11 reproductive high yield

Week 8: Fetal period begins Fetal movement Fetus, 8 weeks.. REPRO3_1- Pregnancy definitions and numbers to remember… Menstrual/gestational age: time since start of last menstrual peri

REPRO1_1- REPRO1_1- 1

REPRO1_1-

Spermatogonia

Primary spermatocytes

Secondary spermatocytes

Spermatozoa

Spermatids

(46, 2n) (46, 4n) (23, 2n) (23, 1n) (23, 1n)

Meiosis I Meiosis II

REPRO1_1-

Kaplan Anatomy: Figure I-10-4

Normal for fertility:

Semen volume: 2-5 ml Total sperm number: > 20 million

Progressive motility: > 50%

Spermatozoa:

75 days for production

- 2/3 time in seminiferous tubules

REPRO1_1-

Kaplan Anatomy 2011: Figure X-10-1

Hormonal control of testes

4

•FA 2013: 519.1 • FA 2012: 534.1 • FA 2011: 481.2

• ME 3e: 401 • ME4e: 401

REPRO1_2-

Oogonium

Primary Oocyte

Secondary

Polar Bodies

Prophase I Arrest (until ovulation)

Metaphase II Arrest (until fertilization) Replication

Oogenesis

1

•FA 2013: 522.1 • FA 2012: 537.1 • FA 2011: 484.2

• ME 3e: 404 • ME4e: 404

REPRO1_3-

Chris, commons.wikimedia.org Used with permission

Menstrual cycle

1

•FA 2013: 521.2 • FA 2012: 536.1 • FA 2011: 483.2

• ME 3e: 405 • ME4e: 405

REPRO1_3-

Ed Uthman, commons.wikimedia.org

Used with permission

Kaplan Physiology: Figure X-11-3

Luteal phase

5

•FA 2013: 521.2 • FA 2012: 536.1 • FA 2011: 483.2

• ME 3e: 406 • ME4e: 406

REPRO1_3-

• Young females with obesity, amenorrhea, and anovulation

• Hirsutism and acne (due to - testosterone)

• Bilateral cystic ovaries (multiple immature follicles)

REPRO1_3-

Menses Proliferative Secretory Chris, commons.wikimedia.org

Used with permission

Uterine cycle

7

•FA 2013: 521.2 • FA 2012: 536.1 • FA 2011: 483.2

• ME 3e: 405 • ME4e: 405

REPRO1_3-

• Synthesized in preoptic nucleus of hypothalamus

• Pulsatile secretion

• Continuous application leads to downregulation of

GnRH receptors in the anterior pituitary

• GnRH agonists (e.g leuprolide)

• pulsatile - treat infertility by inducing ovulation

• continuous - ¯ estrogen to treat endometriosis, fibroids

GnRH

8

•FA 2013: 538.1 • FA 2012: 553.1 • FA 2011: 497.1

• ME 3e: 403 • ME4e: 403

REPRO1_4-

• Abrupt decrease in estrogen in aging women

• Due to loss of ovarian follicles with time

• Average age of onset: 52 years

• Progressive increase in LH/FSH (loss of inhibitory feedback)

Menopause

1

•FA 2013: 523.3 • FA 2012: 538.2 • FA 2011: 485.2

• ME 3e: 403 • ME4e: 403

REPRO1_4-

• Menopause

• Premature ovarian failure

• PCOS (obesity and estrogen excess)

• Asherman syndrome (uterine adhesions, scar tissue)

• Hyperprolactinemia, thyroid disease

• Eating disorders, excessive exercise

• (Rarely) Cushing’s syndrome

Possible causes of anovulation

2

•FA 2013: 529.5 • FA 2012: 544.5 • FA 2011: 489.6

• ME 3e: 403 • ME4e: 403

REPRO1_4-

• Vaginal dryness

• Thermoregulatory dysfunction – “hot flashes”

(first 5 years after onset)

• Night sweats

• Loss of bone density -

(begins at age 30, accelerates 5-7 years after menopause)

Symptoms alleviated by hormone replacement therapy

BUT:

• Increased risk of clot formation, stroke, breast cancer

• Progesterone must be given with estrogen to prevent

RESPRO2_1- 3

• Endometriosis

• Pelvic inflammatory disease

• Previous pelvic/tubal surgery

• Diethylstilbestrol (DES) exposure (now rare)

