Gynaecology

1. Anovulation, Ovarian Disorders
Natangwe Shimhanda
MBChB V, UNAM SOM
10/08/16

2. Anovulation

4. Anovulation
• Failure or absence of Ovulation
• Ovulation: The release of a secondary oocyte
from the mature graafian follicle in response
to LH surge

5. The normal menstrual cycle
• Menarche 10-15 years
• Cycle 28 (+-) 7 days
• Flow 4 (+/-) 2 days
• Blood loss 20-80mls
• Ovulation occurs on day (+/-) 14 [in-between
the follicular and the luteal phase]

6. The Menstrual cycle
Ovarian Phases:
Follicular; Ovulation
and Luteal
Uterine Phases:
Proliferative and
Secretory
(Menstruation)

7. Ovarian Cycle

9. Ovarian Phases
Follicular Phase [Day 1 14]
• This is the first day of menses
• There’s development of the ovarian
follicles in response to FSH
• From birth each ovary is packed with
many primordial follicles each containing
an immature ovum (primary Oocyte)
• At start of each cycle, several of the
follicles enlarge (antrum formation)
• On Day 6, one of the follicles in one of
the ovaries starts to grow rapidly,
becoming the dominant follicle (ability of
follicle to produce estrogen, determines
which follicle is “chosen”)
• Others regress becoming atretic follicles
(involves apoptosis).

10. Follicular Phase
• FSH and LH secretion is affected by the negative
feedback loop from estrogen and progesterone

11. Day 14, Ovulation
• On Day 14, distended follicle ruptures releasing the secondary
oocyte due the production of collagenases preceded by the
LH surge
• The ruptured follicle fills with blood, forming a corpus
hemorrhagicum
• This causes minor bleeding from follicle into the abdominal
cavity in turn causing peritoneal irritation and fleeting
abdominal pain (“mittelschmerz”)
• Follicle proliferates, fills with luteal cells and forms the corpus
luteum. This initiates the luteal phase of the menstrual cycle

12. Luteal Phase
• During this luteal phase, luteal cells secrete progesterone and
estrogen
• If pregnancy (fertilization of extruded ovum) occurs, corpus
luteum persists and there are usually no more periods until
after delivery
• If pregnancy does not occur, corpus luteum begins to
degenerate at about Day 24 and is replaced by scar tissue
forming a corpus albicans

13. Causes of amenorrhea
• Primary amenorrhea is the failure of menses to occur by age
16 years, in the presence of normal growth and secondary
sexual characteristics.
• Secondary Amenorrhea: absence of menses for > 6 months
after documented menarche or 3 consecutive cycles

14. Primary amenorrhoea

15. Definition
 Absence of menses by the age 16yrs or
 When pubertal changes precede menarche and they still haven’t reached
menarche by the age of 16 or
 Having no sign of secondary sexual characteristics, such as thelarche or
pubarche—thus are without evidence of initiation of puberty

16. Causes
Ovarian:
 Gonadal dysgenesis (Turner's syndrome, most
common)
 Pure gonadal dysgenesis
 XY gonadal dysgenesis (Swyer's syndrome)
 Mixed gonadal dysgenesis
 Galactosaemia (causes ovarian failure)
 Chronic functional anovulation of pubertal onset
 Androgen insensitivity syndrome (Testicular
feminization syndrome)
 Prader-Willi syndrome(hypogonadism, rare)
 Aromatase deficiency (leads to virilization)

17. Uterine
 Müllerian agenesis/ Mayer-Rokitansky-Küster-Hauser (Second most
common)
 Cervical agenesis
 Congenital absence of the uterus and vagina (idiopathic)
Vaginal: Outflow tract obstructions also known as cryptomenorrhoea
 Vaginal atresia,
 imperforate hymen
 Transverse Vaginal septum
Adrenal
 17 α-hydroxylase deficiency (congenital adrenal hyperplasia)
Thyroid
 hypothyroidism
Endocrinology:
 Abnormal hypothalamic-pituitary function
 Hypothalamic: Kallmann syndrome
Others
 Anorexia nervosa
 obesity

