Module 7 Urogenital Flashcards
Pelvic cavity borders
Pelvic inlet: pubic crest and pectineal line, arcuate line, ala of sacrum, sacral promontory (S1 vertebra)
Pelvic outlet: pubic arch, ischial tuberosities, sacrotuberous ligaments, coccyx
Greater/false pelvis: area superior to the pelvic inlet, contains most abdominal organs
Lesser/true pelvis: area between the pelvic inlet and pelvic floor
Perineum: inferior to the pelvic floor
Pelvic girdle Sex differences
Feature Female Male
General structure Lighter, thinner Heavier, thicker
Iliac crest Straight Curved
Pelvic inlet Oval, large Heart-shaped, small
Pelvic outlet Wide Narrow
Pubic arch >90 degrees <90 degrees
Sacrum Curved anteriorly Straighter anteriorly
Coccyx Moveable, curved anteriorly Rigid, straighter anteriorly
Greater sciatic notch Wide Narrow/ acute
Obturator foramen Oval Circular
Birth canal measurements
Obstetric conjugate (inlet)
Bispinous diameter (midplane)
Bituberous diameter (outlet)
Anteroposterior sagittal diameter (outlet)
Pelvic floor components and innervation
Formed by levator ani muscles + coccygeus muscle
Levator ani has three parts:
Puborectalis
Pubococcygeus
Iliococcygeus
Urogenital hiatus allows passage of the urethra, anus, and the vagina into the perineum
Levator ani innervated by ant. ramus of S4 and the pudendal nerve.
Coccygeus innervated by ant. rami if S3 – S4
Pelvic wall: component elements
Bony elements: innominate bones, sacrum, coccyx
Ligaments: sacrospinous, sacrotuberous
Muscles: obturator internus, piriformis
Pelvic floor innervation
Levator ani innervated by ant. ramus of S4 and the pudendal nerve.
Coccygeus innervated by ant. rami if S3 – S4
Pudendal nerve roots, function and route of travel
From sacral plexus (ant. rami of S2 – S4 spinal nerves)
Somatic innervation to perineum
Exits pelvic cavity through greater sciatic foramen
Re-enters pelvic cavity through lesser sciatic foramen
Travels in pudendal canal in theischioanal fossa
Perineum and perineal triangles
Diamond-shaped area bounded by the pubic symphysis and ischiopubic rami, sacrotuberous ligaments, and coccyx
Bounded superiorly by the pelvic floor muscles and inferiorly by skin
Imaginary line between the ischial tuberosities creates two triangles
Urogenital triangle
Anal triangle
Perineal membrane and the spaces it creates
Triangular fibrous membrane attached to the inferior pubic rami and ischia
Covers the urogenital triangle
Attachment points for the roots of external genitalia and associated muscles
Has openings for the urethra and vagina
Creates two spaces relative to it
Deep perineal pouch (above the perineal membrane)
Superficial perineal pouch (below the perineal membrane
Perineal body
Mass of fibromuscular connective tissue – central tendon of perineum
Found in the midline of the perineum, on the posterior border of the perineal membrane
Between the urogenital and anal triangles
Attachment point for pelvic floor and perineum muscles e.g. levator ani, anal sphincters
Important for strengthening the pelvic floor
Deep perineal pouch location and contents
Space between the pelvic floor muscles and perineal membrane
Female: urethra, vagina and sphincter musculature
Male: contains the urethra, associated sphincter musculature and bulbourethral glands
Deep transverse perineal muscles help to support the perineal body
Superficial perineal pouch location and contents
Internal pudendal artery and its branches (+ veins)
Pudendal nerve + its branches e.g. perineal nerve, dorsal nerve of clitoris/penis
Erectile tissue:corpora cavernosa and corpus spongiosum (bulb)
Muscle covering the erectile tissue: ischiocavernosus and bulbospongiosus muscles
Female:
Labia majora and labia minora
Crura of clitoris – corpora cavernosa
Vestibular (clitoral) bulbs – corpus spongiosum
Greater vestibular (Bartholin’s) glands
Male:
Crura (corpora cavernosa) and bulb of penis (corpus spongiosum)
Urethra
Testes (suspended from abdominal wall)
Scrotum
Effect of childbirth on the perineum
Tearing of the perineum can lead to:
Stress urinary incontinence due to a weaker pelvic floor
Faecal incontinence due to damage to theexternal anal sphincter and pelvic floor muscles
Pelvic organ prolapse due to a weaker pelvic floor
episiotomy
Midline and mediolateral incisions for episiotomies of the perineum to reduce tearing stresses during vaginal delivery
Pelvic fascia
Campers and scarpa’s fascia merge to form Dartos fascia, which then later becomes colles fascia in the perineum
Extravasated fluids in the male urethra can collect where?
Extravasated fluid collects in the superficial perineal pouch, the scrotum, around the penis, and lower abdominal wall
Ischioanal fossa boundaries
Pyramidal, fat-filled space surrounding the rectum and anal canal
Inferior to the pelvic diaphragm
Boundaries:
Roof: pelvic diaphragm
Floor: perineal skin
Medial wall: levator ani, external anal sphincter
Lateral wall: obturator internus and obturator fascia, ischial tuberosity
The left and right sides of the ischioanal fossa communicate posterior to the anal canal
Relevant for the spread of infection
Where can infection spread from left to right and vica versa, in the ischioanal fossa?
The left and right sides of the ischioanal fossa communicate posterior to the anal canal
Relevant for the spread of infection
Ischioanal fossa contents
Subcutaneous fat: allows space foranal canal to distend/expandduring defecation
Pudendal canal (Alcock’s)
Internal pudendal artery and vein
Pudendal nerve
Inferior rectal artery and inferior rectal vein
Pudendal nerve entrapment
Perianal abscesses
Infections usually start in the submucosa around the anus or in subcutaneous tissue.
Can progress to the ischioanal fossa.
Need to be surgically drained.
Anatomical relations of the uterus
Uterus sits in the lesser pelvis, between the bladder and the rectum
Pouches formed by parietal peritoneum between the uterus and bladder (vesicouterine pouch), and uterus and rectum (rectouterine pouch)
In women, what is the lowest point of the abdo cavity fluid can collect in?
rectouterine pouch
Supporting ligaments of the uterus and ovaries
Broad ligament
Mesovarium, mesosalpinx, mesometrium
Uterosacral ligament
Cervix sacrum
Transverse cervical (cardinal)ligament
Cervix lateral pelvic walls. Transmitsuterine vessels and nerves
Round ligament
Uterine horn labia majora (through inguinal canal)
Pubocervical ligament
Cervix pubic symphysis
Ovarian ligament
Ovary uterine horn
Suspensory ligament of ovary
Ovary lateral pelvic wall. Contains ovarian vessels
Pubovesical ligament
Bladder pubic symphysis
Non ligamentous support of uterus
Pelvic floor muscles
Perineal muscles:
Ischiocavernosus
Bulbospongiosus
Deep and superficial transverse perineal muscles
Perineal membrane
Perineal body
Positions of the uterus and cervix
Uterus is usually in an anteverted and anteflexed position
Retroflexion and retroversion can be normal variations.In some casesendometriosis scarring can cause the uterus to be retroverted and/or retroflexed
Vulva anatomy
Labium minus
Glans clitoris
Fourchette
Vaginal opening
Prepuce of clitoris
Mons pubis
Openings of lesser vestibularglands (Skene’s)
Frenulum
Vestibule
Hymen
Urethral opening
Labium majus
Opening for greater vestibular glands (Bartholin’s)
Clitoris
Composed of the two crura (corpora cavernosa) which join in the middle to form the body and the glans
The crura attach to the ischiopubic rami
The body and glans covered by the prepuce when not erect
The crura communicate with the bulbs both contain erectile tissue
Innervated by the dorsal nerve of the clitoris (branch of the pudendal nerve)
The clitoris and bulbs are embryologically homologous with the penis
Vagina and fornices
The vagina is a potential space, compressed by the bladder and rectum.
