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70 Cards in this Set

  • Front
  • Back
Infertility Definition
“the inability of couples to conceive a pregnancy after a year of unprotected intercourse, or the inability to carry a pregnancy to term”
Under 35 and trying to conceive for 12 months

Over 35 and trying to conceive for 6 months
Age Factor
Preconception - History
Smoking
EtOH
Other drugs
Medications
Family history genetic problems / ethnicity (consider targeted genetic tests – CF etc)
Preconception - Examination
WOMEN:
BMI
BP
Breast
Pelvic (at PAP)

MAN:
BMI
Testicular examination at least once in adulthood
Preconception Investigations - Women
PAP (+/- Chlamydia & gonorrhea PCR)


Serology
Rubella
Varicella

HBV
HCV
HIV
Syphillis
FBC +/- thalassaemia screen

Bl Gp & Ab screen

TSH
Vitamin D
ffer CF carrier testing
Offer CF carrier testing (target Caucasians)
TSH – why ?
Overt thyroid disease

Subclinical hypothyroidism
incidence at least 1 in 500, increases with age
Subclinical hypothyroidism - why treat?
Increased demand for thyroxine in the mother – may convert compensated hypothyroidism to overt hypothyroidism
Evidence of reduced neurological outcomes in children of mothers with hypothyroidism (3 studies) several years after birth
Preconception Investigations – Men
Consider
HIV
HBV
HCV

+/- Chlamydia & gonorrhea PCR
Preconception Advice - Women
Immunisations current including:
Rubella (serology)
Varicella (serology)
Influenza
Pertussis

(Pneumococcal); Smokers, Asplenia, - as long as last vaccination > 5yrs ago & not had 2 previous doses, mpaired immunity, Chronic illness
BMI
Don’t smoke
Minimal / no EtOH
Folic acid / vitamins (Vit D, iodine)
Preconception Advice - Men
Don’t smoke
BMI
Pertussis immunity current
Preconception Advice - Couple
Fecundity
Predicting ovulation
Fertile time
SI frequency
Other myths
Predicting ovulation
Fertile time
Predicting ovulation
The BBT temperature rise follows ovulation and is useful only to confirm ovulation has taken place – and, over several cycles – to enable a prediction to be made of the likely day of ovulation for that woman in general.

To anticipate ovulat...
The BBT temperature rise follows ovulation and is useful only to confirm ovulation has taken place – and, over several cycles – to enable a prediction to be made of the likely day of ovulation for that woman in general.

To anticipate ovulation accurately you need all 3 hormones at each measurement.
Predicting ovultion
1. estradiol dip: "mayeb baby)
2. LH surge: LH in urine (fortel)
Degrees of fertility
Infertility assessment – (GP)
Routine preconception as earlier
Women
Previous pregnancies
? Ovulatory
? Risk previous tubal damage (STI, ectopics)
? Endometriosis – premenstrual spotting, secondary dysmenorrhoea, dyspareunia, family history
Men
History undescended testes, orchitis, trauma / torsion
Both
SI timing and frequency – ensure not contraceptive
good sexula positions
When to investigate infertility
Virtually always recommended Ix after 12 months infertility

85% conceive first 12 months
50% of the remaining do so in the next 12 months
Thereafter pregnancy rates very low (10% per annum or less)
What is Andrology?
From the Greek andros meaning ‘man’

Andrology is to men what gynaecology is to women
investigation - Male
- semen
Semen analysis: “SFA + IBT”
= Volume, concentration, motility, morphology and antisperm antibody screen

Analysis, especially morphology very operator dependent

Repeat if abnormal
If repeating consider adding DNA fragmentation analysis if not previously done
No need to repeat IBT (antibody screen)

DNA fragmentation analysis
SCIT
SCSA
Initial investigations - Female
Early follicular (day 2) FSH & oestradiol

Luteal (day 21) progesterone

If irregular cycles / galactorrhoea
Androgen screen (DHEAS, 17-OHP, FAI, testosterone)
Prolactin
Note am, fasting, not stressed, follicular if possible

Above assumes preconception screen including TSH current 
Pelvic ultrasound

Follicular phase
Transvaginal
Consider a HyCoSy
form of fertility treatment
Intrauterine insemination (IUI)
Ovulation induction (OI)
In vitro fertilisation (IVF)
Intracytoplasmic sperm injection(ICSI)
What is IVF?
In Vitro fertilisation – any fertilisation that occurs outside of the body

Originally devised to overcome blocked or absent fallopian tubes

Now used to treat many factors:
Irregular ovulation
Low sperm count or motility
Severe endometriosis
Ovarian issues
Unexplained infertility
What's involved in fertility treatment?
Monitoring the menstrual cycle and ovulation

Blood tests for hormone levels – indicate the number and stage of egg development