18. Secondary Amenorrhoea
absence of menses for > 6 months
after documented menarche or 3
consecutive cycles

19. Causes of secondary amenorrhea
Commonest:
• Pregnancy
• Hypothalamic amenorrhea
• Pituitary amenorrhea
• Androgen disorders : Polycystic ovarian syndrome, adult-onset
adrenal hyperplasia
• Galactorrhea-amenorrhea syndrome
Less Common
• Premature ovarian failure
• Asherman’s syndrome
• Sheehan’s syndrome
• Drug-induced amenorrhea

20. Rare causes
• Diabetes
• Hyperthyroidism or hypothyroidism
• Cushing’s syndrome or Addison’s disease
• Cirrhosis
• Infection (TB, syphilis,encephalitis/meningitis,sarcodosis)
• Chronic renal failure
• Malnutrition
• Irradiation or chemotherapy
• Hemosiderosis
• Surgery

21. Evaluation
History
 Begin with questions regarding purbetal development in terms of onset
and progression
 Regularity of menstrual cycle and its absence
 Cycle interval, duration, and amount of menstrual flow
 Any change in menstrual pattern noted and whether change was sudden
or gradual
 Any correlation of development of amenorrhea with pelvic infection,
surgery, radiation therapy, chemotherapy, or other illnesses
Surgical history
 Prior pelvic surgery particularly intrauterine surgery including dilatation
and curettage
 A focused review of symptoms can be helpful e.g new onset headaches or
visual changes may suggest a tumour of CNS or pituitary gland.
 Bilateral breast discharge is consistent with the Dx of hyperprolactinemia

22.  Thyroid disease presence may be associated with heat or cold
intolerance, weight changes and sleep abnormalities
 Hot flashes and vaginal dryness suggest hypergonadotropic
hypogonadism, that is premature ovarian failure
 Hirsuitism and acne frequently seen with PCOS or with adult-onset
CAH
 Cyclic pain would suggest a reproductive tract outlet obstruction
Family history:
 Any history of premature cessation of menses or a history of
autoimmune disease including thyroid disease, which would suggest
an increased risk for POF.
 History of irregular menses, infertility, or signs of excess androgen
production those with PCOS
 Sudden neonatal death may have occurred in family members
carrying mutations in CYP21 gene responsible for CAH
Social history
 ought to investigate exposure to environmental toxins, including
cigarettes
 Medications that increase prolactin levels such as antipsychotics
ought to be noted

23. Physical examination
 General examination is very important!!
 Checkout for a low BMI, with tooth enamel erosion from recurrent
vomiting may be suggestive of an eating disorder
 Signs of Turner syndrome
 Midline facial defects e.g cleft palate are consistent with a
developmental defect of the hypothalamus or anterior pituitary
gland
 HPT in prepurbetal girl may suggest mutation in CYP17 gene and
shunting of the steroidogenic pathway toward aldosterone.
 Visual fields defects, particularly bi-temporal hemianopsia may
indicate a pituitary gland or central nervous system tumour.
 Skin should be inspected for acanthisis nigricans, hirsuitism, or
acne which may indicate PCOS or other causes of
hyperinsulinemia and/ or hyperandogenism

24.  A sparse or absent female hair pattern may be due to
either lack of adrenarche or androgen insensitivity
syndrome
 Elevated androgens will result in a male pattern of
genital hair growth,signs of verilization such as
clitoromegaly, voice deepening and pattern balding
 Evidence of estrogen production includes a pink, moist
vagina and cervical mucus
 Rectal and digital vaginal examination may help
identify a uterus above an obstruction at the level of
introitus or in the vagina

25. Labaratory tests

27. Imaging

28. Management
• Depends on aetiology
• Aims of patient, such as desire to treat
hirsuitism or become pregnant
• Anatomic abnormalities- Surgical correction if
possible

29. • Individuals desire to Ovulate ( menstruation
and pregnancy)
• Aetiology of Amenorrhea
• Thyroid hormone replacement therapy: if
Amenorrhea is Secondary to Hypothyroidism
• Bromopritine induces ovulation in fifty
percent of patients