• + Pregnancy test

• Vaginal bleeding

• Sudden onset, severe abdominal pain

• Free fluid/blood within abdomen (on rupture)

RESPRO2_2-

Madprime, commons.wikimedia.org Used with permission

1) Urine sample applied to stick

2) Free dye- labeled antibodies bind to β-hCG

(if present)

3) Anchored antibodies bind this complex (so

test can be read)

4) Free, unbound dye-labeled antibodies are

captured as a control to indicate test is

working properly

β-hCG detectable in blood 6 days post

fertilization (reliability detected in urine

RESPRO2_3-

Kaplan Anatomy: Figure II-4-1

3 distinct germ layers

Primitive streak forms

Spleen Kidneys, ureters Reproductive organs

Notochord

Nucleus pulposus

Epithelium of:

GI tract Lower respiratory tract Larynx, trachea, bronchi Lungs

Urinary bladder, urethra Lower vagina

Pharyngeal pouches Auditory tube, middle ear Palatine tonsils

Parathyroid glands Thymus

Parenchyma of:

Liver Pancreas Submandibular glands Sublingual glands Thyroid gland follicles

Germ-layer origins of tissues

2

•FA 2013: 505.1 • FA 2012: 126.1 • FA 2011: 119.1

• ME 3e: 144 • ME4e: 144

Week 8: Fetal period begins

Fetal movement

Fetus, 8 weeks

(Jacopo Werther commons.wikimedia.org Used with permission.)

Embryonic Period: Weeks 3-8

3

•FA 2013: 504.2 • FA 2012: 124.2 • FA 2011: 118.2

• ME 3e: 144 • ME4e: 144

RESPRO2_4- 1

Teratogens

•FA 2013: 506.1 • FA 2012: 127.1 • FA 2011: 120.1

• ME 3e: 146 • ME4e: 146

REPRO3_1-

Pregnancy definitions and numbers to remember…

Menstrual/gestational age: time since start of last menstrual period

(LMP) (will roughly correspond to 2 weeks prior to fertilization)

Normal gestational period: 40 weeks (280 days) after LMP

38 weeks (266 days) after fertilization

Trimesters: First (weeks 1-12)

REPRO3_2-

Ed Uthman, MD commons.wikimedia.org Used with permission

Umbilical artery Umbilical artery

Umbilical vein Urachus

Umbilical Cord (cross section)

2

•FA 2013: 508.2 • FA 2012: 129.2 • FA 2011: 122.2

• ME 3e: 408 • ME4e: 408

REPRO3_2-

National Institutes of Health commons.wikimedia.org Used with permission

• Fetal side of uterine cavity

• Fused with chorion on uterine surface

• Adheres to outer surface of chorionic vessels

Monochorionic diamniotic

Monochorionic monoamniotic

Day 0

Division:

Risk of conjoined twins

Di/Di Twin Gestation

Nevit Dilmen, commons.wikimedia.org Used with permission

Monozygotic twins

1

•FA 2013: 507.2 • FA 2012: 128.2 • FA 2011: 121.1

• ME 3e: 408 • ME4e: 408

REPRO3_4-

First Trimester - Weeks 1-12

• Ends by 12 weeks gestation (10 weeks post fertilization)

• “Crown-rump” length of fetus is 7 cm

• Uterus palpable below pubic symphysis

• Spontaneous abortions common (mainly chromosomal abnormalities)

First trimester

1

•FA 2013: n/a • FA 2012: n/a • FA 2011: 487.2

• ME 3e: 409 • ME4e: 409

REPRO3_4-

1/100 pregnancies result in ectopic implantation

Locations: Tubes (most common)

Cervix Ovaries, broad ligament

other peritoneal or pelvic structures Risk factors:

• Endometriosis

• Pelvic inflammatory disease (infection)

• Previous pelvic/tubal surgery Presentation:

• Abdominal pain (do not confuse with appendicitis)

• Period-like spotting

• Death from intrabdominal hemmorhage

Compagnion, commons.wikimedia.org Used with permission

Ovary

Ectopic Embryo

Ectopic pregnancy

2

Treatment:

• Based on clinical stability

• Unstable = requires surgery

• Stable = consider methotrexate

•FA 2013: 526.2-527.1 • FA 2012: 541.2-542.1

• FA 2011: 488.1 • ME 3e: 409 • ME4e: 409

REPRO3_4-

Second Trimester - Weeks 13-28

• Quickening begins by 20 weeks (fetal movement)

