Ovulatory Dysfunction Flashcards
Review menstral cycle
A menstrual cycle begins with the first day of genital bleeding (day 1; menses) and ends just before the next menstrual period. The median menstrual cycle length is 28 days but ranges from 21 to 35 days.
What happens when a woman doesn’t get pregnant to hormones and endometrium
No hCG gets secreated from luteum, thus progesterone drops and we slough off the lining
What are key hormones during the Follicular phase?
See rise in estradiol leading to the LH surge and peak
this is the proliferative phase of the uterine endometrium
What occurs during the luteal phase?
see LH and FSH go down and Progesterone rise
this is the secreatory phase of the endometrium and build up of lining till sloughing at day 28
The diagnosis of anovulation or ovulatory dysfunction can commonly be made ________ Menstrual bleeding occurring at regular intervals between 21 and 35 days, particularly in the presence of premenstrual moliminal (i.e., breast tenderness, abdominal bloating, mood disturbance) is suggestive of ovulation; bleeding at longer or irregular intervals generally reflects anovulation.
solely on the basis of history.
If the estrogen status of the patient is unclear from the physical examination, a ________ test can be arranged at the same time as the initial blood work.
progestin challenge
Medroxyprogesterone acetate (5 to 10 mg) is adminsted to asses
is administered daily for 7 to 14 days, after which a menstrual bleed should ensue in normally estrogenized patients. Any amount of spotting or bleeding in the 2 weeks after progestin withdrawal is considered a positive progestin challenge.
Your pt has irregular menses and you adminster the progestin challenge. She has no bleeding in the next two weeks. What’s going on?
Most likely hypothalamic amenorrhea leading to ovulatory dysfunction
You are seeing a pt that hasn’t had her period and she is 20 years old. What are the key hormone tests you want to run on top of getting a thorough history?
Get TSH, Prolactin, day 3 FSH and BhCG
You have a pt with amenorrhea and run her FSH levels which are elevated, you run them again one month later and confirm she does have elevated FSH. What is the diagnosis?
Premature Ovarian Failure
Your pt has lack of menstral cycles, you asses her hormone levels and they are normal, you perfrom a progestin challenge and she has spontaneous menses or a + test. What path does this lead us down?
Ovulatory dysfunction
Your patient responded + to the progestin challenge leading you to believe there is ovulatory dysfunction. What would lead you to believe she has PCOS?
Look at biochemical androgen levels or she would have bad acne, hirutism, signs of androgen excess
What do we seen to look at when evalulating for oligo/amenhorrhea
- History and physical exam
- Pregnancy test
- Baseline (day 3) Follicle Stimulating Hormone, Estradiol
- Thyroid stimulating hormone
- Prolactin
Role of the TRH in ovulation dysfunciton
TRH will also stimulate secreation of prolactin which in turn can inhibit GnRH
Thyroid is key for metabolism, devo and steroidogenesis
Beside the progestin challenge, what else can we look at to assess adequate estrogen exposure?
Pelvic ultrasound to demonstrate endometrial thickness
Your pt has withdrawl bleed to progesterone and her FSH, estradiol and prolacint and thryoid levels are normal. ON pelvic ultrasound, her ovaries look like they have cycts all over, Dx?
Polycystic ovarian syndrome
A 30 year old woman with eplilepsy and seizures partially controlled by carbamensepine presents for contraception counseling. What is the best method for her?
Copper IUD bc helps with seizure control
The most common endocrine cause of infertility and irregular menstrual cycles
Polycystic Ovarian Syndrome
What do you need to have to be dx with PCOS?
Need to have 2 of the 3
• Polycystic-like ovaries on ultrasound
- Oligomenorrhea
- Hyperandrogenism
You are working up a pt you expect has PCOS, what causes of hyperandrogenism and oligomenorrhea need to be excluded
- Testosterone secreting tumor
- Congenital adrenal hyperplasia • Thyroid disease
- Hyperprolactinemia
- Cushings’ disease
- Hypothalamic amenorrhea
- Premature ovarian insufficiency
Pt with PCOS needs treatement and is not intersted in getting pregant at this time. what tx do you recommend?
Counsel regarding health risks
• Treatment for endometrial protection: Cyclic progestin and OCP
Your pt was just dx with PCOS and is trying to concieve with her partner. What tx is recommend for her?
- Weight loss recommended as first line therapy in obese women with PCOS seeking pregnancy
- Weight loss is associated with improved ovulation rates in women with PCOS
***Clomiphene
What medical tx is recommend for pt with PCOS who are trying to concieve?
Clomiphene
- First line of treatment in PCOS
- Low cost
- Patient-friendly oral route
- Relatively few adverse effects
- Abundant clinical data regarding safety
MOA of Clomiphene
• Reduces concentration of intracellular estrogen receptors
- Diminishes negative feedback
- Activates mechanism for GnRH secretion
Indicated in:
(1) induction of ovulation in women with anovulatory infertility, and
(2) stimulation of multifollicular ovulation or enhancing ovulation in ovulatory infertile women (e.g., unexplained infertilit Clomiphene Citrate
Clomiphene Citrate
Negative side effects of Clomiphene
hot flashes, bloating, cramping, nausea, mood swings, and rarely visual disturbances.
multiple pregnancy after CC is between 4-10%.
rare risk of Ovarian Hyperstimulation Syndrome
Anti estrogen: endometrial thinning and cervical mucus
Non FDA approved method for ovulation induction with lower rates of multiples dt monofollicular ovulation induction
Aromatase inhibitors
Patient comes in with normal prolactin and thyroid function. Her FSH is elevated and estradiol is LOW. What is the cause of this pts irregular menstral cycles?
