Week 1: Fundamentals of Human Reproduction

Question 1

What cells do FSH and LH stimulate?

Answer 1

FSH: granulosa cells

LH: theca cells (until dominant follicle acquires LH receptors)

Question 2

What are the 3 ovarian and endometrial phases of the menstrual cycle?

Answer 2

Ovarian

1. Follicular
2. Ovulation: follows LH surge that tells granulosa cells in the cumulus oophorus to release enzymes to degrade the stalk…
3. Luteal: theca lutein and theca granulosa

Endometrial

1. Proliferative: in response to estradiol
2. Secretory: progesterone augments blood, mucin, glycogen
3. Atretic: loss of progesterone

Question 3

What is the average menstrual cycle length? What phase of the cycle is most likely to vary?

Answer 3

28 +/- 7

Variation is in the follicular phase- the luteal phase tends to be fairly constant

Question 4

la cycle menstruelle

Answer 4

Question 5

What are the cervical mucus changes following ovulation?

Answer 5

Goes from thin, stretchy and clear pre-ovulation (lets sperm through) to thick, scant, that blocks sperm passage

spinnbarkeit

highest probably of conception is -2 –> ovulation

Question 6

What are the mechanism by which ethinyl estradiol and progesterone prevent conception?

Answer 6

Ethinyl estradiol:

• Inhibits FSH release (and therefore follicular recruitment)

Progesterone

• Suppresses LH release (prevents ovulation) (40% of the time)
• atrophic glands and endometrium with continuous exposure (normally progesterone stabilizes teh endometrium and withdrawal causes menstruation. With continuous exposure endometrial vessels become thin and friable
• thickens cervical mucus (this is the normal state of cervical mucus in the luteal phase…)
• reduced tubal peristalsis

Question 7

What are the benefits of hormonal contraceptive as related to PID, ectopic pregnancy, epithelial ovarian cancer, endometrial cancer?

Answer 7

Decreases all of these!! In particular, risk of endometrial cancer is decreased by 80% and this lasts for 20 yrs after use

Question 8

Define fecundability. What are the normal odds of being pregnant after 3 mo, 6 mo and 13 mo of trying?

Answer 8

The probability of getting pregnant per menstrual cycle (20%)

3 mo= 50%

6 mo = 75%

13 mo = 95%

Question 9

What is the difference between primary and secondary infertility? What are the general causes of primary infertility?

Answer 9

Primary: the couple has never conceived

Secondary: the woman has previously conceived

25% male

25% tubal +endometrial + pelvic

25% ovulatory

Question 10

What is the initial approach to the infertile couple?

Answer 10

Semen analysis (volume, pH, concentration of sperm, motility, morphology (tyberg criteria)

hysterosalpingogram for tubal patency

document ovulation (body temp, midluteal progesterone, ovarian reserve (day 3 FSH), progestin challenge)

consider laparoscopy to r/o pelvic factors, like endometriosis

Question 11

What has the higher chance of getting a woman pregnant: superovultion + intrauterine insemination ,IVF with intracytoplasmic sperm injection (ICSI) or IVF with donor egg?

Answer 11

IVF with donor egg > IVF + ICSI > superovulation + intauterine insemination

Question 12

How to diagnose PCOS?

Answer 12

It is a diagnosis of exclusion. Have to have 2/3 of:

• lab of clinical evidence of androgen excess
• polycystic ovaries on US
• oligo/amenorrhea

Have to exclude:

• Cushing’s (am cortisol)
• Hypothyroid (TSH level)
• CAH (17-OHP)
• Hyperprolactinemia (galactorrhea + prolactin levels)

Question 13

What is the pathogenesis of PCOS?

Answer 13

Increased pulsatility of GnRH leads to :

• preferential release of LH over FSH
• theca cells make a ton of androstendione
• granulosa can’t metabolize into EE because there not enough FSH and the sheer volume is too much. The lack of EE inhibits follicular development.

Increased insulin leads to:

• decreased SHBG (combined with increased theca cell steroid production…the double whammy of androgen excess)

Question 14

How does clomiphene citrate treat infertility in PCOS? What is the risk of multips?

Answer 14

It is an anti-estrogen. It disinhibits the thalamus to make LH and FSH. WE don’t care about LH, it’s the FSH that helps a dominant follicle develop. 10% risk of multips

N.B weight loss is the first line treatment (if patient >BMI)

S/E: uterine lining things, cervical mucus thickens

Question 15

What are the treatments for the infertility and the androgen excess components of PCOS?

Answer 15

Infertility:

1. weight loss
2. clomiphene
3. metformin
4. FSH injections $$$, IVF, ovarian drilling (covered)

Androgen excess:

1. OCP: increases SHBG (does the opposite of insulin!)
2. Anti-androgens: spironolactone, flutamide

Question 16

Synopsis of follicular development

Answer 16

Non-cyclical (happens in utero)

• Primordial follicles–>primary unilaminar follicle

Cyclical

• primary unilaminar –> primary multilaminar–> secondary follicle–> Graffian follicle–> corpus luteum

Question 17

When in spermatogenesis do the cells go from 2n–>n

Answer 17

spermatocyte–>spermatid.

70 days in the tubules, 12 days of maturation

Question 18

What hormones are used for IVF

Answer 18

Give high dose FSH to stimulate follicle maturation.

Give GnRH antagonist when EE starts to rise: want to be able to trigger ovulation when we want.

Trigger ovulation with HCG (shares alpha unit with LH)

Collect eggs

Question 19

The simplest and most accurate test to confirm ovulation is?

Answer 19

A mid-luteal progesterone