitively blocks the action of GnRH, preventing the release of (LH) and (FSH) from the anterior pituitary gland.
However, initially there is a release of FSH and LH, the so-called ‘flare effect’.
GnRH antagonist mode of action
competitively and reversibly bind to GnRH receptors in the pituitary gland, blocking the release of LH and FSH from the pituitary, thus preventing ovulation.
They are rapid acting and do not have a flare effect.
In case of fear pf OHSS which regimen do we use?
GnRH antagonists
Characteristics of using GnRh antagonist regimen
- lowe number of follicles
- dec. risk of OHSS
- Lower period of stimulation
- dec. need to freeze all
Different types of Gonadotropins
- Human menopausal gonadotropin (hMG)
- urinary FSH
- recombinant FSH
GnRH antagonists are used in
- Patients at high risk of OHSS
- in previous porr responders to ttt
- those patients who require timely ttt (fertility preservation)
In case of exaggerated ovarian resposne, we use which trigger
GnRH agonist trriger
Which induces endogenous LH flare instead of hCG
hcg As trigger standard dose
5000-10000 IU
do hCG increases the risk of OHSS
Yes
How to avoid the risk of OHSS with hCG
In agonist protocol: use GnRH agonist as trigger
In antagonist protocol: dual trigger:
GnRH agonist+ hCG 1500 IU
Rate of follicular growth after stimulation
2-3 mm/day + steady increase in serum estradiol level
When to give the trigger
3 or more follicles >17-18 mm
Give subcutaneous
5000-10000 IU of hCG
Or
250-500 mcg of rhCG- alpha
When to consider poor ovarian response
When less than 3 follicles develop after 14 days of gonadotropin ttt
Results in cancellation
Number pf follicles developed in normal cycle
10-20 ovarian antral follicles
Only 1 dominant follicle
How much time does it take for follicular recruitment
First 5 to 6 days to stimulation
Then continue on FSH to maintain follicular growth
COH monitoring is done by
2D TVS &/or hormonal assessment
Monitoring in GnRH AGONIST PROTOCOL
US before FSH stimulation
US after 1 week of stimulation
US w 12-36h of trigger
After we got we need from COH what to do
- Stop pituitary downregulation
- Give LH containg trigger (hCG)
Sperm recovery instructions
- by masturbation
- no lubricants
- after 2-5 days abstinence
- if at home ( keep it room temp - take it to lab in less than 60mins)
If the man cannot masturbate;
Use silastic codom
If the man has ejaculatory dysfunction, how we can collect sperm
Vibratory or electrical stimulation
If the man has retrograde ejac
Urinary sample analyzed for vital spermatozoa
If the man has azoospermia/ ejac failure, how do we collect sperm
Surgical intervention:
- aspirated from epididymis ( percutaneous epididymal sperm aspiration PESA) or ( testicular sperm aspiration TESA)
- extracted from testis ( testicular sperm extraction TESE)
How do we determine fertilization
Presence of 2 pro-nuclei (2 PN)
18-20 hrs post insemination
How much time it takes for fertilization after insemination
18-20 hours
When do we do embryo transfer after fertilization
Day 2 , day 3 ( cleavage stage) or day 5 (blastocyst stage)
If there is no follicle yield an oocyte, what shall we do
Follicle flushing
To encourage the yielding of oocytes
Why the use of flushing is controversial
Fertilization rates reduced the more times the follicle is flushed to obtain the oocyte
Oocytes in most of the antral follicles having completed maturation, will be at
metaphase II. (M2)
What is cumulus complex
The oocytes at the time of retrieval are encased in a mass of granulosa cells called the cumulus complex.
What is the function of the granulosa cells in the cumulus complex
- possess the receptors for FSH and, therefore, gonadotrophin acts on these cells to stimulate growth and estrogen production.
-The granulosa cells communicate with the egg as the egg develops and matures.