30.  Clomiphene Citrate: drug of choice in PCOS patients
who desire pregnancy
 Progestins: given to progestin challenge- positive
patients to avoid endometrial hyperplasia and
increased risk of endometrial carcinoma
 Oral Contraceptives: given to progestin challenge-
negative patients who desire menses without ovulation
 Cabergoline (Dopamine agonists): are effective in
treating Hyperprolactinemia
 Surgical removal of the Adenoma is required if a
patient has amenorrhea-galactorrhea (even though the
cure rate is only about 5-10 %

31. Ovarian Disorders

32. Polycystic Ovarian Syndrome (PCOS)
• also called chronic ovarian androgenism
• PCOS is characterized by persistent anovulation that leads to enlarged
polycystic ovaries, secondary amenorrhea or oligomenorrhea, obesity,
hirsutism and infertility

33. Epidemiology
• Polycystic ovarian syndrome is the most common endocrine
disorder of the reproductive age women and affects
approximately 4 to 12 percent
• 86 percent of women with irregular cycles had polycystic
ovaries
• Younger women have a higher incidence of PCO than woman
over 35 years

34. Aetiology
• The underlying cause of polycystic ovarian syndrome is unknown.
• Genetic
– multifactorial, polygenic
– autosomal dominant inheritance
– Genes involved in androgen synthesis and insulin resistance
• dysregulation of the CYP11a gene
– encodes the cholesterol side-chain cleavage enzyme, which is the
enzyme that performs the rate-limiting step in steroid biosynthesis
• upregulation of other enzymes in the androgen biosynthetic pathway.

35. Diagnosis
2 of 3 to make diagnosis:
• oligomenorrhea/irregular menses for 6 months
• clinical or lab evidence of hyperandrogenism
• polycystic ovaries on U /S

36. Clinical Features
• in adolescents, wait at least 1-2 yrs to make diagnosis
Oligomenorrhea
• Infertility
• abnormal/irregular uterine bleeding, hirsutism, infertility,
obesity, virilization
• insulin resistance occurs in both lean and obese patients
• acanthosis nigricans: browning of skin folds in intertriginous
zones (indicative of insulin resistance)
• family history of diabetes

37. Investigations
Pcos is often reffered to as a diagnosis of exclusion
• goal of investigations is to identify hyperandrogenism or chronic
anovulation and rule out specific pituitary or adrenal disease as the
cause
Diagnosing LAB Pcos includes measurement of:
• Thyroid stimulating hormone
• prolactin
• Testosterone
• Dehydroepiandrosterone
• Gonadotropins
• 17a- hydroxyprogesterone
• Cortisol
• Measurement of insulin resistance and dyslipidemia

38. Thyroid
– Hypo and hyperthyroidism may lead to menstrual dysfunction
Prolactin
– Elevated prolactin levels is a cause of menstrual irregularities and may lead to anovulation
Testosterone
– Elevated free testosterone levels may be as a result of ovarian or adrenal tumours and lead to
virilization
Dehydroepiandosterone Sulfate
– Are only produced in the adrenal gland, so serum DHEAS levels above 700 micrograms/dl is highly
suggestive of adrenal neoplasm
Gonadotropins
– Not all woman with PCOS have an elevated ratio of serum LH: FSH
– Hence LH and FSH have little value to diagnosis of PCOS
17 alpha-hydroxyprogesterone
– Levels above 1000 ng/dl is indicative of late-onset congenital adrenal hyperplasia
Cortisol
– Cushing syndrome results from prolonged exposure to elevated levels of glucocorticoids
Insulin Resistance and dyslipidemia
– Measure fasting blood glucose and 2-hour oral glucose tolerance test
– Depending on the levels, the patient will either be diagnosed with impaired glucose tolerance or
diabetes mellitus
– Fasting lipid profile is used to evaluate dyslipidemia
Summary of testing in PCOS
– FSH, LH, TSH, Total T, PRL, DHEAS, 17-OH-OP, 2hr GTT, lipid profile, measurement of BMI, waist
circumference, BP

39. Transvaginal or Transabdominal U/S
• polycystic-appearing ovaries ("string of pearls" - 12 or more small follicles
2-9 mm, or increased ovarian volume)

40. Management
The primary treatments for PCOS include:
• lifestyle changes,
• medications and
• surgery.
Goals of treatment may be considered under four categories:
• Lowering of insulin resistance levels
• Restoration of fertility
• Treatment of hirsutism or acne
• Restoration of regular menstruation, and prevention of
endometrial hyperplasia and endometrial cancer