Rugae allow for distension of the vaginal canal.
Proximal aspect surrounds the cervix creating the fornices (two lateral, one anterior, one posterior), opens distally at the vestibule
Pelvic prolapses
Cystocele - bladder
Rectocele - rectum
Uterine prolapse
Diagnosed with digital examination
Risk factors include childbirth, menopause, chronic constipation
Parous cervix vs Nulliparous (no pregnancies) cervix
Parous cervix transverse cervical os
Nulliparous cervix circular cervical os
Pelvic arterial supply
Abdominal aorta bifurcates into right and left common iliac arteries at L4 vertebral level
-> Internal iliac arteries -> anterior and posterior trunks
Posterior trunk does not supply pelvic viscera
Iliolumbar artery
Lateral sacral artery
Superior gluteal artery
Anterior trunk
Umbilical - Usually not functional in adults – medial umbilical ligament/fold
Superior vesical - Fundus of bladder, distal ureter, ductus deferens
Uterine - Uterus, cervix, proximal vagina, uterine tubes, part of ovary
Vaginal (inferior vesical in males) Vagina, inferior aspect of bladder
Middle rectal - Middle and lower part of rectum, vagina, seminal vesicles, prostate
Obturator - Adductor muscles in medial compartment of thigh
Internal pudendal - Perineum, skin and muscles of anal and urogenital region, rectum and the erectile tissues of external genitalia
Inferior gluteal - Muscles of gluteal region
aorta ->Ovarian/ testicular (gonadal) Ovaries/ testes
Pelvic arteries mnemonics
Internal iliac artery branches:
I - Iliolumbar
Love - Lateral sacral
Going - Gluteal (superior and inferior)
Places - (internal) Pudendal
In - Inferior vesical
My - Middle rectal
Very - Vaginal
Own - Obturator
Underwear - Uterine and umbilical
Lymphatic drainage – pelvic organs
External and internal iliac lymph nodes receive most of the lymphatic fluid from the pelvic organs
The uterus has extensive lymphatic drainage:
Body + cervix = external iliac, internal iliac nodes
Fundus = lateral aortic nodes
Uterine tubes and round ligament of the uterus = lateral aortic, internal iliac, superficial inguinal nodes
The ovary (and testis) drain directly to lateral aortic (para-aortic, L1/L2 vertebral level) nodes via ducts following the gonadal veins
Lymph from specific areas of the vagina drains to different nodes:
Proximal vagina = internal + external iliac
Middle = internal iliac
Distal vagina = superficial inguinal
Lymphatic drainage - perineum
Superficial inguinal nodes
Superficial perineal region (e.g. superficial perineal pouch)
Labia majora + minora
Scrotal & penile skin + associated connective tissue
Distal part of anal canal (inferior to pectinate line): remember superior to pectinate line = internal iliac nodes
Uterine body via round ligament to labia
Lower limb + lower abdominal wall
Deep inguinal nodes
Lymph from superficial nodes
Clitoris, especially glans – direct drainage (same with penile glans)
Superficial and deep inguinal nodes drain into the common iliac nodes
Pelvic Innervation overview
Sympathetic innervation:
From T10-L2 lumbar splanchnic nerves via hypogastric plexi
From L1-L2/3 sacral splanchnic nerves via sympathetic chain and inferior hypogastric plexus
Parasympathetic innervation:
From S2 – S4 pelvic splanchnic nerves via inferior hypogastric plexus
Somatic innervation to pelvic floor and perineum
Pudendal nerve (anterior rami of S2 – S4 spinal nerves)
Pelvic pain line
Pelvic pain line is marked by the inferior limit of the peritoneum in the pelvic cavity
Visceral afferent (sensory) nerve fibres from the organs above the pelvic pain line travel through sympathetic nerves to reach T10 – L2 spinal cord segments.
Referred pain felt in lower abdomen (hypogastric/pubic region)
Visceral afferent nervefibres from below the pelvic pain line travel to S2 – S4 spinal cordsegments via pelvic splanchnic nerves (parasympathetic)
Referred pain felt in theperineal region
Innervation of the uterus
Uterus innervated by sympathetic (T10 – L2) nerve fibres andparasympathetic (S2 – S4) nerve fibres via the uterovaginal plexus(part oftheinferior hypogastric plexus)
Sympathetic nervefibres contract smooth muscle of myometrium and cause vasoconstriction
Visceral afferents from fundus and body of uterus travel to T10 – L2 spinal cord segments using thesympathetic nerves and sympathetic chain
Referred pain to lower abdomen (hypogastric region)
Parasympathetic nervefibrescontract smooth muscle in uterine cervix and encourage vasodilation.
Visceral afferents fromcervix(below pelvic pain line) travel to S2 – S4 spinal cordsegments using the pelvic splanchnic nerves
Referred pain to perineal region
Innervation of the vagina
Proximalvaginainnervated byuterovaginal plexus
Sympatheticnervefibrestravelling in the sacralsplanchnicnerves (S2 – S4, branches from sacralsympathetic chain)
Parasympatheticnervefibrestravellinginthepelvicsplanchnicnerves (S2 – S4)
Visceral afferents fromproximal vagina (below pelvic pain line)travel to S2 –S4spinalcordsegments using the pelvicsplanchnicnerves
Referred pain felt in perineal region
Distal vaginainnervated by somatic motor (efferent) and somatic afferent nerve fibres in branches of thepudendal nerve (S2–S4)
Somatic afferents are much more sensitive, pain is felt inside distal vagina and not referred across theperineal region
Local anaesthesiaforpain management during childbirth - spinal block
usually for Caesarean section deliveries. Fast-acting but short duration -can be combined with lumbar epidural block for longer duration of anaesthesia
Anaesthetic injected via lumbar puncture into subarachnoid space (intrathecal administration) atL3/L4 or L4/L5 vertebral level
Complete anaesthesia below the waist including lower limbs -anaesthetic spreads widely in subarachnoid space and can even reach as high as the T4 thoracic spinal nerve roots
Anaestheticagent is heavier thanCSFso patientsliein a slightly inclined position to avoid anaesthetic spreading too far superiorly
Risk that CSF may leak out of subarachnoid space - severe headache
Local anaesthesiaforpain management during childbirth - lumbar epidural
Lumbar epidural block commonlyused for pain relief in vaginal deliveries offers a longer duration of anaesthesia than spinal block.
Anaestheticinjected via lumbar puncture into epidural space at L3/L4 or L4/L5 vertebral level
Anaesthetises cervix, vagina, pelvic floor andperineal region.Patients maystill perceive uterine contractions -transmitted by visceral afferentsabove pelvic pain lineto T10 – L2 spinal cordsegments.
Anaestheticspreads less extensively than in spinal block because the epidural space is filled with fat.Lower limb function less affected.
