Reproductive System

Genital Tract Embryology

Primordial Female Male
Gubernaculum Ovarian ligament
Round ligament		 -
Processus vaginalis - Tunica vaginalis
Undifferentiated gonads Ovary Testis
  Theca cell Leydig cell
  Granulosa cell Sertoli cell
Genital ducts Frimbriae Epididymis
  Fallopian tube Vas deferens
  Uterus Seminal vesicle
  Upper vagina Ejaculatory duct
Urogenital sinus Lower vagina Prostatic utricle
  Paraurethral gland of Skene Prostate gland
  Greater vestibular gland of Bartholin Bulbourethral gland of Cowper
Urogenital fold Mons pubis Dorsal penile shaft
  Labia minora Ventral penile shaft
Labioscrotal swelling Labia majora Scrotum
Genital tubercle Clitoris Penis

Ligaments of Uterus and Ovary

Ligament Connects Contents
Broad ligament Uterus ~ Pelvis :: lateral -
Round ligament Uterus ~ Labia majora Gubernaculum
Ovarian ligament Uterus ~ Ovary Gubernaculum
Infundibulopelvic [Suspensory] ligament Ovary ~ Pelvis :: lateral Ovarian vessels
Pubocervical ligament Cervix ~ Pubis -
Cardinal ligament Cervix ~ Pelvis :: lateral Uterine vessels
Uterosacral ligament Cervix ~ Sacrum Inferior hypogastric plexus

Sex Hormone Production

Hormones Regulation Female Male
Progesterone
DHEA
Androstenedione
Testosterone		 ACTH Adrenal gland Adrenal gland
Progesterone
Testosterone		 LH Corpus luteum
Theca cells		 Leydig cells
Anti-Mullerian hormone (AMH)
Estradiol
Inhibin		 FSH Corpus luteum
Granulosa cells		 Sertoli cells
Estrone - Adipocytes Adipocytes
Dihydrotestosterone (DHT) - Peripheral cells Peripheral cells

Estrogens in Females

Estrogen Estrogen Site Precursor Precursor Site Enzyme Timing
Estrone Adipocytes Androstenedione Adrenal gland Aromatase Post-menopause
Estradiol Granulosa cells Testosterone Theca cells Aromatase Non-pregnancy
Estriol Placenta DHEA sulfate (DHEAS) Adrenal gland Sulfatase Pregnancy

Etiology of Incresed Exposure to Estrogen

  • Nulliparity
  • Early menarche
  • Late menopause

Side Effects of Unopposed Estrogen

  • ↑ Thromboembolism
  • ↑ Breast cancer
  • ↑ Endometrial cancer
  • ↑ Bone mineral density

Sexual Development

Female Male
Thelarche Gonadarche
Pubarche Pubarche
Growth spurt Adrenarche
Menarche Growth spurt

Age of Onset of Puberty

Sex Age (years)
Female 8 ~ 13
Male 9 ~ 14

Etiology of Peripheral Precocious Puberty

  • Congenital adrenal hyperplasia
  • Adrenal tumors
  • Gonadal tumors
  • McCune-Albright syndrome
  • Exogenous sex hormone

Etiology of Abnormal Uterine Bleeding (AUB) {PALM-COEIN}

  • Pregnancy
  • Polyps
  • Adenomyosis
  • Leiomyoma
  • Malignancy
  • Coagulopathy
  • Ovulatory dysfunction
  • Endometrium
  • Iatrogenic
  • Not yet classified

Classification of Amenorrhea

  • Primary: no menarche by age 15 years
  • Secondary: no menses for ≥ 3 cycles / ≥ 6 months

Etiology of Primary Amenorrhea

Etiology Breast Uterus Ovary
Outflow obstruction + + +
Anorexia nervosa + + +
Mullerian agenesis + - +
Androgen insensitivity syndrome (AIS) + - -
Constitutional growth delay - + +
Hypogonadotropic Hypogonadism - + +
Turner syndrome - + +
Swyer syndrome - + -

Etiology of Secondary Amenorrhea

Etiology GnRH LH & FSH SH
Pregnancy ↓ ↓ ↑
Menopause [Ovarian failure] ↑ ↑ ↓
Resistant ovary [Savage] syndrome ↑ ↑ ↓
Hypogonadotropic Hypogonadism ↓ ↓ ↓
Polycystic ovary syndrome (PCOS) ↑/↓ ↑/↓ ↓/↑
Asherman syndrome - - -
Outflow obstruction - - -

Presentation of Turner Syndrome

  • Streak gonads
  • Amenorrhea
  • Webbed neck
  • Shield chest
  • Bicuspid aortic valve
  • Coarctation of the aorta
  • Cystic hygroma

