Gynaecology

Question 1

What causes gonads to develop into testis?

Answer 1

• SRY

Question 2

Describe the development of the male sexual organs

Answer 2

• As the gonads become testes, it differentiates into TWO cell types:
  
  • Sertoli cells - produce anti-Mullerian hormone (AMH)
  • Leydig cells - produce testosterone
• AMH suppresses further development of the Mullerian ducts
• Testosterone stimulates the Wolffian ducts to develop into the vas deferens, epididymis and seminal vesicles
• Testosterone is converted to DHT by 5a-reductase in the external genital skin to virilise the external genitalia
• The genital tubercle becomes the penis and the labioscrotal folds fuse to form the scrotum
• The urogenital folds fuse along the ventral surface of the penis and enclose the urethra

Question 3

Describe the development of the female sexual organs

Answer 3

• In the primitive ovary, granulosa cells surround the germ cells and form primordial follicles
• Each follicle consists of an oocyte within a single layer of granulosa cells
• Thecal cells develop from the proliferating coelomic epithelium and are separated from granulosa cells by basal lamina
• The maximum number of primordial follicles are reached at 20 weeks (roughly 6-7 million)
• The numbers reduce by atresia and by birth only 1-2 million remain
• Atresia continues throughout life and about 300,000-400,000 are present at menarche
• The development of an oocyte within the primordial follicle is arrested in prophase of its first meiotic division
• It remains like this until it either undergoes atresia or enters the meiotic process preceding ovulation
• The absence of AMH in the female allows development of the Mullerian structures
• The proximal 2/3 of the vagina develop from the paired Mullerian ducts
• The midline fusion of these structures produces the uterus, cervix and upper vagina
• The unfused caudal segments form the Fallopian tubes
• Cells from the upper part of the urogenital sinus proliferate to produce the sinovaginal bulbs
• The caudal extension of the Mullerian ducts projects into the posterior wall of the urogenital sinus as the Mullerian tubercle
• The Mullerian ducts and the urogenital sinus fuse and canalise starting at the hymen and moving up to the cervix

Question 4

How do the external female genitalia develop?

Answer 4

• Do NOT virilise in the absence of testosterone
• Cloacal folds fuse anteriorly to become the genital tubercle (this becomes the clitoris)
• The cloacal folds anteriorly are called the urethral folds and form the labia minora
• Another pair of folds within the cloacal membrane form the labioscrotal folds which form the labia majora
• The urogenital sinus becomes the vestibule of the vagina

Question 5

What does the vulva (external genitalia) include?

Answer 5

• Mons pubis
• Labia majora
• Labia minora
• Vaginal vestibule
• Clitoris
• Greater vestibular glands

Question 6

Describe the labia majora and minora

Answer 6

• The labia majora contain sebaceous and sweat glands
• There is a core of fatty tissue at the deepest part of each labium
• The labia minora divide anteriorly to form the prepuce and frenulum of the clitoris (clitoral hood)
• Posteriorly they divide to form the fourchette
• The labia minora contain sebaceous glands but no adipose tissue
• Both labia become engorged during sexual arousal

Question 7

What is the clitoris?

Answer 7

• The clitoris is made up of paired columns of erectile and vascular tissue called the corpora cavernosa

Question 8

What is the vestibule?

Answer 8

• The vestibule is the cleft between the labia minora

- It contains openings of the urethra, Bartholin’s glands and the vagina

Question 9

What are the Bartholin’s glands?

Answer 9

• They are bilateral and about the size of a pea

- They open via a 2 cm duct into the vestibule below the hymen and contribute to lubrication during intercourse

Question 10

What is the hymen?

Answer 10

• The hymen is a thin covering mucous membrane across the entrance to the vagina
• It is usually perforated to allow menstruation
• It is ruptured during intercourse
• Any remaining tags are called carunculae myrtiformes

Question 11

Describe the vagina

Answer 11

• The vagina is a fibromuscular canal lines by stratified squamous epithelium
• It is longer in the posterior wall (9 cm) than the anterior wall (7 cm)
• The vault of the vagina is divided into FOUR fornices: posterior, anterior and two lateral
  
  • NOTE: the vault is the expanded region of the vaginal canal at the internal end of the vagina
• The vaginal wall is lined by transverse folds
• The vagina has NO glands and is kept moist by secretions from the uterine and cervical glands and by transudation from the epithelial lining
• The epithelium is thick and rich in glycogen
• Before puberty and after menopause, the vagina has NO glycogen because of a lack of stimulation by oestrogen
• Doderlein’s bacillus is a normal commensal that breaks down glycogen to form lactic acid producing a low pH (this is protective as it prevents the growth of pathogenic bacteria)
• Anteriorly the vagina is in direct contact with the base of the bladder
• Laterally, at the fornices, the vagina is related to the cardinal ligaments
• Below this you see the levator ani muscles and ischiorectal fossae
• The cardinal ligaments and uterosacral ligaments form the parametrium
• At birth, the vagina is under the influence of maternal oestrogens so is well developed
• After a few weeks after birth, these effects will disappear

Question 12

Describe the Uterus

Answer 12

• Maximum external dimensions = 7.5 cm x 5 cm x 3 cm
• Adult uterus weight = 70 g
• The cornu is the site of insertion of the Fallopian tube
• The corpus is the body of the uterus
• The area of the uterus above the cornu is the fundus
• The longitudinal axis of the uterus is roughly at right angles to the vagina and tilts forwards (anteversion)
• The uterus also flexes forwards on itself (anteflexion)
• In 20% of women, the uterus is tilted backwards (retroversion and retroflexion)
• This is of NO pathological significance
• The os is the opening of the cervix
• The internal os is where the mucous membrane of the isthmus becomes that of the cervix
• The uterus has THREE layers:
  
  • Peritoneum - outer serous layer
  • Myometrium - middle muscular layer
  • Endometrium - inner mucous layer
• The peritoneum covers the body of the cervix and the supravaginal part of the cervix
• The peritoneum is attached to the subserous fibrous layer, except laterally where it spreads out to form the leaves of the broad ligament
• Externally, the myometrium consists of mostly longitudinal muscle fibres
• The thicker intermediate layer has interlacing longitudinal, oblique and transverse fibres
• Internally, they are mainly longitudinal and circular
• The inner endometrial layer has tubular glands that dip into the myometrium
• The endometrial layer is covered by a single layer of columnar epithelium

Question 13

Describe the Cervix

Answer 13

• Roughly 2.5 cm in length
• Lateral to the cervix is the parametrium (connective tissue)
• The ureters run 1 cm laterally to the supravaginal part of the cervix
• The mucous membrane of the cervix (endocervix) has anterior and posterior columns from which folds radiate out (arbour vitae)
• It has lots of deep glandular follicles that secrete clear alkaline mucus (the main component of physiological vaginal discharge)
• The epithelium of the endocervix is columnar and ciliated in the upper 2/3
• This will transition to squamous epithelium at the squamocolumnar junction

Question 14

What age related changes happen to the anatomy of the female sexual organs?

Answer 14

• Loss of maternal oestrogens from the circulation after birth causes the uterus to decrease in length and weight
• The cervix will be twice the length of the uterus at this point
• During childhood, the uterus grows slowly
• After the onset of puberty, the dimensions of the uterus start to increase

Question 15

Describe the fallopian tubes

Answer 15

• Extend outwards from the uterine cornu to end near the ovary
• At the abdominal ostium, the tube opens into the peritoneal cavity
• The Fallopian tubes take the ovum from the ovary towards the uterus and promote oxygenation and nutrition for sperm, ovum and zygote
• They run in the upper margin of the broad ligament (mesosalpinx)
• This encloses the tube so that it is completely covered by peritoneum (except for a thin strip on the inferior side)
• Each tube is roughly 10 cm long and has FOUR parts:
  
  • Interstitial portion (lies within the wall of the uterus)
  • Isthmus (narrow portion adjoining the uterus)
  • Ampulla (widest and longest part)
  • Infundibulum or fimbrial portion (opening of the tube into the peritoneal cavity)
• One of the fimbriae extend and partially embrace the ovary
• The muscular wall of the tube has an inner circular and an outer longitudinal layer
• The tube epithelium forms a number of folds or plicae that run longitudinally
• There is NO submucosa and NO glands
• The epithelium has TWO cell types:
  
  • Ciliated cells (produce a constant current of fluid in the direction of the uterus)
  • Secretory cells (contribute to the volume of tubal fluid)

Question 16

Describe the Ovaries

Answer 16

• Size and appearance depends on age and stage of the menstrual cycle
• Proliferation of stromal cells in puberty makes them grow in size (reaching 3 cm long x 1.5 cm wide x 1 cm thick)
• The ovary becomes smaller after menopause
• The ovary is the only intra-abdominal structure that is NOT covered by peritoneum
• Each ovary is attached to the cornu of the uterus by the ovarian ligament
• It is also attached to the broad ligament by the mesovarium, which contains nerves and blood vessels
• Laterally, each ovary is attached to the suspensory ligament of the ovary with folds of peritoneum that become continuous with the overlying psoas major
• Anterior to the ovaries are the Fallopian tubes, superior portion of the bladder and the uterovesical pouch
• Posterior to the ovary is the ureter

Question 17

Describe the structure of the ovaries

Answer 17

• It has a central vascular medulla consisting of loose connective tissue containing elastin fibres and non-striated muscle cells
• It has an outer thicker cortex which is denser than the medulla
• It contains networks of reticular fibres and fusiform cells
• The surface of the ovaries has a single layer of cuboidal cells (germinal epithelium)
• Underneath this layer is another layer called the tunica albuginea (increases in density with age)
• At birth, most primordial follicles are found within the cortex
• After puberty, some follicles become Graafian follicles and ovulate and become the corpus luteum
• This will ultimately undergo atresia and become the corpora albicans

Question 18

Describe the bladder

Answer 18

• The bladder is made of involuntary muscle arranged in an inner longitudinal layer, middle circular layer and outer longitudinal layer
• It is lined by transitional epithelium
• The average capacity is 400 mL
• The ureters open into the base of the bladder after running through the bladder wall for about 1 cm
• The internal meatus of the urethra is known as the trigone
• The base of the bladder is adjacent to the cervix
• It is separated from the anterior vaginal wall by pubocervical fascia that stretches from the pubis to the cervix

Question 19

Describe the urethra

Answer 19

• Roughly 3.5 cm long
• Lined with transitional epithelium
• Smooth muscle of the wall is arranged into outer longitudinal and inner circular layers
• The upper part of the urethra is mobile but the lower part is relatively fixed
• On voluntary voiding of urine, the base of the bladder and the upper part of the urethra descend and the posterior angle disappears so that the base of the bladder and the posterior wall of the urethra come to lie in a straight line

Question 20

Describe the ureter

Answer 20

• As the ureter crosses the pelvic brim, it lies in front of the bifurcation of the common iliac artery
• It reaches the pelvic floor and then passes inwards and forwards to attach to the peritoneum of the back of the broad ligament, passing under the uterine artery
• It then passes through the ureteric canal
• It runs close to the lateral vaginal fornix to enter the trigone of the bladder
• Its blood supply is from small branches of the ovarian artery
• IMPORTANT: the ureter can get damaged during a hysterectomy (e.g. cut, tied, necrosis due to interference with blood supply)

Question 21

Describe the rectum

Answer 21

• The rectum begins at the level of the 3rd sacral vertebra
• The front and sides are covered by the peritoneum of the rectovaginal pouch
• The lower third of the rectum has no peritoneal covering and the rectum is separated from the posterior wall of the vagina by the rectovaginal fascial septum
• Lateral to the rectum are the uterosacral ligaments alongside which run some of the lymphatics draining the cervix and vagina

Question 22

What is intermenstrual bleeding?

Answer 22

• bleeding between periods, often seen with endometrial and cervical polyps and endometriosis

Question 23

What is post-coital bleeding?

Answer 23

• Beeding after sex. Associated with cervical abnormalities

Question 24

What is postmenopausal bleeding?

Answer 24

• Bleeding more than 1 year after cessation of periods. Exclude endometrial pathology or vaginal atrophy

Question 25

What is bleeding of endometrial origin?

Answer 25

• Diagnosis of exclusion that has replaced the term ‘dysfunctional uterine bleeding (DUB)’

Question 26

What is the system for characterising causes of gynae pathology?