Caudalepidural block at sacral hiatus (S4 vertebral level) can also be performed but is now less common
Local anaesthesiaforpain management during childbirth - Pudendal nerve block
Pudendal nerve provides somaticinnervation of the perineum(S2 – S4)
Also conveys sympathetic and parasympathetic nerve fibres to perineum via its branches
Pudendal nerve runs close to the ischial spine onesite for administeringpudendal nerve block
Anaesthetic blocks pain transmission from somatic afferents travelling viathepudendal nerve fromdistal vagina and the perineum to S2 – S4spinal cord segments
Pelvic S and PS action
Sympathetic input:
Inhibits rectal contraction
Secretion (male ejaculate - emission)
Contracts internal anal sphincter
Contracts internal urethral sphincter (male)
Contracts smooth muscle in uterine vessels and myometrium (noradrenaline)
Parasympathetic input:
Rectal contraction
Bladder contraction
Relaxes internal anal sphincter
Relaxes internal urethral sphincter (male)
Contracts uterine smooth muscle, mainly in cervix (acetylcholine)
Breast Internal structure
Breast overlies pectoralis major anteriorly, serratus anterior laterally, and part of rectus abdominis inferiorly
Lies on deep fascia of pectoralis major
Separated by the retromammary space
Mammary glands consist of ducts and secretory lobules
Condense to form 15-20 lactiferous ducts that open at the nipple
Suspensory ligaments of the breast (Cooper’s)
Fibrous connective tissue
Run from clavicle and clavipectoral fascia to the dermis of the skin and fascia
Provide support for the breast
Abnormal tension in these ligaments causes pitting of the skin: peau d’orange
Breast Lymphatic drainage
Most lymph (75%) from breast drains to the axillary nodes e.g. from superior and lateral breast tissue
Relevant for breast cancer metastasis
Axillary nodes
Anterior axillary (pectoral)
Posterior axillary (subscapular)
Central axillary
Lateral axillary (humeral)
Apical axillary (subclavian)
Axillary lymph node clearance (lymph node dissection) – surgical removal of nodes to prevent metastatic spread
Lymph from medial breast tissue drains to parasternal nodes instead
What nerve can be damaged during mastectomy? and what does this cause
Long thoracic nerve -> winging of scapula due to serratus anterior dysfunction
Name a site for administering pudendal nerve block anaesthetic?
Pudendal nerve runs close to the ischial spine onesite for administeringpudendal nerve block
Female Reproductive Lifecycle
Menarche:
first ovarian-controlled uterine bleed
Maturation of HPO axis
increased oestrogen (20 sexual characteristics)
Childbearing years (Menstrual cycle):
Median length 28 days (21-35 considered normal)
menses, menstruation (bleeding phase)
Menopause/Climacteric:
Oestrogen withdrawal, follicle depletion
Cessation of menses
Size, function of ovaries
Mean age 51.4 yr
Ovarian cycle vs uterine cycle
Ovarian cycle:
Interval between successive ovulations
Describes ovum maturation and release under endocrine regulation
Progression of follicle corpus luteum
Follicular (1-14 days) luteal phase (15-28 days
(folliculogenesis)
Uterine cycle:
Effects of ovarian hormones on uterus
Endometrium is central
Proliferative Secretory phase;
Vascular function, menses
Angiogenesis
Reproductive Hormones in FRT
Oestradiol-17b
produced from androstenedione and aromatase in granulosa, CL and adipose
Progesterone (P4)
secreted by corpus luteum
Follicle Stimulating Hormone (FSH)
follicle development and recruitment
Luteinising Hormone (LH)
maturation of dominant follicle, ovulation, maintenance of the CL
Inhibins
produced by ovarian granulosa cells to inhibit FSH secretion; Inhibin A during luteal phase; Inhibin B in follicular phase
Anti-Mullerian Hormone (AMH)
marker of ovarian reserve
Gonadotrophins
Follicle-stimulating hormone, FSH:
28kDa glycoprotein
Produced in gonadotrophs
Ovarian follicle stimulation & growth
Act on
Sertoli cells
Granulosa cells (follicle)
Signal via a G-protein coupled receptor (GPCR)
Luteinising hormone, LH:
28kDa glycoprotein
Produced in gonadotrophs
Ovulation
Act on
- Leydig cells
- Granulosa cells (preovulatory follicle)
- Corpus luteum
Signal via a GPCR
Key actions of the Sex Steroids
Oestrogens (C18 steroid):
Stimulate proliferation of endometrium
Prepare endometrium for progesterone action
Stimulate 20 sex characteristics of female
Stimulate growth (ductal) of breast tissue
Progesterone (C21 steroid):
‘Pro gestation’- hormone of pregnancy
Prepare endometrium for implantation
Stimulate decidualisation of endometrium
Maintain uterus during pregnancy
Stimulate growth (alveolar) of breast tissue
-> Synergistic and opposing effects to oestrogen
Phases of the Menstrual Cycle
Mean length 21-35 days; phasic
Proliferative - oestrogen-dominated
endometrial cell proliferation to prime uterus for progesterone actions
Variable in duration, typically 14 days
Secretory - progesterone-dominated
refers to increased secretory activity of the endometrium
Relatively consistent in length ~ 14 days based on corpus luteum
Hormone Levels in Menstrual Cycle
Day 1 is the first day of bleeding of the menstrual cycle
Oestradiol 17b: levels peak just before the LH surge
Progesterone: increases later in cycle due to corpus luteum
Inhibins: Nonsteroidal effects on pituitary
Endometrial Structure and Histology
Glandular tissue, under endocrine control, with Extensive stroma
Highly vascularised network supplied by spiral arteries
Distinct histological changes with phases of the menstrual cycle - Noyes criteria
Columnar epithelial cell lining proliferates and degenerates in one cycle
Glands extend deep into endometrial stroma
Implantation occurs 6-12 days after fertilisation
Window of implantation - endometrium optimally receptive to blastocyst
Window of implantation
Endometrium optimally receptive to blastocyst
Pinopodes
Markers of Endometrial Receptivity
Endometrial Histology in different phases
Proliferative phase - round regular glands, stroma contains support and nutrients
Secretory phase - Tortuous and twisted glands, glycogen droplets prepares for conception
Endometrial Vascular Aspects
Rapid angiogenesis and spiral artery lengthening in proliferative phase
Then endometrial regression, spiral artery coiling causes resistance to blood flow resulting in endometrial hypoxia followed by tissue degeneration.
Matrix metalloproteinases (MMP-8-9) from endometrial stroma and proteases from invading leukocytes during late secretory phase begin matrix degradation
Mechanism - Progesterone withdrawal increases expression of cyclooxygenase 2 (COX-2) and increased prostaglandin (PGF2a) production by endometrial stromal cells and increased prostaglandin-receptor density on blood vessels vasoconstriction
(Primary dysmenorrhoea caused by PGs inducing myometrial contractions and ischaemia)
Matrix metalloproteinases (MMPs) from endometrial stroma and proteases from invading leukocytes during late secretory phase begin matrix degradation and recovery
Menstrual blood consists of endometrial cells, unfertilised ovum.
Low viscosity blood and lacks prothrombin, thrombin, and fibrinogen that prevent clotting
What layer of the endometrium is shed?
Functionalis layer is shed.
Basalis layer remains
Menstrual/uterine cycle full
Days 1-7 (Follicular/Proliferative Phase):
In the absence of fertilisation, P4 and E2 levels low. Endometrium shed then regrows; menstruation
Increased GnRH secretion from hypothalamus
Decreased P4 and E2 levels due to CL demise → Increased levels of FSH (-ve feedback from steroids)
FSH acts on ovarian follicular cells to increase E2 production
Of several competing follicles, a single dominant follicle is selected; Other recruited follicles undergo atresia
Endometrial glands mostly straight with evidence of mitosis
Days 8-14:
Dominant follicle matures with significant increase in size → Secretes more E2 from increasing number of granulosa cells → Endometrial proliferation and thickening
High E2 circulating levels exceed a certain threshold, switching to +ve feedback on LH production from anterior pituitary.