41. Treatment includes:
• Weight loss (50% of them that lose lose weight, their
Treatment for oligoovulation and anovulation
• Combination oral contraceptive pills (COCs)
• Cyclic progesterone
• Insulin sensitizing agents
Treatment for acne
• Topical retinoids
• Topical benzoyl peroxide
• Topical and systemic antibiotics
• isotretinoin
Treatment for Hirsutism
• Combination oral contraceptive pills
• Gonadotropin-releasing hormone agonist
• Eflonithine
• Androgen-receptor antagonist
• 5-alpha-reductase inhibitors
• For hair removal –depilation and epilation (skin removal above skin surface e.g. shaving and
removal of entire hair shaft e.g. waxing or permanent removal: laser therapy)
Surgical therapy:
• Laparoscopic ovarian drilling restores ovulation to women found to be resistant to clomiphene.
• Oophorectomy is not done for women

42. Differential Diagnosis
• hypothyroidism
• congenital adrenal hyperplasia (21-hydroxylase deficiency)
• Cushing's syndrome
• hyperprolactinemia
• androgen secreting neoplasm's,
• pituitary or adrenal disorders

43. Ovarian tumors
• Non-neoplastic
• Ovarian Neoplasia

44. Characteristics of Benign vs Malignant
Ovarian tumors
Benign
• Reproductive age group
(epithelial cell)
• Very large tumors
• Unilateral
• Freely mobile
• Capsule intact, smooth
surface, cystic, unilocular
• No ascitic fluid
• Smooth peritoneal surfaces
Malignant
• Very young (germinal cell) or
older (epithelial cell) age
groups
• Bilateral
• Fixed, adherent to adjacent
organs
• Multiloculation, thick septa,
disruption of solid areas
• Ascities
• Peritoneal seeding e.g. cul de
sac and bowel serosa

45. Benign ovarian tumors
• Functional tumors
• Follicular cyst; Lutein cyst; theca-Lutein cyst; chocolate
cyst
• Germ cell tumors
• Cystic teratomas/ dermoid cyst
• Epithelial ovarian tumors
• Serous; mucinous; endometroid; brenner;
• Sex cord-stromal ovarian tumors
• Fibromas; granulosa-theca cell tumors; Sertoli-leydig
cell tumors

46. Follicular Cyst
• Follicle fails to rupture during ovulation
• Seldom measures greater than 6-8cm
• Anovulatory Cycles
• Fertility drugs
• Polycystic ovary syndromes
– S&S
• Usually asymptomatic or Mild pain
• May rupture, bleed, twist, and infarct causing pain
• Severe pain -> rupture or haemorrhage in cyst
– DD: Ectopic Pregnancy
– Management
• Conservative (4-6cm), Ultrasound in 2 – 3 weeks Follicular cyst
disappear (often regress with the next cycle)
• If unchanged or larger
– Laparoscopy -> Aspirated -> Cytology

47. Lutein Cyst
– Corpus Luteum fails to regress after day 14 becoming cystic and
persists in a functional state longer than normal
• Clinically
– May rupture, bleed, twist and infarct; mild to severe pain; may
delay onset of next period
• DD: Ectopic
• Ultrasound/Cytology: usually slightly larger and firmer than a
follicular cyst
• Management
– If < 6cm, wait 6 weeks and then re-examine as cyst may regress
– Ovarian suppresion
– Aspiration via laparoscopy

48. Theca-Lutein Cysts
– Due to atretic follicles stimulated by abnormally high blood levels of
beta-hCG
• Clinically
– Periods of amenorrhea followed by heavier than usual uterine
bleeding
– Classically associated with molar pregnancy
– Also occurs with PCOS; DM; Ovulation induction, multiple pregnancy
• DD: Ectopic
• Multiple or larger Theca-Lutein Cysts are associated with trophoblastic
diseases due to hCG stimulation
• Management
– consevative
– Spontanous resolution is normal, cyst will regress as beta-hCG levels
falls

