infertility/menopause Flashcards

1
Q

infertility

Etiology & Pathogenesis

A

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%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
1
Q

infertitility

General

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

female fertility

general

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

female infertility

ovulatory dysfunction

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

female infertility

Tubal factors

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

female infertility

uterine factors

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

male infertility

Endocrine and systemic disorders:

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

male infertility

Testicular defects in spermatogenesis

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

male infertility

Male etiologies and pathophysiology

A

Acquired causes
Varicocele – what side is most common?
Infection
Mumps
Gonorrhea and chlamydia
Chemotherapy
Radiation
Many cases are idiopathic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

male infertility

Sperm transport andsexual dysfunction disorders

A

Congenital abnormalities, dysfunction, or obstruction
Epididymis
Vas deferens
Ejaculatory ducts
Sexual dysfunction
Erectile dysfunction (ED)
Ejaculatory dysfunction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

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

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

female infertility

labs

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

female infertility

imaging (3)

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

male infertility

Semen analysis (normal parameters listed):

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

male infertility

Laboratory and imaging ifsemen analysisis abnormal:

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

infertility

lifestyle factors

A

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

16
Q

infertiltiy - management

Clomiphene citrate

Ovulation induction, ovarian hyperstimulation, and insemination

A

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)

17
Q

female fertility - management

insemination and in vitro

Ovulation induction, ovarian hyperstimulation, and insemination

A

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

18
Q

Menopause

general

A

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)

19
Q

Perimenopause

general

A

Transitional period (2-8 years) from reproductive to nonreproductive stage marked by menstrual irregularity and fluctuating hormone levels

20
Q

menopause

physiology

A

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

21
Q

Perimenopause

Clinical Presentation

A

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

22
Q

Postmenopause

Complications

A

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)

23
Q

Perimenopause

Dx

A

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

24
# peri/ppost menopause management
Majority of women in perimenopause and postmenopause do not require treatment Primary goals Relief of bothersome symptoms **Ensuring health through appropriate screening** 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
25
# 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 Patients within 10 years of menopause Patients < 60–65 years of age Symptoms severe enough to affect quality of life No contraindications
26
# Hormone replacement therapy (HRT) Estrogen
Effective for treating **Vasomotor symptoms:** hot flushes, night sweats → sleep disturbances **Mood symptoms** in perimenopause, but not postmenopause **GSM:** vaginal dryness, dyspareunia Routes of therapy: Systemic therapy: oral, transdermal patches, topical gels Vaginal therapy: creams, vaginal tablets, ring Estrogen stimulates endometrium → progestin required if patient has uterus
27
# HRT Progestin
Higher risk of adverse events than estrogen therapy **Required for endometrial protection in patients with uterus** Selection of route and dosing: Usually oral Give cyclically if still menstruating regularly Give continuously if post-menopausal
28
# menopause Contraindications to HRT
Hormone-sensitive breast cancer High-risk endometrial cancer Unexplained vaginal bleeding Cardiovascular disease Venous thromboembolism Stroke or transient ischemic attack (TIA) Acute liver disease
29
# Menopasue Other management options - Vasomotor symptoms
**Selective estrogen receptor modulators (SERMs)** Modulate effects of estrogen  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):  Paroxetine is the only FDA-approved SSRI Serotonin-norepinepherine reuptake inhibitors (SNRIs) Gabapentin Clonidine **Lifestyle changes** Layered clothing Maintain lower ambient temperature at home Avoid alcohol and caffeine Stress management
30
# genitourinary syndrome of menopause Management options
Low-dose vaginal estrogen Most effective treatment Doses are low enough that progestins are not required for endometrial protection Vaginal lubricants Vaginal moisturizers Regular sexual activity