Answer 26

• PALM- visually objective structural criteria
  
  • Polyps
  • Adenomyosis
  • Leiomyoma
  • Malignancy
• COEIN- causes unrelated to structural anomalies
  
  • Coagulopathy
  • Ovulatory disorders
  • Endometrial
  • Iatrogenic
  • No classified

Question 27

What is the definition of heavy menstrual bleeding?

Answer 27

• Blood loss of > 80 mL per period
• As this is difficult to quantify in practice, the definition has since changed such that heavy menstrual bleeding is whatever the patient regards as being abnormally heavy
• NOTE: methods of quantifying blood loss is impractical and inaccurate so the diagnosis relies on the patient’s perception of blood loss
  20-30% of women of reproductive age suffer from HMB

Question 28

What are common causes of heavy menstrual bleeding?

Answer 28

• Polyps (endometrial)
• Adenomyosis
• Leiomyoma (fibroids)
• Malignancy (endometrial and cervical carcinoma)
• Coagulation disorders
• Intrauterine devices (IUDs)
• Pelvic inflammatory disease
• Thyroid disease
• Drug therapy (e.g. warfarin)
• Often no pathology is identified

Question 29

What are key features in history for HMB?

Answer 29

• Heaviness of period
• Extent to which it disrupts the woman’s life and causes anaemia
• Did the HMB start at menarche or has it changed since?
• Regularity of the menstrual cycle

Question 30

What are irregular bleeding, PCB and IMB suggestive of?

Answer 30

• Endometrial or cervical polyps

- Other cervical abnormalities

Question 31

What are excessive bruising/bleeding from other sites, Hx of PPH, excessive postoperative bleeding, FHx of bleeding problems suggestive of?

Answer 31

• Coagulation disorders (coagulation disorders will be present in 20% of those presenting with unexplained HMB

Question 32

What is unusual vaginal discharge associated with?

Answer 32

• PID

Question 33

What are urinary symptoms, abdominal masses or abdominal fullness suggestive of?

Answer 33

• Pressure from fibroids

Question 34

What investigations should be done for HMB?

Answer 34

• Abdominal and pelvic examinations should be performed
  
  • This enables palpation of pelvic masses and the visualisation of polyps/carcinomas of the cervix
  • It also allows smears to be taken
• FBC
• Coagulation screen if HMB since menarche or family history of coagulation defects
• Pelvic ultrasound scan
  
  • If the history suggests structural/histological problem (e.g. post-coital bleeding, intermenstrual bleeding, pain/pressure symptoms or enlarged uterus/vaginal mass)
• High vaginal or endocervical swabs
• Endometrial biopsy
  
  • Only if risk factors (e.g. > 45 years, treatment failure)
  • Indications
    
    • PMB and endometrial thickness on TVUSS > 4 mm
    • HMB > 45 years
    • HMB associated with IMB
    • Treatment failure
    • Prior to ablative techniques
• Thyroid function test
• Outpatient hysteroscopy with guided biopsy if:
  
  • Endometrial biopsy fails
  • Endometrial biopsy sample is insufficient
  • TVUSS is inconclusive
  • Abnormality of TVUSS is amenable to treatment
• NOTE: if the patient cannot tolerate an outpatient hysteroscopy, a hysteroscopy under GA may be needed

Question 35

What are the factors to consider when managing heavy menstrual bleeding?

Answer 35

• Patient’s preference
• Risks/benefits of each option
• Contraceptive requirements (Family complete? Current contraception?)
• Past medical history (any contraindications? Suitability for anaesthetic?)
• Previous surgical history on uterus
• Blood loss may be normal

Question 36

What is the medical management of heavy menstrual bleeding?

Answer 36

• Levonorgestrel Intrauterine System (LNG-IUS, Mirena)
  
  • Requires long-term use (at least 12 months)
  • Reduces mean blood loss
  • Should be considered in the majority of women as an alternative to surgical treatment
  • NOT suitable in women wishing to conceive
• Tranexamic acid
  
  • Antifibrinolytic that reduces blood loss by 50%
  • Taken during menstruation
  • Mefenamic acid inhibits prostaglandin synthesis and reduces blood loss by 30%
  • COCP induces slightly lighter periods
• Norethisterone
  
  • 15 mg daily in a cyclical pattern from day 6-26 of the menstrual cycle
• Gonadotrophin Releasing Hormone (GnRH) agonists

Question 37

What is the surgical management of heavy menstrual bleeding?

Answer 37

• Usually only considered in women for whom medical treatment has failed
• Women contemplating surgery must be certain that their family is complete
• Women wishing to preserve their fertility should go for medical options
• Endometrial Ablation
  
  • Ablation to a sufficient depth to prevent regeneration
  • Suitable for women with a uterus < 10 weeks size and with fibroids < 3 cm
  • Methods
    
    • Impedance controlled endometrial ablation
    • Thermal uterine balloon therapy
    • Microwave ablation
  • 80% will have markedly reduced menstrual bleeding or become amenorrhoeic
• Uterine Artery Embolisation
  
  • Useful for HMB associated with fibroids
• Myomectomy
  
  • Useful for women with HMB secondary to large fibroids with pressure symptoms who wish to conceive
• Transcervical Resection of Fibroids
  
  • Used for resection of large submucosal fibroids
  • May reduce HMB and is appropriate for women wishing to conceive
• Hysterectomy
  
  • Surgical removal of the uterus
  • Considered in women with HMB associated with large fibroids with pressure symptoms

Question 38

What is the management of acute menstrual bleeding?

Answer 38

ABCDE

• Admit
• Pelvic examination
• FBC, coagulopathy screen, biochemistry
• IV access and fluid resuscitation
• Tranexamic acid oral or IV
• TVUSS
• High-dose progestogens to arrest bleeding
• Consider suppression with GnRH or ulipristal acetate
• Longer-term plan when diagnosis has been made

Question 39

What is dysmenorrhoea and what are the types?

Answer 39

• Painful menstruation
• Primary dysmenorrhoea = painful periods since onset of menarche (unlikely to be associated with pathology)
• Secondary dysmenorrhoea = painful periods that have developed over time and usually have a secondary cause

Question 40

What are causes of secondary dysmenorrhoea?

Answer 40

• Endometriosis or adenomyosis
• Pelvic inflammatory disease
• Cervical stenosis and haematometra (rare)

Question 41

Describe the history and examination of dysmenorrhoea?

Answer 41

• Some patients may just need reassurance
• Others may like the ability to alter the menstrual cycle to avoid having a period during key events (e.g. school examinations)
• Important to distinguish between menstrual pain that precedes the period and pain that only occurs with bleeding
• Secondary dysmenorrhoea may be associated with dyspareunia or AUB (suggesting pathology)
• Abdominal and pelvic examination should be performed
  
  • Pelvic mass - endometriosis?
  • Fixed uterus - adhesions?
  • Endometriotic nodule
  • Enlarged uterus - fibroids?
  • Abnormal discharge and tenderness - PID?

Question 42

Questions to gauge severity of the pain in dysmenorrhoea?

Answer 42

• Do you need to take painkillers for this pain? Which tablets help?
• Have you needed to take any time off work/school due to pain?

Question 43

What are the investigations for dysmenorrhoea?

Answer 43

• High vaginal and endocervical swabs
• TVUSS is useful to detect endometriomas and adenomyosis
• Diagnostic laparoscopy - to investigate secondary dysmenorrhoea
  
  • When the history suggests endometriosis
  • When swabs and ultrasound scans are normal but symptoms persist
  • When the patient wants a definitive diagnosis or wants reassurance

Question 44

What is the management of dysmenorrhoea?

Answer 44

• NSAIDs
• COCP
  
  • Widely used but may not be effective
  • Progestogens may be useful to cause anovulation and amenorrhoea
• LNG-IUS
  
  • Effective treatment for underlying causes (e.g. endometriosis and adenomyosis)
• Lifestyle changes
  
  • Exercise and dietary (vegetarian) changes may help
• Heat
  
  • Old but effective
• GnRH analogues
  
  • Useful in the short-term to manage symptoms if awaiting hysterectomy
• Surgery

Question 45

What does the hypothalamus do? (O&G)

Answer 45

• Secretes GnRH which controls pituitary hormone secretion

- GnRH is released in a pulsatile manner to stimulate pituitary secretion of LH and FSH

Question 46

What does GnRH do?

Answer 46

• GnRH stimulates basophil cells in the anterior pituitary gland which synthesise and release FSH and LH
• This is modulated by oestrogen and progesterone

Question 47

What effect does low oestrogen have on LH production?

Answer 47

• Low oestrogen has an inhibitory effect on LH production (negative feedback)
• The COCP maintains a constant serum oestrogen level that is within the NEGATIVE feedback range, thereby preventing an LH surge

Question 48

How does high oestrogen affect LH production?

Answer 48

• HIGH oestrogen will increase LH production (positive feedback)
  
  • This works by increasing concentrations of GnRH receptors
• The high levels of oestrogen in the late follicular phase act via positive feedback to generate a periovulatory LH surge

Question 49

How does low progesterone affect FSH and LH secretion?

Answer 49

• Low progesterone has a POSITIVE feedback effect on pituitary LH and FSH secretion

Question 50

How does high progesterone affect FSH and LH production?

Answer 50

• High progesterone will INHIBIT pituitary LH and FSH production
  
  • This works by increasing sensitivity to GnRH in the pituitary

Question 51

Describe ovulation and menstruation

Answer 51

• Starting at menarche, the primordial follicles which had been arrested in prophase of meiotic division, will start to activate and grow in a cyclical fashion leading to ovulation and menstruation

Question 52

What are the three phases the ovaries go through in a cycle?

Answer 52

• Follicular
• Ovulatory
• Luteal

Question 53

Describe the follicular phase

Answer 53

• Follicular development will fail at the preantral stage and follicular atresia will occur if LH and FSH are absent
• FSH rises in the first days of the menstrual cycle whilst oestrogen, progesterone and inhibin levels are low
• This FSH rise will stimulate a cohort of small antral follicles to grow
• Within the follicles there are TWO cell types:
  
  • Theca Cells - LH stimulates production of androgens from cholesterol
  • Granulosa Cells - convert androgens from theca cells into oestrogens via the process of aromatisation under the influence of FSH
• As follicles grow, oestrogen secretion increases
• This has a NEGATIVE feedback effect on FSH leading to a decrease in FSH
• This assists in the selection of the dominant follicle (smaller follicles will undergo atresia)
• Inhibin is secreted by the granulosa cells and downregulates FSH release and enhances androgen synthesis
• Activin is produced by granulosa cells and the pituitary and acts to increase FSH binding on the follicles
• NOTE: IGF-I and IGF-III also act as paracrine regulators as do Kisspeptins

Question 54

Describe ovulation

Answer 54

• By the end of the follicular phase, the dominant follicle will be about 20 mm in diameter
• FSH induces LH receptors on the granulosa cells to compensate for lower FSH levels and prepare for the signal for ovulation
• Production of oestrogen increases until it reaches a threshold to exert POSITIVE feedback on the hypothalamus resulting in an LH surge
• This happens over 24-36 hours
• LH-induced luteinisation of granulosa cells in the dominant follicle cause progesterone to be produced
• This exerts more positive feedback for LH secretion and causes a small rise in FSH
• The LH surge also stimulates the resumption of meiosis
• The physical ovulation occurs after breakdown of the follicular wall under the influence of LH, FSH, proteolytic enzymes and prostaglandins
• IMPORTANT: inhibition of prostaglandin production can affect ovulation, therefore women wanting to become pregnant should avoid taking PG synthetase inhibitors (e.g. aspirin, ibuprofen)

Question 55

Describe the Luteal Phase

Answer 55

• After release of the oocyte, the remaining granulosa and theca cells form the corpus luteum
• It undergoes extensive vascularisation to supply granulosa cells with a rich blood supply for continued steroid production (aided by local VEGF production)
• On going pituitary LH secretion and granulosa activity provides a supply of progesterone, which stabilises the endometrium in preparation of pregnancy
• The progesterone also suppresses FSH and LH to prevent further follicular growth
• The luteal phase lasts 14 days
• In the absence of b-hCG produced by the implanting embryo, the corpus luteum will regress via luteolysis
• The mature corpus luteum will produce less progesterone, which will eventually result in menstruation
• A reduction in progesterone, oestrogen and inhibin feeding back to the pituitary cause increased FSH secretion
• New preantral follicles will be stimulates and the cycle begins again

Question 56

What happens to the endometrium during the proliferative phase?