Indicators of Ovarian Reserve

Indicator Normal
FSH :: follicular phase 2 ~ 8
Anti-Mullerian hormone (AMH) 1 ~ 5
Antral follicle count (AFC) 5 ~ 10

Presentation of Menopause {HAVOCS}

  • Hot flashes
  • Atrophy of the vagina
  • Osteoporosis
  • Cardiovascular disease
  • Sleep disturbances

Treatment of Menopause

  • Topical estrogen
  • Hormone replacement therapy (HRT)
  • SSRIs & SNRIs
  • Calcium & Vitamin D supplements

Side Effects of Hormone Replacement Therapy (HRT)

  • ↑ Thromboembolism
  • Breast cancer
    • ↑ if estrogen + progesterone
    • ↓ if estrogen alone
  • Endometrial cancer
    • ↓ if estrogen + progesterone
    • ↑ if estrogen alone
  • ↓ Fractures

Hormones Changes in PCOS

Hormone Changes
GnRH ↑/↓
LH ↑
FSH ↓
LH/FSH ↑
Progesterone ↓
Testosterone ↑
Estrogen ↑

Rotterdam Criteria for Diagnosis of PCOS

  • Anovulation
  • Hyperandrogenism
  • Polycystic ovaries

Treatment of PCOS

  • Ovulation induction
    • Estrogen modulators :: Clomiphene
    • Aromatase inhibitors
  • Combined hormonal contraception
  • Androgen antagonists
  • 5α-Reductase inhibitors
  • Metformin ± Statins
  • Lifestyle modification

Non-surgical Treatment of Pelvic Organ Prolapse (POP)

  • Kegel exercise
  • Topical estrogen
  • Pessary

Pathogens of Genital Tract Infection

Pathogen Presentation Treatment
Neisseria gonorrhoeae Discharge :: greenish-yellow
Pelvic inflammatory disease (PID)		 3° Cephalosporins
Macrolides
Haemophilus ducreyi Painful chancroid -
Klebsiella granulomatis Granuloma inguinale Macrolides
Doxycycline
Treponema pallidum Painless chancre
Condyloma lata		 Penicillin
Chlamydia trachomatis Discharge :: greenish-yellow
Lymphogranuloma venereum (LGV)
Pelvic inflammatory disease (PID)		 Macrolides
Doxycycline
Gardnerella vaginalis Discharge :: grayish & fishy Metronidazole
Candida albicans Discharge :: white & curdy -Conazoles
Trichomonas vaginalis Discharge :: greenish-yellow & frothy Metronidazole
HPV Condyloma accumulata
Verruca vulgaris		 -
HSV Paniful ulcers -

Comparison Between Testicular Torsion and Epididymitis

  Testicular Torsion Epididymitis
Prehn sign - +
Cremasteric reflex - +
Blood flow ↓ ↑

Medications for BPH

Mechanism Medication
α1 antagonists Tamsulosin
Terazosin
Doxazosin
Prazosin
5α-Reductase inhibitors Finasteride

Reproductive Tumors

Epithelial Tumors

  • Serous cystadenoma
    cystadenocarcinoma
  • Mucinous cystadenoma
    cystadenocarcinoma
  • Endometrioid carcinoma
  • Clear cell carcinoma
  • Mixed cell carcinoma
  • Transitional cell carcinoma [Brenner tumor]
  • Carcinosarcoma [Malignant mixed Mullerian tumor (MMMT)]

Stromal Tumors

Female Male Markers
Theca cell tumor [Thecoma] Leydig cell tumor -
Granulosa cell tumor Sertoli cell tumor Inhibin
Fibroma Fibroma -

Germ Cell Tumors (GCT)

Female Male Markers
Dysgerminoma Seminoma ALP & LDH
Choriocarcinoma Choriocarcinoma hCG
Endodermal sinus tumor (EST) Endodermal sinus tumor (EST) AFP
Embryonal carcinoma Embryonal carcinoma hCG & AFP
Teratoma Teratoma hCG & AFP

Triad of Meigs Syndrome

  • Ovarian fibroma
  • Pleural effusion
  • Ascites

Types of Endometrial Cancer

Type 1 2
Histology Endometrioid Non-endometrioid
Risk factors Estrogen -
Prognosis Favorable Poor

Bethesda System for Pap Smear Results

  • Squamous cell abnormalities
    • Atypical squamous cell (ASC)
    • Low-grade squamous intraepithelial lesion (LSIL)
    • High-grade squamous intraepithelial lesion (HSIL)
    • Squamous cell carcinoma
  • Glandular cell abnormalities
    • Atypical glandular cell (AGC)
    • Adenocarcinoma in situ (AIS)
    • Adenocarcinoma