49. Germ cell tumors
• Arise from totipotential differentiated germ
cells
-> Embryonic
-> Extra embryonic
• Benign Teratoma (mature tissue)
– Dermatoid Cyst

50. Cystic Teratoma
• Commonest single ovarian tumour in young women
• Usually symptomless but torsion or rupture -> acute
abdomen
• Bilateral in 20%
• Mostly contains dermal appendages (sweat sebaceous
glands, cartilage, hair follicles, neural tissue and teeth)
• Smooth walled, mobile, often unilocular, ultrasound
may show calcification
• Management: cystectomy, may recur

51. Surface epithelial Tumors
1. Serous papillary tumours
• Benign serous cystadenoma
• 10% of ovarian tumours
• Bilateral in 50%
• Unilocular with smooth cut surface
• Lining cells are cuboidal and columnar
2.Mucinous tumour
• Benign mucinous cytsadenoma
• 30% of Ovarian tumours
• Large, unilateral, multilocular cysts
• Lined with mucous – secreting columnar cells
• Pseudo myxoma peritoneum

52. 3. Endometroid tumor
• Solid tumour
• Contain elements of both serous and mucinous tumour
4. Brenner Tumor
• Usually benign
• Unilateral
• Squamous cells surrounding a central core of columnar
epithelium and fibrous tissue

53. Sex cord-stromal tumors
Fibroma/Thecoma(benign)
• From mature fibroblasts in ovarian stroma
• Non-functioning
• Occasionally associated with Meig’s syndrome
(benign ovarian tumour and ascites and
pleural effusion)
• Firm, smooth rounded tumour with interlacing
fibrocytes

54. Granulosa-Theca Cell Tumours
(benign/malignant)
• Can be associated with endometrial cancer
• Inhibin is tumour marker.
• Estrogen-producing ->feminizing effects
(precocious puberty, menorrhagia,
postmenopausal bleeding)
• Histologic hallmark of cancer is small groups
of cells known as Call-Exner bodies

55. Sertoli-Leydig Cell Tumour
(benign/malignant)
• Can measure elevated androgens as tumour
markers.
• Androgen-producing -> virilizing effects
(hirsutism, deep voice, recession of front
hairline)

56. General Treatment
• Surgical resection of tumour
• Chemotherapy may be used for unresectable
metastatic disease

57. MALIGNANT OVARIAN TUMOURS
Epidemiology
• lifetime risk 1.4% (1/70)
• in women >50 yr, more than 50% of ovarian tumors
are malignant
• 65% epithelial; 35% non-epithelial
• 5-10% of epithelial ovarian cancers are related to
hereditary predisposition

58. Risk Factors
• excess estrogen
• ƒnulliparity
• ƒearly menarche/late menopause
• age
• family history of breast, colon, endometrial, ovarian cancer
• race: Caucasian
• OCP is protective (likely due to ovulation suppression)

59. Clinical features
• most women with epithelial ovarian cancer present with
advanced stage disease since often “asymptomatic” until
disseminated disease (symptoms with early stage disease are
vague and non-specific)
• when present, symptoms may include:
• ƒabdominal symptoms (nausea, bloating, dyspepsia, anorexia,
early satiety)
• ƒsymptoms of mass effect
• Šincreased abdominal girth – from ascites or tumour itself
• Šurinary frequency
• Šconstipation
• ƒpostmenopausal bleeding; irregular menses if pre-
menopausal (rare)

60. • Age
• Tumour in childhood frequently malignant
• 45% of tumour removed from women aged 45yrs or over are malignant
• Pain
• Benign are never painfull unless complicated
• Malignant -> dull aching pain
• -> Sacral nerve root pain
• Growth
• Rapid growth suggest malignancy
• Bilateral
• 75% of malignant tumours are bilateral
• 15 % of benign are bilateral
• Consistency -> Malignant
• Solid
• Nodular
• Irregular
• Fixed
• Ascites
• Usually a sign of peritoneal metastasis

61. • Oedema of legs and Vulva
• Venous obstruction -> Suggestive of malignancy
• Metastatic deposits
• Liver
• Supraclavicular lymph nodes
• Pouch of Douglas
Surgical staging and histological staging are more
important prognostic indicators than the type of
tumour

