Infertility (subfertility)

Question 1

What is infertility?

Answer 1

An inability to conceive
- >1 yrs of UPSI in women <35 yrs
- after 6 months in women >35 yrs

Also inc diagnosed problems such as:
- anovulation, tubal blockage, low sperm count

Question 2

What factors are involved in male infertility?

Answer 2

Structural or anatomical problems

Vasectomy

Sperm production disorders (motility, morphology, low sperm count)

Male immune system (attack own sperm) = glucocorticoids can help but are second line

Question 3

What is empirical therapy for male infertility?

Answer 3

hormones and hormone antagonists (gonadotrophins, androgens, antiestrogens) = unexplained infertility

IVF = severe persistent oligospermia

Question 4

When is gonadotrophin therapy indicated in male infertility?

Answer 4

only in Gn deficient men to induce spermatogenesis

6 months of HCG IM or SC 2-3/7
^ stimulates ICSH activity = add FSH after 6 months

Question 5

What factors influence female fertility?

Answer 5

Tubal disease

Endo

Age

anovulation

BMI

Question 6

How can uterine tubes effect/cause infertility?

Answer 6

Fallopian tubes blocked or damaged

Causes = scar tissue, infections, tubal ligation

Question 7

How is infertility due to tubal disease treated?

Answer 7

Surgical procedure

IVF to bypass blockage

Question 8

How do does anovulation influence infertility?

Answer 8

10-20% of couples infertility is largely due to anovulation

diagnosed on basis of irregular or absent menstruation

Cycles may be more or less regular and only sign is absence of PMS symptoms

Question 9

Explain the WHO Class I cause of anovulation

Answer 9

Caused by/type = hypothalamic/pituitary

prognosis = excellent

Question 10

Explain the WHO Class II cause of anovulation

Answer 10

Caused by/type = PCOS

prognosis = variable

Question 11

Explain the WHO Class III cause of anovulation

Answer 11

Caused by/type = premature ovarian failure (menopause before 40)

prognosis = poor

Question 12

What is the aim and pharmacotherapy for ovulation inducation?

Answer 12

Aim = development of single oocyte (high risk of many occurring)

Pharmacotherapy = clomifene or gonadotrophins

Question 13

What syndrome can be caused by ovulation induction?

Answer 13

Can cause ovarian hyperstimulation syndrome

Symptoms/effects:
- renal insufficiency
- severe abdo discomfort (ascites, ovarian enlargement
- coagulation disorders
- can be fatal = acute renal failure, venous/arterial thrombosis

Question 14

Discuss the use of ovulation induction in amenorrhoeic women

Answer 14

Short course of progestin to induce uterine bleeding = medroxyprogesterone acetate, norethisterone

make endometrium suitable for implantation, help guide specialist choice of ovulation induction

Question 15

What does it mean if ovulation induction in amenorrhoeic women does not cause a bleed?

Answer 15

progestogen, letrozole or clomifene unlikely to be effective

Question 16

List the ovulatory stimulants

Answer 16

Clomifene

Letrozole

Gonadotrophins

Question 17

Discuss letrozole as an ovulation stimulant

Answer 17

More effective than clomifene = higher preg rate, less multiples (not TGA registered for this indication)

Typically used in PCOS for ovulation induction

Req specialist guidance/monitoring

Question 18

When is letrozole started?

Answer 18

Between days 2 to 5 of menstrual cycle

No ovulation = inc dose over next 2 cycles, then consider other drugs

Question 19

Discuss clomifene as an ovulation stimulant

Answer 19

Competitive antagonist of oestrogen receptor in hypothalamus –> block -ve feedback to pituitary

Inc pituitary gonadotrophins (esp LH)

Induce ovulation in 80% of patients, preg only in 35-40% (over 6 months)

Question 20

When is clomifene started?

Answer 20

Started between days 2-5 of the menstrual cycle

Start any time if no recent uterine bleeding

For spontaneous or progestin induced bleeding –> commence on or about 5th day of cycle

Usually 50mg, use 25mg for those with lower BMI

Question 21

How long is clomifene used for?

Answer 21

<12 months, max 6 cycles

risk of multiple pregnancies, ovariance cancer

Question 22

What are some ADRs of clomifene?

Answer 22

Mood changes, hot flushes, abdominal discomfort, visual dist, reversible ovarian enlargement/cyst formation

Abnormal uterine bleeding, nausea, vomiting

Hair loss (reversible), ovarian hyperstimulation syndrome

Question 23

Name a precaution of clomifene

Answer 23

Stop treatment if vision alters

Warn patient about visual symptoms

Question 24

Discuss PCOS associated infertility (how influence fertility? how treat?)

Answer 24

Not absolute, time to conception longer

Weight loss = +/- metformin, +/- clomifene, +/- letrozole

Ovulation induction is high risk = multiple follicles, ovarian hyperstimulation

Question 25

Discuss the use of metformin in PCOS

Answer 25

Sig effect on reducing fasting insulin levels, blood pressure, LDL

Effective treatment for those with anovulation

Ovulation rates are higher when combined with clomifene = 76% vs 46%

Question 26

Discuss invitro assisted conception

Answer 26

Any invitro fertilisation req formation of zygote or embryos outside of body (IVF, ZIFT, TET, PROST)

In vitro maturation (IVM) = eggs are collected and mature in vitro –> req less/no ovarian stimulation