infertility/menopause Flashcards
infertility
Etiology & Pathogenesis
To achievepregnancy
Female must be ovulatory with patentfallopian tubesand a receptiveuterus
Male must be able to produce sperm in adequate numbers that is capable of fertilizing the oocyte
Etiologies of couples
Female factor: 40%
Male factor: 40%
Unexplained infertility: 20%
Couples often have more than 1 contributing etiology
Both female and male factors: 35%
infertitility
General
Inability of a couple to conceive:
After 12 months of timed, unprotected intercourse or donor insemination when the woman is < 35 years of age
After 6 months of timed, unprotected intercourse or donor insemination when the woman is> 35 years of age
Types:
Primary infertility
Couple has never conceived
Secondary infertility
Couple who have been able to get pregnant at least once, but now are unable
~80%–90% of healthy couples will conceive within 12 months
female fertility
general
A woman’s peak reproductive years are between the late teens and late 20s
By age 30, fertility starts to decline; with decline happening faster once a woman reaches their mid-30s
By 45, fertility has declined so much that getting pregnant naturally is unlikely
Categorized as:
Ovulatory dysfunction
Tubal factors
Uterine factors
female infertility
ovulatory dysfunction
Ovulatory dysfunction:
Etiologies
Hypogonadotropic hypogonadism:
Hypothalamusis not functioning properly
↓ Gonadotropin-releasing hormone (GnRH) → ↓ follicle-stimulating hormone (FSH) → ↓ oocyte maturation → anovulation (overexercise, eating disorders, stress)
Normogonadotropic normoestrogenic ovulatory dysfunction:
Normal GnRH and estrogens, but ↓FSH
Often oligomenorrhea and ↑androgens (PCOS)
Hypergonadotropic hypogonadism:
Ovaries not responsive toFSH
↑ GnRH → ↑FSH→ nonresponsiveovaries→ anovulation (Primary ovarian insufficiency (POI))
Oocyte aging
Fewer ovarian follicles that ovulate (atresia) →↓ estrogens
Estrogen normally inhibits FSH, but when levels are low there will be increased FSH
Diminished capacity to secrete inhibin
Inhibin decreases the release of FSH from the anterior pituitary (negative feedback)
Hyperprolactinemia
↑ Prolactin causes ↓ GnRH release
Hypothyroidism
Low levels of thyroid hormone can interfere with the release of an egg from the ovary
Estrogen- or androgen-secreting tumors
Sex cord-stromal tumors
Adrenal tumors
female infertility
Tubal factors
Prevention of sperm reaching the egg
Occlusion (usually from adhesions)
Inflammation
Pelvic inflammatory disease - major causes include chlamydia orgonorrhea
Hydrosalpinges
Blockage of the distal fallopian tube with the accumulation of clear or serous fluid
Endometriosis
Fertility challenges due to both tubal adhesions and inflammation
Prior tubal surgery
Priorectopic pregnancy
female infertility
uterine factors
Uterine factors:
Impairedimplantation
Mechanical issues
↓ Endometrial receptivity
Causes
Leiomyoma (uterine fibroids) that impinge on uterine cavity
Endometrial polyps
Adhesions from prior surgery
Müllerian anomalies (septateuterus)
Stenosis of the cervix
male infertility
Endocrine and systemic disorders:
Congenital/genetic causes
Hypogonadotropic hypogonadism due to decreased secretion of gonadotropin-releasing hormone (GnRH) by the hypothalamus
Genetic defects affecting gonadotropins
Klinefelter syndrome(47,XXY): one of the most common causes ofprimary hypogonadismin men
Acquired conditions leading to hypothalamic or pituitarydysfunction
Hyperprolactinemia (medication induced)
Thyroid disorders
Hormone-secreting tumors
Systemic diseases – cystic fibrosis, diabetes
Obesity (can ↓testosteroneand testicular function
male infertility
Testicular defects in spermatogenesis
Azoospermia: no sperm in the ejaculate
Oligospermia: ↓ sperm count
In 80% of infertile men
The most common cause of infertility in men
Asthenospermia: ↓ spermmotility
Occurs when less than 32% of sperm in a sample are able to move efficiently
Teratospermia: ↑ number of sperm with abnormal morphology
Cryptorchidism:undescended testes
male infertility
Male etiologies and pathophysiology
Acquired causes
Varicocele – what side is most common?