Answer 56

• Begins immediately after menstruation, when glandular and stromal growth begins
• The epithelium will change from a single layer of columnar cells to pseudostratified epithelium with frequent mitoses
• Endometrial thickness at menstruation = 0.5 mm
• Endometrial thickness at the end of the proliferative phase = 3.5-5 mm

Question 57

What happens to the endometrium during the secretory phase?

Answer 57

• After ovulation, there is a period of secretory activity
• After the LH surge, the oestrogen-induced proliferation is inhibited so that the endometrium does not get any thicker
• The endometrial glands, however, become more tortuous, spiral arteries will grow and fluid is secreted into the glandular cells and uterine lumen
• Progesterone induces the formation of a temporary layer (decidua) in the endometrial stroma
• Apical membrane projections of epithelial cells (pinopodes) appear after day 21-22 which makes the endometrium receptive for implantation

Question 58

What happens to the endometrium during menstruation?

Answer 58

• Shedding of dead endometrium
• Immediately before menstruation, there are THREE layers of the endometrium:
  
  • Basalis - lower 25% which remains throughout the menstrual cycle
  • Stratum spongiosum - oedematous stroma and exhausted glands
  • Stratum compactum - upper 25% with prominent decidualised stromal cells
• A fall in oestrogen and progesterone at the end of the luteal phase leads to loss of tissue fluid, vasoconstriction of spiral arterioles and distal ischaemia
• This leads to tissue breakdown and loss of upper layers
• NOTE: patients on HRT or COCP will have a withdrawal bleed during their pill-free week because of the lack of oestrogen and progesterone
• Vaginal bleeding will stop after 5-10 days
• NOTE: haemostasis is different in the endometrium because it does NOT involve clot formation and fibrosis
• Other factors involved in menstruation: prostaglandins, endothelins, platelet activating factor, prostacyclin, nitric oxide
• VEGF and fibroblast growth factor are powerful angiogenic agents that promote endometrial repair (requires glandular and stromal regeneration and angiogenesis)
• Epidermal growth factor (EGF) is important in oestrogen-induced glandular and stromal regeneration

Question 59

What happens during normal puberty?

Answer 59

• During childhood the HPO axis is suppressed and levels of GnRH, FSH and LH are very low
• From the age of 8-9 years, the GnRH pulsations increase in amplitude and frequency
• The increase in FSH and LH triggers follicular growth and steroidogenesis in the ovary
• The oestrogen produced by the ovaries initiates the physical changes of puberty
• Leptin plays a permissive role in puberty (hence why people who are very underweight will fail to go through puberty)

Question 60

What physical changes happen in puberty?

Answer 60

• Breast development (thelarche)
• Pubic and axillary hair growth (adrenarche)
• Growth spurt (due to growth hormone secretion)
• Onset of menstruation (menarche)

Question 61

What is the mean age of menarche?

Answer 61

• Mean age of menarche = 12.8 years

Question 62

What can be used to describe pubertal development?

Answer 62

• Tanner Staging

Question 63

What is precocious puberty?

Answer 63

• Onset of puberty before the age of:
  
  • 8 in a girl
  • 9 in a boy

Question 64

How is precocious puberty classified as?

Answer 64

• Central - gonadotrophin dependent
• Peripheral - gonadotrophin independent
  • This is ALWAYS pathological
  • May be caused by exogenous ingestion of oestrogen or a hormone-producing tumou

Question 65

What is delayed puberty?

Answer 65

• When there are no signs of secondary sexual characteristics by age of 14 years

Question 66

What are the central defect causes of delayed puberty?

Answer 66

• Anorexia nervosa
• Excessive exercise
• Chronic illness
• Kallmann’s syndrome
• May be associated with delayed puberty and primary amenorrhoea

Question 67

What are the causes of delayed puberty related to gonadal failure?

Answer 67

• Caused by gonadal failure (it does NOT respond to gonadotrophins)
• Associated with Turner syndrome and XX gonadal dysgenesis
• Premature ovarian failure can occur at any age (may be idiopathic, autoimmune, metabolic, or following chemo/radiotherapy in childhood)
• Associated with delayed puberty and primary amenorrhoea
• It can also occur later in life and cause secondary amenorrhoea

Question 68

What are the features of Turner Syndrome?

Answer 68

• 45X
• Most common chromosomal abnormality in females
• It can also cause a mosaic karyotype
• Main clinical features
  
  • Short stature
  • Webbing of the neck
  • Wide carrying angle
• Associated medical condition
  
  • Coarctation of the aorta
  • Inflammatory bowel disease
  • Sensorineural and conduction deafness
  • Renal anomalies
  • Endocrine dysfunction (e.g. thyroid disease)
• The ovary does NOT complete its normal development and only stroma is present at birth
• The gonads are called streak gonads and do NOT function to produce oestrogen or oocytes
• Diagnosis is made at birth (except in 10% of cases)
• As the gonads do NOT produce oestrogen, the physical changes of puberty do not happen

Question 69

What is the management of Turner syndrome?

Answer 69

• During childhood, the focus is on growth
• In adolescence, it focuses on the induction of puberty
• Pregnancy is only possible with ovum donation
• In girl with mosaicism, they may undergo normal puberty and menstruation may occur

Question 70

What is 46 XY Gonadal Dysgenesis?

Answer 70

• The gonads do not develop into testis
• May be due to SRY gene mutation
• In complete gonadal dysgenesis (Swyer syndrome), the gonad remains as a streak and does not produce any hormones
• The absence of anti-Mullerian hormone, the Mullerian structures (uterus, vagina and Fallopian tube) will develop normally
• The absence of testosterone means the foetus does NOT virilise
• The baby is phenotypically FEMALE but has an XY chromosome
• The gonads do NOT function and the patient will present with delayed puberty
• The dysgenetic gonad has a high malignancy risk and should be removed when the diagnosis is made
• Puberty must be induced with oestrogen
• Pregnancy may be possible with a oocyte donor
• In mixed gonadal dysgenesis, both functioning ovarian and testicular tissue can be present (this is known as ovotesticular DSD)
• The anatomical findings depend on the function of the gonads

Question 71

What is 46 XY DSD?

Answer 71

• Most common cause is complete androgen insensitivity
• In this condition, virilisation of the external genitalia does NOT occur due to partial or complete inability of the androgen receptor to respond to androgen stimulation
• In these patients, testes form normally due to action of the SRY gene
• The testes will secrete anti-Mullerian hormone leading to regression of the Mullerian ducts (so they do NOT have a uterus)
• Testosterone is also produced BUT the androgen receptors does NOT respond so the external genitalia does NOT virilise and instead undergoes female development
• The baby is born with:
  
  • Normal female external genitalia
  • Absent uterus
  • Test found somewhere in the line of descent
• Presentation is usually at puberty with primary amenorrhoea
• NOTE: the testes could cause a hernia
• Initial diagnosis should be accompanied by:
  
  • Psychological support
  • Full disclosure of the XY karyotype
  • Information about infertility
• Gonadectomy is recommended because of the small long-term risk of testicular malignancy
• Long-term HRT will be required
• The vagina may need to be lengthened to be suitable for penetrative intercourse (vaginal dilatation)
• In partial androgen insensitivity, the patient may be partially virilised and the baby may be diagnosed at birth with ambiguous genitalia

Question 72

What is 5-alpha reductase deficiency?

Answer 72

• The foetus is XY and has normal functioning testes that both produce testosterone and AMH
• BUT, the foetus cannot convert testosterone to DHT so CANNOT virilise normally
• Presentation is usually with ambiguous genitalia
• It may also present with increasing virilisation of a female child at puberty

Question 73

What is 46 XX DSD?

Answer 73

• Most common cause is congenital adrenal hyperplasia (CAH)
• Causes virilisation of the female foetus
• Enzyme deficiency in the corticosteroid synthesis pathway (mainly 21-hydroxylase - converts progesterone to deoxycorticosterone and 17-hydroxyprogesterone to deoxycortisol) leads to shunting of precursors into the androgen synthesis pathway
• Reduced negative feedback due to low output of cortisol leads to adrenal hyperplasia
• Physical Changes due to Virilisation
  
  • Enlarged clitoris
  • Fused labia (scrotal in appearance)
  • Upper vagina joins the urethra and opens as one common channel into the perineum
• 2/3 with 21-hydroxylase deficiency will have a salt-losing variety due to inadequate aldosterone production (can cause a salt-losing crisis soon after birth)
• Affected individuals require lifelong steroid replacement
• Surgical treatment of the genitalia may be considered

Question 74

What is the definition of amenorrhoea?

Answer 74

• Absence of menstruation for more than 6 months in the absence of pregnancy in a woman of fertile age

Question 75

What is primary amenorrhoea?

Answer 75

• When a girl fails to menstruate by 16 years of age

Question 76

What is secondary amenorrhoea?

Answer 76

• Absence of menstruation for > 6 months in a normal female of reproductive age that is not due to pregnancy, lactation or menopause

Question 77

What is oligomenorrhoea?

Answer 77

• Irregular periods at intervals of more than 35 days , with only 4-9 periods per year

Question 78

What are the causes of hypothalamic disorders?

Answer 78

• Excessive exercise, weight loss and stress
• Hypothalamic lesions (craniopharyngioma, glioma)
• Head injuries
• Kallmann’s syndrome (genetic condition causing lack of GnRH)
• Systemic disorders (sarcoidosis, TB)
• Drugs (progestogens, HRT, dopamine antagonists)

Question 79

What are the causes of pituitary disorders?

Answer 79

• Adenomas (prolactinoma is most common)
• Pituitary necrosis (e.g. Sheehan’s syndrome)
• Iatrogenic (surgery, radiotherapy)
• Congenital failure of pituitary development

Question 80

What are causes of hypogonadotrophic hypogonadism?

Answer 80

• Hypothalamic and Pituitary disorders

- Polycystic ovarian syndrome

Question 81

What are examples of some ovarian disorders that cause amenorrhoea/oligomenorrhoea?

Answer 81

• Polycystic ovarian syndrome (PCOS)
  
  • This causes hypergonadotrophic hypogonadism
• Premature ovarian failure: cessation of periods < 40 years of age

Question 82

What are some endometrial disorders that cause amenorrheoa/oligomenorrhoea?

Answer 82

• Primary amenorrhoea may result from Mullerian defects in the genital tract (e.g. absent uterus) causing haematocolpos (vagina filled with blood)
• Secondary amenorrhoea may be due to scarring of the endometrium (Asherman syndrome)

Question 83

What investigations would you do for amenorrhoea/oligomenorrhoea?

Answer 83

• A pregnancy test should be carried out if the patient is sexually active
• Blood can be taken to measure hormone levels
  
  • Raised LH + raised testosterone –> PCOS
  • Raised FSH –> POF
  • Raised prolactin –> prolactinoma
  • Thyroid function if clinically indicated
• Ultrasound would be useful to visualise polycystic ovaries
• MRI can be used to visualise the pituitary gland
• Other investigations include:
  
  • Hysteroscopy - Asherman syndrome, cervical stenosis
  • Karyotyping - Turner’s and other chromosomal abnormalities

Question 84

What are the features of polycystic ovarian syndrome?

Answer 84

• Cardinal features:
  
  • Hyperandrogenism
  • Polycystic ovarian morphology
• About 25% of all women have polycystic ovaries on ultrasound but it does not always cause the full syndrome
• Associated with an increased risk of:
  
  • T2DM
  • Cardiovascular events
• It tends to have a familial trend

Question 85

What are the clinical features of PCOS?

Answer 85

• Oligomenorrhoea/amenorrhoea due to chronic anovulation in 75%
• Hirsutism
• Subfertility in up to 75%
• Obesity in at least 40%
• Acanthosis nigricans
• May be ASYMPTOMATIC

Question 86

How do you diagnose PCOS?

Answer 86

• Rotterdam Consensus Criteria - must have TWO of THREE features:
  
  • Amenorrhoea/oligomenorrhoea
  • Clinical or biochemical hyperandrogenism
  • Polycystic ovaries on ultrasound
    
    • 12 or more subcapsular follicular cysts < 10 mm in diameter and increased ovarian stroma
• NOTE: they will also have high LH

Question 87

What is the management of PCOS?

