T2 L7 Causes and Treatment of Subfertility

Question 1

What are the requirements for conception?

Answer 1

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

Question 2

What is infertility?

Answer 2

Inability to conceive after 2 year of frequent unprotected intercourse

Reasonable to investigate after 1 year unless there is a concern

Question 3

What is the cumulative probability of pregnancy after 1, 2 and 3 years?

Answer 3

84%, 92% & 93% after 1,2 & 3 years

Question 4

Why is fertility defined as being “after 2 years of frequent unprotected intercourse”?

Answer 4

The gap of the cumulative probability is bigger between 1 and 2 years

Question 5

What is the NICE definition of infertility?

Answer 5

“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”

Question 6

What are the various causes of infertility?

Answer 6

• 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)

Question 7

What % of infertility cases was due to infertility problems in both the male and female?

Answer 7

39%

Question 8

What are the indications for early referral/investigation in a female?

Answer 8

1. Aged over 35 years
2. Amenorrhoea/oligomenorrhoea
3. Previous abdominal/pelvic surgery
4. Previous PID/STD
5. Abnormal pelvic examination

Question 9

What are the indications for early referral/investigation in a male?

Answer 9

1. Previous genital pathology (history of testicular maldescent, surgery, infection or trauma, there is a greater incidence of abnormal semen parameters)
2. Previous STD
3. Significant systemic illness
4. Abnormal genital examination

Question 10

Describe a “normal result” in a semen analysis

Answer 10

Count > 15 x 10^6 / ml

Motility > 40%

Morphology > 4%

Volume 1.5-6 mls

Question 11

What is the most common cause for oligo/azoospermia?

Answer 11

Primary testicular failure

Question 12

What is non-obstructive azoospermia?

Answer 12

No spermatogenesis (could be due to hypogonadotropic hypogonadism)

These men usually have a smaller penis

Question 13

What causes obstructive azoospermia?

Answer 13

Blockage of the epididymis and the vas deferens

Question 14

Which conditions should you consider if the sperm count is < 5 million?

Answer 14

Y chromosome microdeletion

Cystic fibrosis

Question 15

What is the single, most important factor for infertility in females?

Answer 15

AGE

A woman’s fertility declines with age

Question 16

Why does a woman’s fertility decrease with age?

Answer 16

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

Question 17

If a woman is over 45 years old, what is she advised to consider if she is trying to get pregnant?

Answer 17

Advised to consider egg donation, because the chance of having a live birth decreases due to an increase in chromosomal abnormality

Question 18

How is the female assessed for infertility?

Answer 18

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

Question 19

What is AMH? When is it produced in a female?

Answer 19

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

Question 20

When do the granulosa cells stop producing AMH in females?

Answer 20

Once they reach 8mm

Question 21

What happens to the concentration of AMH during the monthly period?

Answer 21

Remains constant

Question 22

How is AMH used in fertility assessment (of a female)?

Answer 22

Circulating AMH may accurately reflect the total developing follicular cohort

This may represent the total ovarian reserve

Question 23

What happens to the concentration of AMH as age increases?

Answer 23

It reduces

Question 24

How many days is a regular menstrual cycle in most women? During this period, what will most women undergo?

Answer 24

26-35 days

Women who have regular menstrual cycles will ovulate

Question 25

What is BBT and how is it used? What are NICE guidelines on BBT?

Answer 25

BBT = Basal Body Temperature Used to monitor ovulation NICE guidelines advice against use of BBT

Question 26

What other ways can ovulation can be monitored?

Answer 26

- Ovulation detection kits - Cervical mucous pattern - Follicular tracking or mid-luteal phase P4 (7 days before menstruation)

Question 27

What levels of mid-luteal P4 is accepted as evidence of ovulation?

Answer 27

30nmol/L

Question 28

What else can make the mid-luteal P4 > 30nmol/L?

Answer 28

A leutinised unruptured follicle, which has not released an egg yet

Question 29

What is a more reliable method for monitoring ovulation (in comparison to mid-luteal P4)?

Answer 29

Follicular tracking NOTE: This method is costly & labour intensive

Question 30

What is the most common cause of anovulation and primary or secondary oligo/amenorrhea?

Answer 30

PCOS (polycystic ovarian syndrome) Makes up 85% of cases

Question 31

What test could you do to confirm oligo/amenorrhea?

Answer 31

- FSH/LH - E2 - prolactin - TFT - androgens & SHBG

Question 32

What happens to the levels of FSH/LH and E2 in PCOS?

Answer 32

normal FSH/LH & E2

Question 33

What % of anovulation and primary or secondary oligo/amenorrhea is due to POF?

Answer 33

5%

Question 34

What happens to the levels of FSH/LH and E2 in POF?

Answer 34

- high FSH | - low E2

Question 35

What % of anovulation and primary or secondary oligo/amenorrhea is due to hypogonadotrophic hypogonadism?

Answer 35

10%

Question 36

What happens to the levels of FSH/LH and E2 in hypogonadotrophic hypogonadism?

