Female Repro Physio (Day 2 - Fertility)

Question 1

What hormone has a negative feedback on FSH production and causes thickening of the endometrium?

Answer 1

Estrogen

Question 2

Describe the mechanism by which Clomiphene is a treatment for infertility.

Answer 2

Clomiphene is an estrogen receptor-alpha antagonist that blocks the E2-dependent negative feedback effect, so that FSH secretion can go on unhindered. This helps develop many pre-ovulatory follicles in which one may eventually make a viable oocyte for fertilization.

Question 3

What ovarian structure surprisingly still works despite the process of extracting and culturing the oocyte for in vitro fertilization (IVF)?

Answer 3

Corpus Luteum still functions to make Progesterone and estrogen despite oocyte retrieval being performed just before the day of ovulation.

Question 4

What hormone is more potent than LH to its own receptor? What is its clinical significance?

Answer 4

Human Chorionic Gonadotropin (hCG) binds more strongly to LH receptor and is supplied as an exogenous gonadotropin to control follicular growth. This is an early marker for pregnancy.

Question 5

Define primary amenorrhea. How does it differ from the secondary condition?

Answer 5

Primary amenorrhea is the status of a female that has never had a period. Secondary amenorrhea describes having had periods that abruptly stopped.

Question 6

Name some signs and symptoms associated with higher than normal levels of testosterone in women.

Answer 6

Severe facial acne and a lot of body hair.

A risk of dyslipidemia that can lower HDL, thus being a cardiovascular risk factor.

Question 7

List at least 3 signs associated with a loss of function in Estrogen-receptor-alpha?

Answer 7

Estrogen-resistant Syndrome is associated with…

1. High FSH and E2 levels - no negative feedback
2. Osteoporosis - lack of ER-alpha
3. Short stature - growth plates prematurely close

Question 8

What treatment can be provided to a woman with primary amenorrhea that results form a loss of ER-alpha?

Answer 8

Norethindrone = Progestin contraceptive would enable negative feedback to occur in order to disrupt the GnRH pulse generator. This lowers E2 and gonadotropins. It also reduces the size of ovarian cysts.

Question 9

What is the significance of days 20-24 in the menstrual cycle, in regards to pregnancy?

Answer 9

This is the window for implantation within the luteal phase that is brought upon by high E2 and P4 levels.

Question 10

What weeks are in the 3rd trimester of pregnancy?

Answer 10

Weeks 27-39 of gestation

Question 11

What weeks are in the 2nd trimester?

Answer 11

Weeks 13-26 of gestation

Question 12

What weeks are in the 1st trimester of gestation?

Answer 12

Weeks 1-12 of gestation after implantation.

Question 13

During what part of gestation is delivery supposed to occur?

Answer 13

Weeks 39-42 of gestation

Question 14

Describe the mechanism for maternal recognition of pregnancy.

Answer 14

At weeks 3-4 the neuroendocrine function in HPA shifts to the placenta. Placental GnRH stimulates trophoblast to secrete hCG which bings LH-R. This stimulates a potent LH activity at the corpus luteum to make A LOT of Progesterone which inhibits pituitary gonadotropins. This effectively stops the mother-to-be’s cycling pattern.

Question 15

What are the respective roles of Cortisol and DHEAS in the fetus? What stimulates the fetal adrenal gland to secrete these things?

Answer 15

Cortisol is essential for the development and growth of the fetus. DHEAS is a substrate for placental steroidogenesis to make Estriol (E3). The maternal P4 stimulates the fetal adrenal gland to secrete these products.

Question 16

Why does E3 supercede E2 in the 3rd trimester of gestation? What are these estrogens involved in at this time?

Answer 16

E3 is necessary for activation of uterine Estrogen receptor, when E3:E2 ratio increases to 10:1. They are involved in myometrial function and mammary gland development for lactation.

Question 17

Describe the functions of Progesterone (P4) in the mother during gestation.

Answer 17

P4 is the mother of all pregnancy hormones, necessary for maintaining a quiescent myometrium. It also increases intravascular volume, elicits vasodilation to perfuse the placenta, increases RBCs and maternal HR.

Question 18

During pregnancy, why is maternal central venous pressure and pulmonary artery pressure unchanged, despite the increased HR?

Answer 18

Cardiac output increases to match the increase in venous return and reduction in pulmonary vascular resistance, respectively.

Question 19

How does a pregnant woman’s cardiac curve reflect in terms of cardiac output and total peripheral resistance compared to non-gravid?

