Monica Moore MSN RNC Fertile Health LLC Objectives Part 1 The normal hypothalamicpituitaryovarian axis HPO Axis Distinguish the structures of the HPOA and describe how they interact as a feedback cycle ID: 1000348
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1. The HPO Axis/Menstrual Cycle BasicsMonica Moore, MSN, RNCFertile Health, LLC
2. ObjectivesPart 1: The normal hypothalamic-pituitary-ovarian axis (HPO Axis)Distinguish the structures of the HPOA and describe how they interact as a feedback cycleDiscuss the major hormones involved in the HPOA
3. ObjectivesPart 2: The Menstrual CycleIdentify the major hormones of the menstrual cycle and describe their major functionsExplore the different phases of the menstrual cycle-ovarian and uterine
4. ObjectivesPart 3: Female Fertility Identify the basic principles of female fertility as they relate to the HPOA and menstrual cycle
5. Part 1: the HPO Axis
6. Hypothalamic-Pituitary-Ovarian AxisCoordinated by system of feedback loopsDependent upon the interaction of the hypothalamus, pituitary gland, and ovaries
7. HPO Basics: The HypothalamusDrives the cycleSecretes Gonadotropin Releasing Hormone (GnRH) in a pulsatile manner every 60-120 minutesAltering the amplitude or frequency of the pulses can trigger negative or positive feedbackAlso secretes TRH, CRH and other hormones (influences thyroid and adrenal function) and metabolic homeostasis.CRH
8. HPO Basics: The Anterior PituitaryHypothalamus acts on anterior pituitary gland to secrete gonadotropins: follicle stimulating hormone (FSH) and luteinizing hormone (LH) And TSH and PRLPRL
9. HPOA BasicsThe anterior pituitary acts on the ovary to secrete estradiol and progesterone
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11. Hormones of the hpo axis
12. FSHStimulates the follicles to growInduces LH receptors on folliclesIncreases estrogen and inhibin secretion
13. LHAids in follicular growth(Increases androgens)Causes ovulation to occurSustained E2 levels-change to positive feedbackCauses the Corpus Luteum to secrete progesteroneActivates and matures eggs that are “frozen” in Meiosis 1
14. Ovulation in Relation to LH Surge 24-36 hours after E2 peak10-12 hours after LH peakOvulation occurs:
15. EstrogenEstrogen is made by the granulosa cells in the follicleCauses the lining of the uterus to growFeeds back to the Hypo and Pituitary to regulate GnRH, FSH and LH secretionStops menstrual bleeding
16. Ovarian FolliclesOvarian follicles found in the cortex (outer part of ovary).
17. Ovarian FolliclesEach follicle consists of an oocyte surrounded by layers of granulosa and theca cellsDominant follicle acquires highest concentration of FSH receptors
18. Estrogen Production
19.