Answer 87

• COCP to regulate menstruation
  
  • This increases sex hormone-binding globulin which helps relieve androgenic symptoms
• Cyclical oral progesterone
  
  • Regulate the withdrawal bleed
• Clomiphene
  
  • Induce ovulation if subfertility is an issue
  • It is a selective oestrogen receptor modulator (SERM)
• Lifestyle advice
  
  • Dietary modification and exercise if at increased risk of developing T2DM and cardiovascular disease
• Weight reduction
• Ovarian drilling
  
  • Procedure that destroys the ovarian stroma and may prompt ovulatory cycles
• Treatment of androgenic/hirsutism symptoms
  
  • Topical eflornithinecream
  • Cyproterone acetate (antiandrogen)
  • Metformin
  • GnRH analogues (reserved for women who are intolerant of other therapies)
  • Surgical treatment (laser or electrolysis

Question 88

What is premenstrual syndrome?

Answer 88

• Occurrence of cyclical somatic, psychological and emotional symptoms occurring in the luteal phase
• They resolve by the time menstruation ceases
• Clinical Features
  
  • Bloating
  • Cyclical weight gain
  • Mastalgia
  • Abdominal cramps
  • Fatigue
  • Headache
  • Depression
  • Irritability

Question 89

What is conservative management of PMS?

Answer 89

• Stress reduction
• Alcohol and caffeine limitation
• Exercise
• Alternatives:
  
  • Vitamins
  • St John’s wort

Question 90

What is the medical management of PMS?

Answer 90

• COCP
  
  • Bicycling or tricycling pill packets (taking 2 or 3 without a scheduled break) is effective
  • NOTE: it is recommended that low-dose progesterone is also given as this
• Transdermal oestrogen
  
  • Reduces symptoms by overcoming the fluctuations in a normal cycle
• GnRH analogues
  
  • Turn off ovarian activity
  • HRT should also be administered to prevent osteoporosis
• SSRIs (severe PMS)

Question 91

Apart from conservative and medical management, what else can be done for PMS?

Answer 91

• CBT (for depression)
• LAST RESORT: Hysterectomy with bilateral salpingo-oophorectomy
  • Only if all other measures fail

Question 92

What does the corpus luteum do after ovulation?

Answer 92

• After ovulation, the corpus luteum produces large amounts of progesterone
• The progesterone prepares the endometrium to support a pregnancy
• Successful implantation is when the oocyte is fertilised in the Fallopian tube and implants in the endometrium around 7 days after ovulation
• The implanted blastocyst secretes hCG which acts on the corpus luteum to rescue it from luteolysis to maintain progesterone secretion, prevent menstruation and support the early conceptus

Question 93

How long does the corpus luteum support pregnancy?

Answer 93

• 8 weeks

Question 94

What is the main supply of progesterone after the corpus luteum?

Answer 94

• The early placental tissue

Question 95

What is biochemical pregnancy?

Answer 95

• A positive pregnancy test could occur prior to the time of the expected period, followed by a negative pregnancy test after the period
• A positive pregnancy test could occur prior to the time of the expected period, followed by a negative pregnancy test after the period

Question 96

When can a TVUSS detect an early intrauterine gestational sac?

Answer 96

• At around 5 weeks

Question 97

When is the foetal heartbeat visible (TVUSS)?

Answer 97

• 6 week gestation

Question 98

How does serum hCG change during early pregnancy?

Answer 98

• Doubles every 48 hours

Question 99

What is confirmed as intrauterine on TVUSS for a normal pregnancy?

Answer 99

• Serum hCG > 1500 U/L

Question 100

What is miscarriage and its main clinical feature?

Answer 100

• Pregnancy that ends spontaneously before 24 weeks of pregnancy

Question 101

What is the incidence of miscarriage?

Answer 101

• Occurs in 10-20% of clinical pregnancies

- Risk increases with maternal age

Question 102

What are the aetiological factors for miscarriage?

Answer 102

• Chromosomal abnormalities
• Medical/endocrine disorders
• Uterine abnormalities
• Infections
• Drugs/chemicals

Question 103

What investigations should be done for miscarriage?

Answer 103

• ABCDE
• Abdomino-pelvic examination
• Address psychological symptoms
• TVUSS
  
  • Can diagnose a miscarriage if there is no pregnancy within the uterine cavity
• Haemoglobin and group and save (or cross-match if severely compromised)
  
  • Measure to assess degree of vaginal loss and rhesus status

Question 104

What is the management of threatened miscarriage according to the NICE guidelines?

Answer 104

• If the woman has vaginal bleeding and a confirmed intrauterine pregnancy with a foetal heart beat:
  
  • Return for further assessment if the bleeding gets worse or persists beyond 14 days
  • Continue routine antenatal care if the bleeding stops

Question 105

What is expectant management of miscarriage according to the NICE guidelines?

Answer 105

• Use expectant management for 7-14 days as FIRST LINE in women with confirmed miscarriage
• Explore other options if:
  
  • Increased risk of haemorrhage (e.g. late first trimester)
  • Previous adverse/traumatic event associated with pregnancy
  • Increased risk from effects of haemorrhage (e.g. unable to have blood transfusion)
  • Evidence of infection
• Offer medical management if expectant management is not acceptable
• If bleeding and pain resolves within 7-14 days of starting expectant management, advise taking a pregnancy test after 3 weeks and returning to see the doctor if it is positive
• Offer repeat scan if after the period of expectant management the bleeding and pain:
• Has not started (suggests miscarriage has not begun)
• Persisting and/or increasing (suggesting incomplete miscarriage)

Question 106

What is the medical management for miscarriage?

Answer 106

• Do NOT offer mifepristone for miscarriage
• Offer vaginal misoprostol (oral preparation can also be used depending on patient preference)
• If the bleeding has NOT started within 24 hours of treatment, contact a healthcare professional
• Offer pain relief and anti-emetics to all patients undergoing medical management of miscarriage
• Inform patient about what to expect: vaginal bleeding, pain, diarrhoea and vomiting
• Advise taking pregnancy test 3 weeks after medical management
• NOTE: medical management has a 10% failure rate

Question 107

What is the surgical management for miscarriage?

Answer 107

• Manual vacuum aspiration under local anaesthetic
• Surgical management in theatre under general anaesthetic
• Vaginal or sublingual misoprostol if often used to ripen the cervix to facilitate cervical dilatation for suction insertion
• Offer anti-D prophylaxis to all Rhesus-negative women undergoing surgical management of miscarriage

Question 108

What is recurrent miscarriage?

Answer 108

• Loss of three or more consecutive pregnancies

- Affects 1% of couples

Question 109

What are the risk factors for recurrent miscarriage?

Answer 109

• Advancing maternal and paternal age
• Obesity
• Balanced chromosomal translocations
• Uterine structural anomalies
• Antiphospholipid syndrome

Question 110

What are the causes of recurrent miscarriage?

Answer 110

• Antiphospholipid syndrome
• Cervical abnormalities
• Foetal chromosomal abnormalities
• Uterine malformations
• Thrombophilia

Question 111

What investigations should be done for recurrent miscarriage? (Green Top Guidelines)

Answer 111

• Screen for antiphospholipid syndrome
  
  • Lupus anticoagulant
  • Anti-cardiolipin antibodies
  • DIAGNOSTIC: 2 positive results at least 12 weeks apart
• Cytogenetic analysis
  
  • Of products of conception in the last miscarriage
  • Of both partners peripheral blood
• Transvaginal ultrasound to assess for uterine anomalies
• Screen for inherited thrombophilia (e.g. factor V leiden)

Question 112

What is the management of recurrent miscarriage (Green Top Guidelines)?

Answer 112

• Anti-phospholipid syndrome
  
  • Low-dose aspirin + LMWH in future pregnancy reduces risk of miscarriage by 54%
• NOTE: steroids and IVIG have NO proven benefit
• If abnormal parental genetics are found, refer to clinical geneticist
• Cervical issues may be treated with cerclage

Question 113

What is an ectopic pregnancy?

Answer 113

• Implantation of a pregnancy outside the normal uterine cavity
• Over 98% of ectopic pregnancies will implant in the Fallopian tube
• Rare sites: interstitium of the tube, ovary, cervix, abdominal cavity or C-section scars

Question 114

What is a heterotopic pregnancy?

Answer 114

• Simultaneous development of two pregnancies, one within and one outside the uterine cavity
  
  • Incidence is higher in patients receiving IVF

Question 115

What is the incidence of ectopic pregnancy?

Answer 115

• 1 in 80 pregnancies

- Responsible for 9-13% of maternal deaths

Question 116

What is the aetiology of ectopic pregnancy?

Answer 116

• Fallopian tube damage due to pelvic infection, previous ectopic pregnancy and previous tubal surgery
• Functional alterations in the Fallopian tube due to smoking and increased maternal age
• Previous abdominal surgery
• Subfertility
• IVF
• Use of intrauterine contraceptive devices
• Endometriosis
• Conception on oral contraceptive/morning after pill

Question 117

What is the clinical presentation of ectopic pregnancy?

Answer 117

• Abdominal pain and/or vaginal bleeding in early pregnancy
• Rarely, patients will present very acutely with rupture of the ectopic pregnancy and massive intraperitoneal bleeding
  
  • The free blood in the peritoneal cavity can cause diaphragmatic irritation and shoulder tip pain
• Signs of acute abdomen and hypovolaemic shock with a positive pregnancy test

Question 118

What are the investigations for ectopic pregnancy?

Answer 118

• ABCDE
• Abdominopelvic examination
• TVUSS
  
  • Identification of intrauterine pregnancy excludes ectopic pregnancy (except with heterotopic pregnancy)
  • Ectopic pregnancy will appear as an empty uterus with an adnexal mass
  • Presence of moderate to significant free fluid on TVUSS is suggestive of a ruptured ectopic pregnancy
• Serum hCG
  
  • Should double every 48 hours in a normal pregnancy
  • In ectopic pregnancy, the rise in hCG is often suboptimal
  • Serial measurements 48 hours apart may show this
• Haemoglobin and Group and Save (or crossmatch if severely compromised)
  
  • Measure to assess degree of intra-abdominal bleeding and Rhesus status

Question 119

What is pregnancy of unknown location?

Answer 119

• In 40% of women with ectopic pregnancy, the diagnosis is NOT made on first attendance and are labelled as having pregnancy of unknown location (PUL)
• TVUSS shows an empty uterus with no evidence of an adnexal mass in a patient with a positive pregnancy test
• Investigate with consecutive measurement of serum hCG
• Endometrial biopsy may be helpful if hCG levels are static

Question 120

What is the expectant management of ectopic pregnancy? (NICE guidelines)

Answer 120

• Based on the assumption that a significant proportion of ectopic pregnancies will resolve without treatment
• Suitable for patients who are haemodynamically stable and asymptomatic
• The patient should have serial hCG measurements until the levels are undetectable

Question 121

What is the medical management of ectopic pregnancy? (NICE guidelines)

Answer 121

• Provide advice on how to contact a healthcare professional if needed and when to get help in an emergency
• Offer IM METHOTREXATE as 1st line if able to attend follow-up and provided that all of the following criteria are fulfilled:
  
  • No significant pain
  • Unruptured ectopic pregnancy with adnexal mass < 35 mm with no visible heartbeat
  • Serum b-hCG < 1500 iU/L
  • No intrauterine pregnancy (confirmed by USS)
  • FOLLOW-UP
    
    • Take 2 serum hCG measurements at days 4 and 7
    • Take 1 serum hCG per week until a negative result is obtained
    • Avoid sexual intercourse during treatment
    • Avoid conceiving for 3 months after methotrexate
    • Avoid alcohol and prolonged exposure to sunlight
• Offer a CHOICE of either methotrexate or surgery if b-hCG 1500-5000 iU/L and:
  
  • No significant pain
  • Unruptured ectopic with adnexal mass < 35 mm with no visible heartbeat
  • No intrauterine pregnancy identified on USS
• IMPORTANT: methotrexate carries a greater risk of urgent re-admission

Question 122

What is the surgical management of ectopic pregnancy? (NICE guidelines)

Answer 122

• Offer SURGERY as 1st line if unable to return for follow-up or any of the following:
  
  • Significant pain
  • Adnexal mass > 35 mm
  • Ectopic pregnancy with a foetal heartbeat visible on ultrasound scan
  • Serum b-HCG > 5000 iU/L
• SURGERY
  
  • Laparoscopic where possible
  • Offer salpingectomy unless there are other risk factors for infertility
  • Consider salpingotomy if there are risk factors for infertility or contralateral tubal damage
  • WARNING: 1 in 5 women who have salpingotomy need further treatment (methotrexate and/or salpingectomy)
  • FOLLOW-UP for Salpingotomy: 1 serum hCG at 1 weeks, then 1 serum hCG per week until negative result is obtained
  • FOLLOW-UP for Salpingectomy: urine pregnancy test at 3 weeks

Question 123

How is anti-D prophylaxis relevant to ectopic pregnancy?

