206/207: Female and Male Infertility

Question 1

How does testosterone excess affect sperm levels?

Answer 1

Excess testosterone → decreased sperm

• Testosterone inhibits GnRH, LH/FSH via negative feedback
  
  • Brain sees enough testosterone, shuts down the axis
  • Gonadotropins LH and FSH are needed for spermatogenesis
• Most commonly from anabolic steroids.

Question 2

How does a varicocele affect sperm production?

Answer 2

Impairs sperm production through hyperthermia

• Varicocele causes blood to pool in the piniform plexus
• More blood = increased testicular temperature
  
  • Disrupts the counter-current heat exchange
• -> impaired sperm production

Tx = surgical intervention or radiologic embolization

Question 3

What causes Asherman’s syndrome?

Answer 3

Uterine scarring, usually iatrogenic

Can interfere with fertility

Question 4

How does marijuana affect sperm count?

Answer 4

Decreased, due to suppressed LH and testosterone

Question 5

How does prolactin excess affect sperm levels?

Answer 5

Prolactin inhibits hypothalamic GnRH secretion

• -> Decreased LH/FSH
• -> Decreased spermatogenesis
• Clinical sign is gynecomastia

Question 6

What is the prevalence of infertility?

Answer 6

15%

Question 7

What genetic testing should be ordered for men with congenital bilateral absence of the vas deferens (CBAVD)?

Answer 7

CFTR mutation - likely that they are a carrier

Test BOTH partners

• Even if pt with CBAVD is negative for known CFTR mutations, they may be a carrier of an unidentified mutation; need to know CFTR status of partner
• Carrier of CFTR mutation can have CBAVD without other symptoms*

Question 8

Which aspect of fertility is most affected by maternal age?

Answer 8

Egg quality and quantity

Decreased ovarian reserve

Poor egg quality (higher risk of aneuoploidy-→ miscarriage)

Note: uterus largely unaffeted; donor eggs have the same success rate in older vs. younger uteri

Question 9

Describe the clinical features of congenital bilateral absence of the vas deferens

Answer 9

• Missing vas deferens, distal 2/3 of epididymis, seminal vesicle
• Infertility
• Likely a carrier of CFTR mutation
• Semen sample will have low pH, low ejaculate volume, azospermia

Question 10

What are the most common causes of infertility in a person with a uterus?

Answer 10

• Anatomic abnormality
  
  • Uterine and/or fallopian tube
• Ovulatory dysfunction

Also aging (decreased ovarian reserve)

Question 11

Define infertility

Answer 11

Inability to conceive after one year of unprotected intercourse

Note: For female patients 35 and older, consider intervention after 6 months without conceiving - don’t want to waste time

Question 12

Which part of the hypothalamic/pituitary/gonadal axis is interrupted in hypothalamic amenorrhea?

Answer 12

Pulsatile GnRH secretions from the hypothalamus

This is when the body is stressed out (too much exercise, anorexia, too much work/life stress)

Remember that both absent and continuous GnRH secretions will inhibit LH/FSH secretion

Question 13

What is the most effective form of male contraception?

Answer 13

Vasectomy (cut the vas deferens)

Pull out method and/or condoms have higher failure rates b/c may not always be properly executed (obviously)

Question 14

What is the best treatment option for a woman with bilaterally blocked fallopian tubes who wishes to conceive a child?

Answer 14

IVF

No way for the eggs to get to the uterus/meet a sperm

Age and ovarian reserve play a role in likelihood of success

Question 15

Is a vasectomy immediately effective?

Answer 15

NO!

• Must check to make sure ejaculate has few (<100,00) nonmotile after 4 months
  
  • Takes time to clear all the sperm hanging out in the system
• Surgery is a failure if any motile sperm persist at >6 months; repeat procedure

Question 16

How long does it take after fever for sperm levels to return to normal?

Answer 16

Up to 3 months

Hyperthermia messes up spermatogenesis at all stages. Have to start over and replenish

If a pt has abnormal semen results <3 months after fever, rechek later

Question 17

Sperm count below ___ is an indication for karyotype testing

Answer 17

Sperm count below 5 million is an indication for karyotype testing

Could be Kleinfelter (47, XXY) (Small firm testes, gynecomastia, azospermia)

Or microdeletions on the y-chromosome

Question 18

What is the first line treatment for ovulation induction in a patient with PCOS?

Describe the MOA

Answer 18

Letrozole

• Oral non-steroidal aromatase inhibitor
  
  • Aromatase converts testosterone to estrogen
• Decreased estrogen level -> brain releases more LH/FSH
• Ovulation!

Question 19

List the steps of a complete evaluation for infertility in a person with a uterus

Answer 19

• History
• Physical
• Assess uterine cavity
• Document tubal patency
• Confirm ovulation
• Assess ovarian reserve

Order of evaluation depends on the patient

Ex: history of PID→ more worried about tubal patency

Question 20

What is the MOA of clopiphene citrate?

Answer 20

Selective estrogen receptor modulator (SERM)

• Blocks hypothalamic estrogen receptors
• This tricks the brain into thinking there isn’t enough estrogen
• -> Increased LH and FSH
• -> induces ovulation

Question 21

What is the most common genetic caues of azoospermia?

Answer 21

Klinefelter syndrome (47, XXY)

Question 22

How will semen differ in retrograde ejaculation vs. ejaculatory duct obstruction?

Answer 22

Both: Low ejaculatory volume

• Retrograde ejaculation
  
  • Normal semen pH (≥7.2)
• Ejaculatory duct obstructions
  
  • Acidic semen pH => seminal vesicle secretions are not getting into the ejaculate
  • Seen in CBAVD (congenital bilateral absence of the vas deferens, seen in CFTR carriers)
• Prostate secretions are acidic*
• Seminal vesicle secretions are alkaline*

Question 23

At what age does fertility peak in a person with a uterus?

When does it begin to significantly decline?

Answer 23

20-24 years old

Significant decline begins at 30-32ish

OH NOOOOOOOOO. :((

Question 24

What are the downsides of injectable gonadotropins?

Answer 24

Increased risk of multiple pregnancies

Work too well! Ovaries likely to develop >1 follicles

BUT, are used in IVF treatments when want to harvest as many eggs as possible

Question 25

What are the different treatment options for obstructive vs non-obstructive azospermia?

Answer 25

Obstructive: surgically correct the obstruction if feasible (sperm are there, just need the open pathway)

Nonobstructive: microTESE + IVF/ICSI (not making many sperm at all, need to find them and directly combine with eggs)