• Fetal skin has fine hair

• Uterus at the maternal umbilicus

• Spontaneous abortions can be due to:

REPRO3_5-

Bleeding during third trimester (weeks 29-40) may be due to:

Placental abruption: Placenta detaches from uterine wall

Painful bleeding, DIC

Associated with cocaine, smoking, HTN, trauma

Placenta previa: Placenta forms over inner cervical os

Painless bleeding

Often requires hysterectomy

Fetal blood bleeds into vagina High fetal mortality rate

Third trimester bleeding

1

•FA 2013: 526.2-527.1 • FA 2012: 541.2-542.1

• FA 2011: 488.1 • ME 3e: 409 • ME4e: 409

REPRO3_5-

Eclampsia: Seizures in the setting of preeclampsia

Underlying maternal hypertension Pregnancy-induced hypertension Hypertension with symptoms of preeclampsia

Preeclampsia: By definition is hypertension with proteinuria

Severe preeclampsia: Headache, visual disturbances, oliguria, pulmonary edema,

fetal growth restriction

Hemolysis Elevated Liver enzymes Low Platelets

REPRO3_5-

Molar pregnancy can also present with symptoms of preeclampsia

If symptoms of preeclampsia < 20 weeks → molar pregnancy likely

> 20 weeks → gestational preeclampsia

Molar pregnancy and preeclampsia

3

•FA 2013: 526.1 • FA 2012: 541.1 • FA 2011: 487.3

• ME 3e: 409 • ME4e: 409

REPRO3_5-

Polyhydramnios

Causes:

Excess amniotic fluid

Idiopathic (most commonly) Esophageal atresia

Neural tube defects Fetal polyuria and maternal diabetes

Oligohydramnios

Causes:

Too little amniotic fluid

Renal agenesis Posterior urethral valves (males)

DrMiKey, commons.wikimedia.org Used with permission

prolactin release and prohibits

its action on the breast

Post partum:

The drop in estrogen/estriol

levels allow for prolactin action

upon the breast, stimulating

REPRO4_1- 2

Kaplan Anatomy 2011: Figure II-1-1

Male Female

Genital embryology

•FA 2013: 512.1 • FA 2012: 141.1 • FA 2011: 133.1

• ME 3e: 394 • ME4e: 394

No female internal genitalia

Male external genitalia, prostate

Control of male gonadogenesis

1

•FA 2013: 513.1 • FA 2012: 142.1 • FA 2011: 486.7

• ME 3e: 394 • ME4e: 394

Bulbourethral glands Prostate gland

Ventral shaft of penis (penile urethra)

• Anchors testes within scrotum

• Female remnant: Ovarian ligament and round ligament of uterus

• Forms tunica vaginalis

• Obliterated in female

Cryptorchidism:

• Failure of one/both testes to descend into scrotum before birth (3% males)

• Higher intra-abdominal temperatures leads to sperm agenesis

• Increased risk of testicular cancer

•FA 2013: 514.`1 • FA 2012: 143.2 • FA 2011: 134.3

• ME 3e: 398 • ME4e: 398

Greater vestibular glands Urethral and paraurethral glands

REPRO4_4-

Androgen insensitivity syndrome

(aka testicular feminization syndrome)

• Defect in androgen receptors

• Female phenotype, male genotype (46, XY)

• No sexual hair (no adrenarche)

• Some breast development (thelarche)

• Female external genitalia and rudimentary vagina

• No uterus or uterine tubes

• Testes develop, found within labia majora

(usually surgically removed to prevent malignancy)

Partially incomplete fusion

Associated with: Infertility

Miscarriage Pre-term labor Urinary tract abnormalities

Bicornuate Uterus

commons.wikimedia.org Used with permission

Onset of puberty:

