T2 L7 Causes and Treatment of Subfertility Flashcards
What are the requirements for conception?
Progressively motile normal sperm capable of reaching and fertilizing the oocyte
Timely release of a competent oocyte
Free passage for the sperm to reach the oocyte and for the embryo to reach the uterus
A mature endometrium that allows implantation
What is infertility?
Inability to conceive after 2 year of frequent unprotected intercourse
Reasonable to investigate after 1 year unless there is a concern
What is the cumulative probability of pregnancy after 1, 2 and 3 years?
84%, 92% & 93% after 1,2 & 3 years
Why is fertility defined as being “after 2 years of frequent unprotected intercourse”?
The gap of the cumulative probability is bigger between 1 and 2 years
What is the NICE definition of infertility?
“The period of time people have been trying to conceive without success after which formal investigation is justified and possible treatment implemented”
“If a woman has not conceived after a year, offer further clinical assessment and investigation, along with her partner”
What are the various causes of infertility?
- Unexplained 30%
- Ovulatory 27%
- Male factor 19% (now 25-30%)
- Tubal 14%
- Endometriosis 5% (this is present in 10-15% of women)
- Other factors 5% (uterine, endometrial, gamete or embryo defect)
What % of infertility cases was due to infertility problems in both the male and female?
39%
What are the indications for early referral/investigation in a female?
- Aged over 35 years
- Amenorrhoea/oligomenorrhoea
- Previous abdominal/pelvic surgery
- Previous PID/STD
- Abnormal pelvic examination
What are the indications for early referral/investigation in a male?
- Previous genital pathology (history of testicular maldescent, surgery, infection or trauma, there is a greater incidence of abnormal semen parameters)
- Previous STD
- Significant systemic illness
- Abnormal genital examination
Describe a “normal result” in a semen analysis
Count > 15 x 10^6 / ml
Motility > 40%
Morphology > 4%
Volume 1.5-6 mls
What is the most common cause for oligo/azoospermia?
Primary testicular failure
What is non-obstructive azoospermia?
No spermatogenesis (could be due to hypogonadotropic hypogonadism)
These men usually have a smaller penis
What causes obstructive azoospermia?
Blockage of the epididymis and the vas deferens
Which conditions should you consider if the sperm count is < 5 million?
Y chromosome microdeletion
Cystic fibrosis
What is the single, most important factor for infertility in females?
AGE
A woman’s fertility declines with age
Why does a woman’s fertility decrease with age?
Decline in oocyte number and quality rather than uterine receptivity
The increased rate of chromosomal abnormalities in the oocyte also results in higher aneuploidy and miscarriage rates
If a woman is over 45 years old, what is she advised to consider if she is trying to get pregnant?
Advised to consider egg donation, because the chance of having a live birth decreases due to an increase in chromosomal abnormality
How is the female assessed for infertility?
Screen for chlamydia & Rubella
Ovarian reserve
- Early follicular phase hormone level (FSH, LH & E2)
- AMH (Anti-Mullarian Hormone)
- AFC (Antral Follicle Count)
Ovulation test
Tubal test
What is AMH? When is it produced in a female?
Anti-mullerian hormone
First produced by the granulosa cells of the early growing follicle
It continues to be produced by the granulosa cells of growing follicles up until the early antral stage after which it declines precipitously
When do the granulosa cells stop producing AMH in females?
Once they reach 8mm
What happens to the concentration of AMH during the monthly period?
Remains constant
How is AMH used in fertility assessment (of a female)?
Circulating AMH may accurately reflect the total developing follicular cohort
This may represent the total ovarian reserve
What happens to the concentration of AMH as age increases?
It reduces
How many days is a regular menstrual cycle in most women? During this period, what will most women undergo?
26-35 days
Women who have regular menstrual cycles will ovulate
What is BBT and how is it used? What are NICE guidelines on BBT?
BBT = Basal Body Temperature
Used to monitor ovulation
NICE guidelines advice against use of BBT
What other ways can ovulation can be monitored?
- Ovulation detection kits
- Cervical mucous pattern
- Follicular tracking or mid-luteal phase P4 (7 days before menstruation)
What levels of mid-luteal P4 is accepted as evidence of ovulation?
30nmol/L
What else can make the mid-luteal P4 > 30nmol/L?
A leutinised unruptured follicle, which has not released an egg yet
What is a more reliable method for monitoring ovulation (in comparison to mid-luteal P4)?
Follicular tracking
NOTE: This method is costly & labour intensive
What is the most common cause of anovulation and primary or secondary oligo/amenorrhea?
PCOS (polycystic ovarian syndrome)
Makes up 85% of cases
What test could you do to confirm oligo/amenorrhea?
- FSH/LH
- E2
- prolactin
- TFT
- androgens & SHBG
What happens to the levels of FSH/LH and E2 in PCOS?
normal FSH/LH & E2
What % of anovulation and primary or secondary oligo/amenorrhea is due to POF?
5%
What happens to the levels of FSH/LH and E2 in POF?
- high FSH
- low E2
What % of anovulation and primary or secondary oligo/amenorrhea is due to hypogonadotrophic hypogonadism?