Answer 123

• Offer anti-D prophylaxis (250 iU) to all RhD-negative women who have a SURGICAL management of ectopic pregnancy or miscarriage
• Do NOT do Kleihauer test
• Do NOT offer anti-D prophylaxis if:
  
  • Solely medical management
  • Threatened miscarriage
  • Complete miscarriage
  • Pregnancy of unknown origin

Question 124

What is the mechanism of actions for contraceptives?

Answer 124

• Prevent ovulation
  
  • Combined hormonal methods (pill, patch and vaginal ring)
  • Progesterone-only injectables
  • Progesterone-only implant (Nexplanon)
  • Oral emergency contraception
  • Lactational amenorrhoea
• Prevent sperm reaching the oocyte
  
  • Female sterilisation
  • Male sterilisation (vasectomy)
• Prevent an embryo implanting in the uterus
  
  • Cu-IUD
  • LNG-IUS
• Poison sperm that enter the vagina
  
  • Spermicides
• Block the passage of sperm beyond the vagina
  
  • Diaphragm
  • Cap
  • Progestogens
• Prevent sperm entering the vagina
  
  • Male and female condoms
  • Avoid sex during the fertile time of the cycle
  • Fertility awareness-based methods (FAB)

Question 125

What is LARC?

Answer 125

• LARC is defined in the UK as a method that requires administration less than once per month (e.g. injectable, implant, IUD)

Question 126

What is the WHO medical eligibility criteria?

Answer 126

• The WHO medical eligibility criteria (MEC) is a guidance document with recommendations for whether or not a woman with medical conditions is eligible to use a particular contraceptive method
• Category 4 = ABSOLUTE contraindication

Question 127

How does contraception interact with other medicines?

Answer 127

• Several medicine (e.g. anticonvulsants, antifungals, antibiotics, antiretrovirals) induce liver enzymes and reduce the efficacy of hormonal contraception such as pills, patch and ring
• If a woman using enzyme-inducing medication wants to use hormonal methods of contraception, consistent use of condoms is also advised
• Effectiveness of the COCP is not affected by administration of most broad-spectrum antibiotics

Question 128

What contraception methods are not affected by enzyme induction?

Answer 128

• Cu-IUD
• LNG-IUS
• Progesterone-only injectable

Question 129

What are side effects of contraception?

Answer 129

• Unexpected bleeding
• Weight gain (IMPORTANT)
• Headaches
• Mood swings
• Loss of libido
• There is no evidence that hormonal methods (except the progestogen-only injectable) causes weight gain
• There is no evidence that the intrauterine methods cause weight gain
• Unexpected bleeding is common and may settle with time
  
  • If it does NOT settle, changing the contraceptive or using a different dose may help
  • If bleeding continues for > 3 months, investigations to exclude other causes (e.g. polyps, chlamydia infection) should be considered
• If women using COCP experience headaches in the pill-free week, they may benefit from continuing packets of pills to avoid the hormone-free interval
• If headaches occur during the use of the hormonal method that are severe, frequent or migraine, changing the method of contraception is advisable

Question 130

What are the determinants of contraceptive method acceptability?

Answer 130

• Personal characteristics (e.g. age)
• Fertility intentions
• Perceptions of effectiveness
• Perceptions of safety
• Fear of side-effects
• Familiarity
• Experience of others
• Ease of use and of access
• Need to see a health professional
• Intrusiveness
• Non-contraceptive benefits

Question 131

What do women to know before starting a method of contraception?

Answer 131

• How to use the method and what to do when misused (e.g. missed pill)
• Typical failure rates
• Common side-effects
• Health benefits
• Fertility returning on stopping
• When she requires review

Question 132

What hormones does the combined hormonal contraception contain?

Answer 132

• Oestrogen

- Progestogen

Question 133

What formulation can combined hormonal contraception come in?

Answer 133

• Oral pill
• Transdermal patch
• Vaginal ring
• They are similar in terms of effectiveness, safety and side-effects
• They work by inhibition of ovulation via negative feedback of oestrogen and progestogen on the pituitary with suppression of FSH and LH

Question 134

Describe the combined contraceptive pill?

Answer 134

• Most commonly used COCPs contain ethinyl oestradiol (15-35 mcg)
• Some newer pills contain oestradiol valerate or oestradiol hemihydrate
• Most preparations contain 21 pills followed by a 7-day pill-free interval (or 7 placebo tablets)
• Some preparations will contain 24 pills with a shorter pill-free interval
• Preparations are usually monophasic (same dose of hormones throughout)
• The 21 days on 7 days off regimen usually results in a withdrawal bleed during the pill-free interval
• IMPORTANT: there is no reason why women cannot take the pill continuously
• Women with dysmenorrhoea or headaches during the pill-free interval are advised to avoid recurrence of symptoms by tricycling (taking 3 packets without a break)

Question 135

How are the progestogens in the pill categorised?

Answer 135

• 2nd Generation: levonorgestrel, norethisterone
• 3rd Generation: gestodene desogestrel
• 4th Generation: drospirenone, dienogest
• IMPORTANT: 2nd generation progestogens are recommended because 3rd and 4th generation progestogens are associated with an increased risk of venous thrombosis

Question 136

Describe the combined hormonal contraceptive patch

Answer 136

• Combined hormonal transdermal patch releases 33.9 mcg ethinyl oestradiol per day and norelgestromin 203 mcg/day
• It is applied to the skin of the lower abdomen, buttock or arm for 7 days
• Usually involves application of patches for a total of 21 days followed by a 7-day hormone free interval
• Continued use (tricycling) is also possible
• Problems include patch adherence or skin sensitivity

Question 137

Described the combined hormonal ring

Answer 137

• Flexible ring of 54 mm diameter that releases 15 mcg ethinyloestradiol and 120 mcg etonorgestrel daily
• This is lowest dose combined hormonal method
• The ring is inserted and worn in the vagina for 21 days followed by a 7-day hormone free period during which withdrawal bleeding occurs
• Women should not feel discomfort from the ring

Question 138

Describe missed pills, patches, rings

Answer 138

• Missed pills are common
• 2 or more missed pills places the woman at risk of ovulation
• Additional contraceptive cover (condoms or abstinence) is required for most monophasic ethinyloestradiol-containing pills during the next 7 days of pill taking
• Additional precautions should also be taken if:
  
  • Patch is not applied for 48 hours
  • Ring is not applied for more than 3 hours
• If sexual intercourse has occurred during this time, there is a risk of pregnancy and emergency contraception is recommended

Question 139

What are the cancer risks in COCP users?

Answer 139

• 12% reduced risk of any cancer
• Reduced risk of colorectal, endometrial and ovarian cancer
• Increased risk of breast cancer during use
• Increased risk of cervical cancer
• Protection from endometrial and ovarian cancer seems to persist for more than 15 years after stopping the pill
• The risk of breast cancer is increased during use, but will decrease to the same as women who have never used the pill after 10 years

Question 140

Describe the risk of VTE and arterial disease with the COCP

Answer 140

• CHC increases the tendency to thrombosis
• The absolute risk of thrombosis is VERY SMALL and much less than that associated with pregnancy
• Risk is greatest within the first year of use
• Women should be asked about personal or family history of VTE (contraindications)
• Women > 35 years who smoke are NOT eligible for CHC because of an increased risk of arterial disease
• It is also contraindicated in women who have migraine with aura as this condition is associated with cerebral vasospasm and women may be at increased risk of stroke if they use a CHC

Question 141

What are the formulations of the progestogen-only contraceptive methods?

Answer 141

• Oral
• Injectable
• Implant
• Intrauterine system
• The injectable, implant and desogestrel-containing progestogen-only pill inhibit ovulation
• All progestogen-only contraceptives thicken cervical mucus thereby reducing sperm penetrability and transport
• The LNG-IUS has little effect on ovarian activity but causes marked endometrial atrophy meaning that implantation is not possible

Question 142

Describe the Progestogen-only pill? (POP)

Answer 142

• Needs to be taken continuously
• Medium-dose pills (e.g. desogestrel) inhibit ovulation in 99% of cycles
• Lower-dose pills inhibit ovulation less frequently and rely on thickening of cervical mucus for its contraceptive effect
• If MISSED, the woman should continue taking POP and use extra precautions (e.g. condoms) for the next 48 hours
• If unprotected sex occurs during this time, emergency contraception is recommended

Question 143

What are the side effects of POP?

Answer 143

• Irregular bleeding
• Persistent ovarian follicles (simple cysts)
• Acne

Question 144

Describe the progestogen only implant

Answer 144

• Currently available method: single rod (Nexplanon) containing progestogen etonorgestrel
• Nexplanon contains 68 mg of 3-keto-desogestral
• Provides contraception for 3 years
• Initial release arte of 60-70 mcg/day
• Other types of implant: Uniplant, Jadelle
• Nexplanon is inserted subdermally 8 cm above the medial epicondyle usually in the non-dominant arm under local anaesthesia
• The implant is NOT visible but should be easily palpable
• It shows up on X-rays
• Once inserted, there is NO need for follow-up until the device is due for removal
• Fertility is restored immediately after removal

Question 145

What is the most commonly used progestogen-only injectable?

Answer 145

• A depot injection of medroxyprogesterone acetate

Question 146

What are the administrations of progestogen-only injectables?

Answer 146

• IM Depoprovera (150 mg)

- SC Sayana press (104 mg)

Question 147

Describe the use of progestogen-only injectables

Answer 147

• Injection interval = 12-14 weeks
• Similar bleeding pattern for both - 50% amenorrhoea rates at 1 year
• SC injections are more practical
• May delay return of fertility after discontinuation - may take up to 1 year after the last injection for ovulation to return
• No long-term change in fertility but will be inappropriate for women requiring short-term contraception
• May cause weight gain in some patients and loss of bone mineral density
  
  • NOTE: this has not been associated with osteoporotic fractures and is reversible once it is stopped

Question 148

Describe the progestogen-releasing intrauterine system

Answer 148

• TWO LNG-IUS available in Europe and USA:
  
  • 52 mg LNG-IUS (Mirena)
    
    • Licensed for 5 years for contraceptive use
• 13.5 mg LNG-IUS (Jaydess)
  
  • Licensed for 3 years for contraceptive use
  • Slightly smaller which may make insertion easier in young/nulliparous women
  • Has a silver band at the proximal end helping distinguish it on ultrasound
• LNG-IUS works by preventing endometrial proliferation and implantation
• The progestogens also thicken cervical mucus

It does NOT prevent ovulation

• Many women experience unpredictable bleeding in the first few months
• This usually improves with time
• NOTE: 13.5 mg LNG-IUS is NOT licensed as a treatment for HMB but may reduce blood loss to some extent

Question 149

What are side effects of Progestogen-releasing Intrauterine System?

Answer 149

• Acne
• Breast tenderness
• Mood disturbance
• Headaches

Question 150

What are the non-contraceptive benefits of LNG-IUS?

Answer 150

• Reducing heavy menstrual bleeding
• Treating dysmenorrhoea
• Reducing pain associated with endometriosis and adenomyosis
• Protecting the endometrium against hyperplasia

Question 151

What are the types of intrauterine contraception?

Answer 151

• Cu-IUD
  
  • Used for 3-10 years
  • If a woman has a Cu-IUD inserted at > 40 years, it can be left until menopause
  • IMPORTANT: can be used as EMERGENCY CONTRACEPTION
• LNG-IUS
  
  • If a woman has an LNG-IUS inserted at > 45 years, it can be left until menopause
• Both have threads that protrude out of the cervical canal into the upper vagina for easy removal
• These methods do NOT delay the return of fertility or increase the risk of infertility

Question 152

What are the modes of action of intrauterine contraception?

