Infertility & Assisted Reproduction

Question 1

What is infertility?

Answer 1

It is defined as the inability to conceive following 1 year of regular, appropriately timed intercourse in the absence of contraception.

Question 2

What is anovulation?

Answer 2

It is a failure to ovulate in cyclical manner, it can present as amenorrhea or irregular bleeding

Question 3

What are the methods of investigation of anovulation?

Answer 3

1. Mittlesmertz is a good indicator
2. Fluctuation of basal body temperature
3. Midcycle LH surge monitoring (urinary dipstick)

Most Reliable
4. Measure mid-luteal serum progesterone

Question 4

What are some HPO axis, causes of anovulation?

Answer 4

1. Stress/ extreme illness, low weight, extreme physical activity
2. Pituitary Tumour (Prolactinoma)
3. Infiltrative Disease
4. Hyper/ Hypothyroidism
5. Kallmann’s Syndrome
6. PCOS, high levels of LH

Question 5

What are the causes of ovarian Failure?

Answer 5

It is a failure to respond to gonadotrophins LH and FSH, causes low levels of estrogen being produced.

Requires Lifestyle Modification

Question 6

What are causes of ovarian failure?

Answer 6

1. Iatrogenic (ablation)
2. Genetic Causes (Fragile X, Turners XO)
3. Autoimmune (SLE, RA)
4. Physiological >45

Requires Induction of Ovulation

Question 7

What is the most common cause of anovulation? How? How do you deal?

Answer 7

Most common cause of anovulation is PCOS. This is hyperandrogenism which causes oligo or anovulation. The method of dealing with this is weight loss and ovulation induction

Question 8

Name some anatomical factors? Congenital.

Answer 8

Mullerian Duct abnormalities
Disorders of sexual development

These factors may require karoytyping

Question 9

What are some acquired anatomical factors, For example think tubular disorder?

Answer 9

Compromised tubular patency due to:

• Previous PID causing scarring ( CT, NG)
• Instrumentation post abortion PID
• IUD placement (PID)
• Appendicitis Peritonitis

Hydrosalpinx – dilation of a chronically obstructed tube – cause pain, prevent ovum transport through the affected tube and reduces chance of spontaneous conception through contralateral patent tube or IVF conceptions. Fluid in hydrosalpinx is toxic to the embryo and prevents implantation.

Question 10

What are other acquired anatomical causes?

Answer 10

Endometriosis - Adhesions distort or obstruct, impair fimbriae capturing eggs

Fibroids - Impinging of uterine cavity

Endometrial polyps, preventing implantation

Diagnosed by US, HSG or saline contrasts US
Gold standard is hysteroscopy D & C, which also enables treatment

Ashermanns Syndrome: Intrauterine Adhesions which are caused by curettage, infection or pregnancy: Presents as amenorrhea, dysmenorrhea and recurrent miscarriage. Increases the risk of placenta accrete. Diagnosed with hysterogram, sonogram or hysteroscopically. Management: Hysteroscopy with placement of IUD to estrogenise the lining.

Question 11

What happens to cervical mucus and egg quality as you age?

Answer 11

it decreases, remember that anti-mullerian hormone is a biomarker of ovarian reserve.

Question 12

What are other factors, which may lead to unexplained infertility?

Answer 12

Behavioural factors, lack of coitus

Immune factors

Question 13

Male Factor Infertility? What the male causes?

Answer 13

Hypothalamic Pituitary Dysfunction
Testicular failure with absent or reduced or abnormal sperm
Obstructive Azoospermia ( no sperm of spermatogenic cells in semen)

Question 14

What causes Hypothalamic Pituitary Dysfunction?
Congenital Cause?
Pituitary Issues?
What investigations would help us?
What immediate management may be applied?

Answer 14

Rare cause for infertility.
Congenital absence of GnRH producing neurons result in hypogonadotrophic hypogonadism which may be associated with anosmia – Kallman’s syndrome
Pituitary dysfunction resulting in disordered FSH and LH production can also occur:
Hyperprolactinaemia
Pituitary lesions
Anabolic steroid abuse – feedback of high androgen levels
Investigation:
Low serum testosterone, FSH, and LH.
Prolactin
MRI pituitary
Management:
Treat the pathology
Withdrawal of exogenous anabolic steroids
Administration of gonadotrophins

Question 15

Explain Testicular Failure

Answer 15

Impaired spermatogenesis may occur despite high or normal levels of gonadotrophins – suggests testicular dysfunction.
Congenital causes:
Congenital disorders of sex chromosomes (eg. Kleinfelter’s syndrome
Y chromosome microdeletions
Undescended testes
Testicular dysgenesis
Anorchia
Acquired causes:
Torsion
Trauma
Orchitis
Chemotherapy/radiotherapy
Diagnosis:
Raised FSH/LH in the setting of normal testosterone
Karyotype should be performed
Investigate for Y chromosome microdeletions
Prognosis: variable depending on whether sperm can be identified on biopsy of the testicle to allow the use of IVF with intra-cytoplasmic sperm injection

Question 16

What are obstructive causes?

Answer 16

• Cystic Fibrosis
• Epidydimitis
• Surgery
• Varicocele
• Should have normal testosterone, FSH and LH
• Treated with surgery or IVF using ICSI
• Laternatively can use donor sperm

Question 17

What is the agent used for ovulation induction? what does it do?

Answer 17

Anti-estrogenic effect, prevents negative feedback on estrogen receptors in the hypothalamus. There is a perception of estrogen deficiency and thus and increase in FSH and LH. Only effective if HP is intact.

• Clomiphene citrate ( use midluteal progesterone to monitor)
• Letrozole ( aromatase inhibitor)
• Tamoxifen (agonist at endometrium/ antagonist at HP)
• Metformin/ Insulin - used in pCOS

Following Clomiphene May use

2. Injection of Gonadotrophin LH and FSH, US and serum estradiol with close monitoring of multiple pregnancy is . It is a daily self injection
3. Laparoscopic ovarian diathermy - making small holes in the ovaries, avoids multiple pregnancy and ovarian hyperstimulation