Answer 36

- low FSH, LH | - low E2

Question 37

What is the most common cause of tubal damage?

Answer 37

PID (pelvic inflammatory disease) | -secondary to chlamydia

Question 38

What are different types of tubal disease/damage?

Answer 38

- proximal (25%) | - distal – fimbriael end of the tube (75%)

Question 39

What are the risk of tubal damage after 1, 2, or 3 episodes of pelvic infection?

Answer 39

- 12% after one episode - 23% after two episodes - 54% after three episodes

Question 40

Name other causes of tubal damage

Answer 40

- septic abortion - ruptured appendix - pelvic surgery - ectopic pregnancy

Question 41

What are the different imaging that can be done to examine the fallopian tubes?

Answer 41

Hysterosalpingogram (HSG) Hysterosalpingo-contrast-ultrasonography (HyCoSy) Laparoscopy & dye

Question 42

If there is a low risk of tubal disease which imaging technique should be offered?

Answer 42

HSG | HyCoSy

Question 43

Why should you screen for chlamydia before carrying out imaging?

Answer 43

By injecting the dye into the cervix, the Chlamydia trachomatis can be pushed towards the fallopian tube

Question 44

When is HSG carried out?

Answer 44

2-5 days after menstruation

Question 45

Why should antibiotics be given when doing a HSG?

Answer 45

To prevent the flare-up of infection if there is a history of PID (pelvic inflammatory disease)

Question 46

What is the overall risk of infection when doing a HSG? How does this differ in high-risk populations?

Answer 46

1% In high-risk population this can rise to 3%

Question 47

What are the advantages and disadvantages of HSG?

Answer 47

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

Question 48

Describe HyCoSy

Answer 48

Similar to HSG Ovarian and uterine assessment is possible

Question 49

What are the advantages and disadvantages of HyCoSy?

Answer 49

Advantages -No radiation = Relatively safer Disadvantage -Time-consuming & requires training

Question 50

What are the advantages and disadvantages of lap & dye?

Answer 50

Advantage - more sensitive & specific - chance to diagnose & treat endometriosis & adhesions Disadvantage -invasive procedure with inherent risks of visceral injury to the patient

Question 51

Name the uterine abnormalities estimated to be a factor in 10-15% of couple seeking fertility treatment

Answer 51

- adhesions - polyps - submucous fibroids and septae

Question 52

What imaging techniques can be used to detect the uterine abnormalities?

Answer 52

HSG (hysterosalpingogram) TVS (transvaginal ultrasound) hysteroscopy

Question 53

Which imaging technique is the best at detecting uterine abnormalities?

Answer 53

Hysteroscopy

Question 54

What drug is used to induced in women that have PCOS?

Answer 54

Clomid (Clomifene Citrate) It has an anti-oestrogen effect on hypothalamic pituitary axis. It inhibits negative feedback of oestrogen on gonadotropin release.

Question 55

What drug is used to induced in women that have resistant PCOS or Hypogonadotrophic Hypogonadism?

Answer 55

FSH injections

Question 56

What is the risk of ovulation induction?

Answer 56

Multiple pregnancies NOTE: Monitor 1st cycle using USS (to make sure that the woman is responding but not excessively)

Question 57

What is IUI? What are the indications for using this treatment?

Answer 57

Intrauterine insemination Indications - unexplained - mild male factor - mild endometriosis

Question 58

What are the advantages of IUI treatment?

Answer 58

- Less stress - Less invasive - Less tech - Cheap

Question 59

What is the success rate of IUI treatment?

Answer 59

10% (per cycle)

Question 60

What are the NICE guidelines on IUI treatment?

Answer 60

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

Question 61

What are the main indications for IVF?

Answer 61

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)

Question 62

What occurs in Controlled Ovarian Hyperstimulation?

Answer 62

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)

Question 63

How frequently does an ultrasound examination and blood take place, during IVF? Why?

Answer 63

Every other week for IVF To make sure that the woman is responding to treatment but not excessively

Question 64

How are the eggs collected? How long does this take?

Answer 64

Collected using needle using ultrasound guidance Collection takes approximate 20 minutes NOTE: The woman is either sedated or under general anaesthetics

Question 65

What is intra-cytoplasmic sperm injection?

Answer 65

The sperm is directly injected into the egg (used in men with a low sperm count)

Question 66

What are the risks associated with intra-cytoplasmic sperm injection?

Answer 66

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

Question 67

When is the embryo transferred to the uterus?

Answer 67

Most embryo transfers occurs at day 5 At this stage the embryo is better synchronised with the endometrium which is more ready for implantation

Question 68

What is the national average for IVF live birth rates (LBR)?

Answer 68

30-35% (< 35 year old)

Question 69

What is the IVF live birth rates dependent on?

Answer 69

Depends on female partner’s age The unit IVF is being carried out in. The LBR varies from one unit to another

Question 70

From which age is the success rate of frozen embryos bigger than fresh embryos?

Answer 70

40 years