20. Peak E2E2>150 to 250 pg/ml> 36 hours results in LH surge
21. ProgesteroneProgesterone is made by the Corpus LuteumFeeds back to Hypo and Pit to regulate GnRH, FSH and LH secretionIs secreted in small amounts by growing follicleStops the growth of the endometrium and causes it to secrete substances to support an early pregnancy
22. P4 Relative to Initiation of LH Surge 0.3 at surge1 @ 24 hours3 @ 48 hours
23. Part 2: Menstrual Cycle basics
24. Menstrual Cycle Basic TermsNormal Values:Duration: 28 +/- 7dAmenorrheaOligomenorrheaIntervals >35 daysPolymenorrheaIntervals < 21 days
25. Phases of Menstrual CycleProliferativeSecretoryFollicularLuteal
26. Menstrual Cycle BasicsFollicular phase is variableCorpus Luteum has a finite lifespan (14d) unless rescued by hCGE and P start to drop 7d prior to mensesMenses starts about 3d after P <1 ng/ml
27. Uterine PhasesProliferativeSecretory
28. Ovarian and Uterine Events are Highly Synchronized
29. Window of ReceptivityIn a natural cycle, ovary and uterus in synchrony, so need to replicate this in stimulated cycle.It closes prematurely if:Endogenous P4 is elevated at triggerExogenous P4 is given too earlyTiming of P4 “starts the clock” and can alter the window
30. Part 3: Female fertility: basic principles
31. Female Fertility: Basic PrinciplesHPO Axis needs to be functioning properlyUterus needs to be receptive to hormonal stimulation and implantation.Cervix needs to allow the entry of spermOvaries need to have viable follicles that respond to hormonal stimulation and ovulate
32. The Infertility EvaluationMenstrual historyDay 3 FSH, LH and E2 (normal levels depend on lab assay)E2<70FSH<10LH<10Luteal Prog level?Evaluation of uterine cavity
33. Luteal Phase DefectHow do you determine this?Low luteal progesterone levels? Endometrial biopsyHistology results are subjectiveGives limited information i.e. dating of endometrium, but receptivity is only implied
34. Principles of SuperovulationIn gonadotropin-treated cycles:Small (<10 mm) follicles need constant, exogenous FSH in order to grow and matureFSH levels rise and stay elevated until trigger shotOnce follicles reach 10-12 mm, granulosa cells become receptive to LH stimulationMaturing follicle may become less dependent on FSH at this point*Stanger, et al, 1985; Howles et al, 1986; Regan, et al, 1990
35. Nursing ConsiderationsThe fact that a woman has regular cycles has no bearing on her ovarian reserve and her risk for aneuploidy.
36. Day 2-4E2<85P<2.5bHCG<5Day 10-12“Midcycle”E>150 (unless femara)P<3LH<15Day 19-21“luteal levels”E>120P>12Mature follicle=20 mm (but ≥ 15 mm responds to trigger shot.Endo lining ≤ 5 mmEndo lining ≥ 7 mmType 1-2 (trilaminar)
37. A word about amh
38. AMHAnti-Mullerian Hormone (AMH) or Mullerian Inhibiting Substance (MIS)What does it do?Primary role: regression of mullerian ducts in male fetus AMH expression is produced by ovarian granulosa cellsAMH levels are predictive of ovarian responseHigher = betterLower = worse (opposite of FSH)Cycle IndependentNo need to draw on certain cycle days
39. How Do We Counsel Pt’s?AMH LevelOvarian Reserve?Implications for Pt:0.1-0.3Severe DORTreat as if FSH>140.3-1.0Gray RangeTreat As if FSH ≈10-131.0-3.5NormalTreat as if FSH <10>3.5PCOS?OHSS precautions
40. ConclusionThe hormones produced by a normally functioning hypothalamic-pituitary-ovarian axis (HPO Axis) interact in a feedback cycle. The menstrual cycle is a result of ovarian and uterine synchronyWhen there is a disruption in the HPO axis, it can result in ovulatory dysfunction.
41. Question and Answer Session
42. Q & AIn the early follicular phase, which hormone is responsible for follicular growth?EstrogenProgesteroneLHFSH
43. Q & AKeeping in mind the 2 cell theory, LH acts on which cells to produce androgens as a substrate for estrogen formation?SertoliGranulosaThecaLeydig
44. Q & AWhich of the following hormones provide feedback to the pituitary to decrease FSH secretion?GnRHLHEstrogenInhibin
45. Q & AWhat is the name of the process by which androgens get converted to estrogen in the ovary?Aromatization
46. Q & AThe secretory phase of the endometrium is dominated by the presence of which hormone?ProgesteroneWhat is the name of the hormone that “rescues” the corpus luteum?hCG
47. Q & AWhich of the following is NOT true about AMH?It is responsible for the regression of the Mullerian ducts in XY malesIt is elevated in women with PCOSIt should be checked on day 3 with the FSH levelIt is made by small, antral follicles