Patient has premature ovarian insufficiency and is approaching menopause
Pt is given the progestin challenge with Medroxyprogesterone acetate for 10 days: she did not have withdrawl bleed. This is most likely due to
Atrophic endometrium d/t lack fo ciruculating estradiol
reasons for lack of withdrawal bleeding in response to progesterone therapy
- Lack of circulating Estradiol resulting in inadequate endometrial proliferation thus wont respond to increase in progestin
- Severe endometrial adhesions
- Pregnancy
• Condition of low/normal FSH and low estradiol
- Absence of sellar mass
- May be Stress or weight related
Hypogonadotropic hypogonadism
Pathophysiology of Hypogonadotropic hypogonadism
Condition of low/normal FSH and low estrodiol and absence of sellar mass
Causes of hypogonadotropic hypogonadism
- Kallman’s syndrome- congenital GnRH deficiency
- GnRH receptor mutations
- Treatable with injectable gonadotropins
or stress/weight releated
defined as hypergonadotropic hypogonadism before age 40, commonly but not uniformly associated with depletion of ovarian follicles, as is seen in menopause. It results in cessation of regular menses. This condition affects approximately 1% of all women, with 90% of cases occurring between ages 30 and 40.
Premature ovarian failure (POF) or premature ovarian insufficiency (POI)
can obliterate the endometrial cavity and produce secondary amenorrhea and most likely to result from procedures that can damage the endometrial cavity.
Intrauterine adhesions (IUAs) or synechiae (Asherman’s syndrome)
What do we see with Intrauterine adhesions or Ashermans syndrome
Can obliterate the endometrial cavity and produce secondary amenorrhea
Can result in lack of withdrawal bleed in response to progesterone if patient is amenorrheic
• Most likely to result from procedures that can damage the endometrial cavity.
Causes of Premature Menopause/ Prematuer ovarian Insufficiency (POI)
- Genetic
- Chromosomal number: 45X or 45X/XX (Turner’s syndrome and Turner’s mosaic)
- Fragile X
- Autoimmune
- Iatrogenic (treatment-related) • Chemotherapy
- Radiation
• Idiopathic
What hormone triggers ovulation?
LH
premutation carriers are at an increased risk for premature ovarian failure, with an incidence of 16% to 21%. Expansion of a triplet repeat within exon 1 of the FMR1 X-linked gene causes this syndrome. Expansions of between 50 and 200 repeats are premutations.
Fragile X syndrome
Many individuals with POI (30-50%) also have an
autoimmune disease such as hypoparathyroidism, Hashimoto’s thyroiditis, Addison’s disease, vitiligo, myasthenia gravis, Sjögren syndrome, systemic lupus erythematosus, celiac disease, rheumatoid arthritis, or pernicious anemia.
Reproductive option in pts with premature ovarian insufficiency
oocyte donation, adoption, extremely low likelihood of spontaneous conception
Three most common causes of infertility in couples
Ovulatory, Tubal and Pelvic, Male factor
Time table of expected pregnancy:
3 months:
6 months:
1 year
2 years
3 months: 57%
6 months: 72%
1 year: 85%
2 years: 95%
• Usually determined by menstrual history
- Anovulation
- Oligoovulation
- Early Ovulation/dysfunctional cycle
all ovulation disorders
What happens to ovarian reserve with increasing age?
Acceleration of follicular loss, depleation of oocyte pool and decreased oocyte quality
How do we test for ovarian reserve?
Perform a Day 3 FSH/Estradiol level
Antral follicle couts
Anti-Mullerian hormone level
Day 2 or 3 Follicle Stimulating Hormone (FSH) and Estradiol
-An ____ FSH and/or estradiol is consistent with diminished ovarian reserve due to the hypothalamic-pituitary-ovarian feedback loop
elevated
This beta-glycoprotein is synthesized by granulosa cells in small antral and preantral follicles in the ovary and is directly proportional to a woman’s ovarian reserve.
Antimullerian Hormone
What tests can be done to eval uterine and tubal anatomy?
Risk factors for tubal disease
• History of pelvic infections
- Tubal or pelvic surgery
- Endometriosis
What three pt populations would benefit from Intrauterine insemination or IUI
Mild male factor infertility
Women with cervical mucus abnormalities
Couples with unexplained infertility
Patients often treated with ovulation induction medications prior to IUI
What are indications for IVF?
- Severe male factor
- Tubal disease
- Endometriosis
- Diminished ovarian reserve
- Unexplained infertility
- Failed more conservative measures
Overview of IVF
- Ovarian stimulation with injectable gonadotropins :FSH, HMG (LH/FSH)
- Oocyte retrieval
- Fertilization
- Embryo transfer
is indicated for ovulation induction in
(1) Patients who have hypothalamic amenorrhea,
(2) Anovulatory patients who do not respond to Clomiphene citrate or aromatase inhibitors, or
(3) Patients undergoing hormonal stimulation for in vitro fertilization or less commonly for purposes of multifollicular recruitment to be paired with intrauterine insemination.
Gonadotropin therapy
Pergonal, Humegon, Menopur are all examples of
Human menopausal Gonadotropin :
(1) Patients who have hypothalamic amenorrhea,
(2) Anovulatory patients who do not respond to Clomiphene citrate or aromatase inhibitors, or
(3) Patients undergoing hormonal stimulation for in vitro fertilization or less commonly for purposes of multifollicular recruitment to be paired with intrauterine insemination.
are also approved for preventing the LH surge during controlled ovarian hyperstimulation.
The GnRH antagonists (ganirelix and cetrorelix )
Bravelle, Metrodin,Gonal-F, Follistim
all examples of FSH
s administered intramuscularly to induce follicular maturation and ovulation.
hCG