62. Aids to Diagnosis
• Ultrasound
• CAT Scan
• MRI
• Tumour Markers
– Epithelial cell – CA-125
– Stromal
• Granulosa cell – inhibin
• Sertoli-Leydig – androgens
– Germ cell
• Dysgerminoma – LDH
• Yolk sac – AFP
– Choriocarcinoma – beta-hCG
– Immature Teratoma – none
– Embryonal cell – AFP + beta-hCG
• Laparoscopy

63. FIGO Staging

64. MALIGNANT GERM-CELL TUMOURS
1. Malignant Teratoma
• Embryonic (immature tissue) structures
2.Extra-embryonic germ cell tumours
• Choriocarcinoma - ↑↑↑ Beta-HCG
• Yolksac Tumours - ↑↑↑ AFP
3.Dysgerminoma
• From undifferentiated Germ Cells
• Counterpart of Seminoma in males
• Arising 20-30yrs of age
• Conservative surgery
• VERY radiosensitive

65. MALIGNANT GERM-CELL TUMOURS
Management
• Surgical resection (often conservative
unilateral salpingo-oophorectomy ± nodes) ±
chemo
• Usually very responsive to chemotherapy,
therefore complete resection is not necessary
for cure
• More aggressive subtype, often need chemo
(bleomycin, etoposide, cisplatin, BEP)

66. Malignant serous epithelial tumors
1. Malignant serous cystadenocarcinoma
• 10% of ovarian neoplasia
• Bilateral in 50%
• Lining cells cuboidal or columnar epithelium resembling endosalpinx
2. Mucinous Cystadenocarcinoma
• 30- 40% of ovarian neoplasm
• Large unilateral mutlilocular cyst
• Lined by tall mucous secreting columnar cells
• Cyst rupture -> cells implant on peritoneum -> pseudomyxomaperitonei
3. Endometroid
• Solid
• Associated with endometrial Ca
• Good prognosis
4. Clean Cell (mesonephroid) tumours
• Ovarian and Endometrial tumours, co-exist

67. Management of malignant epithelial
cell tumors
Borderline
• Cystectomy vs. unilateral salpingo-oophorectomy
Malignant
1. Early stage (stage 1 ): BSO ± hysterectomy ±
omentectomy ± peritoneal washings ± staging (peritoneal
biopsies + node dissection) ± adjuvant chemotherapy
2. Advanced stage:
• Upfront cytoreductive (debulking) surgery vs.
neoadjuvant chemotherapy
• Adjuvant chemotherapy: IP chemotherapy vs. IV
Carbo/Taxol

68. METASTATIC OVARIAN TUMOURS
• 4-8% of ovarian malignancies
• From Gl tract, breast, endometrium,
lymphoma, uterus, large bowel
• Krukenberg tumour = metastatic ovarian
tumour from other site (usually Gl tract,
commonly stomach or colon, breast) with
"signet-ring" cells

69. Malignant Ovarian Tumour Prognosis
5 Year Survival
• Stage I 75-95%
• Stage II 60-75%
• Stage III 23-41%
• Stage IV 11%

70. Differential
• Variety of pelvic and abdominal swellings
– Physiological
• Full bladder, pregnancy, obesity, flatus
– Congenital
• Uterine anomaly, pelvic and polycystic kidney
– Traumatic
• Rectus abdominis haematoma
– Infective
• Pelvic abscess, pyosalpinx, hydrosalpinx, appendectal absess,
diverticulitis
– Neoplastic
• Fibroids, tumours of Colon, Ascites, Mesenteric Cyst
– Pregnancy associated
• Pregnancy in uterine horn, ectopic, Corpus Luteum of Pregnancy

71. References
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Amenorrhea in the Adolescent. Stanford University School of
Medicine: USA, California
• Decherney., A.H., & Nathan.,L. (2007). Current diagnosis &
treatment. USA: The McGraw hill, Cenveo publisher.
• Hoffman., B.L., Schorge.J.O & Schaffer., J.I. (2012). William
Gynecology. USA, Texas:The McGraw hill
• Adam J, Polson DW, Franks S: prevalence of polycystic ovaries in
women with anovulation and idiopathic hirsutism. Br Med J(Clin
Res) 293:355, 1986.
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