Subfertility

Question 1

Definition of subfertility

Answer 1

Inability for a couple to achieve clinical pregnancy after 12 months of regular unprotected sexual intercourse

Question 2

Primary and secondary subfertility

Answer 2

Primary - no previous pregnancy

Secondary - at least one previous pregnancy

Question 3

Incidence of subfertility within the general population

Answer 3

1 in 7 couples in the UK have trouble conceiving

- 84% of couples will get pregnant after having unprotected sexual intercourse for 1 year

Question 4

Causes of male subfertility

Answer 4

Azospermia - no sperm seen in sample

• obstructive
• non-obstructive OR failure to stimulate spermatogenesis

Question 5

Describe obstructive azospermia

Answer 5

Normal spermatogenesis, however there is an inability for sperm to leave in the ejaculate
Causes
- blockage in vas deferns or epididymis
- congenital absence of vas deferens (test for CF)

Question 6

Describe non-obstructive azospermia

Answer 6

There is testicular failure (increased FSH)
- biopsy in case there are islands for spermatogenesis
Causes
- XXY karyotype (Kleinfelter’s)
- Y microdeletions
Rarely can be caused by failure of stimulation of spermatogenesis (decreased FSH)
- hypogonadotrophic hypogonadism

Question 7

What are the female causes of subfertility

Answer 7

Ovulatory causes
- hypothalamic-pituitary failure
- HPO-axis dysfunction
- ovarian failure
Tubal causes  
Endometriosis related causes 
Unexplained subfertility

Question 8

Important factors in the assessment of ovulatory subefertility

Answer 8

Primary or secondary
- primary is he failure of onset of ovulation by the age of 16 in women
- secondary is no menstruation for 6 months or more in a woman who previous had periods
Check ovulation
- day 21 progesterone (if cycle is regular) as progesterone increases once the egg is released
- retrospective diagnosis

Question 9

Describe hypothalamic-pituitary failure as a cause of subfertility

Answer 9

GnRH release from the hypothalamus, or FSH/LH release from the pituitary is inhibited
Presents with amenorrhoea and shows a decreased LH and FSH on investigation

Question 10

Causes of hypothalamic-pituitary failure

Answer 10

Unknown
Hypothalamus - weight, stress, exercise and craniopharyngioma
Pituitary - tumour, Sheehan’s syndrome and cerebral radiotherapy

Question 11

Management of hypothalamic-pituitary failure

Answer 11

Increase BMI and decrease exercise
GnRH agonist
- pulsatile release
- mono-ovulation and increased live-birth success
Gonadotropin injections
- causes ovarian hyperstimulation, leading to multiple pregnancy
- FSH/LH

Question 12

Causes of HPO-axis dysfunction as a cause of subfertility

Answer 12

Most common cause of anovulatory subfertility
Causes
- PCOS
- hyperprolactinaemia
hypothyroidism, hyperthyroidism and adrenal insufficiency

Question 13

How is PCOS diagnosed

Answer 13

Rotterdam criteria (2 out of 3)
- hyperandrogenism (increased testosterone or hirsutism) 
- anovulation
- ultrasound shows features of PCO
Bloods results expected 
- decreased FSH
- increased LH
- increased oestrogen 
- hyperprolactinaemia
- increased free androgen index

Question 14

How is PCOS managed

Answer 14

Weight reduction (10% weight loss causes an 80% increase in ovulation)
Letrozole
- aromatase inhibitor
- blocks oestrogen biosynthesis, so negative feedback loop is blocked, increasing FSH production and ovarian stimulation
- stimulates one follicle at a time, so has lower rates of multiple pregnancy
Clomiphene
- SERM (selective oestrogen receptor modulator)
- blocks E2 at pituitary (stops negative feedback)
- increases FSH and ovulation
- has a risk of ovarian hyperstimulation and ovarian cancer if used for >12 months
IVF (after GnRH analogue)
Ovarian drilling

Question 15

What is ovarian failure as a cause of subfertility

Answer 15

It is a failure of the ovaries despite normal action by the pituitary and hypothalamus

• causes amenorrhoea
• increased FSH
• decreased E2

Question 16

Causes of ovarian failure

Answer 16

Idiopathic 
Chemo/radiotherapy 
Oophorectomy 
Autoimmune
Chromosomal (45XO - Turner's syndrome) 
Pure gonadal dysgenesis 
Androgen insensitivity (genetically male - 46XY)

Question 17

Describe premature ovarian insufficiency

Answer 17

In women <40 years
75% of women with 46XX spontaneous POI have potentially functional graafian follicles remaining in the ovary
- some women conceive without treatment, but pregnancy rates are low

Question 18

How is ovarian failure managed?