Oocyte classification is based on
- cumulus expansion
- corona cell dispersion
- coronal association with zona pellucida
These are good predictors of maturity
How oocyte is checked for maturity
Presence of polar body
ICSI is recommended for which cases
-Obstructive and non-obstructive azoospermia
-Poor history of fertilization
- Previous ivf failure
Fertilization rate of ICSI
60-70%
In non male sub-fertility, which is better IVF OR ICSI
IVF
Time to check for fertilization (2 PN)
Pro nuclei are visible for finite time
12-21 hours
It is imp to check the eggs for 2 PN within this finite time, as often cannot be distinguished from abnormal 3 PN or activated 1 PN after cleavage
Following embryonic cleavage, what does 1 pro nuclei means
Indicataive or spontaneous activation of oocyte without fertilization
What does 3 pro nuclei mean
Abnormally fertilized eggs:
- 2 sperms fertilizing 1 egg
- failure of emission of 2nd polar body (digynic fertilization)
- rarely, injection of diploid sperm cell
Rate of normal fertilization (2PN)
50-70% of insiminated eggs should form at least 2 pronuclei
Indication of embryonic viability
- Distance between 1st & 2nd polar bodies
- orientation of PN relative to polar bodies
- distribution of nucleoli with pronuclei
If the indication for ICSI is severe semen quality or azoospermia, shall we do karyotyping
Yes
What is assisted hatching
Small crack in zona pellucida
Assisted hatching is recommended for
- pts w/ hx of failed IVF/ICSI who have a good embryo quality
- pts >38 years
- those w/ elevated FSH
- pts w/ thickened or abnormal zona pellucida
Does assisted hatching increase embryo implantation potential
It’s hypothetical, but no strong evidence for this
When do we do embryo transfer
Day 2/3 or day 4/5 after retrival
Embryos are graded for quality on day 2/3 depending on
- number of cells (D2: 4 cells, D3: 8 cells)
- degree of fragmentation
- cell symmetry
- granularity
- vacuolisation
- membrane definition (compaction)
Embryos are graded for quality on day 5 (blastocyst)depending on
- cavitation
- expansion
- zona thinning
- presence of inner cell mass and hatching
Where in uterus do we transfer embryos
Midcavity (maximal implantation point MIP)
For better results
How many embryos do we transfer
2 embryos
Unless there is no more than 3 to transfer so transfer 3
Minimal endometrial thickness for embryo transfer
Transfer in endo <5 mm is unlikely to result in pregnancy
Does bed rest after IVF ttt improves its outcome
Bed rest for more then 20 mins after IVF doesn’t improve outcome
Number pf embryo transfer in women <37 years
1st full cycle: single
2nd full cycle: single (if 1 or more top quality embryos) - 2 embryos (if no top quality)
3rd full cycle: no more than 2 embryos
Number pf embryo transfer in women 37-39 years
If 1st/2nd cycles: single (if 1 or more of top quality) - 2 embryos (if no top quality)
If 3rd cycle: 2 embryos
Number pf embryo transfer in women 40-42years
No more than 2 embryos
When to transfer single embryo
When you have a top quality embryo
Why do women need luteal support after ET
D.t. desensitization of pituitary and aspiration of granulosa cells, so prevents adequate progesterone production
How do we do luteal support
With Progesterone supplements during luteal phase to increase endometrial receptivity
When to start luteal support
Give progesterone supplements in the luteal phase within two days of oocyte retrival
Duration of progesterone supplementation as luteal support
Its given until positive or negative pregnancy test was obtained and till the end of the first trimester
NICE: not more than 8 weeks of gestation
Use of hCG as luteal support
Isn’t recommended as it inc risk of OHSS
How cryopreservation increases pregnancy rate
By increasing number of potential embryo replacement cycles without additional egg retrieval.
And it also decreases risk of OHSS
What have the most significant impact on post thaw survivals of embryos
Embryo quality
Live birth rates from frozen thawed embryos
<35 y: 31% per transfer
41-42 y: 19% per transfer
In semen analysis, what absence of fructose may indicate?
It indicates obstructive azoospermia..
Most common cause of obstructive is vasectomy.