Vaginal ultrasound examinations to count and measure follicles on the ovary
Depending on age, between 1-30 follicles will develop during a women's menstrual cycle

In a natural cycle only 1 of these will develop to full maturity and be ovulated

In fertility treatment the aim is to increase the number of follicles with mature eggs
A typical patient experience with fertility treatment
Contact Genea nurses on first day of period

Start daily injections of FSH. Injections will last for 10-14 days

During this stimulation period patients will attend clinic for 3-6 blood tests and ultrasounds to monitor follicle growth

Start medication on about day 7 to suppress natural ovulation

Once follicles reach 18-20 mm in diameter patient will take a trigger injection to mature the eggs
Egg Retrieval
36 hours after the trigger injection patients attend day surgery for egg collection
36 hours after the trigger injection patients attend day surgery for egg collection
Semen collection
On the day of egg pick up the male partner will collect his sample either at the clinic or at home

Also possible to collect and freeze sperm prior to egg collection
Insemination
Insemination performed either by:
IVF – Sperm added to eggs in a dish
ICSI – Sperm injected into egg directly by embryologist
Embryo culture and development
Ultrasound guided embryo transfer
Usually on day 5 (or 6), less frequently on day 3

Committed to single embryos transfer to prevent multiple births

Simple, relatively painless procedure performed in day surgery without any medication. Similar to pap smear.
Usually on day 5 (or 6), less frequently on day 3

Committed to single embryos transfer to prevent multiple births

Simple, relatively painless procedure performed in day surgery without any medication. Similar to pap smear.
Embryo storage
Excess embryos are vitrified (frozen) for storage until required

Allows patients to have another embryo transfer without undergoing stimulation
After embryo transfer – the “2 week wait”
Can be a difficult period for patients as they await their results – Genea counsellors offer support.

Endometrial support provided through doses of hCG or progesterone pessaries

Blood pregnancy test performed 10 to 12 days after embryo transfer/16 days after egg collection day
Chance of pregnancy
The chance of pregnancy will depend on:

Woman's age

Reason for infertility

Quality of the embryo transferred
Antimullerian Hormone
Can perform anywhere in menstrual cycle
Can perform when on oral contraception
Different assays in different laboratories – less of a problem now (mainly Gen II)
Some intra-individual variation : best to repeat if big decisions are about to be made on it

Shall I order it?
Will it change behaviour or management
Careful counseling especially in single women
What would you do if it’s normal
What would you do if it’s abnormal
AMH- what do we know
Consistently the best predictor of oocyte reserve
Good predictor of response to IVF in terms of number of eggs
Helpful for IVF dosing
Predicts susceptibility of ovarian follicles to damage with chemotherapy
AMH defining Normal
Low AMH for age
Earlier menopause likely
Narrowed window of opportunity for pregnancy
Risk of poor response to IVF
Narrowed window of opportunity for IVF to work
Not necessarily less fertile or less likely to fall pregnant naturally (if not yet trying)
Pathological concerns especially if markedly abnormal for age
Genetic conditions? Endometriosis?
Excludes PCOS
High AMH for age
Associated with PCOS
Not (yet) a diagnostic criterion
At risk of ovarian hyperstimulation
High AMH in women over 40
IVF more likely to be successful

AMH therefore may be useful to INCLUDE patients in to IVF but can it be used to EXCLUDE???
AMH – what we don’t know
Does a low AMH predict a low pregnancy rate with IVF (< 40 yrs)?

Does a low AMH predict miscarriage?