Answer 152

• Stimulate an inflammatory reaction in the uterus
• Concentration of macrophages, leucocytes, prostaglandins and enzymes increase significantly
• These are toxic to both the sperm and the egg
• Inhibits implantation

Question 153

What are the bleeding patterns with IUD?

Answer 153

• LNG-IUS = tend to experience lighter, less painful menses
• Cu-IUD = may experience more painful or heavier menses
• NSAIDs may help lessen the pain and blood loss
• Tranexamic acid during menses may also reduce blood loss with the Cu-IUD
• If the heavy bleeding becomes a problem, the woman can switch to an LNG-IUS

Question 154

What are the risks of intrauterine contraception?

Answer 154

• Risk of ectopic pregnancy is much lower compared to women using NO contraception
• However, if a pregnancy does occur whilst the IUD is in situ, the relative risk of the pregnancy being ectopic is higher
• If a woman becomes pregnant with an IUD, an ultrasound scan should be performed to exclude an ectopic pregnancy
• IUDs should be removed before 12 weeks gestation

Question 155

What are the risks of leaving the IUD in situ?

Answer 155

• Miscarriage
• Preterm delivery
• Septic abortion
• Chorioamnionitis

Question 156

What are the perforation and expulsion risks of inserting an IUD?

Answer 156

• Perforation
  
  • Especially if breastfeeding or < 6 months postpartum
  • Usually presents with ‘missing threads’ and severe pain following insertion
  • Ultrasound will show no IUD in the uterus
  • Abdominal X-ray shows an IUD
  • Laparoscopic removal is possible in most cases
• Expulsion
  
  • 1 in 20 will be expelled in the first 3 months after insertion
  • After this, the risk of expulsion diminishes
  • IUD users should be advised to regularly check the presence of threads in the upper vagina

Question 157

What are the infection and “missing threads” risk of IUD insertion?

Answer 157

• Infection
  
  • 1 in 100 risk of pelvic infection in the first 3 weeks after insertion
  • Thereafter, the risk is the same as normal women
  • In most cases, IUD can be left in situ and antibiotics commenced
  • Actinomyces-like organisms (ALOs) are commonly identified on cervical smears of women with and without IUDs
  • If ALOs are present in a women with an IUD who has symptoms of infection, the device should be removed and penicillin-based antibiotics given
  • Women should also be tested for STIs before insertion of the IUD
  • Prophylactic antibiotics should be given to women at high risk of infection if insertion needs to be done before test results (e.g. emergency Cu-IUD)
• Missing threads
  
  • May indicate pregnancy, expulsion or perforation
  • Pregnancy test should be performed and emergency contraception/alternative contraception provided until the IUD an be confirmed to be in situ
  • This can be done by visualisation of threads on speculum examination or an ultrasound

Question 158

What are some barrier contraception?

Answer 158

• Condoms
  
  • Protect against STIs including HIV
  • Only reversible male method
  • Failure rates of 24%
  • Female condoms are inserted into the vagina
• Diaphragm and Cap
  
  • Latex or non-latex devices that are inserted into the vagina to prevent passage of sperm into the cervix
  • They can be inserted before sex
  • Caps fit over the cervix
  • Diaphragms form a hammock between the post-fornix and the symphysis pubis
  • Often used in conjunction with a spermicide
  • Women need to be taught how to correctly insert and remove the device
  • Failure rate = 18%
  • May be associated with increased vaginal discharge and UTIs
• Spermicides
  
  • Spermicides alone are NOT recommended for prevention of pregnancy
  • Nonoxynol 9 is a spermicidal product sold for use with diaphragm and caps
  • May increase HIV transmission
  • NOT recommended for women who are at high risk of HIV

Question 159

What is female sterilisation and its three approaches?

Answer 159

• Permanent method of contraception preventing the sperm reaching the oocyte in the Fallopian tube
• Three approaches
  • Laparoscopy
  • Hysteroscopy
  • Laparotomy (e.g. at C-section)

Question 160

What is laparoscopic sterilisation?

Answer 160

• Most commonly occludes the Fallopian tube using Filshie clips
• Effective contraception should be used until the next menses after the procedure
• Women with a high surgical risk may be better suited to a hysteroscopic approach
• Valid consent is very important as this leads to permanent loss of fertility

Question 161

What are some advise for women considering sterilisation?

Answer 161

• Method is irreversible
• Vasectomy is safer, quicker and associated with less morbidity
• High proportion of women regret sterilisation
• Does not protect against STIs
• Effective contraception is required until the menstrual period following laparoscopic procedure or 3 months following hysteroscopic procedure
• Pregnancy following female sterilisation is rare but has an increased risk of ectopic pregnancy
• Reversal is highly skilled and difficult

Question 162

What is hysteroscopic sterilisation?

Answer 162

• Can be performed as an outpatient without general anaesthetic
• Expanding springs (microinserts) are inserted into the tubal ostia via a hysteroscope
• These induce fibrosis in the cornual section of each Fallopian tube over 3 months
• Contraception is required during these 3 months and can be discontinued once correct placement of the inserts is confirmed by X-ray or ultrasound

Question 163

What is a vasectomy?

Answer 163

• Interrupting the vas deferens to provide permanent occlusion
• Small risk of scrotal haematoma and infection
• Post-vasectomy semen analysis should be conducted at 12 weeks to confirm the absence of spermatozoa in the ejaculate

Question 164

What are fertility awareness-based methods?

Answer 164

• Aka natural family planning
• Relies on avoidance of intercourse during the fertile period
• Failure rates are high

Question 165

What is the calendar or rhythm method?

Answer 165

• Fertile days are calculated based upon the cycle length recorded over at least 6 cycles
• First fertile day = shortest cycle minus 20
• Last fertile day = longest cycle minus 10

Question 166

What is the temperature method?

Answer 166

• Relies on increase in basal body temperature (0.2-0.4 degrees) due to a rise in progesterone following ovulation
• Daily temperatures should be measured
• Can be affected by infection, exercise and some medications

Question 167

What is the cervical mucus method?

Answer 167

• Mucus on toilet tissue after wiping the vulva can be examined for consistency
• Midcycle mucus due to rising oestradiol levels is clear, watery and slippery
• Following ovulation, the mucus becomes thick and opaque due to progesterone

Question 168

What is cervical palpation and personal fertility monitoring?

Answer 168

• Cervical Palpation
  
  • The cervix rises 1-2 cm midcycle
• Personal Fertility Monitoring
  
  • Analyses disposable urine dipsticks to record the presence of metabolites of oestrogen and LH in the urine

Question 169

What is lactational amenorrhoea?

Answer 169

• Low risk of breastfeeding when fully breastfeeding

- After 6 months, or if menses occur or breastfeeding is reduced, alternative contraception should be started

Question 170

Describe emergency contraception

Answer 170

• Cu-IUD is the MOST EFFECTIVE method of emergency contraception and should ideally be offered as the first choice
• It can be removed once pregnancy has been excluded or it can remain in place as a form of contraception
• An emergency Cu-IUD can be inserted up to 5 days after unprotected sex or 5 days after predicted ovulation
• NOTE: the blastocyst will implant between day 6-10 following fertilisation
• Women should be encouraged to start an effective method of contraception immediately after EC to protect against future pregnancies

Question 171

What are two oral methods of emergency contraception?

Answer 171

• Levonorgestrel (LNG 1.5 mg)
  
  • Effective up to 72 hours (3 days) after unprotected sex
• Ulipristal acetate (30 mg)
  
  • Progesterone receptor modulator
  • Effective up to 120 hours (5 days) after unprotected sex
• Both methods delay ovulation
• Oral methods are much less effective than the Cu-IUD and prevents only 2/3 of pregnancies

Question 172

What length of birth to pregnancy intervals are associated with an increased risk of childhood mortality?

Answer 172

• < 12 months

- Maternal and child deaths could be prevented if couples spaced their pregnancies more than 2 years apart

Question 173

What is the UK Abortion Law?

Answer 173

• 1967 Abortion Act states that abortion can be performed if two registered medical practitioners acting in good faith agree that the pregnancy should be terminated on one of the recognised legal grounds
• This does NOT apply to Northern Ireland
• Most abortions are based on Ground C

Question 174

What are preabortion investigations?

Answer 174

• Recommended
  
  • Gestation assessment (ultrasound or clinical)
  • Rhesus status (anti-D required if non-immunised RhD-negative)
• Consider
  
  • STI testing
  • FBC (determine if anaemic)

Question 175

What is involved in a medical abortion?

Answer 175

• This involves a combination of:
  
  • Mifepristone (progesterone receptor modulator)
  • Followed by misoprostol (prostaglandin analogue)
• Progesterone is needed to maintain uterine quiescence
• Administration of mifepristone brings about an increase in uterine contractility
• It also sensitises the uterus to exogenous prostaglandins, so misoprostol can bring about expulsion
• Effect of mifepristone is maximal at 48 hours
• If misoprostol is administered at an interval of 24-48 hours later, then there is an increase in cramping pain, bleeding and expulsion of the foetus through the slightly dilated cervix

Question 176

What happens in the first 9 weeks of pregnancy regarding a medical abortion?

Answer 176

• In the first 9 weeks of pregnancy, women safely administer these medications are home
• Simple oral analgesia (e.g. ibuprofen) can be used for pain relief
• At 9 weeks gestation, they will bleed for around 2 weeks following the medical abortion

Question 177

What happens after 9 weeks of pregnancy regarding a medical abortion?

Answer 177

• The same drugs are used but requires repeated doses of misoprostol every 3 hours until expulsion occurs
• Because of the discomfort, increased bleeding and passage of a larger foetus, this should be done in a clinical setting
• In the 2nd trimester, average induction of abortion time is 7 hours

Question 178

What happens after 21 completed weeks?

Answer 178

• Feticide should be used to eliminate the possibility of the aborted foetus displaying any signs of life
• Usually achieved by intracardiac injection of potassium chloride or intrafoetal/intramniotic digoxin

Question 179

Describe a vacuum aspiration

Answer 179

• Should be used to conduct surgical TOP up to 14 weeks
• Involves gently dilating the cervix with gradual dilators then evacuating the cavity with gentle suction
• Usually takes < 10 mins
• Can be performed using manual vacuum aspiration or electrical vacuum aspiration
• Can be performed under local or general anaesthesia
• Consider pre-treatment of the cervix with misoprostol (causes cervical dilatation)
  
  • This should always be used after 12 weeks gestation or if nulliparous/adolescent/previous cervical surgery
  • Optimal regimen: 400 mcg misoprostol sublingually 1 hour before the surgical procedure
• Prophylactic antibiotics reduce the risk of postabortal infection

Question 180

Describe dilatation and evacuation

Answer 180

• After 14 weeks, this is the surgical intervention of choice
• Needs good cervical dilatation (20 mm) to remove larger foetal parts
• Achieved using:
  
  • Osmotic dilators
  • Misoprostol (vaginal or sublingual)
  • Mifepristone (oral)
• At surgery, the cervix is further dilated and the contents of the uterus are removed using aspiration and extraction of the foetal tissue with appropriate instruments
• Ultrasound is performed to confirm evacuation

Question 181

Describe sequelae of abortion

Answer 181

• Both medical and surgical abortion have a low complication rate
• Complications
  
  • Failure to end pregnancy
  • Incomplete abortion requiring evacuation
  • Infection
  • Haemorrhage
• Without complications, there is NO impact on future reproductive potential
• NO associated with future pregnancy or ectopic pregnancy

Question 182

What happens at the follow-up after abortion?

Answer 182

• No medical need for follow-up after uncomplicated abortion
• Provide good advice about when to seek help
• Provide ongoing contraception
• Women who have an early medical abortion at home, they should have a scheduled ultrasound to exclude ongoing pregnancy or a self-performed urine pregnancy test

Question 183

What is postabortal contraception?

Answer 183

• Most women ovulate in the first month after abortion
• Effective contraception should be started IMMEDIATELY
• LARC has the best success rates at preventing unintended pregnancy
• IUDs can be inserted at the time of surgical abortion

Question 184

What is subfertility?

Answer 184

• Failure to conceive after 12 months of regular unprotected intercourse
• Affects 1 in 7 heterosexual couples
• Can be primary (couples that have never conceived together) or secondary (couples who have previously conceived together)

Question 185

What’s the chance of a healthy couple conceiving after having frequent intercourse in a single menstrual cycle?