Management of Abnormal Pap Smear Results

Result Age (years) HPV Management
- < 30 ±/? Routine screening
- > 30 -/? Routine screening
- > 30 + Repeat screening in 1 year
ASC-US < 25 - Routine screening
ASC-US < 25 +/? Repeat screening in 1 year
ASC-US > 25 - Repeat screening in 3 years
ASC-US > 25 ? Repeat screening in 1 year
LSIL < 25 ±/? Repeat screening in 1 year
LSIL > 25 - Repeat screening in 1 year
Consecutive
Otherwise		 Any ±/? Colposcopy ± Biopsy

Management of Cervical Intraepithelial Neoplasia (CIN)

CIN Management
I Repeat screening in 1 year
II
III		 Cryotherapy
Laser ablation
Conization
Loop electrosurgical excision procedure (LEEP)

Management of Seminoma

  • Radical orchiectomy
  • Radiotherapy
  • Chemotherapy

Contraception Methods

  • Barrier contraception
  • Combined hormonal contraception
    • Oral contraceptive pills (OCPs)
    • Contraceptive patch
    • contraceptive ring
  • Depot medroxyprogesterone
  • Progestin subdermal implant
  • Intrauterine devices
    • Progestin intrauterine device
    • Copper intrauterine device

Side Effects of Combined Hormonal Contraception

  • ↑ Thromboembolism
  • ↑ Breast cancer
  • ↓ Endometrial cancer
  • ↓ Ovarian cancer

Contraindications to Combined Hormonal Contraception

  • Age ≥ 35 years
    Smoking ≥ 15 cigarettes/day
  • History of thromboembolism
  • Active breast cancer
  • Liver failure
  • Migraines with aura

Contraindications to Intrauterine Device (IUD)

  • Pregnancy
  • Unexplained vaginal bleeding
  • Endometrial cancer
  • Cervical cancer
  • Pelvic inflammatory disease (PID)

Reference Limits of Semen Analysis

  • Volume > 1.5 mL
  • Sperm concentration > 15 M/mL
  • Total sperm count > 39 M
  • Normal forms > 4%
  • Vitality > 58%
  • Progressive motility > 32%
  • Total motility > 40%

Indications for Assisted Reproductive Technology (ART)

Intrauterine Insemination (IUI)

  • Cervical factors
  • Male factors
  • Donor sperms

In Vitro Fertilization (IVF)

  • Tubal factors
  • Donor eggs
  • Genetic screening
  • Failed intrauterine insemination (IUI)

Controlled Ovarian Hyperstimulation

Suppression of Spontaneous Ovulation

Protocol Timing
GnRH agonist long protocol Last luteal phase
GnRH agonist short protocol Menstruation
GnRH antagonist protocol Leading follicle > 14 mm

Ovulation Induction

  • (Follicles > 18 mm) ≥ 2
  • Estradiol per co-dominant follicle > 200 pg/mL
Mechanism Medication
GnRH agonists Leuprolide
hCG agonists Choriogonadotropin

Breast Imaging Reporting and Data System (BI-RADS)

Category Interpretation Management Likelihood of cancer
0 Inconclusive Repeat -
1 Negative Routine 0
2 Benign Routine 0
3 Probably benign Every 6 months < 2%
4 Suspicious Biopsy 2 ~ 95%
5 Highly suggestive Biopsy > 95%
6 Biopsy-proven - -

Breast Tumors

Epithelial Tumors

  • Fibrocystic change
  • Intraductal papilloma
  • Ductal carcinoma in situ (DCIS)
    Invasive ductal carcinoma (IDC)
  • Lobular carcinoma in situ (LCIS)
    Invasive lobular carcinoma (ILC)
  • Medullary carcinoma

Stromal Tumors

  • Fibroadenoma
  • Phyllodes tumor

Molecular Subtypes of Breast Cancer

Subtype Receptors Mutations
Luminal A PR & ER -
Luminal B PR & ER -
HER2-enriched HER2 -
Basal-like - BRCA
Claudin-low - BRCA
Interferon-rich - BRCA

Types of Flaps for Breast Reconstruction

  • Transverse rectus abdominis myocutaneous (TRAM) flap
  • Latissimus dorsi (LD) flap
  • Deep inferior epigastric perforator (DIEP) flap
  • Superficial inferior epigastric artery (SIEA) flap
  • Gluteal flap
  • Transverse upper gracilis (TUG) flap
  • Profunda artery perforator (PAP) flap