Infertility Flashcards
Meanings
Fertility
measure of the actual outcome of the reproductive process
- number of children born to an individual/couple.
Meaning
Fecundity
measure of the ability to conceive AND produce a live birth.
Meanings
Fecundability
probability of conceiving each month - the monthly chance of pregnancy, or monthly fertility rate
-either for an individual (measured over time)
-or for a population (the number of conceptions occurring in one month).
Meaning
Infertility
The inability to conceive after a period of unprotected intercourse or the inability to carry a pregnancy to term.
Meaning
How does NICE define infertlity
defined as failing to get pregnant after two years of regular unprotected sex
Meanings
Subfertility
A state of reduced fertility.
When do people typically advice medically
one year -> subfertlity
most couples are unaware of fertility status until trying for child
Of 100 couples without a fertility issue trying to conceive naturally:
20 will conceive within one month
70 will conceive within six months
85 will conceive within a year
90 will conceive within 18 months
95 will conceive within two years
How many couples have difficulty concieving?
1 in 6
Infertility commonest reason for women aged 20-45 to see their GP
majority may become naturally pregnant down the line (if you try early enough)
Only 20% of these cases arise through actual sterility
What factors can affect fertility
- Age
- Smoking status
- Obesity
- Increasing prevalence of STIs such as chlamydia
chlamydia: are damaging the reproductive tract and so reduce fertility
If a couple turn up and ask about concieving what is the first you should do
- ASK: how long have you been trying
- family history
- is there lots of miscarriages
- current sexual history
- do they know they are ovulating,
- are they are trying correctly
- past sexual history
- whats its like with other partners
- may not always say things in front of their other partners
- if a female says they got pregnant, its smth you can rely on it, whereas men may say they have fathered pregnancy … (???)
What females factors can affect conception
like physiologically
- Ovulatory disorders
- Tubal damage
- Endometriosis
- Uterine abnormalities
- Implantation, growth and development
Female
What tests would be conducted
- via blood analysis
- FSH, LH (day 2-4) -> check ovarian reserve
- day 21 progesterone -> to investigate ovulation
- via ultrasound (laparoscopy, or radiogram)
- hysterosalpingogram
- dye spill means the fallopian tube is clear, the egg can go down, and sperm can go up
- Laparoscopy
- involves looking inside the abdomen to visualize the uterus, fallopian tubes and ovaries
- to check they have normal appearance.
What are the causes of infertlity in women
Ovulation disorders (40%)
Meanings
Primary amenorrhoea
No cycles ever happened
Secondary amenorrhoea
occurs when a patient who has passed menarche goes six months or longer without menses
What is oligomenorrhoea
Irregular cycles
How would check for an anvoluatry cycle
take a day-21 progestorone
What other factors can ovulation disorders be associated with
things outside the body
ovulation disorders can be associated with stress, obesity, strenuous exercise, anorexia nervosa and drug use
stress axis is important
around 30% of cases, treatment with placebo is affective in getting cycles to resume and restoring fertility
Possible failure of maturation of neuroendocrine system at puberty can also cause annovulation
What disorders can cause annovulation
**Idiopathic ovarian failure
**
- Gonadotrophin secretion is normal but is insufficient to support a normal cycle → end organ insensitivity
- oestrogen levels fail to rise and follicles fail to mature (many small follicles)
**Polycystic ovarian syndrome (PCOS)
**
- Associated with LH and usually increases androgens (mild increase in follicular phase)
**Anovulatory cycles – endocrinologically normal
**
- Luteinised unruptured follicle syndrome (LUF) – eggs ‘deficient’
**Abbreviated luteal phase
**
- decreased Progesterone →poor luteinization
- you don’t maintain endometrium
What disorders of the female tract can impact conception
**Tubal obstruction
**- can be due to
- secondary consequence of pelvic infection
- increase the incidence of STDs, e.g gonorrhoea, chlamydia and tuberculosis
- Post-abortal or post-pregnancy sepsis
- scarring may affect surface of fallopian rube, can affect sperm going up, or egg going down
- infection → impaired oocyte and sperm transport due to loss of cilia on intraluminal cells and scarring => adhesions
