• Information
  1. Infections
  2. Ectopic Pregnancy

• OVARY
  1. Normal Cell Types
  2. Ovulation
  3. Cysts
  4. Polycystic Ovary Syndrome
  5. Tumors Metastatic to the Ovary

A. Infections

1. Usually result from ascending infection from lower genital tract
2. Common causative organisms (infection is usually polymicrobial)
   1. N. gonorrhea: primary infecting organism, typically leads to secondary infection
   2. E. coli
   3. Chlamydia trachomatis
   4. Mycoplasma
   5. Anaerobes (Clostridium perfringes, Bacteroides, Peptostreptococcus) usually secondary
3. Acute Pathology
   1. Neutrophil (PMN) infiltrate
   2. Marked edema
   3. Congestion of mucosal folds (plicae)
4. Chronic Pathology
   1. Lymphocyte and plasma cell infiltrate
   2. Fibrosis, fibrin bridges, adherence of fimbria
   3. Late stages may show fibrotic occlusion, pus (pyosalpinx), or hydrosalpinx
5. Adjacent ovary may become involved in fibrosis, with abscess formation
   1. Tubo-ovarian abscess is major complication
   2. End result is pelvic inflammatory disease (PID)
6. Mechanical Obstruction
   1. Both scarring and tube dysfunction can occur
   2. May block sperm passage or lead to ectopic pregnancy
7. Symptoms
   1. Abnormal bleeding
   2. Pain, usually following menstrual cycle
   3. Increased risk of ectopic pregnancy and sterility

B. Ectopic Pregnancy

1. Any implantation that develops outside of the endometrium
2. About 95% occur in fallopian tube, 80% at ampulla
3. In USA, about 0.5% of pregnancies are ectopic
4. Major problem is invasion of structure by trophoblast
   1. This leads to bleeding into peritoneum which can lead to hemorrhagic shock
   2. Abdominal pain is major initial complaint
   3. Vaginal bleeding occurs due to low levels of ß-hCG unable to maintain endometrium
5. Blood in Fallopian tube is ectopic pregnancy until proven otherwise
   1. Diagnosis made with quantitative ß-hCG and pelvic ultrasound
   2. Patients with ß-hCG >1500-2000 should have visible intrauterine pregnancy (IUP)
   3. If there is no IUP and there is an adnexal mass on ultrasound, diagnosis is made
   4. Laparoscopy can then be done to confirm diagnosis and remove contents (treatment)
6. Termination
   1. Methotrexate + Misoprostal - very effective for terminating unruptured pregnancies
   2. Vaginal misoprostal is preferred and safer route [1]
   3. These agents may be used for elective abortions [2]
   4. Combination of agents is more effective [3] than misoprostal alone
   5. RU486 (mifepristone) is also effective but not available in USA
   6. Surgery is often required; laparoscopic methods now available

1. Surface epithelium (serosa; derived from mesoderm)
2. Stromal Cells (granulosa and theca; derived from mesoderm)
3. Germ Cells (derived from endoderm, yolk sac)

B. Ovulation [4]

1. Hypothalamic-Pituitary-Ovarian Axis Overview
   1. Pituitary secretion of follicle stimulating hormone (FSH)
   2. FSH stimulates ovarian follicle development and ovarian estradiol production
   3. Estrogen maintains low FSH levels throughout cycle (negative feedback)
   4. Estrogen stimulates LH surge (in presence of FSH) by pituitary
   5. Ovulation and luteinization of the follicle (formation of corpus luteum)
2. Menopause
   1. Defined as normal loss in oocytes by age ~50
   2. Loss in oocytes leads to lost follicles leads to reduced estradiol and inhibin secretion
   3. Lack of feedback on hypothalamus leads to increased chronic FSH and LH levels
   4. Increased FSH and/or LH, normal or decreased estradiol, amenorrhea
   5. Failure of ovary to properly respond to estrogen and pituitary hormones (FSH, LH)
   6. The process of menopause may take 6-12 months

C. Cysts

1. Most common cause of enlarged ovaries
2. Types
   1. Serous Cyst: from invagination of surface epithelium surrounding ovary
   2. Follicle Cyst
   3. Corpus Luteum Cyst
   4. Neoplastic
3. Follicle Cysts
   1. Thin walled, fluid filled structures which usually regress within two months
   2. Lined internally by granulosa, externally by theca interna
   3. Occur up to any age prior to menopause
   4. Probably related to abnormalities in release of pituitary gonadotrophins
   5. If cyst persists, hormones can lead to precocious puberty or menstrual irregularities
   6. Rarely exceed 5cm. in diameter
4. Corpus Luteum Cyst
   1. Delayed resolution of central cavity of corpus luteum
   2. Results in continued progesterone synthesis ±> abnormal menstruation
   3. Rupture of cyst can lead to hemorrhage to abdominal cavity
   4. Cysts are 3-5cm in diameter, typically yellow walled
   5. Composed of large luteinized granulosa cells

D. Polycystic Ovary Syndrome

1. One of most common causes of infertility
2. Also called Stein-Leventhal Syndrome
3. Characteristics
   1. Anovulation due to high androgen levels
   2. Hirsutism due to androgen overproduction
   3. Obesity from excess estrogens
4. Pathology
   1. Ovaries are grossly enlarged bilaterally due to multiple cysts
   2. Surface of ovary is thick and smooth consistent with anovulation
   3. The ovaries contain many small subcapsular cysts
   4. Numerous follicles in early stages of development or atresia only
   5. Later stage follicles and corpus luteal cysts are not found

D. Tumors Metastatic to the Ovary

1. About 2% of ovarian tumors arise outside the ovary
   1. Breast > Colon > Stomach > Genital Tract
   2. Breast metastases usually microscopic, not clinically detectable
   3. Such metastases are found in ~10% of ovaries removed for advanced breast cancer
2. Colon Cancer Metastases almost always mimic primary ovarian mass
3. Krukenberg tumors are ovarian metastases with the following characteristics:
   1. Single or multiple nests of mucin filled "signet ring" cells
   2. Cellular stroma derived from the ovary
   3. Stomach is primary site in 75% of cases
4. Bilateral ovarian involvement is clue to diagnosis of metastatic disease
   1. Both ovaries involved grossly in ~75% of disease
   2. Microscopic mets are often found in the unaffected ovary in "unilateral" disease
   3. Thus, both ovaries are always removed prophylactically

References

1. El-Fafaey H, Rajasekar D, Abdalla M, et al. 1995. NEJM. 332:983
2. Hausknecht RU. 1995. NEJM. 333(9):537
3. Crenin MD and Vittinghoff E. 1994. JAMA. 272:1190
4. Weiss G, Skurnick JH, Goldsmith LT, et al. 2004. JAMA. 292(24):2991