Answer 185

• 18-20%

Question 186

After 12 months, what percentage of couples should have conceived?

Answer 186

• 80%

Question 187

What’s the most important factor affecting fertility age?

Answer 187

• Female age

- Related to decline in quantity and quality of eggs

Question 188

When does female quality and sperm fertility decrease in quality?

Answer 188

• Female fertility falls sharply at the age of 36 years

- Semen quality falls over the age of 50 years

Question 189

Describe natural conception

Answer 189

• Having intercourse 3 x per week is associated with a 3 x increased risk of conceiving compared to couples having intercourse once per week
• Maximum efficiency is probably achieved by having sex every other day
• Increased frequency should be encouraged in the periovulatory stage
• Eggs are fertilisable for about 12-24 hours after ovulation
• Sperm can survive within the female reproductive tract for up to 72 hours
• Ovulation usually occurs 14 days before menstruation
• The fertile window will be different depending on the usual length of the cycle
• NOTE: smoking can decrease quality and quantity of eggs and sperm
  
  • Extremes of BMI are also associated with reduced change of conceiving
  • Stress can affect the regulation of ovulation
• IMPORTANT: all women intending to conceive should commence folic acid (400 mcg/day) to reduce risk of neural tube defects

Question 190

What are causes of female subfertility?

Answer 190

• Ovulatory disorders
• Tubal problems
• Uterine disorders
• Endometrial pathology
• Endometriosis
• General medical conditions (e.g. diabetes, epilepsy, thyroid problems)

Question 191

How do ovulatory disorders affect subfertility?

Answer 191

• MOST COMMON causes of issues with ovulation is polycystic ovarian syndrome (PCOS)
• Oligomenorrhoea in PCOS may require treatment, HOWEVER, the treatments may be incompatible with conceiving (e.g. COCP)
• Hypothalamic disorders (e.g. hypothalamic hypogonadism) and pituitary disease (e.g. hyperprolactinaemia) are less common causes of anovulation

Question 192

How do tubal disorders affect subfertility?

Answer 192

• Blockage is associated with inflammatory processes such as:
  
  • Pelvic Inflammatory Disease (PID)
    
    • Particularly chlamydia infection
• Endometriosis
• Previous pelvic or abdominal surgery (resulting in scar tissue and adhesions)

Question 193

How do uterine disorders affect subfertility?

Answer 193

• Particularly, fibroids
• Submucosal fibroids have an impact on embryo implantation
• Intramural fibroids may reduce fertility if large
• Subserosal fibroids have little impact
• Endometrial polyps can reduce change of implantation
• Endometrial scarring (Asherman’s syndrome) from surgery or infection can be associated with lighter periods and a significantly reduced chance of conception

Question 194

Describe male subfertility

Answer 194

• Reduce sperm count and quality
• Spermatogonial cells can be damaged by inflammation or damage to the epididymis (responsible for storing sperm)
• Pelvic radiotherapy/surgery
• Diabetes mellitus
• Erectile difficulties/problems with ejaculation
• Aneuploidy of sex chromosomes

Question 195

What are key points in a female subfertility history?

Answer 195

• Age
• Length of time spent trying for pregnancy
• Any previous pregnancies
• Coital frequency
• Occupation
• General gynaecological history
• Previous history of pelvic inflammatory disease
• Previous medical or surgical history
• Previous fertility treatment
• Cervical smear history
• General health - screen for history of thyroid disorders

Examination
- Pelvic examination (watch out for pathology such as fibroids, adnexal masses or tenderness)

• General blood pressure, pulse, height and weight

Question 196

What are key points in a male subfertility history?

Answer 196

• Age
• Length of time trying for pregnancy
• Fathered any previous pregnancies
• History of mumps or measles
• History of testicular trauma, surgery to testis
• Occupation
• Medical and surgical history

Testicular examination
- Volume, consistency, masses, varicocoele, surgical scars

Question 197

When are investigations considered for subfertility?

Answer 197

• Investigations may be considered in couples who have not conceived after 1 years of regular unprotected sex
• Investigations are indicated more strongly if the couple have a history of predisposing factors (e.g. oligomenorrhoea, PID)

Question 198

What female investigations should be done for subfertility?

Answer 198

• Blood hormone profile
  
  • Look at early follicular phase FSH, LH and oestradiol levels
  • Anti-Mullerian hormone (AMH) is helpful for assessing ovarian reserve
    
    • It is independent of the menstrual cycle
  • Mid-luteal progesterone should also be measured to confirm ovulation
• If irregular menstrual cycle, TFTs, prolactin and testosterone may also be useful
• Chlamydia testing
• HIV, hepatitis B and hepatitis C screening if assisted reproductive technology (ART) is being considered
• TVUSS
  
  • Assessment of pelvic anatomy
  • Antral follicle count (important parameter of ovarian reserve)
  • Identify pathology (e.g. hydrosalpinges, endometriotic cyst)

Question 199

What is measurement of ovarian reserve?

Answer 199

• Female reproductive potential is directly proportionate to the remaining number of oocytes in the ovaries (ovarian reserve)
• This declines after 35 years
• This can be accelerated by genetic predisposition, surgery or following exposure to toxins
• Ovarian reserve can help predict response to ovarian stimulation by ART
• The antral follicle count (AFC) seen on TVUSS is a good indicator of ovarian reserve (
  
  • < 4 = poor response
  • 16+ = good response
• Anti-Mullerian hormone is produced by granulosa cells and does NOT change in response to gonadotrophins so it is the most successful biomarker of ovarian reserve
• Most clinics use both AMH and AFC to assess ovarian reserve

Question 200

Describe tubal assessment for subfertility

Answer 200

• Usually assessed using hysterosalpingography (HSG) using X-ray or ultrasound
• Tubal patency is not the same as tubal function

Question 201

What are male investigations for subfertility?

Answer 201

• Main investigation is semen fluid analysis (SFA)
• Looks at: volume, sperm concentration, total sperm number, motility, morphology, vitality and pH
• Most places recommended 2-4 day abstinence from ejaculation before providing a semen sample
• If initial SFA is abnormal, it should be repeated 3 months later (because sometimes SFA can be distorted by viral infection)
• A hormone profile will be performed in men with a low sperm count or azoospermia (no sperm in the semen)

Question 202

What is the medical management of subfertility?

Answer 202

• Ovulation induction- clomiphene or FSH
  
  • If anovulation (PCOS, idiopathic)
• Intrauterine insemination (with or without stimulation with FSH)
  
  • Unexplained infertility
  • Anovulation unresponsive to OI
  • Mild male factor
  • Minimal to mild endometriosis
• Donor insemination
  
  • Presence of azoospermia
  • Single women
  • Same sex couples
• IVF
  
  • Patients with tubal pathology
  • Patients who underwent above treatments with no success
• Donor egg with IVF
  
  • Women whose egg quality is poor
  • Previous surgery/chemotherapy where ovarian function was adversely affected

Question 203

What is the surgical management of subfertility?

Answer 203

• Operative laparoscopy to treat disease and restore anatomy
  
  • Adhesions
  • Endometriosis
  • Ovarian cyst
• Myomectomy - hysteroscopy, laparoscopy, laparotomy, fibroid embolisation
  
  • Fibroid uterus
• Tubal surgery
  
  • Blocked Fallopian tubes amenable to repair
• Laparoscopic ovarian drilling
  
  • PCOS unresponsive to medical treatment
• Often used as an adjunct to ART (e.g. removal of hydrosalpinges is associated with a significant improvement in the success of IVF)
• Usually a minimum access surgery (MAS) approach is taken

Question 204

What is ovarian induction?

Answer 204

• This is the first line option for patients with PCOS ovulatory problems (provided tubal patency and normal semen analysis)
• The most commonly used agent is clomiphene citrate (antioestrogen)
  
  • It binds to oestrogen receptors in the hypothalamus and pituitary thereby blocking the negative feedback exerted by oestrogen
  • This leads to a surge in gonadotrophin release
  • This stimulates the ovary to recruit more follicles for maturation
  • 70% of women on clomiphene will ovulate
  • 50% will of these women will become pregnant within 6 months
  • 12% risk of multiple pregnancy (requires ultrasound monitoring to track the growth of follicles and identify the time of ovulation to reduce the risk of multiple pregnancy)
• Options in clomiphene-resistant women
  
  • Augmentation with metformin
  • Aromatase inhibitors
  • Injectable gonadotrophins
• Ovarian induction can also be achieved by laparoscopic ovarian drilling (LOD) in PCOS
  
  • Only considered if unresponsive to clomiphene
• If the anovulation is due to a hypothalamic issue, injectable gonadotrophins are more effective

Question 205

Describe intrauterine insemination

Answer 205

• Performed by introducing a small sample of prepared sperm into the uterine cavity with a fine uterine catheter
  
  • May be useful in:
    
    • Mild endometriosis
    • Mild male factor
    • Couples who do not have intercourse
    • Single women
    • Same sex couples using donor sperm
• 10-20% success rate per treatment cycle
• May be preceded by several days of mild stimulation with SC injections of FSH
• This aims to stimulate the ovaries to produce 2-3 mature follicles (this practice is called stimulated IUI)
• Follicular tracking with ultrasound is essential to avoid over- or understimulation
• Triggering ovulation and timing the insemination is achieved by a SC hCG injection
• This mimics the endogenous LH surge

Question 206

Which causes of subfertility is IVF used for?

Answer 206

• Tubal disease
• Endometriosis
• Failed ovulation induction
• Failed IUI
• Donor eggs

Question 207

How does the IVF process work?

Answer 207

• Pituitary downregulation
  
  • The pituitary gland is down-regulated to prevent endogenous LH surges and premature ovulation
  • GnRH agonist is used to block FSH and LH release
  • Newer approaches using GnRH antagonists can shorten treatment time
• Controlled Ovarian Stimulation
  
  • Achieved by daily SC doses of gonadotrophins
  • This causes multiple follicle recruitment
  • Close monitoring with TVUSS predicts the number of follicles and the timing of the egg collection
• Inhibition of Premature Ovulation
  
  • The feedback from rising oestradiol levels due to follicular development should lead to an LH surge which causes ovulation
  • This is blocked in IVF to allow scheduling of egg collection
  • This is done using GnRH agonists or with newer GnRH antagonists
• hCG trigger
  
  • hCG is a surrogate for the endogenous LH surge
  • It causes final maturation and enables egg collection
• Egg Collection
  
  • Performed about 37 hours after hCG trigger
  • Under anaesthesia, a needle is inserted into the ovaries under TVUSS control, and follicular fluid is aspirated from each follicle that contains an oocyte
• Fertilisation
  
  • Performed using prepared sperm
  • Usually involved insemination of around 100,000 sperm in a petri-dish with an egg
  • If the sperm are poor, individual sperm can be isolated and directly injected into the cytoplasm of the oocyte (intracytoplasmic sperm injection (ICSI))
  • Success rates:
    
    • IVF = 60%
    • ICSI = 70%
• Embryo Culture
  
  • Incubated under strict conditions
  • May be transferred into the uterus after 2, 3 or 5 days after development
• Embryo Transfer
  
  • Transferred into the uterus using a soft plastic catheter
  • The choice of how many to transfer depends on the couple (after medical/embryological advice)
  • Usually performed under transabdominal ultrasound guidance
• Embryo cryopreservation
  
  • Spare embryos of good quality may be cryopreserved for future use
  • Same success rate as fresh embryos
• Luteal Phase Support
  
  • Use of gonadotrophin agonists/antagonists to prevent premature LH surge leads to a reduction in the corpus luteum’s ability to produce progesterone
  • Patients are supplemented with progesterone following egg collection
  • Pregnancy test is performed 14 days after embryo transfer
• Donor Gametes
  
  • Used when the male partner is azoospermic or in the case of single women or female same sex couples
  • IUI and IVF are both possible
  • Donor eggs may be used if the female has undergone early menopause or if other IVF treatments have been unsuccessful
• Surgical Sperm Retrieval
  
  • If the sperm quality and quantity is low but they are present, ICSI is required to help achieve pregnancy
  • However, if azoospermic, surgical sperm retrieval may be required
  • The extracted sperm can be cryopreserved
• Preimplantation Genetic Diagnosis
  
  • Couples who carry a genetic disease (but are fertile) may choose IVF and preimplantation genetic diagnosis to avoid an affected pregnancy
  • IVF creates multiple embryos and they can be genetically tested
  • Only embryos free of the disease will be transferred into the uterus
• Success rates depend on the inheritance pattern of the disease

Question 208

How is fertility preserved?