LH surge induced; ~24-36 h later, follicle rupture → oocyte released → OVULATION
Ovum picked up by fimbriae of fallopian tube and enters oviduct
Days 14-28 (Luteal/Secretory Phase):
Under influence of LH, empty follicle converted into corpus luteum -secretes mostly P4 but also E2
P4 causes differentiation of endometrial glands to prepare for implantation
P4 maintains endometrium; induces decidualisation
High P4 levels suppress LH and FSH release
Oocyte remains in oviduct
If no fertilisation, CL degenerates → reduced P4
Vasoconstriction via prostaglandins (PGs), ischaemia; no vascular support for endometrium, menses
Low P4/E2 levels GnRH brake release; FSH and cycle begins again
Decidualisation
Transformation of endometrial stromal cells to decidual cells by cAMP, progesterone
Secretory, glycogen-rich, lipid-rich cells
Early nutrition for embryo
Secrete prolactin (anterior pituitary)
Decidua rich in uterine NK cells
Plays a role in immune tolerance
Impaired decidualisation implicated in miscarriage, endometriosis
Cervical Mucus in phases
Proliferative phase
Under E2 influence, mucus is thin, watery, stretchy to aid sperm transport.
Secretory phase
Thick, impenetrable mucus
Basis of contraception?
Spinnbarkeit:
Spinnbarkeit: Describes property of stretch in cervical fluids with ‘ferning’ as a sign of ovulation
Menstrual Disorders
Painful periods/cramps - dysmenorrhoea
- Primary – absence of underlying pelvic pathology,
- Secondary – underlying pelvic pathology
Ovulation pain - Mittelschmerz (middle pain’)
Swelling/stretching or rupture of follicle on ovary’; bleed
Premenstrual syndrome (PMS)
Fluctuating hormone levels – mood swings, irritability, fatigue,
Affects 75% of women at some point in their lives.
Absence / Heavy / Irregular periods
Endometriosis
Painful condition where endometrial tissue found outside uterus commonly e.g. ovaries, fallopian tubes, pelvic peritoneum; less common – bladder, intestinal wall; rare distant sites – brain, lungs
Global incidence 10% premenopausal women
~delay of 6-7yrs in diagnosis (dyspareunia, pelvic pain)
Cause of infertility; adhesions may cause bowel obstructions
Bladder involvement may cause dysuria
Explants remain responsive to hormonal stimulation
Causes:
Retrograde menstruation
Inflammation, cytokines
Reduced apoptosis/stem cells
Angiogenesis/dissemination through lymphatics
Leiomyomas (Fibroids)
Derived from uterine smooth muscle (myometrium)
Hormone dependent, so will progressively enlarge and regress after menopause
Most common benign tumour in females; no progression to cancer
Frequently manifests with menorrhagia, sometimes with metrorrhagia
Often asymptomatic but symptoms vary and all associated with the presence of a mass e.g. pelvic/back pain/pressure, feeling bloated, constipated, urinary frequency, dyspareunia.
Pregnancy and infertility
Leiomyomas can prevent the blastocyst attachment to the uterine wall
Depending on the size and location, they may block the fallopian tubes
Leiomyomas can lead to difficulties during labour, and therefore the need for a caesarean section
Menorrhagia ……….
Hypomenorrhoea…
Menorrhagia…
Polymenorrhoea..
Oligomenorrhoea…
heavy: Menorrhagia Heavy > 80 ml and/or
Light: Hypomenorrhoea
Prolonged: Menorrhagia > 8 days
too short: Polymenorrhoea
Too long: Oligomenorrhoea
AUB Causes / mechanisms
Coagulopathy
Ovulatory
Idiopathic (80%)
Not yet classified
Polyp
Adenomyosis
Leiomyoma
Malignancy
Management strategies of functional AUB
Coagulopathy
e.g. stop anticoagulant
Ovulatory
PCOS: COC
Thyroid
Obesity
Idiopathic: bleeding
Non-hormonal
Hormonal
Management strategies of structural AUB
Remove the pathology
Remove the endometrium
Remove the uterus
Gynaecological causes of CPP?
Unexplained (~30%)
Endometriosis
Adhesions
Ovarian cyst
Fibroid
Non-gynaecological causes of CPP?
Bowel
Urinary
Musculoskeletal
Neuropathic
Psychological
Endometriosis
Endometrial like tissue outside the uterine cavity
Pain Management of endometriosis
Non-medical: local heat – tens machine
Pain killers: NSAID’s/ Paracetamol / Codeine
Pain modulators: amitriptyline
Nerve block
Hormonal treatment of endometriosis
Induce Pseudo-pregnancy:
Progestogens - POP, IUS (LNG), Depot (MPA)
COC
Induce Pseudo-menopause:
GnRH analogues
Ovarian Cancer Risk Factors
50 years of age or older
Familial factors
Family history of breast, ovarian, or colon cancer (3x baseline risk).
Personal history of breast or colon cancer
Familial cancer syndrome (10%)
BRCA (breast cancer) gene mutation
Hereditary non-polyposis colon cancer (HNPCC), Lynch syndrome.
Other potential risk factors
Early menarche (younger than 12 years of age)
Late menopause (older than 52 years of age)
First pregnancy at older than 30 years of age
Infertility, endometriosis
Hormone replacement therapy.
Oral contraceptive (OC) use: longer duration of OC use (10+ years) ….. the risk of ovarian cancer.
Oral contraceptive (OC) use: longer duration of OC use (10+ years) reduces the risk of ovarian cancer.
Ovarian Cancer – Classification
Primary:
1- Epithelial (90%)
Serous
Endometrioid
Clear cell
Mucinous
Undifferentiated (unclassified)
2- Germ Cell: primitive streak that ultimately migrated to the gonads.
Teratoma (benign).
Dysgerminoma Choriocarcinoma
3- Sex cord-Stromal (Originate from the stroma)
Fibroma
Granulosa theca cell tumour
Sertoli-Leydig cell tumour
Secondary / Metastatic: Often bilateral and from other tumours such as colon /stomach breast, uterus and cervix.
Teratoma
Teratomas are germ cell tumours that are composed of different cell types derived from 1 or more of the 3 germ cell layers.
Cell types present may be ectodermal (e.g., skin, hair follicles), mesodermal (e.g., muscle, bone, teeth), or endodermal in origin (e.g., lung, gastrointestinal cells).
These tumours are broadly differentiated into benign, well-differentiated cystic lesions (mature) and malignant, poorly differentiated solid lesions (immature).
90% are benign and occur in patients <20 years
Clinical staging of ovarian cancer (FIGO)
Stage 1: Tumour limited to ovary.
Stage 2: Involvement of other pelvic structures.
Stage 3: Intra-abdominal spread beyond pelvis.
Stage 4: Distant metastases
Ovarian cancer - presentation
Abdominal symptoms:
Dull abdominal pain
Abdominal bloating.
Dyspepsia.
Constipation
Urinary symptoms:
An Increased Urge to urinate
General symptoms of any cancer
Other symptoms:
Menstrual Irregularities
Painful Intercourse
Ovarian cancer Diagnosis
1- Patients with symptoms:
Imaging: transabdominal or transvaginal ultrasound.