-
Endometriosis
- endometrial tissue growth escalates in ectopic sites – oviduct, ovary or peritoneal cavity => scarring/adhesions
- pain
female
Apart from ovulation and tubal disorders what other factors can affect pregnancy
- cervical incompetence
- implantation defects
- autoimmune (lupusP
- immunological incompatibly
- rhesus, ABO
Basically, can get prgenant but something downstream is affecting it
How do we detect a pregnancy biochemically and clinically
**- biochemical pregnancy
** - tested with the presence of hCG in blood and urine after 18-30 days start of last period
**- clinical pregnancy
** - ultrasound at 5 weeks
- foetal heart at 7 weeks
What are the two types of loss
-sponetanous
-abnormal conceptus
How does a sponetnous loss occur after a clinical pregancy
after 5-7 weeks
- 4/5 cycles involving unprotected intercourse don’t cause pregnancy
- when sperm meets egg it may not always implant
- flushing of the human uterus revealed that at day 4/5 only 20% of embryos recovered where blastocysts
- 15-25% of clinical pregnancies fail (1st trimester)
What percentages of pregnancies end up in a live birth
15-25% have a live birth
Why does pregnancy loss due to abnormal conceptus happen
60% of the time, have sponetonus abortion because the sperm or egg gave the wrong amount of chromosomes
Chromosomal abonromalities types
-Translocations
-Errors of ploidy
-Deletions or duplications of a complete set of haploid chromosomes
Errors of chromosome number or ‘somy’
How can age affect conception
- as females gets older
- chance of miscarriage goes up
- live birth goes down
- aneuploidy in oocyte is more common
- this is related to egg quality, not he uterus, or endometrium
if we give a lady of 44 a donor egg, she will have same chance of pregnancy and no increased risk of miscarriage.
I.e. as you age, egg quality decreases -> aneuplodiy point
What are the effects of delayed reproduction
causes
- caused by age-related factors
- diabetes
- hypertension
- increase in miscarriage and imprinting disorders go beyond 45 years
- increase of autism increases as men get older
What happens with egg and sperm as they both get older
as eggs get older, the eggs struggle to deal with problems older sperm brings them
-miscarriages
How can male disorders about sperm
so what about sperm can it affect
- Production of spermatozoa
- Transport of spermatozoa
- Transmission of spermatozoa
- Sperm function in the female tract
- Fertilization and events afte
What could be causing male infertitiy
- dentify potentially correctable conditions
- Ductal obstruction or hypogonadotropic hypogonadism
- can you give gondotrophins and spermtagonsis may start
- Ductal obstruction or hypogonadotropic hypogonadism
- Identify potentially irreversible conditions requiring assisted reproductive technique using the sperm of the male partner.
- like he’s doesn’t have a VAS and you can use a technqiye to get a around that
- Identify irreversible conditions for which donor insemination or adoption are the possible options
- identify life-threatening conditions
- testicular cancer, pituitary tumours
- identify genetic abnormalities that may affect the health of offspring if assisted reproductive techniques should be employed
What tests do you need to do intially for men
- reproductive history
- semen analysis
- one semen analysis
- if it comes with abodnomal result
- if he gives a reason, like i had the flu, or smth then do a repeat
- additional blood analysis
male infertility
What examinnations
Examine male
- General weight, BP, urinalysis
- Secondary sexual characteristics
- does he loo like he’s gone through puberty
- Signs of endocrine disease
- Gynaecomastia
- Abdominal examination
- Genital examination
- Digital PR
- unusual in UK
- you would check for prostatitis
What endocrine evaluation would you do
- abnormally low sperm count (5 million)
- if he says he has impaired sexual function you would do bloods as soon as possible
- other clinical findings
Definitions
normozoospermic
normal semen sample
>16 million spermatozoa/ml; >30% rapid forward progressive motility and >4% normal morphology
Defintions
Oligozoospermic
low sperm count
<16 million spermatozoa/ml
Defintions
Asthenozoospermic
about sperm motlity -> reduced motlity
< 42% rapid and normal forward progressive motility
Teratozoospermic
a condition in which a man has a high amount of abnormal shaped sperm
< 4% spermatozoa with normal morphology
azoospermic
means no sperm in ejaculate
what does zoospermic mean