10%
What happens to the levels of FSH/LH and E2 in hypogonadotrophic hypogonadism?
- low FSH, LH
- low E2
What is the most common cause of tubal damage?
PID (pelvic inflammatory disease)
-secondary to chlamydia
What are different types of tubal disease/damage?
- proximal (25%)
- distal – fimbriael end of the tube (75%)
What are the risk of tubal damage after 1, 2, or 3 episodes of pelvic infection?
- 12% after one episode
- 23% after two episodes
- 54% after three episodes
Name other causes of tubal damage
- septic abortion
- ruptured appendix
- pelvic surgery
- ectopic pregnancy
What are the different imaging that can be done to examine the fallopian tubes?
Hysterosalpingogram (HSG)
Hysterosalpingo-contrast-ultrasonography (HyCoSy)
Laparoscopy & dye
If there is a low risk of tubal disease which imaging technique should be offered?
HSG
HyCoSy
Why should you screen for chlamydia before carrying out imaging?
By injecting the dye into the cervix, the Chlamydia trachomatis can be pushed towards the fallopian tube
When is HSG carried out?
2-5 days after menstruation
Why should antibiotics be given when doing a HSG?
To prevent the flare-up of infection
if there is a history of PID (pelvic inflammatory disease)
What is the overall risk of infection when doing a HSG? How does this differ in high-risk populations?
1%
In high-risk population this can rise to 3%
What are the advantages and disadvantages of HSG?
Advantages:
- relative safety
- ease of use
- delineation of the uterine cavity and Fallopian tubes
Disadvatages:
-inability to assess the pelvic peritoneum
NOTE: this is an ideal screening test for the majority of the patients
Describe HyCoSy
Similar to HSG
Ovarian and uterine assessment is possible
What are the advantages and disadvantages of HyCoSy?
Advantages
-No radiation = Relatively safer
Disadvantage
-Time-consuming & requires training
What are the advantages and disadvantages of lap & dye?
Advantage
- more sensitive & specific
- chance to diagnose & treat endometriosis & adhesions
Disadvantage
-invasive procedure with inherent risks of visceral injury to the patient
Name the uterine abnormalities estimated to be a factor in 10-15% of couple seeking fertility treatment
- adhesions
- polyps
- submucous fibroids and septae
What imaging techniques can be used to detect the uterine abnormalities?
HSG (hysterosalpingogram)
TVS (transvaginal ultrasound)
hysteroscopy
Which imaging technique is the best at detecting uterine abnormalities?
Hysteroscopy
What drug is used to induced in women that have PCOS?
Clomid (Clomifene Citrate)
It has an anti-oestrogen effect on hypothalamic pituitary axis. It inhibits negative feedback of oestrogen on gonadotropin release.
What drug is used to induced in women that have resistant PCOS or Hypogonadotrophic Hypogonadism?
FSH injections
What is the risk of ovulation induction?
Multiple pregnancies
NOTE: Monitor 1st cycle using USS (to make sure that the woman is responding but not excessively)
What is IUI? What are the indications for using this treatment?
Intrauterine insemination
Indications
- unexplained
- mild male factor
- mild endometriosis
What are the advantages of IUI treatment?
- Less stress
- Less invasive
- Less tech
- Cheap
What is the success rate of IUI treatment?
10% (per cycle)
What are the NICE guidelines on IUI treatment?
Do not offer IUI for couples who have unexplained infertility
IUI for single women, same sex couple or heterosexual couple who have problem with intercourse
IVF for couples who have unexplained infertility
What are the main indications for IVF?
Tubal damage
Low sperm quality
Unexplained infertility
Low ovarian reserve (time is of the essence and the couple needs to go for the most effective treatment which is IVF)
What occurs in Controlled Ovarian Hyperstimulation?
Ovulation by multiple ovarian follicles is induced
The multiple follicles can be taken out by oocyte retrieval (egg collection) for use in in vitro fertilisation (IVF)
How frequently does an ultrasound examination and blood take place, during IVF? Why?
Every other week for IVF
To make sure that the woman is responding to treatment but not excessively
How are the eggs collected? How long does this take?
Collected using needle using ultrasound guidance
Collection takes approximate 20 minutes
NOTE: The woman is either sedated or under general anaesthetics
What is intra-cytoplasmic sperm injection?
The sperm is directly injected into the egg (used in men with a low sperm count)
What are the risks associated with intra-cytoplasmic sperm injection?
Higher risk of congenital/chromosomal abnormality. This could be because the sperm from men with a low sperm count are more likely to have genetic abnormalities
When is the embryo transferred to the uterus?
Most embryo transfers occurs at day 5
At this stage the embryo is better synchronised with the endometrium which is more ready for implantation
What is the national average for IVF live birth rates (LBR)?
30-35% (< 35 year old)
What is the IVF live birth rates dependent on?
Depends on female partner’s age
The unit IVF is being carried out in. The LBR varies from one unit to another
From which age is the success rate of frozen embryos bigger than fresh embryos?
40 years