Answer 208

• Surgery, radiotherapy and chemotherapy may reduce reproductive potential
• Men can bank sperm ahead of these treatments
• Young women can go through IVF can freeze oocytes

Question 209

What is menopause?

Answer 209

• Women’s final menstrual period. The accepted confirmation of this is made retrospectively after 1 year of amenorrhoea.
• It is caused by the cessation of regular ovarian function

Question 210

What is perimenopause?

Answer 210

• Time from the onset of ovarian dysfunction until 1 year after the last period (i.e. when the diagnosis of menopause is made)
  
  • Aka climacteric

Question 211

What is postmenopause?

Answer 211

• All women who have been at least 1 year since their last period

Question 212

What is the median age of physical menopause?

Answer 212

• 51 - 52

Question 213

What are the endocrine changes of physical menopause?

Answer 213

• Menopause occurs when you run out of oocytes
• Inhibin B is produced by the follicles within the ovary, so as the number of follicles declines, the production of inhibin B declines
• In the perimenopausal years, small declines in inhibin drive an overall increase in pulsatility of GnRH secretion and overall FSH and LH levels
• This results in an increased drive to the remaining follicles in an attempt to maintain follicle production and oestrogen levels
• Decline in ovarian testosterone and other androgens as women age
  
  • NOTE: androgens come from ovaries, peripheral adipose tissue and adrenal glands

Question 214

How is physical menopause diagnosed?

Answer 214

• Largely clinical
• Symptoms
  
  • Menstrual irregularities/amenorrhoea
  • Oestrogen deficiency symptoms (e.g. hot flushes)
• High FSH with low oestradiol may be suggestive of menopause (but can occur at certain points during a normal menstrual cycle)
• In all women in whom a diagnosis of menopause is being considered, also consider the possibility of pregnancy

Question 215

What is premature ovarian insufficiency?

Answer 215

• Menopause occurring before the age of 40 years
• This is a distressing diagnosis, particularly if it happens before completion of her family
• Gamete donation is the only option for young women who would like to conceive again
• Women with POI may experience unpredictable ovarian activity leading to irregular vaginal bleeding and a small risk of pregnancy
• All women with POI should be offered supportive care and counselling from a specialist unit
• They should receive an individualised package of care

Question 216

What are the causes of premature ovarian insufficiency?

Answer 216

• Primary
  
  • Chromosomal abnormalities (e.g. Turner’s syndrome, fragile X)
  • Autoimmune disease (e.g. hypothyroidism, Addison’s, myasthenia gravis)
  • Enzyme deficiencies (e.g. galactosaemia, 17a-hydroxylase deficiency)
• Secondary
  
  • Chemotherapy or radiotherapy
  • Infections (e.g. TB, mumps, malaria, varicella)

Question 217

Describe medical treatments and menopause after cancer

Answer 217

• Appropriate counselling before definitive irreversible treatment that may compromise fertility is important
• GnRH agonists (e.g. buserelin, goserelin) can be used as treatments for endometriosis and other gynaecological issues but constant stimulation of GnRH receptors leads to desensitisation and reduces LH and FSH release
• This can induce a temporary menopause

Question 218

What is surgical menopause?

Answer 218

• May occur in the surgical management of fibroids, endometriosis and other gynaecological conditions
• Bilateral salpingo-oophorectomy may be performed prophylactically in women at high risk of inherited malignancies (e.g. breast and ovarian cancer) with BRCA1/2 mutation screening
• These women should be counselled so that they can choose the correct time for the procedure and counselling on how to manage the sudden hormone deficit
• They will lose the effect of oestrogen and testosterone

Question 219

What are the vasomotor symptoms of menopause?

Answer 219

• Some of the earliest changes during menopause
• Colloquially referred to as hot flushes
• Hot flushes occurring at night are called night sweats
• Thought to be due to loss of the modulating effect of oestrogen on serotoninergic receptors within the thermoregulatory centre in the brain
• This leads to exaggerated peripheral vasodilatory responses to slight changes in environmental temperature
• Occur in up to 80% of women
• Night sweats are particularly distressing as it can disturb sleep leading to exhaustion and impaired quality of life
• Triggers include alcohol, caffeine and smoking
• Symptoms tend to be worse in obese women

Question 220

What are the psychological symptoms of menopause?

Answer 220

• Associated with low mood, lack of energy, tiredness and impaired quality of life
• Consider the impact of external influences (e.g. relationships, previous history of depression)

Question 221

Describe cognitive function in menopause

Answer 221

• Many women complain of some change in memory/global cognitive function
• No change in onset or incidence of dementia

Question 222

How does the endometrium change during menopause?

Answer 222

• Initial irregular or scanty vaginal bleeding is due to the reduction in oestrogenic endometrial stimulation with failing ovarian function (eventually resulting in secondary amenorrhoea)
• Irregular heavy bleeding can occur due to episodic infrequent ovulation with fluctuations in oestrogen and unpredictable progesterone levels

Question 223

Describe Urogenital Tract and Vulvovaginal Atrophy in menopause

Answer 223

• Vaginal dryness, irritation, burning, soreness and dyspareunia
• Loss of oestrogenic support to the vaginal epithelium leads to reduced cellular turnover and reduced glandular activity
• This means that the vaginal epithelium is less elastic and more easily traumatised
• The urogenital system also becomes weaker as a barrier to infection
• Thought to be due to increase in pH
• Incidence of UTI increases (and the incidence of minor cystitis following sexual intercourse)
• Small petechial haemorrhages may be seen on the surface of the vagina in severe cases
• Older women may also have shrinkage and fusion of the labia with narrowing of the introitus

Question 224

Describe bone health in menopause

Answer 224

• Bone density reaches a peak at 20-30 years
• After this peak is reached, there is a steady decline in BMD until menopause
• Then, bone loss is accelerated until the age of 60 years
• Then there is further steady decline until death

Question 225

What is osteoporosis?

Answer 225

• Osteoporosis: a skeletal disorder characterised by compromised bone strength predisposing to an increased fracture risk.
• It is 4 x more common in women

Question 226

What are risk factors for osteoporosis?

Answer 226

• Family history
• Smoking
• Alcoholism
• Long-term steroid use
• POI and hypogonadism
• Medical treatment with induced menopause
• Disorders of thyroid and parathyroid
• Immobility
• Disorders of gut absorption, malnutrition and liver disease

Question 227

How is the cardiovascular system affected by menopause?

Answer 227

• Although outside the remit of a gynaecologist, they can identify and improve modifiable risk factors in patients
• Change from a gynaecoid (breast and hip fat) to android (abdominal fat) pattern of fat distribution
• Rise in triglycerides, total cholesterol and LDLs
• Reduction in HDLs
• Oestrogen has a supportive effect on the vessel wall favouring vasodilation and preventing atherogenesis

Question 228

What is the management of menopause?

Answer 228

• The main aim is the prevention of long-term health problems
• Diet and Lifestyle
• Non-Hormonal Approaches
• Alternative and Complementary Therapies
• Non-Hormonal Prescription Treatments
• HRT

Question 229

How do non-hormonal approaches manage menopause?

Answer 229

• Many women will present after trying ‘natural’ methods
• They should be informed that the beneficial effect of lifestyle measures should be checked before exploring appropriate non-hormonal measures

Question 230

How do alternative and complementary therapies manage menopause?

Answer 230

• No evidence base
• Potential for interactions with other pharmaceutical agents
• Most of these are essentially weak HRT, so, if they are taking a high dose then they may be exposing themselves to the risks of HRT

Question 231

Describe non-hormonal prescription treatments for menopause

Answer 231

• Alpha agonists
  
  • Clonidine
• Beta-blockers
  
  • Propranolol
• Modulators of central neurotransmission
  
  • Venlafaxine
  • Fluoxetine
  • Paroxetine
  • Citalopram
  • Gabapentin
• May reduce symptoms of hot flushes
• Other symptomatic treatments include:
  
  • Vaginal moisturisers
  • Lubricants
  • Osteoporosis treatments
    
    • Bisphosphonates
    • Raloxifene
    • Denosumab
    • Teriparatide

Question 232

What hormones are used in HRT?

Answer 232

• Oestrogens
  
  • Oestadiol
  • Oestrone sulphate
  • Oestriol
  • Conjugated equine oestrogen
• Progestogens
  
  • Norethisterone
  • Levonorgestrel
  • Dydrogesterone
  • Medroxyprogesterone acetate
  • Drospirenone
  • Micronised progesterone

Question 233

How is oestrogen used in HRT?

Answer 233

• Oestrogen
  
  • If given WITHOUT progestogenic opposition there is a risk of endometrial hyperplasia and cancer
  • ONLY SUITABLE for women who no longer have a uterus because of hysterectomy
• Oestrogen with progestogen
  
  • Administration of progestogen is necessary to protect the endometrium
  • Normally given cyclically in preparations over a 28-day cycle
    
    • 16-18 days = oestrogen ALONE
    • 10-12 days = oestrogen AND progesterone
    • This is called cyclical HRT
    • This results in monthly menstruation (suitable for perimenopause or early postmenopause)
  • Oestrogen and progesterone may also be given continuously (continuous combined HRT) to women who are:
    
    • Known to be post-menopausal
    • 54+ years
    • NOTE: about 90% will not experience any vaginal bleeding
• There are a variety of progestogens that can be used - these may be switched to reduce side-effects

Question 234

How is testosterone used in HRT?

Answer 234

• Used to be used for disorders of sexual desire and energy levels in women who failed to respond to normal HRT

Question 235

What are the two main routes of administration for HRT?

Answer 235

• Oral
• Transdermal
• Oral is convenient and cheap but influences lipid metabolism and the coagulation system through its effect on the liver during first-pass metabolism
• The transdermal route has the advantage of directly delivering the hormones to the systemic circulation, thereby avoiding the aforementioned adverse effects
• Oestradiol and oestriol are also available as vaginal creams
• Progestogen as levonorgestrel can be administered as an IUD

Question 236

What are the benefits of HRT?

Answer 236

• Symptoms improved:
  
  • Vasomotor symptoms
  • Sleep patterns
  • Performance during the day
• Prevention of osteoporosis
  
  • Increased BMD
  • Reduced incidence of fragility fractures
• Lower genital tract
  
  • Dryness
  • Soreness
  • Dyspareunia
  • CVD (preventative if started early)

Question 237

What are absolute contraindications to HRT?

Answer 237

• Suspected pregnancy
• Breast cancer
• Endometrial cancer
• Active liver disease
• Uncontrolled hypertension
• Known current VTE
• Known thrombophilia (e.g. factor V leiden)
• Otosclerosis

Question 238

What are relative contraindications to HRT?

Answer 238

• Uninvestigated abnormal bleeding
• Large uterine fibroids
• Past history of benign breast disease
• Unconfirmed personal history or a strong family history of VTE
• Chronic stable liver disease
• Migraine with aura

Question 239

What are the side effects of HRT?

Answer 239

Side-Effects associated with Oestrogen

• Breast tenderness/swelling
• Nausea
• Leg cramps
• Headaches

Side-Effects associated with Progestogen

• Fluid retention
• Breast tenderness
• Headaches
• Mood swings
• Depression
• Acne

Question 240

What are the risks of HRT?

Answer 240

• Cancer
  
  • HRT does not drastically increase breast cancer risk
  • There is no increase in mortality from breast cancer
  • HRT may promote growth of cancer cells rather than initiate them
  • Endometrial cancer and ovarian cancer are NOT significant risks of HRT use
  • Endometrial cancer risk is more or less eliminated if women are given progestogens
• Cardiovascular disease and stroke
  
  • HRT in younger women is protective
  • HRT in older women may increase the risk of cardiovascular disease and stroke
    
    • This is a small effect - an additional 2 women per 10,000
• Venous Thromboembolism
  
  • Similar effect to the OCP
  • Background incidence of VTE in women > 50 = 15-20 per 10,000
  • HRT doubles this risk
  • NOTE: transdermal HRT may not have as big an effect