Infection
Mumps
Gonorrhea and chlamydia
Chemotherapy
Radiation
Many cases are idiopathic
male infertility
Sperm transport andsexual dysfunction disorders
Congenital abnormalities, dysfunction, or obstruction
Epididymis
Vas deferens
Ejaculatory ducts
Sexual dysfunction
Erectile dysfunction (ED)
Ejaculatory dysfunction
female infertility
Patients do not fit the defined criteria for infertility, but have at least one identifiable infertility factor, they still qualify for a basic infertility workup
Age ≥ 40 years
Oocyte quantity and quality decline over time
Amenorrhea
No menstrual bleeding for 3 months in individuals with previously regular cycles
No menstrual bleeding for 6 months in those with previously irregular cycles
Known or suspected uterine, tubal, or peritoneal disease
Stage 3 or 4 endometriosis
Cause inflammation and scarring that alter pelvic anatomy
Suspected male factor infertility
female infertility
labs
Laboratory tests:
Cycle day 3FSH,LH, andestradiol
↓FSHwith ↓ estrogen → functional hypothalamic amenorrhea
High GnRH, LH:FSHratio > 2 with normal estrogen →PCOS
↑FSHwith ↓ estrogen → Primary ovarian insufficiency
↓FSHwith ↑ estrogen → estrogen secreting tumor
Cycle day 21(mid-luteal) progesterone
↑Progesteronein theluteal phase confirms ovulation
↑ Prolactin → hyperprolactinemia
↑Thyroid-stimulating hormone→ hypothyroidism
↑ Testosterone →PCOS
female infertility
imaging (3)
Ultrasound (transvaginal)
Antral follicle count (assessment of ovarian reserve)
Leiomyomas
Polycystic-appearingovaries
Ovarian tumors
Saline infusion sonogram(SIS)
Injection of saline into the uterine cavity to distend it duringsonography
Aids in the diagnosis of uterine factors - polyps, uterine septa, etc.
Hysterosalpingogram
Inject radiopaque dye into the uterine cavity underfluoroscopy
Bilateral “fill and spill” of dye confirms tubal patency
male infertility
Semen analysis (normal parameters listed):
Volume: 1.5-5.0 mL
pH: > 7.2
Concentration (density): > 15 million/mL
Number of sperm found in one milliliter of a semen sample
Count: > 40 million/mL
Motility: 40%
Morphology: > 4% normal
Agglutination: < 2
Motile spermatozoa stick to each other, head to head, midpiece to midpiece, tail to tail, or mixed
Due to semen antibodies
Liquefaction: 15-30 minutes
Semen is initially thick; liquefies (watery consistency) to help sperm motility
male infertility
Laboratory and imaging ifsemen analysisis abnormal:
FSH, LH, and morning total testosterone
↑FSH and LH with ↓testosterone→ hypergonadotropic hypogonadism (testicular defects)
Normal or ↓FSHandLHwith ↓testosterone→ hypogonadotropic hypogonadism (hypothalamic or pituitary defects)
↓ LHwith ↑ musclemass→ suspect androgen abuse
Scrotal and transrectal ultrasound
infertility
lifestyle factors
Coital frequency of every 1–2 days around ovulation
Smoking cessation
Limit excessive alcohol andcaffeineintake
Fertility-friendly lubricants (many common brands inhibit spermmotility)
Weight lossin the case ofobesityor overweight women
Weight gain for women who are underweight
Surgical correction of uterine anomalies
infertiltiy - management
Clomiphene citrate
Ovulation induction, ovarian hyperstimulation, and insemination
Clomiphene citrate:
Selective estrogen receptor modulator → ↓pituitaryinhibition → ↑FSH
Used in normogonadotropic normoestrogenic ovulatory dysfunction
Requirements:
Ovaries capable of normal function
Patent tubes
Sperm
Injectable gonadotropins (FSH)
High risk of multiples
Used in egg retrieval prior toin vitro fertilization (IVF)
female fertility - management
insemination and in vitro
Ovulation induction, ovarian hyperstimulation, and insemination
Intrauterine insemination (IUI)
Injection of a processed semen sample into theuterus
Often combined with ovulation induction to ↑ pregnancy rates
In vitrofertilization
For patients with:
Failed ovulation induction/IUI
Severe tubal disease
Advanced age
Procedure:
Oocytesare surgically retrieved using ultrasound guidance
Fertilizationoccurs via:
Introduction of sperm from a semen sample
Embryos are cultivated in a Petri dish and reimplanted into theendometrium
Menopause
general
Physiologic process in women characterized by the permanent cessation ofmenstruationthat occurs after the loss of ovarian activity (decreased estrogen production)
Epidemiology
Average age: 51 years
Typical range: 44–55 years of age (95% of women)
Perimenopause
general
Transitional period (2-8 years) from reproductive to nonreproductive stage marked by menstrual irregularity and fluctuating hormone levels
menopause
physiology
Hormone levels fluctuate significantly in the perimenopausal period
Perimenopause FSH
IncreasedFSH due to
↓ in oocytes due to progressive degeneration of ovarian follicles that do not ovulate (atresia) →↓ estrogens
What does estrogen do to FSH prior to perimenopause?