Tumour markers:
A. CA125.
Human epididymis protein 4 (HE4)
AFP (Alpha photo protein) for teratoma.
HCG (Human Chorionic Gonadotropin) for Choriocarcinoma.
CEA (Carcinoembryonic antigen)
C. Chest X-ray (for metastasis)
2- Patients without symptoms but with family history:
a. Refer the patient to the genetic clinic to check BRCA1/BRCA2 mutation.
Cervical Carcinoma
Incidence: Dramatically reduced since introduction of screening. From most common female cancer to 13th.
Types: 90% squamous carcinoma (squamous cells) 10% adenocarcinoma (glandular cells).
Peak incidence: 30 years for cervical intraepithelial neoplasm (CIN), 45-50 years for invasive carcinoma (long onset).
Presenting symptoms: post coital/unexpected bleeding. Dyspareunia, dysuria for more advanced cancer.
Detection: cervical screening for early stages
Cervical cancer RISK FACTORS
Human papilloma virus (HPV)
Multiple sexual partners.
Smoking
Multiple pregnancies
Long-term use of the contraceptive pill
Family history
Normal cellular changes in the cervix
The endocervix (endocervical canal) is a luminal cavity between the external os and the internal os and lined by a simple columnar epithelium that secretes mucus.
The ectocervix is covered by stratified squamous epithelium.
The squamocolumnar junction (SCJ) is defined as the junction between the squamous epithelium and the columnar epithelium. Its location on the cervix is variable.
Age and hormonal status are the most important factors influencing location of SCJ.
At birth and during premenarchal years, the SCJ is located at
or very close to the external os (original SCJ).
During reproductive age, the SCJ is located at variable distances from the external os.
In a postmenopausal woman, the new SCJ is not visible and has receded into the endocervix.
Ectropion, Metaplasia, Dysplasia and Neoplasia
Ectropion is defined as eversion onto the ectocervix of the SCJ along with large portions of replacement of columnar epithelium. “ COLUMNAR IS COMING”.
Exposure of the everted columnar epithelium (ectropion) to irritation by acidic vaginal environment and progressively through a process called metaplasia the ectropion is replaced by metaplastic squamous epithelium.
Transformation zone: Area between the original SCJ and the new SCJ where the columnar epithelium (ectropion) has been replaced by the new metaplastic squamous epithelium.
The metaplastic squamous epithelium are vulnerable to dysplasia and neoplasia
Degree of dysplasia in the cells; classified as:
Cervical intraepithelial neoplasm (CIN) stages 1-3
Nuclear atypia characterized by: nuclear enlargement, hyperchromasia (dark staining), coarse chromatin granules, and variation in nuclear size and shape and a clear zone around the nucleus indicative of HPV infection (koilocyte).
CIN staging
CIN I – mild dysplasia involves about one-third of the thickness of the epithelium.
CIN II – moderate dysplasia involves about two-thirds of the thickness of the epithelium.
CIN III – severe dysplasia and carcinoma in situ involves more than two-thirds of the thickness of the epithelium or the full thickness but intact basement membrane.
Prognosis of CIN:
1) about half of CIN I will regress and only 20% of CIN I will progress over many years to CIN III.
2) About 20% of CIN III will become invasive carcinoma over 10 years.
Staging and prognosis of cervical cancer
Stage I- Cancer is confined to the cervix.
Stage II- Cancer at this stage includes the cervix and uterus, but has not spread to the pelvic wall or the lower portion of the vagina.
Stage III- Cancer at this stage has moved beyond the cervix and uterus to the pelvic wall or the lower portion of the vagina.
Stage IV- At this stage, cancer has spread to nearby organs, such as the bladder or rectum, or it has spread to other areas of the body, such as the lungs, liver or bones.
5 year survival at:
Stage I – 90%
Stage II – 82%
Stage III – 35%
Stage IV – 10%
Human Papilloma Virus (HPV) infection
Sexually transmitted.
HPV type 16 and 18 are responsible for most of cervical carcinoma.
Most common gynae cancer?
Uterine carcinoma
Uterine carcinoma risk factors
Exposure to oestrogen is a key risk factor: Risk is increased with dose and time exposed
a) Endogenous oestrogen
–obesity
– Polycystic ovary syndrome (PCOS).
b) Exogenous oestrogen
– Hormone replacement without progestin.
– Tamoxifen (oestrogen agonist in the endometrium)
Early menarche < 12 Years of age.
Late menopause > 52 Years of age.
Nulliparity
Diabetic and hypertensive women develop endometrial cancer
Previous history of breast, ovarian& colorectal Ca.
Family History of endometrial Cancer
uterine cancer s+s
Bleeding
– Present in 90% of all cases
– 15% of patients with postmenopausal bleeding will have endometrial cancer
Other Signs/Symptoms
– Vaginal Discharge(80-90%)
– Pelvic Pain, Pressure
– Change in Bowel Habits
STAGES OF ENDOMETRIAL CANCER
Stage1- Growth of tumour is confined to endometrium.
Stage 2- Growth extend to cervix.
Stage 3- Growth extends to vagina including lymph nodes.
Stage 4- Growth invades rectum or bladder and structure beyond pelvis
Uterine vs cervical vs ovarian main symptoms
Ovarian: pain + uro changes
Cervical: post coital/ unexpected bleeding + dysuria, dysparunia
Uterine: (postmenopausal) bleeding + pain
Which STIs are Bacterial?
Chlamydia
Gonorrhoea
Syphilis
Which STIs are Parasitic?
lice
scabies
Which STIs are Viral?
HIV and AIDS
Genital Warts (HPV)
Genital Herpes
Hepatitis B and C
Which STIs are Blood-Borne?
HIV and AIDS
Hepatitis B and C
Complications of STIs
Infertility (male and female)
Pelvic inflammatory disease (PID) in woman
Epididymitis in men
Urinary tract complications
Cervical cancer
Psychological impact
Serious illness and death
Gonorrhoea
Caused by Neisseria gonorrhoeae - Gram negative cocci (diplococci)
Virulent factors
- Pilus for cell attachment
- Lipopolysaccharide (LPS) endotoxin
- Capsule rendering phagocytosis resistant.
- IgA protease destroy IgA1 (mucosal immunity)
Clinical presentation:
Symptoms develop 2-7 days after infection.
Around 50% female asymptomatic:
Purulent urethral / vaginal discharge
Dysuria
Rectal infection
Neonatal gonococcal eye infection
Pelvic inflammatory disease
Untreated may result in infertility
Diagnosis
MC+S
Culture swabs from infected area or discharge (kept warm in charcoal-enriched transport medium and sent to lab without delay).
Nucleic Acid Amplification Test (NAAT)_urine sample
Culture still vital – need antibiotics sensitivity for treatment due to multi-resistant strains
Chlamydia
Caused by Chlamydia trachomatis serotypes D to K: Very small obligate intracellular bacteria, Gram negative (if stained, normally very weak)
Clinical presentation
Approx. Male 50%, female 70% asymptomatic
If symptomatic
Female
Vaginal discharge, intermenstrual bleeding, deep dyspareunia, lower abdominal pain or discomfort
Male
Urethral discharge, dysuria
Ocular infections in neonates infected during birth may cause blindness. Infected neonates also prone to
C trachomatis pneumonia
Diagnosis:
Requires specialised techniques (cell culture using McCoy cell lines).
