Infertility & assisted conception

Question 1

How common is infertility ?

Answer 1

Very, affects 1:6 couples (15%)

Question 2

List some of the reasons for increasing rates of infertility

Answer 2

• Women are older when trying to concieve
• Rise in chlamydia infections
• Increase obesity
• Increase in male factor infertility
• Increased awareness of infertility treatments available

Question 3

List the factors which increase the chances of conception

Answer 3

• Women < 30
• Previous pregnancy
• < 3yrs trying to concieve
• Intercourse occuring around ovulation
• Womans BMI 18.5-30
• Both partners non-smokers
• Caffeine intake < 2 cups daily
• No recreational drug use

Question 4

What happens to fertility as we get older ?

Answer 4

Question 5

Define infertility

Answer 5

This is failure to achieve clinical pregnancy after ≥ 12 months of regular unprotected sexual intercourse (in absence of known reason) in a couple who have never had a child

This can be further divided into:

1. Primary = couple have never concieved
2. Secondary = couple previously concieved but pregnancy was not successful e.g. misscariage or ectopic pregnancy

Question 6

What reasurance should be be given to couples presenting with concerns over infertility ?

Answer 6

Reasure that 84% of couples will concieve within the 1st year of having unprotected sexual intercourse & 92% will within 2 years

Question 7

What is the initial general advice provided to couples wishing/struggling to concieve ?

Answer 7

• Folic acid 400 micrograms (5mg if them or partner have a NTD, or previous baby with NTD, or a fam history of NTD’s or they have diabetes)
• Aim for BMI 20-25
• Advice regular sexual intercourse every 2-3 days
• Smoking, alcohol & caffeine advice
• Stop recreational drugs or methadone

Question 8

List the general different causes of infertility

Answer 8

• Male factor infertility
• Multiple factors (female & male)
• Multiple factors (female only)
• Tubal factor
• Endometriosis
• Diminished ovarian reserve
• Ovulatory dysfunction
• Uterine factor - structural
• Unexplained
• Other causes

Question 9

Ovulatory dysfunction is covered in ovulatory disorders deck in Endocrine week 5

Question 10

What are the causes of tubal disease resulting in infertility ?

Answer 10

• PID - usually due to chlamydia or gonorrhoea resulting in hydrosalpinx or pyosalpinx
• Endometriosis
• Transperitoneal spread from abdo infections e.g. appendicitis, abdominal abscess etc
• Following procedures - IUCD insertion, hysteroscopy, HSG, ectopic pregnancy, sterilisation
• Fibroids
• Polyps

Question 11

What are the uterine/ structural abnormalities (affecting meeting of egg & sperm) which can result in infertility ?

Answer 11

• Fibroids
• Vaginal septum
• Adhesions
• Polyps

Question 12

What are the causes of male factor infertility ?

Answer 12

IDIOPATHIC: most common cause (>50%)

OBSTRUCTIVE: vasectomy, cystic fibrosis (congenital absence of vas deferens), infection

NON-OBSTRUCTIVE:

• Congenital: Cryoptorchidism
• Infection: mumps orchitis
• Iatrogenic: chemotherapy/radiotherapy
• Pathological: testicular tumour
• Genetic: chromosomal (Klinefelter’s syndrome, microdeletions of Y chromosome, Robertsonian translocation)
• Specific semen abnormality e.g. globozoospermia
• Systemic disorder
• Endocrine

Question 13

When should someone be investigated for a cause of infertility ?

Answer 13

Once they meet the definition of it i.e. after 12 months of trying

Question 14

How should infertility be initially investigated ?

Answer 14

See as couple in designated infertility clinic & carry out:

History: infertility history, gynaecology, andrology, sexual history, social history, PMH, PSH, POH

Examination of female:

• BMI
• General examination, assessing body hair distribution, galactorrhoea
• Pelvic examination, assessing for uterine and ovarian abnormalities/tenderness/mobility

Examination of male:

• BMI
• General examination
• Genital examination, assessing size/position testes, penile abnormalities, presence vas deferens, presence varicoceles

Question 15

What are the initial female investigations which should be done in someone presenting with infertility ?

Answer 15

• Endocervical swab for chlamydia
• Cervical smear if due
• Blood for rubella immunity
• Midluteal progesterone level (day 21 of 28 day cycle or 7 days prior to expected period in prolonged cycles), progesterone > 30nmol/l suggestive ovulation
• Test of tubal patency: hysterosalpingiogram or laparoscopy

Others if indicated: e.g. hysteroscopy, ultrasound scan, endocrine profile and chromosomes

Question 16

What is the 1st line investigation for investigating tubal patency ?

Answer 16

1st line = Hysterosalpingiogram (HSG)

Done in women who are not known to have comorbidities/risk factors of tubal/ pelvic pathology e.g. PID, previous ectopic pregnancy or endometriosis) or when laparoscopy is contraindicated i.e. obesity, previous pelvic surgery, Crohn’s disease

Question 17

What is the 2nd line investigation done for assessing tubal patency and when is it done ?