Answer 19

Increased CO (from HR) and decreased TPR (from vasodilation)

Question 20

Define the origin and effects of Relaxin.

Answer 20

Relaxin is a local vasodilator secreted from corpus luteum that, when combined with P4, vasodilates over Angiotensin II’s effect (that was stimulated by E2). This protein also softens the rib ligaments of the mother thus increasing the subcostal angle and decreasing FRC + ERV (restrictive pattern).

Question 21

What effect does Progesterone and E2 have on AVP? What are the downstream effects?

Answer 21

P4 and E2 increase AVP secretion from posterior pituitary that was activated by magnocellular neurons in the hypothalamus. AVP indirectly increases Cortisol levels and distal water reabsorption. The vasoconstrictive effects are hampered by CL’s Relaxin and Placental P4.

Question 22

How does pregnancy relate to glucosuria at the level of the kidney?

Answer 22

Pregnancy is associated with decreased vascular resistance and increased perfusion. This increases GFR which enables SGLT to saturate glucose resulting in glucosuria. It is also associated with low creatinine and BUN levels.

Question 23

List some factors that decrease TPR from the 2nd trimester to the time just before delivery.

Answer 23

Relaxin, Estrogen, Progesterone, Nitric Oxide decrease TPR and diastolic pressure during this time of gestation.

Question 24

List at least 5 factors that control arterial blood gases.

Answer 24

Cardiac output (Q), ventilation (V), diffusion, Hb content, pH, temperature, 2,3-BPG

Question 25

How does increased levels of Progesterone in the expecting mother increase RR?

Answer 25

Progesterone increases basal body rate which increases CO2 in blood. This stimulates carotid body chemoceptors to send hypoxic signals to medullary respiratory centers. This finally stimulates minute ventilation and tidal volume.

Question 26

What is the consequence of decreased PaCO2 levels during pregnancy?

Answer 26

PaCO2 levels at around 26-32 mm Hg results in a respiratory alkalosis that is compensated at the kidneys by HCO3 excretion.

Question 27

What is the maternal acid-base status during a healthy pregnancy, that might seem abnormal in a non-gravid state?

Answer 27

Chronic Respiratory Alkalosis:

HCO3 (18-21), PaCO2 (26-32), pH (7.44-7.45)

Question 28

What is the physiologic significance of the shifts in the Oxygen-hemoglobin saturation curves? (In terms of maternal to fetal O2 transfer).

Answer 28

2,3-BPG production from the increased maternal metabolism as well as rising temperature leads for the maternal curve to shift right. This enables O2 offloading that supplies O2 to the fetus instead.

Question 29

What feature of the pregnant female’s cardiovascular system prevents the bad outcomes that can result form increased cardiac output and intravascular volume?

Answer 29

Vasodilated state maintained by Progesterone and Relaxin.

Question 30

Describe 2 reasons why placental CRH is so important in the hormonal regulation of labor.

Answer 30

Placental CRH stimulates Cortisol…

1. To cause the myometrium to start contracting (labor)
2. To promote fetal surfactant production and maturation

Question 31

Describe at least 2 hormonal mechanisms that can lead to myometrial contractions.

Answer 31

1. DHEAS secreted by the maternal adrenal gland, which is predominated by the fetal adrenal gland’s DHEA.
2. Oxytocin, Prostaglandins or Effective P4 withdrawal can stimulate the myometrium to contract as well.

Question 32

Name at least 4 functions of Relaxin produced by the Corpus Luteum.

Answer 32

1. Maternal Vasodilation
2. Maternal Rib Ligament Softening
3. Pelvic Ligament Softening
4. Cervical Opening (preceding labor/delivery)

Question 33

How does the placenta stave off the potentially harmful effects of maternal cortisol?

Answer 33

Placenta expresses the 11-Beta-HSD2 enzyme (also expressed in kidney) that converts cortisol into inactive cortisone. This lowers the affinity for glucocorticoid receptor thus reducing Cortisol’s effects on the fetus.

Question 34

Describe 3 ways that pregnant women can manage preterm labor contractions.

Answer 34

1. 17-alpha-OHP4 = progestin that stimulates quiescence of myometrium
2. Corticosteroids = fetal development via organ growth
3. Tocolytic agents = competitive inhibitor of Ca++ reduce muscular contractions

Question 35

What week is the cutoff for preterm survival and what trimester of gestation does this fall in?

Answer 35

Week 24 near the end of the 2nd trimester (weeks 13-26) is the preterm survival cutoff.