Nucleic Acid Amplification Test (NAAT)
Enzyme-linked Immunosorbent Assay (ELISA)
Currently off the shelf test kits are available
Syphilis
Caused by Treponema pallidum (spirochete) - Gram negative (if stained, normally very weak)
Motile with corkscrew motility pattern
Sensitive to heat, drying ; Can not be cultured in vitro
Clinical presentation - Four clinical stages of infection
1 - 10 to 90 days post infection - Small, red oral or lesions on genital, chancre (painless lesions)
2 - 2 to 10 weeks after primary stage - Brown rash on palms and soles, fever, lymphadenopathy, muscle and joint pain, hair loss in patchy pattern, rash on mucosa (mouth, throat and cervix)
Latent - asymptomatic
3 - Can manifest many years after latency - Disfiguration, neuropathy, CVS abnormality, gumma (rubbery masses of tissue in organs)
Diagnosis
Microscopy – dark ground or immunofluorescent
Can not be cultured
Most commonly used serological tests
RPR (Rapid plasma reagin)
VDRL (Venereal Disease Reference Laboratory)
TPHA (Treponema Pallidum HaemAgglutination)
Chancroid
Caused by Haemophilus ducreyi - Gram negative coccobacilli - Primarily in Africa and Asia but also becoming a sexual health issue in UK
Clinical presentation
Painful non-indurated genital ulcers
Ulcers may look like herpes
Lymphadenopathy
Diagnosis
MC+S
Gram stain on aspirate from ulcer
Culture may take 2 to 9 days
Herpes
Caused by Herpes simplex virus
Type I oral and Type II genital
Clinical presentation
Painful sores often blisters filled with fluid
May have fever, muscle pain, malaise, itching in infected areas
Treatment
Symptomatic relief only
If pregnant – immediate daily suppressive aciclovir
Genital wart
Caused by Human Papilloma Virus
HPV over 120 types, with less than 50% homology in genome
HPV 6 and 11 cause 90% genital warts
HPV 16 and 18 – high risk types causing 70% cervical cancer
Clinical presentation
Itchy or burning lesions developing into raised lumps with characteristic cauliflower appearance
Treatment: Conventionally surgical or liquid nitrogen removal, more recently thermal incision. Topical applications such as trichloroacetic acid
NHS vaccines available for 12 to 18 y.o.
Human Immunodeficiency Virus (HIV) Infection, target and sequalae
Infections by HIV does not equal AIDS (Acquired Immunodeficiency Syndrome)
HIV surface glycoprotein gp120 binds CD4
CD4 lymphocytes (and other CD4 pos cells) infected
Immune function ‘shut down’ due to loss of CD4 helper lymphocytes (red line on graph) – when drops to below 200 / ml
Opportunistic pathogen infections may become fatal
Hepatitis Infections
Primarily Hepatitis B
Can Hepatitis C be transmitted sexually? What are the transmission routes of Hep C
Hepatitis C co-infection with HIV also been reported
? Other factors involved – drug use
Trichomonaisis
Caused by Trichomonas vaginalis
Both male and female approx. 50% asymptomatic
Common symptom: Vaginal or urethral discharge, dysuria, vaginitis
Diagnosis :Microscopy and culture both successful. Also NAAT
Pubic lice
Caused by the crab louse Phthirus pubis
Clinical presentation
Incubation between 5 day to weeks
Itch caused by hypersensitivity reaction, bites may become visible (maculae ceruleae)
Eggs on hair may be visible
Diagnosis
Microscopy reveals adult lice and eggs
Treatment
As per head lice
Malathion applied to dry hair and wash out Permethrin cream
Scabies
Caused by Sarcoptes scabiei
Can survive for up to 7 days
Symptoms may begin 3 to 6 weeks
Nocturnal pruritus
Diagnosis
Nocturnal pruritus
Microscopy
NAAT or antibody assays
Treatment as per head lice
Permethrin or malathion cream
Candidiasis
80 to 90% caused by Candida albicans. Other Candida species also involved
Vaginal discharge being main clinical presentation
Microscopy reveal yeast particles sometimes with hyphae
Vaginal swab culture also reveal fungal growth (pure or heavy growth. If scanty or light growth, non-significant)
Although candidiasis can be transmitted sexually, most cases of candidiasis are general health issues rather than STIs
What is a core group? (STI)
A core group is a sub-group within a population that has a much higher rate of STIs. An example would be the population of sex workers within a city. It is within such subpopulations that STIs are endemic.
What is a periphery group (STI)
A periphery group is a subpopulation that has a much lower rate of STIs than the core group. They tend to have fewer sexual partners.
What is bridge population (STI)
A bridge population is a subpopulation of people withing a community that transmits an STI from a core group to a periphery group. An example would be married men who have sex with a sex worker.
What are the 3 social factors related to reproductive rate of STIs?
1 Safe sex practices (e.g., the use of condoms)
2. The number of partners a person has (and time between partners)
3. Relationship between social class and seeking medical treatment for an STI
What aspect of stigma does STIs have that other forms of illness generally do not have?
Someone having an STI can be stigmatised because of society’s view of the morality about sexuality.
What are three kinds of response to STIs that relate to Tannahill’s model of public health?
Prevention: Sexual Health Services (SHSs) & condoms
Education: sex education and public health campaigns
Protection: partner tracing
Genetic Sex Determination
Biological sex – male (XY), female (XX)
Lack of Y chromosome female
SRY gene - sex determining region of the Y chromosome
SRY acts via SOX-9 (transcription factor) to active genes involved in fetal testis differentiation and repressing ovarian differentiation genes
Sex chromosome aneuploidies (through non-disjunction) describe conditions with loss or gain of one or more sex chromosomes
When does crossing over occur in meiosis?
Prophase I
Oogenesis
Primordial germ cells multiply by mitosis as they migrate
After entering the ovary, oogonia undergo further expansion by mitosis
At birth, ~2 million primary oocytes present ↓ Puberty ~400,000
Meiosis I begins but arrests at prophase I (primary oocytes)
Meiosis I does not complete until just before ovulation several years later
Secondary oocyte division arrests again at Metaphase II until fertilisation
Spermatogenesis SITE and CELLS
Testes
- Produce testosterone
- Produce sperm
Seminiferous tubules sites of sperm production
Sertoli cell – nourish and support sperm production
Sperm – undifferentiated and non-motile; transported to epididymis by contractions, for storage and become motile
Spermatogenesis
Primordial germ cells multiply as they migrate -> enter testis (spermatogonia) and arrest in G1
After birth spermatogonia undergo expansion by mitosis in the testis giving rise to two cell types -> Type A cells are stem cells that ensure a continued pool for and Type B cells that differentiate into primary spermatocytes
Meiosis begins at puberty. Completion of meiosis I gives secondary spermatocytes and meiosis II spermatids
Differentiation (Spermiogenesis) then gives rise to mature spermatozoa
Last stage of spermatogenesis, sperm still attached to the Sertoli (sustentacular) cells, which maintain the blood-testis barrier (tight junctions, prevent contact of sperm specific antigens and components of the immune system)
Maintain high concentration of androgens, oestrogens, K+ in tubular fluid
Androgen binding protein (ABP) – binds testosterone/DHT- concentrated- to enable spermatogenesis and maturation
Support spermiogenesis (nutrients, etc)
Secretion of anti-Mullerian hormone in the developing testis
Spermiogenesis
Last stage of spermatogenesis, sperm still attached to the
Sertoli (sustentacular) cells, which maintain the blood-testis barrier (tight junctions, prevent contact of sperm specific antigens and components of the immune system)
Maintain high concentration of androgens, oestrogens, K+ in tubular fluid
Androgen binding protein (ABP) – binds testosterone/DHT- concentrated- to enable spermatogenesis and maturation
Support spermiogenesis (nutrients, etc)
Secretion of anti-Mullerian hormone in the developing testis
Golgi vesicles combine to form acrosomal vesicle
Centrosomes organise microtubules in the developing flagellum
Mitochondria accumulate in the midpiece
Nucleus condenses and is stabilised by protamines (replace histones) for denser packing of most (~96% of genome)
Excess cytoplasm is pinched off as a residual body
Fertilisation
Ovulation releases the secondary oocyte and 1st polar body (with surrounding corona radiata cells). Oocyte suspended at metaphase of meiosis II
Acrosomal enzymes (e.g. hyaluroidase, acrosin) break down ECM components holding corona radiata cells together.