Answer 17

2nd line = Laparoscopy

Done if:

• They have possible tubal/pelvic disease: e.g.PID
• Known previous pathology: e.g. ectopic pregnancy, ruptured appendix, endometriosis
• History suggestive of pathology: e.g. dysmenorrhoea, dysparunia
• Previously abnormal HSG

Question 18

When is hysteroscopy performed in the assessment of a women presenting with infertility ?

Answer 18

Only performed in cases where suspected or known endometrial pathology: i.e. uterine septum, adhesions, polyp

Question 19

When is pelvic ultrasound performed in the assessment of a women with infertility

Answer 19

• Perform when abnormality on pelvic examination: e.g. enlarged uterus /adnexal mass
• When required from other investigations: e.g. possible polyp seen at HSG

Question 20

If a women being investigated for infertility has an anovulatory cycle or infrequent periods what additional investigations should be done ?

Answer 20

Endocrine profile:

• Urine HCG
• Prolactin
• TSH
• Testosterone and SHBG
• LH, FSH and oestradiol

Question 21

If a women being investigated for infertility has hirtuism what additional investigations should be done ?

Answer 21

Testosterone and SHBG

Question 22

If a women being investigated for infertility presents with amenorrhoea what additional investigations should be done ?

Answer 22

• Endocrine profile (as in anovulatory cycle)
• Chromosome analysis

Question 23

What is the treatment of ovulatory disorders causing infertility ?

Answer 23

Refer to ovulatory disorders deck in endocrine week 5

Question 24

What are the 2 main reasons reproductive surgery is used in the management of infertility ?

Answer 24

1. Primary surgical treatment for infertility
2. Surgery to enhance IVF outcome

Question 25

What are the main conditions causing infertility which are treated by surgery ?

Answer 25

1. Pelvic adhesions 2. Grade 1& 2 Endometriosis 3. Chocolate cysts in Ovary 4. Tubal Block

Question 26

What is the surgical treatment done for infertility due to mild tubal disease ?

Answer 26

Tubal surgery

Question 27

What is the surgical treatment done for infertility due to proximal tubal obstruction ?

Answer 27

Either selective salpingography + tubal catherterisation or hysteroscopic tubal cannulation

Question 28

What is the surgical treatment done for infertility due to hydrosalpinges before IVF and why ?

Answer 28

Laproscopic salpingectomy - this is done because it improves the chances of live birth with IVF treatment

Question 29

What is the surgical treatment done for inferility because of intrauterine adhesions ?

Answer 29

Hysteroscopic adhesiolysis

Question 30

What is the surgical treatment of endometriosis causing infertility ?

Answer 30

* Minimal or mild endometriosis tx = surgical ablation or resection of endometriosis + laparoscopic adhesiolysis * Women with ovarian endometriomas tx = laparoscopic cystectomy * Women with moderate or severe endometriosis tx = surgery

Question 31

What is the treatment of fibroids causing infertility ?

Answer 31

Polypectomy or myomectomy

Question 32

What is the treatment of uterine septum causing infertility?

Answer 32

Metroplasty

Question 33

What is the treatment of unexplained infertility ?

Answer 33

* 1st line = try to concieve for a total of 2 years * 2nd line = after trying to concieve natrually treat with IVF

Question 34

List the different causes for needing assisted conception treatment (ACT)

Answer 34

* Endometriosis * Male factor infertility * Tubal disease * Multiple male and female factors * Unexplained * Ovulatory disorder * Multiple female factors * Fertility preservation in cancer patients * Treatment to avoid transmission of blood born viruses between patients * Pre-implantation diagnosis of inherited disorders * Treatment of single parents or same sex couples * Others: cryopreservation of gametes for social reasons, treatment when absent/abnormal

Question 35

What needs to be done before ACT begins ?

Answer 35

* Alcohol: females limit to 4 units per week * Weight: between 19-29 optimal both male and female * Smoking: advise to stop smoking * Folic acid: 0.4mg/day preconception-12 weeks gestation (5mg increase risk NTD/obese) * Rubella: check if female immune to rubella, if not immunise * Cervical smears: check up to date according to national screening programme * Occupational factors: exposure to hazards * Drugs: prescribed, over-the-counter and recreational such as steroids * Screen for blood born viruses: hep B/C and HIV * Assess ovarian reserve: antral follicle count or AMH * Counselling: offer supportive counselling

Question 36

List the different ACT avaliable

Answer 36

* Donor insemination * Intra-Uterine Insemination (IUI) * In Vitro Fertilisation (IVF) * Intra-Cytoplasmic Sperm Injection (ICSI) * Fertility Preservation * Surrogacy

Question 37

What are the indications for intrauterine insemination (IUI) ACT?

Answer 37

* sexual problems (physical or psychological) or same sex relationships * discordant BBV * unexplained infertility * mild or moderate endometriosis * mild male factor infertility * abandoned IVF

Question 38

Describe what is done in IUI

Answer 38

* Can be in natural/stimulated cycle * Prepared semen inserted into uterine cavity around time of ovulation

Question 39

What are the indications for In vitro fertilisation (IVF) ACT ?