↑ pulsatile release of GnRH by hypothalamus

↑ LH/FSH release by anterior pituitary

↑ estrogen – drives puberty

see also Kaplan Physiology 2011: Figure X-10-3

Birth to puberty

1

Hormones from Mother

•FA 2013: 520.1 • FA 2012: 535.1 • FA 2011: 482.2

• ME 3e: 403 • ME4e: 403

Ovarian release of sex steroids

Process takes 4.5 years to complete

Stages of puberty

2

•FA 2013: n/a • FA 2012: n/a • FA 2011: n/a

• ME 3e: 8 • ME4e: 8

REPRO4_5-

M.Komorniczak, commons.wikimedia.org Used with permission

Breast Pubic hair

Male genitalia

Testicular size

Tanner stages

3

•FA 2013: 521.1 • FA 2012: 535.3 • FA 2011: 60.4

• ME 3e: 9 • ME4e: 9

REPRO4_6-

Precocious puberty

1

Defined as: Early appearance of secondary sex characteristics

before age 8 in girls; before age 9 in boys

Two types: Central and peripheral

•FA 2013: n/a • FA 2012: n/a • FA 2011: n/a

• ME 3e: 8 • ME4e: 8

REPRO4_6-

Central precocious puberty

2

• Idiopathic - early initiation of pulsatile GnRH release

• CNS abnormality - tumor, inflammation, trauma

• Congenital hypothalamic hamartomas

Follows normal progression of puberty (see stages of puberty)

Causes:

•FA 2013: n/a • FA 2012: n/a • FA 2011: n/a

• ME 3e: n/a • ME4e: n/a

• Gonadal or adrenal tumors

• Congenital adrenal hyperplasia

• Enzyme deficiency (21- or 11 β-hydroxylase deficiency)

• Other congenital adrenal hyperplasias

• Enzyme deficiency (21- or 17-hydroxylase deficiency)

• Other congenital adrenal hyperplasias

• McCune-Albright syndrome

• Hypothyroidism in children (TSH activates FSH receptors)

•FA 2013: n/a • FA 2012: n/a • FA 2011: n/a

• ME 3e: n/a • ME4e: n/a

REPRO4_6-

McCune-Albright syndrome

4

• Endocrine hyperfunction leading to precocious puberty

• Polyostotic fibrous dysplasia (bone fractures and deformation)

• Unilateral café-au-lait spots

↑ estradiol, ↓ LH/FSH

•FA 2013: 388.2 • FA 2012: 415.2 • FA 2011: 380.3

• ME 3e: 487 • ME4e: 487

REPRO5_1-

Hypergonadotropic hypogonadism

(aka, primary hypogonadism)

Failure of gonads to produce sex steroids (estrogen/testosterone)

Therefore, low sex steroids and high LH/FSH (due to lack of feedback

REPRO5_1-

Turner syndrome (46, XO)

inability of ovaries to respond to LH/FSH

• Short stature

• Webbing of neck

• Shield chest

• Primary amenorrhea

• Ovarian dysgenesis (streak ovary and infertility)

• Increased risk for gonadoblastoma

4

Turner syndrome

•FA 2013: 524.1 • FA 2012: 539.1 • FA 2011: 485.2

• ME 3e: 74 • ME4e: 74

REPRO5_1-

Mixed gonadal dysgenesis

Genitalia: female, male, or ambiguous (determined by in utero testosterone exposure)

Most common form due to mosaicism 45, X / 46, XY

If Y chromosome present, increased risk of gonadoblastoma

Gonadal dysgenesis

46, XX karyotype: Streaked ovaries, otherwise normal internal and external genitalia

46, XY karyotype: External or internal genitalia ambiguous

risk of dysgerminoma or gonadoblastoma

Note: these are referred to as pseudohermaphroditisms

5

Gonadal dysgenesis

•FA 2013: 524.3 • FA 2012: 539.3 • FA 2011: 486.2

• ME 3e: 394 • ME4e: 394

REPRO5_1-

Klinefelter’s syndrome (47, XXY)

• Most common cause of primary testicular failure

• Small testes, azoospermia

• Eunuchoid body shape

• Increased risk for hypogonadism, testicular atrophy, gynecomastia

• Possible developmental delay

REPRO5_1-

Double Y males (47, XYY)

• Normal male phenotype

• Tall, severe acne

• More predisposed to antisocial behavior (1-2% XYY males)

REPRO5_1-

Androgen insensitivity syndrome

(aka testicular feminization syndrome)

• Genetically male, phenotypically female

• Shortened vagina

• Uterus and uterine tubes absent

• Female external genitalia

• Absence of axillary/pubic hair

REPRO5_2-

Hypogonadotropic hypogonadism

• Idiopathic

• Kallman’s syndrome (autosomal dominant, or X-linked)

( ↓ anterior pituitary function, congenital anosmia)

• Congenital hypopituitarism (w/ diabetes insipidus or hyperprolactinemia)