Multiple sperm are required.
One sperm makes contact with the oocyte membrane - fusion triggers oocyte activation and meiosis II completes (2nd polar body ejected)
Oocyte membrane depolarises and cortical reaction occurs which acts as a block to polyspermy
Pronuclei and spindle fibres begin to form
Pronuclei fuse (amphimixis) and the first division completes about 30 hours later
Structure of the ovary
Inner medulla - loose areolar tissue - vessels
Outer cortex - stroma & follicles
Tunica Albuginea
Germinal epithelium
In-Utero Oogenesis
3-4 wks: Primordial germ cells (PGC) - (20 – 30 cells)
Migration (4 weeks): from allantois to gonadal ridge
Proliferation & Differentiation into Oogonia
4 – 20 weeks: Oogonia
Proliferation (Mitosis) until 20 wk -> 7 million
20 weeks: Primary Oocytes
Meiosis (no further proliferation) -> 1ry oocytes
Arrest at Prophase I oocytes
In-Utero primordial follicles
Resting (primordial) follicles: (ovarian reserve - 7 m at 20 wk)
Each 1ry Oocytes - surrounded by granulosa cells
Resting follicles (7 million at 20 weeks)
Rapid Depletion of primordial follicles in-utero:
From 24 weeks until birth
By degeneration (90%) or entering the growth phase
From 7 million at 20 wk
to 2 million at birth
Folliculogenesis
Primordial follicles:
Every day, a cohort will start to grow
120 days -> primary follicle
Primary follicles:
3 cycles (70 days) -> small antral follicles (2-5 mm)
Small antral follicles:
FSH window -> recruited into ovulatory cycle
No FSH window -> atresia
FSH threshold / window
Daily, a cohort of follicles reach FSH regulated stage
If FSH < threshold -> atresia by default
If FSH > threshold -> rescued
FSH window: 5 days
Inter-cycle FSH increased > threshold – lasts 5 days (FSH window) -> mono-follicular development
Ovarian hyper-stimulation:
Widening the FSH window multi-follicular development
Big increased FSH for a short period mono-follicular development
Classification of anovulation: WHO Group I
Main features: [Amenorrhea - decreased FSH - decreased E2]
Causes [HP failure]
Hypothalamic failure: (no GnRH)
Excessive exercise
BMI <20 kg/m2
Eating disorders
Anorexia nervosa
Kalman’s syndrome
Pituitary failure: hypopituitarism (no FSH / LH)
Congenital
Sheehan
Radiotherapy
Trauma (surgery, fracture base of skull)
Neoplasia
Classification of anovulation: WHO Group II
Main features: [Oligo/Amenorrhea – N FSH - N E2]
Hypothalamic dysfunctions
- Eating & weight disorders
- Psychological - emotional
- Ovarian Dysfunction (PCOS)
obesity
- Hyperprolactinaemia
Hypothyroidism
- Adrenal disease: CAH & Cushing
Classification of anovulation: WHO Group III
Main features: [Amenorrhea - Increased FSH - Decreased E2]
1 Chromosomal Mosaic Turner (45X/46XX)
2 Autoimmune
3 Ovarian Pathology
- Infection
- Severe endometriosis
4. Iatrogenic
- Chemotherapy
- Radiotherapy
- Surgery
5. Idiopathic: majority
Detection of ovulation; Best test
D21 progesterone
What is PCOS
Androgen excess from Insulin resistance, or LH excess
From pituitary or ovarian dysfunction
Leads to: Follicular arrest in small antral phase
Failure to escape atresia -> Polycystic ovary
or failure to select -> anovulation
Consequences of PCOS - short and long term
Short-term
Reproductive
Androgenic (Acne, hirsutism, baldness)
Metabolic (Obesity, IGT)
Long-term
Diabetes (3-fold )
Cardiovascular disease (IHD, BP)
Endometrial Cancer
Ovarian Cancer [2-3 fold ]
Clinical features of PCOS
Anovulation
Oligo/Amenorrhoea/DUB
Infertility
Hyperandrogenism -> acne, hirsutism
Insulin resistance (Obesity, IGTT)
Diagnosis of PCOS - when to suspect?
Age of onset: 15 - 25
1. Oligo/amenorrhoea (85% PCOS)
2. Skin manifestations (HA)
3. Overweight / Obesity
What are the 3 most common causes of infertility?
Anovulation
Sperm abnormality
Tubal
To investigate a patient’s infertility, laparoscopy and Hysterosalpingography were completed. A proximal occlusion & adhesions were noted, regarding the uterine tubes.
What is the most likely aetiology of these findings?
Pelvic inflammatory disease
Oligoasthenoteratozoospermia
Low sperm count
Low motility
Abnormal morphology
Role of the uterine tube in fertility - structure function
Fimbria: capture the egg
Cilia: unidirectional beating
Peristaltic contractions
Secretions: fertilisation & nourishment
Types of tubal disease
Occlusion
Proximal
Distal
Adhesions
Kinking / distortion
Disturbance of tubo-ovarian anatomy
Common Aetiologies of tubal disease
Infection: PID -> occlusion & adhesions
Endometriosis -> adhesions
Pelvic surgery -> adhesions
Testicular causes of infertility
Genetic
Klienfelter syndrome,
Y chromosome deletion
Immotile cilia syndrome
Orchitis
Infective (e.g. viral)
Traumatic
Environmental:
Smoking
Alcohol
Occupational
Immunologic
Congenital
Cryptorchidism
Vascular
Torsion
Varicocele
Iatrogenic
Chemotherapy
Radiotherapy
Antispermatogenic agents
Idiopathic [90% of cases]
A female patient is found to have anti-sperm antibodies, adding to their own fertility problems.
What kind of infertility is this?
Cervical Factor
Hormonal: defective response to E2
Infection: Hostile secretions
Damage
Immunological: anti-sperm antibodies
Ovarian factor infertility
Structural defects e.g.
Asherman syndrome – abnormal scar tissue
Congenital septum
Onset of Puberty
Begins in late childhood:
8-13 years for females
9-14 years for males.
Puberty: Physical Changes
Development of secondary sex characteristics
Physical growth
Sexual development
Psychological development.
Growth spurt
Mass and fat distribution
Bone maturation
Adult height.
Spermatogenesis (boys) / Ovulation (girls)
Adrenarche
Is the activation of production of androgens by the adrenal cortex, which begins before age 8. It is responsible for appearance of pubic and auxiliary and acne (Pubarche).
Gonadarche
Is the activation of the gonads by the pituitary hormones FSH and LH. It is responsible for the production of oestrogens and testosterone. Sexual maturation and development of reproductive maturity.
Hormones in puberty; gnrh
Hypothalamus releases GnRH in bursts occurring at approximately two-hour intervals.