Answer 39

* Unexplained infertility (\> 2 years durations) (if \< 40 give 3 cycles, if 40-42 only 1 cycle) * Pelvic disease (endometriosis, tubal disease, fibriods) * Anovulatory infertility (after failed ovulation induction) * Male factor infertility (if \> 1 X 10⁶ motile sperm) * Failed Intra-uterine insemination (after 6 cycles) * Others (pre-implantation genetic diagnosis)

Question 40

List the main steps that make up IVF ACT

Answer 40

1. Down regulation 2. Ovarian stimulation 3. Oocyte collection 4. Fertilisation 5. Day 5 after fertilisation - day of transfer & cryopreservation 6. Embryo transfer

Question 41

Describe what down regulation is in relation to IVF

Answer 41

* Down-regulation essentially "turns off" the ovaries to better control ovulation and egg maturation during treatment. * It allows precise timing of oocyte recovery by using HCG trigger

Question 42

How is down regulation during IVF treatment achieved ?

Answer 42

Using a GnRH agonist or antagonist.

Question 43

What are the side effects a patient may experience from recieiving down regulation of their ovaries ?

Answer 43

* Hot flushes and mood swings * Nasal irritation * Headaches

Question 44

How is down regulation of the ovaries confirmed in IVF treatment ?

Answer 44

Using a US scan

Question 45

Describe what happens during the second stage of IVF treatment (ovarian stimulation)

Answer 45

* The goal of this process is to produce as many eggs as possible for collection * Patient is given injections of Gonadotrophin Hormone containing either synthetic or urinary gonadotrophins (FSH+/- LH) for 8-14 days * A trigger shot of HCG (mimics the LH surge) is then given to stimulate ovulation 36hrs prior to oocyte collection

Question 46

Prior to oocyte collection what does the male partner need to do during IVF treatment ?

Answer 46

Provide semen (needs to abstain for 72hrs prior to this) which then needs to be assesed for: * Volume * Density - numbers of sperm * Motility - what proportion are moving * Progression - how well they move

Question 47

What are the risks accompanied with oocyte collection ?

Answer 47

* Bleeding * Pelvic infection * Failure to obtain oocytes

Question 48

After oocyte collection what is done ?

Answer 48

* Search through the follicular fluid * Identify eggs and surrounding mass of cells * Collect them into cell culture medium * Incubate at 370C

Question 49

What is the 4th stage of IVF treatment ?

Answer 49

Ferilisation - artificially (done outside the women by scientists)

Question 50

Following fertilisation of the oocyte by scientists during IVF treatment when is the fertilised oocyte (embryo) transferred and what is also done ?

Answer 50

* Embryo is transferred on day 5 after fertilisation * Cryopreservation of the other collected eggs is done I believe

Question 51

What happens to fertility as we get older ?

Answer 51

Question 52

How long after embryo transfer should a pregnancy test be done to confirm if IVF treatment has been successful or not ?

Answer 52

16 days

Question 53

What are the indications for intracytoplasmic sperm injection (ICSI)?

Answer 53

* Severe male factor infertility (\< 1x10⁶) * Previous failed fertilisation with IVF * Preimplantation genetic diagnosis

Question 54

When doing ICSI, if the patient has azoospermia what needs to be done for sperm collection ?

Answer 54

Surgical sperm aspiration - Can be extracted from epididymis (if obstructive) or testicular tissue (non-obstructive)

Question 55

What are the main complications of assisted reproductive treatments ?

Answer 55

1. Ovarian hyperstimulation syndrome (OHSS) 2. Multiple pregnancies 3. Ectopic pregnancies

Question 56

What are the signs/symptoms of OHSS?

Answer 56

Question 57

What assisted reproductive treatment is the most likely to result in OHSS?

Answer 57

IVF

Question 58

What is done to try to prevent OHSS in IVF treatment ?

Answer 58

Prevention: * Low dose protocols * Use of antagonist for suppression (referring to GnRH anatagnoist)

Question 59

What is the treatment of OHSS?

Answer 59

Treatment before embryo transfer: * Elective freeze * Single embryo transfer Treatment after embryo transfer: * Monitoring with scans and bloods * Reduce risk thrombosis: Fluids, TED stockings and fragmin * Analgesia * Hospital admission if required IV fluids/more intensive monitoring/paracentesis

Question 60

List some of the additional problems with assissted reproductive treatments

Answer 60

* No eggs retrieved (very uncommon: 0.2%) * Surgical risks of oocyte retrieval (bleeding, infection) * Surgical risks of surgical sperm aspiration (haematoma, infection) * Failed fertilisation (approx. 4%) * Problems in early pregnancy: increase miscarriage and ectopic pregnancy * Increase risk in on-going pregnancy (possible increase in prematurity and intra-uterine growth retardation, congenital abnormalities) * Psychological problems * Failed treatment

Question 61

What is the success rates of IVF treatment ?

Answer 61

Approx. 35%