Does AMH reflect egg QUALITY?
AMH – useful indications (our opinion!)
Unexplained subfertility
Triage into keep trying vs moving to ART
Older women considering IVF/oocyte freezing
Suspected PCOS that doesn’t quite fit the diagnosis
All women about to undergo IVF stimulation to get dosing right
Counseling patients about to undergo chemotherapy
Follow up of patients that have previously had chemotherapy
Karyotype
? all infertile couples ?
or
Targeted
Men: severe oligozoospermia
Women: POF, poor ovarian reserve
Couples: recurrent miscarriage, recurrent IVF failure
Fecundability
Fecundability - probability of
achieving pregnancy in one menstrual cycle (0.25 in the
first 3 months and 0.15 during next 9 months)
Prevalence of infertility
> 1 in 6 couples
> Female factors 37%, male factors in 8%, both in 35%,
5% unexplained
> 15% conceive during investigations
Anti-Mullerian hormone (AMH)
• Originally described in human fetal sexual
differentiation
• Produced by granulosa cells of primary follicles /
small follicles (not visible on ultrasound)
• A reflection of total oocyte pool
• Cycle independent
• Does not necessarily relate to egg quality
Causes of anovulation
• Polycystic ovary syndrome (PCOS)
• Hypothalamic disturbance (functional)
• Hyperprolactinaemia
• Primary ovarian failure
• Other endocrine disease
• Other - organic pituitary / hypothalamic
Polycystic ovary
- 20% of the female population
- in combination with clinical/biochemical changes
= polycystic ovary syndrome
- 20% of the female population
- in combination with clinical/biochemical changes
= polycystic ovary syndrome
Effect of obesity on fertility
• Anovulation
• 50% more likely if BMI >25
• 300% more likely if BMI>30
• Increased hip-waist ratio alone also affects fertility
in ovulating women
• Adverse effect of insulin
Tubal disease / anatomy
• Pelvic inflammatory disease (PID)
• STD
• other
• Previous surgery
• Congenital anomalies
Laproscopy Normal
testing patency of the reproductive tract
Hydrosalpinx
can get back in and can upset the implantation phase (so better off to remove)
can get back in and can upset the implantation phase (so better off to remove)
Hydrosalpinx Laproscopy
Adhesions
Submucous fibroids, Endometrial polyps
can affect fertility acting like an IUD
- can be surgically removed allowing the female a chance
can affect fertility acting like an IUD
- can be surgically removed allowing the female a chance
Endometriosis and infertility
• Prostaglandin production
• oocyte function
• sperm transport
• Autoimmune response
• macrophage phagocytosis of sperm
• autoimmune response to endometrium/ovarian
tissue
• Luteinised unruptured follicle syndrome (LUF)
• Altered eutopic endometrium
Non-active Endometerosis
Active endometerosis
can affect the quality of the egg
can affect the quality of the egg
Azoospermia
1. Obstructive
• congenital = BCAVD
• infection
• vasectomy
2. Non - obstructive
• genetic
• maldescent
• chemotherapy / radiotherapy
• mumps
Reduced sperm parameters
• Genetic
• Local genital causes
• Medical disease
• Medications
• Noxious agents
• ?Environmental
Male obesity and fertility
• Sperm count reduced 50%
• 50% reduction in chance of conception
• Increased sperm DNA fragmentation
• Erectile dysfunction x 2
Male obesity - mechanism
• Reduced total and free testosterone
• Increased Estrone and E2
• Reduced FSH and LH
• Reduced spermatogenesis and testosterone
production
• Increased testicular temperature
Male age and fertility
• Independent effect (far less than the effect of female
age)
• Lower potency / lower ejaculation frequency
• Higher rates of infertility
• Higher rates of aneuploidy – Down’s
• Increase in relative risk for autism – spectrum
disorders
Known karyotype errors associated with male factor
infertility
• 47 XXY – Klinefelter’s syndrome
• Klinefelter – related mosaicism
• Balanced translocation between autosomes
• XX male – transposition of SRY gene to an autosome
Human Y chromosome
Y has no paterner to swap or recombine with... 
thus the Y chromosome is gorwing shorter with bits flying off 

Areas of the Y chromosome that are cut off and they have low sperm counts and thus the kids will have the same problem (have to tell...
Y has no paterner to swap or recombine with...
thus the Y chromosome is gorwing shorter with bits flying off

Areas of the Y chromosome that are cut off and they have low sperm counts and thus the kids will have the same problem (have to tell the couple this)
Y chromosome microdeletions
• Can be detected in a proportion of men with sperm
concentrations below 2 million / ml
• Can involve AZF A, B or C regions
• Have been detected in male offspring from
successful ICSI treatments
Semen analysis
problems
• Problems with collection / delivery
• Lab variability
• Variation in reference standards
Semen analysis - parameters
• Volume 1.5 ml
• Density 15 million / ml
• Overall motility 40%
• Progressive motility 32%
• Normal morphology 4%
Sperm chromatin structural assay (SCSA)
• Analyzes degree of DNA damage to sperm, often
secondary to reactive oxygen species in seminal fluid
• Consider in cases of
– Recurrent miscarriage
– Otherwise unexplained infertility
– Smokers / infrequent intercourse
– Poor embryo development in IVF
• Antioxidants / frequent ejaculations
Important work up in male factor infertility
> Examination
> Hormone profile including FSH, LH, testosterone,
prolactin, thyroid function
> Scrotal ultrasound
> Karyotype if concentration < 10 mill / ml
> Y chromosome microdeletions if concentration < 2 mill
/ ml
> Cystic fibrosis screening if obstructive azoospermia
Antisperm Ab
- measure infemale serum
- measure in males too; can be higher after infection, post-vasectomy... (due to back pressure and breakdown of the blood testies barrier)

- female; serum and cervix
- Consider: postcoital test
Klinefelter’s Syndrome
> 1 in 650 men
> Testes 1-4 ml in 99% of cases
> Up to 75% never diagnosed