to do with sperm
if there is a problem with the ejaculate
spermia
What are the causes of failure in sperm production
Congenital testicular deficiency
- Klinefelter (47, XXY)
- Y Chromosome deletions
Maldescended testes - cryptorchidism
- didn’t get normal testicular decent
- Reduced spermatogenesis
- Increased risk for testicular cancer
Acquired
- Trauma - testis torsion
- may have cut off the blood supply
- hit with cricket bat or smth
- Orchitis (mumps)
- Endocrine disorders
What clinical tests can you do for sperm
- leucocytes in semen over 1 million per ml
- tells you man have some kind of infection
- sperm viability tests
- to test if sperm or dead or nah
- sperm vitality tests
- if sperm are alive, but they aren’t moving suggests, that sperm does not move
- anti-sperm antibodies
- computer aided sperm analysis
What are non standard sperm tests
- DNA damage (TUNEL / SCSA / SDFA / Comet assays)
- Aneuploidy (usually chromosomes 13, 18, 21, X and Y)
- OxidaAve Stress Tests (MiOxsys, Luminol, TOS, TAC)
- Cervical mucus penetraAon(CMT) and the post coital test (PCT)
- Hemizona assay
- Acrosome reacAon (AR)
- Zona free hamster egg sperm penetraAon (SPA)
(most people do non-standard tests are ripping them off)
What can cause sperm to fail to transmit themselves
tranmsit: from penis to vagina
- erectile dysfunction
- will affect delivery of sperm to female tract
- ejaculatory dysfunction
- retrograde
- defects of accessory sex glands
Descirbe how ejaculations usually happens
- Contraction of musculature of prostate
- seminal vesicles and vas deferens => seminal fluid and sperm => move out through urethra
- Under sympathetic nerve control
- Contraction of urethral and pelvic floor musculature => ejaculation
- the vesicular urethral sphincter closes bladder neck
- need to close this
What is reterograde ejaculation
- Incompetence of urethral sphincter
- Ejaculation into the bladder (retrograde)the path of least resistance
What conditions are associated with reterograde ejaculation
- Diabetes
- post traumatic paraplegia
- post bladder neck surgery
What are the signs of reterograde ejaculatiomn
tests
Ejaculate volume nil or low
Confirmation in urine – see if sperm in urine.
Why would you do a post ejaculatory urine analysis
low volume ejaculate
Absent ejaculate (Aspermia)
Avoid if CBAVD / hypogonadism features
What are the causes of low volume / no ejaculate:
- retrograde ejaculation
- Lack of emission
- Ejaculatory duct obstruction
sperm
What can cause a total failure in transport
- post-infection
- bilateral epididymal/ vas occlusion
- can be injury or by an STI
- bilateral epididymal/ vas occlusion
- congenital bilateral absence of vas defferns
- CBAVD
- ejaculate he thinks is normal, but there’s no sperm in ejauclate
- Azoospermic semen samples – obstructive azoospermia
What are the indications for genetic testing
- genetic abnormalities may cause infertility
- they can affect sperm production or transport
- Chromosomal abnormalities resulting in impaired testicular function. Klinefelter’s or translocations or inversions.
- men with non obstructive azoospermia, or oligozoospermia
What do 10-15% of men with severe oligo or azoospermia have
Y chromosome microdeletion
if the man goes onto have a son, the son may have the same phenotype or worse
What is CNAVD
what is it associated with causes etc
- Linked to CFTR gene (causes Cystic Fibrosis)
- CFTR gene mutation on chromosome 7
- CF associated with CBAVD.
- It is an improper development of vas deferens (c.f. vasectomy)
- > 95% of men with CF have CBAVD
85% of men with CBAVD have only one severely mutated allele => no other CF symptoms… In this situation you can take sperm for testes or epididymis and perform assisted reproduction.
- Check female partner when relevant
- but if she has a CF mutation, there’s a 25% chance they would make a baby with CF
What is the sperms role in fertilisation
– Centriole function (spindle formation)
– Chromatin decondensation
– Protamine exchange
– Pronuclear fusion
– Activation of genes for placenta formation
if you can select the sperm, you can skew the odds of things workings
What is the unexplained infertility …
it is when - Normal frequency and distribution of unprotected intercourse
- No obstructions of malformations in female or male genital tracts
- Normal follicle growth, maturation and ovulation; no signs of ongoing inflammatory reactions
- Normal concentration of motile spermatozoa, no anti-sperm antibodies or other signs of ongoing inflammatory reaction is …