Aging oocytes exhibit diminished capacity to secrete inhibin
During the perimenopausal period, women can still become pregnant; often ovulate twice → twin pregnancy
Primaryestrogenswitches fromestradiol toestrone
Estradiol(E2)
Primaryestrogenin premenopausal women
Starts to decrease within 1 year of menopause
Produced inovaries
Estrone(E1)
Primaryestrogenin postmenopausal women
Produced primarily inadipose tissue
Perimenopause
Clinical Presentation
Symptoms are caused by fluctuating hormone levels
Menstrual changes:
Late reproductive years
Menstrual cycles shorten (cycles get closer)
Menopausal transition
Shorter cycles → longer cycles → very irregular/sporadiccycles → final menstrual period
Emotional symptoms:
Mood swings and irritability
Stress andanxiety
Vasomotor symptoms:
Hot flushes
Occur in 50%–90% of women
Usually last 1–5 minutes, but may last up to 45 minutes
Night sweats
Can significantly disruptsleep→chronic fatigue
Symptoms related to sexual function:
Genitourinary syndrome of menopause (GSM):
Vulvovaginalatrophy
Vaginal dryness and itching
Dyspareunia
Postmenopause
Complications
Bone loss:
Osteoporosis → fragility fractures
Cardiovascular disease:
Lipid profiles worsen (↑cholesterol)
Weight gain
↑ Risk formyocardial infarctionand thromboembolic events
Hair, muscle, andskinchanges:
Hair thins
Skin becomes drier and rougher
↓Leanmassandmuscle tone
↑ Fatmass
Symptoms of GSM:
Dryness/dyspareunia
↑ Risk ofpelvic organ prolapse
Incontinence issues
↑Urinary tract infections(UTIs)
Perimenopause
Dx
Primarily clinical
Pelvic exam
Assess vaginalatrophyin context of sexual complaints
Routine lab evaluation NOT indicated
FSH,LH, andestrogenlevels fluctuate significantly and are not clinically useful in most cases
Exception: if patient is around age of menopause with abnormal bleeding, ↑FSHmay be helpful in clarifying menopausal status
peri/ppost menopause
management
Majority of women inperimenopauseand postmenopause do not require treatment
Primary goals
Relief of bothersome symptoms
Ensuring health through appropriatescreening
Cervical cytology: up to age 65/every 3 years
Diabetes testing: at age 45/every 3 years
Colonoscopy: at age 45/every 10 years
Mammography: at age 40 or 50/annually
Bone mineral density: at age 65/every 2 years if risk factors present
Hormone Replacement Therapy (HRT)
candidates for tx
Controversial – 1990s clinical trials showed greater detrimental effects than beneficial effects
Use lowest dose for shortest duration required to treat symptoms
Candidates for therapy
Patientswithin 10 years of menopause
Patients< 60–65 years of age
Symptoms severe enough toaffectqualityof life
No contraindications
Hormone replacement therapy (HRT)
Estrogen
Effective for treating
Vasomotor symptoms: hot flushes, night sweats →sleepdisturbances
Mood symptoms in perimenopause, but not postmenopause
GSM: vaginal dryness,dyspareunia
Routes of therapy:
Systemic therapy: oral, transdermalpatches, topical gels
Vaginal therapy: creams, vaginal tablets, ring
Estrogen stimulatesendometrium→ progestin required if patient hasuterus
HRT
Progestin
Higher risk of adverse events thanestrogentherapy
Required for endometrial protection in patients withuterus
Selectionof route and dosing:
Usually oral
Give cyclically if still menstruating regularly
Give continuously if post-menopausal
menopause
Contraindications toHRT
Hormone-sensitivebreast cancer
High-riskendometrial cancer
Unexplained vaginal bleeding
Cardiovascular disease
Venous thromboembolism
Stroke ortransient ischemic attack(TIA)
Acute liver disease
Menopasue
Other management options - Vasomotor symptoms
Selective estrogen receptor modulators(SERMs)
Modulate effects ofestrogen
Ability to bind and activate estrogen receptors but act as either an agonist or antagonist depending on the tissue type
Non-hormonal medications
Selective serotonin reuptake inhibitors(SSRIs):
Paroxetineis the only FDA-approved SSRI
Serotonin-norepinepherine reuptake inhibitors (SNRIs)
Gabapentin
Clonidine
Lifestyle changes
Layered clothing
Maintain lower ambient temperature at home
Avoid alcohol andcaffeine
Stress management
genitourinary syndrome of menopause
Management options
Low-dose vaginalestrogen
Most effective treatment
Doses are low enough that progestins arenotrequired for endometrial protection
Vaginal lubricants
Vaginal moisturizers
Regularsexual activity