Answer 18

IVF with/without oocyte donation
Embryo donation
Adoption

Question 19

How are the male causes of subfertility managed?

Answer 19

ICSI - works better in obstructive causes rather than non-obstructive
Donor insemination

Question 20

What is tubal subfertility

Answer 20

Dysfunction either of egg reception or transportation

Question 21

How is tubal patency assessed

Answer 21

Hysterosalpingogram
- X-Ray with radio-opaque dye in the uterus
Laparoscopy of dye insufflation
- allows assessment of pelvis and external uterus
Hysterosalpingo-contrast-ultrasonography (Hy-Co-Sy)
- assess tubal and uterine pathology
Swabs
TV USS

Question 22

What other factors can be complicating conception?

Answer 22

Timing of intercourse

• sperm needs to be deposited BEFORE ovulation as progesterone affects cervical mucus
• 2/3 times a week

Question 23

Briefly describe endometriosis related subfertility and its management

Answer 23

Abnormal ovum pick-up and release
Management 
- treat symptoms
- surgery for diathermy or ovarian cystectomy
- IVF

Question 24

Describe unexplained subfertility and it’s management

Answer 24

Common
Where a cause of the subfertility can’t be found
- normal examination and investigations
Spontaneous conception is common in younger people, resolves within 3 years of trying regularly
IVF offered if >3 years of trying

Question 25

What factors assess fertility in both men and women

Answer 25

Age - mainly a female issue, some evidence of male age influence
Previous pregnancy
Duration of subfertility
Timing of intercourse
Weight (female)
- best BMI between 20 and 30
- increased weight has association pregnancy problems and a risk of miscarriage

Question 26

How are are men assessed for causes of subfertility

Answer 26

Semen analysis
- volume
- concentration (>15mmol/ml)
- motility (>40% motile)
- normal forms (>4% normal)
Sample provided after 2-5 days of abstinence 
Abnormal results are due to 
- azoospermia (absent sperm)
- oligospermia (few sperm)
- asthenospermia (immobile)
Karyotype
CF status 
Y microdeletions
FSH

Question 27

How are tubal causes of subfertility managed?

Answer 27

Laparoscopic salpingostomy

- success most obvious in distal blockages

Question 28

What is IVF

Answer 28

Fertilisation outside the body, where sperm fertilises the egg of its own accord

Question 29

How is IVF performed

Answer 29

GnRH analogues are used to prevent action of endogenous hormones
- then FSH injected to stimulate the ovary
Patient is scanned, and eggs (between 16 and 18mm are removed)
- via TV USS and needle
Sperm washing removes inactive cells and seminal fluid
Co-incubation for 1-4 hours in a test tube
Fertilised eggs are put in growth medium for 2 days until it is 4-6 cells big
- embryo transfer

Question 30

What is ICSI

Answer 30

Intracytoplasmic sperm injection

- done in cases of low sperm count or motility

Question 31

What is intrauterine insemination and when is it used?

Answer 31

Follicular development is induced and ovulation carried out as in IVF
36 hours after ovulation, prepared sperm is placed into the uterine cavity using intrauterine catheter
Performed in cases of donor insemination for couples where the sperm is poor quality and ICSI is unsuccessful

Question 32

What is ovarian hyperstimulation and its main complications

Answer 32

Gonadotropin therapy can lead to ovarian hyperstimulation syndrome
- a serious condition in which the ovaries are enlarged with cysts, related to multiple follicular development
Mild
- patients experience little abdominal discomfort
Severe
- nausea and vomiting
- profound and painful abdominal distension
- fluid shifts resulting in ascites and pleural effusion
- hepatorenal failure and adult respiratory distress are possible

Question 33

What are the consequences of PCOS

Answer 33

Reduced fertility 
Insulin resistance and diabetes 
Hypertension 
Endometrial cancer - due to unopposed oestrogen 
Depression and mood swings
Snoring and daytime drowsiness