Patho/Pharmacology of Infertility Flashcards
Define infertility
Inability to conceive after 1 year of frequent contraception-free intercourse
15 months with oral contraceptive use
Define Primary infertility
Couple has never conceived a child
Define Secondary infertility
Couple has previously conceived a child and is unable to achieve a new pregnancy
About 10% of US women experience
Some degree of impaired fertility
Conception rates and male partners?
Conception rates decrease with age and 30-40% of couple infertility are the male’s fault
Why are normal menstural cycle necessary?
Sufficient estrogen in follicular phase so you have good endometrial lining and thin cervical mucus
Sufficient progesterone in luteal phase for oviducts and uterus accept the egg
Appropriate FSH and LH
Factors that contribute to female infertility?
Delay in childbearing
Contraceptive practices
High risk sexual practices
Increase in therapeutic abortions
What else can cause female infertility?
Chronic hypothalamic dysfunction Hyperandrogencity, PCOS Pelvic Inflammatory disease Endometriosis/adhesion Hyperprolactinemia Drugs Immunologic reactions Age-related changes Infectious disease Environmental toxins or recreational drugs
Define Chronic Hypothalamic Dysfunction
Causes anovulation and menstrual problems with normal prolactin and androgen levels
Cyclic secretion of GnRH is impaired which interferes with normal function of the HPO axis
Chronic Hypothalamic Dysfunction is caused by
Weight loss >15% or eating disorder
Intense exercise Stress
Define Hyperandrogenicity
Polycystic Ovarian Syndrome
Increased LH levels which cause stimulation of follicular production of androgens which leads to anovulation by enhancing follicular atresia
Define Hyperprolactinemia
Turns down GnRH secretion
Define Hypothyroidism
Leads to hyperprolactinemia
Drugs stimulate?
prolactin secretion
What decreases prolactin synthesis?
Dopamine
When will a patient workup for infertility occur
12 months after trying
OR known/suspected uterine/tubal disease or endometriosis, female >35, history of oligomenorrhea/amenorrhea or pelvic inflammatory disease, partner is known to be subfertile
Define Oligomenorrhea
Less than 9 periods a year
What is involved in a female evaluation
Medical, surgical, family and social history PE Screen for chlamydia and gonorrhea Confirm ovulation Hysterosalpingogram
Define Hysterosalpingogram
Fluoroscopic and radiographic visualization of the interior of the upper genital tract
Basal Body Temperature Counseling
Each morning before any activity or getting out of bed
Measure to the nearest 0.1 degree
Rise of 0.4-0.6 indicated ovulation occured
Basal Body Temperature Charting
Progesterone production by the corpus luteum causes the BBT to raise during luteal phase (after ovulation
Counseling for Ovulation Kits
Measures LH in urine
Clear blue fertility monitoring
Daily monitoring
Fertility scope monitors via
saliva
First response monitors
FSH on day 3
OvWatch measures
chloride levels in sweat
SpermCheck
MALE sperm count test
Define Hyperprolactinemia
Depresses GnRH secretion; lowers LH and FSH secretion; compromises testosterone and sperm
What can cause Male Infertility?
Endocrine disorder Anatomical or ejaculation problems Low sperm count or immotile sperm Psychological problems Lifestyle issues (tight unders
Semen Analysis
Abstain from ejaculation for 2-3 days before test
- Volume, viscosity, density, morphology and motility
- Abnormal results should be confirmed on 2-3 evals
Non-pharm treatment of Male infertility
Reduce BMI <30
Females avoid NSAIDs and ASA before or around the time of ovulation
Anything that causes hyperprolactinemia or impair spermatogenesis
Avoid lubricants
Intrauterine Insemination
Sperm are separated from semen and better quality sperm are extracted for insemination
Sperm is injected trans-cervically into uterus
AFTER ovulation
Assisted Reproductive Therapy (ART)
Direct retrieval of oocytes and manipulation of sperm to achieve pregnancy
Not very common
1+ Egg transferred
Types of ART
In Vitro Fertilization and Embryo Transfer
Gamete Intrafallopian Transfer (GIFT)
Zygote Intrafallopian Transfer (ZIFT)
What is GIFT/ZIFT?
Placement of human ova and sperm or zygote into the distal end of the oviduct
Fertilization occurs within the Fallopian tubes
What is IVF
Fertilization of the egg is done in the lab and then fertilized egg is placed in the fallopian tube
If it works, it will then implant into the uterus
Clomiphene citrate
Non-steroidal estrogen receptor modulator
Blocks feedback inhibition of the hypothalamus
Raise FSH and LH levels
Gonadotropin therapy Examples
Menotropin and urofollitropin
Clomiphene citrate MOA
Anti-estrogen
Blocks estrogen inhibitory activity at pituitary and hypo and releases feedback inhibition at these tissues
Upregulates LH, FSH and GnRH
What does upregulation of LH, FSH, GnRH cause?
Enlargement of the ovaries and drug induced ovulation
How is clomiphene citrate eliminated?
Metabolites via CYP 2D6
5-7 day plasma life
Common adverse reactions in clomiphene citrate?
Hot flashes
Ab discomfort, visual blurring
Reversible ovarian enlargement and cyst formation
Letrozole (Femara) is what class?
Aromatase inhibitor
Letrozole (Femara) MOA
Inhibit testosterone to estradiol
Decrease estrogen stimulates release of FSH and LH
Letrozole (Femara) Side Effects
Hot flashes
Headaches
Breast tenderness
Counseling points for Clomiphene and Letrozole
Ovulation expected 5-10 days after last dose and intercourse should occur every other day for 1 week
Monitor ovulation is key
Gonadotropins
Relatively safe
Expensive and IV
Require extensive monitoring
Gonadotropins include:
LH, FSH and hCG
Gonadotropins Structure
Each hormone is glycosylated heterodimer and contains a common alpha and beta subunits
Gonadotropins MOA
Male: stimulates spermatogenesis
Female: FSH - maturation and development of the follicle; LH - ovulaiton and stimulates corpus luteum
Requirement for gonadotropin treatment?
Ovaries must be able to respond normally to FSH and LH
hCG works well in?
Women who have infertility due to lack of midcycle gonadotropin surge
hCG works how?
Identical action as LH with a longer half life
Male: spermatogenesis who have hypofunction in pituitary
hCG Adverse Effects
Headache Irritability Restlessness Fatigue Edema Gynecomastia Pain at injection site
GnRH
Gonadorelin (Lutrepulse)
Administered via portable pump (SC/IV)
EXPENSIVE
GnRH Drugs Advantage?
They match the natural ovulation induction more closely and minimal monitoring
GnRH Side Effects
Tachyphylaxis (pituitary cells are less responsive)
Hyperstimulation
Multiple gestations
Define Ovarian Hyperstimulation Syndrome
Enlarged ovaries with multiple developing follicles
Increased level of growth factor and hormone which increase permeability of blood vessels which moves the fluid form the vascular to the abdominal and pleural cavities
GnRH Agonists Examples
Goserlin (Zoladex) Nafarelin (synarel) Histerlin (Vantas, Supprelain) Buserelin (Suprefact) Triptorelin (Relstar) Leuprolide (Lupron END IN -LIN
GnRH Agonists Advantage
After stimulation of Gn they down regulat the receptor and inhibit secretion which is good in PCOS due to decrease number of oocytes are released prematurely and increased quality
GnRH Agonists AE
Vaginal blleding and breast tenderness
Hot flashes, headache vaginal dryness
GnRH Antagonists Examples
Abarelix (Plenaxis)
Cetrorelix (Cetrotide)
Ganirelix (Antagon)
Use of GnRH Antagonists?
Prevent premature LH surge or premature ovulation
Suppresses LH surge
Estrogen use
Stimulate endometrial growth and cervical mucus production
Progestin use
Promote endometrial development and maintenance during luteal
Metformin use
Restore menstrual cycle and ovarian function
Guanifenesin use
Can help improve cervical mucus quality
Dopamine agonists use
Treat infertility related to hyperprolactinemia
Aspirin use
Increase uterine and ovarian blood flow velocity