This causes rates of Follicle-stimulating hormone (FSH) and Luteinizing (LH) secretion to rise during bursts and fall between bursts.
At the beginning of puberty, however, pulsatile GnRH secretion rises dramatically inresponse to a change in brain activity that alters neural input to thehypothalamus. (The precise nature of this change in brain activity ispresently unknown)
The pattern of GnRH signaling is important indetermining the quantity and quality of gonadotropins secreted.
The amplitude, frequency, andcontour of GnRH pulses can all vary, and each of thesecharacteristics can influence gonadotrophic responses, providing a mechanism for the differential synthesis and secretion of the two gonadotropins, LH and FSH.
GnRH -> LH FSH Secretion Regulation
The frequency of pulsatile gonadotropin-releasing hormone (GnRH) administration has differential effects on gonadotropin secretion:
More rapid GnRHpulse frequencies favor luteinizing hormone (LH) secretion
Slower pulse frequencies favor follicle-stimulatinghormone (FSH)
Timing and Onset of Puberty Modulation
Genetic Neural Control:
Balance in the inhibitory and excitatory factors through coordinated changes in transsynaptic and glial-neuronalcommunication.
Glial cells affect GnRH secretion through growth factor–dependent cell-cell signaling coordinated by numerousunrelated genes.
Nutrition and Metabolic Control:
Some alteration of body metabolism linked to energymetabolism may affect the CNS restraints on pubertal onset and progression.
Leptin:
Afferent satiety factor inhumans, acting on the hypothalamus, including nucleicontrolling appetite, to suppress appetite.
Leptin reflectsbody fat and energy stores and has an important role in the control of body weight and the regulation ofmetabolism.
Leptin increases gradually during the prepubertal years, with similar levels in the two sexes.
During puberty, leptin continued to rise in girls, whereasin boys, the mean levels peaked at Tanner stage 2 and decreased to prepubertal concentrations by genitalstage 5.
Orchidometer can diagnose… 2 e.g.
Hypogonadism (small testes)
Fragile X syndrome (large testes)
Precocious Puberty definition
Defined as development of secondary sexual characteristics before the age of
8 years in girls and 9 years in boys.
Gonadotropin-dependent precocious puberty (GDPP or true):
The treatment options depend upon the cause of the precocious puberty: Identifiable central nervous system (CNS) lesion, therapy is directed toward the underlying pathology.
Primary treatment option is gonadotropin-releasing hormone (GnRH) antagonist which slows accelerated puberty and improves final height.
Use of GnRH antagonist depends on: - child’s age - the rate of pubertal progression - height velocity - rate of bone age advancement.
Gonadotropin-independent precocious puberty (GIPP or pseudo)
GIPP: Gonadotropin-independent precocious
Not respond to GnRH antagonist therapy. Treatment is directed at the underlying pathology.
Children with tumours of the testis, adrenal gland, and ovary treated by surgery.
hCG-secreting tumours combination of surgery, radiation therapy, and chemotherapy depending upon the site and histologic type.
Incomplete Puberty Definition and three types
Isolated manifestations of precocity without development of other signs of puberty.
Premature thelarche: Transient condition of isolated breast development in the first 2 yrs. of life, often persists for 3-5 yrs., and is rarely progressive. Mostly idiopathic.
Premature pubarche: Appearance of sexual hair before the age of 8 yrs. in girls or 9 yrs. in boys without other evidence of maturation.
Premature menarche: Isolated vaginal bleeding in the absence of other secondary sexual characteristics. Very rare.
Delayed Puberty definition and types
Delayed puberty is indicated if no signs of puberty are observed in a girl by 14 years and in a boy by 15 years
Hypergonadotropic Hypogonadism
Hypogonadotropic Hypogonadism
Eugonadotropic Pubertal Delay:
Hypergonadotropic Hypogonadism
Circulating levels of LH & FSH are high (hyper-gonadotropic hypogonadism)
Congenital
Turner Syndrome
Klinefelter’s Syndrome
Complete androgen insensitivity
Acquired
Chemotherapy/Radiation/Surgery
Post infectious (i.e. mumps orchitis, coxsackievirus infection, dengue, shigella, malaria, varicella)
Testicular torsion
Autoimmune/metabolic (autoimmune polyglandular syndromes)
“Vanishing Testes syndrome”
“Resistant Ovaries syndrome” (gonadotropin receptor problems)
Hypogonadotropic Hypogonadism
Constitutional Delay of Puberty
Malnutrition
Excessive Exercise
Growth Hormone Deficiency
Isolated Gonadotropin Deficiency
Endocrine Causes
Miscellaneous syndrome complexes
Brain tumors
Craniopharyngioma, astrocytoma, gliomas, histiocytosis X, germinomas, prolactinomas
Iron overload (pituitary damage)
GnRH receptor abnormalities
Eugonadotropic Pubertal Delay:
Congenital Anatomic Anomalies
Imperforate hymen
Vaginal atresia
Vaginal aplasia
PCOS (Polycystic ovary syndrome)
Hypothyroidism
Interferes with gonadotropin secretion
Hyperprolactinemia
Interfere with gonadotropin production
Treatment of Delayed Puberty
Male:
Testosterone is usually continued until there is clear evidence of spontaneous puberty (testicular growth). The duration and dosage of therapy should be monitored by a pediatric endocrinologist as over dosage or excessively long courses can reduce the period of pubertal growth.
hCG (human chorionic gonadotropin): to stimulate development of secondary sexual characteristics . Increases testicular size.
Female:
Testosterone is usually continued until there is clear evidence of spontaneous puberty (testicular growth). The duration and dosage of therapy should be monitored by a pediatric endocrinologist as over dosage or excessively long courses can reduce the period of pubertal growth.
hCG (human chorionic gonadotropin): to stimulate development of secondary sexual characteristics . Increases testicular size.
Menarche hormones
First menstrual bleed
Occurs near the end of Tanner stage 4 as oestradiol levels continue to rise daily
High levels exert a negative feedback effect on the axis leading to cyclic oestrogen levels and uterine bleeding
Positive feedback is not yet established, so ovulation rarely occurs – anovulatory
Uterine bleeding regularity will vary until the hormone axis has matured and ovulatory cycles begin – can be a year or more after menarche
Health Implications of Early or Late Menarche
Early menarche:
Abdominal type obesity
Insulin resistance Glucose intolerance
Cardiovascular risk
Coronary heart disease
Increased bone mineral density
Increased cancer mortality
Late:
Osteoporosis
Adolescent depression
Social anxiety
Menopause phases
Late reproductive – probability a female will conceive within a set time i.e one menstrual cycle (fecundability) reduces
Early menopausal transition – menstrual cycle and endocrine changes, cycle length > 7 days from normal
Late menopausal transition – ≥ 2 missed cycles and > 60 days amenorrhoea, can last 1-3 years
Final menstrual period (FMP) – end of transition, cannot be confirmed until 1 year later
Early postmenopause – changes in FSH and oestradiol, menopausal symptoms most likely to be seen in this time, lasts about 2 years (includes confirmation year)
Middle postmenopause – stabilisation of high FSH and low oestradiol, lasts 3-6 years
Late postmenopause – limited reproductive endocrine changes, stage lasts until death
Menopause symptoms
Hot Flashes/Flushes
Hallmark symptom of menopause
Transient period of intense heat in upper arms and face – lasts 30-60 seconds
Following by skin flushing and profuse sweating
Can be followed by chills, palpitations and can lead to anxiety
Often at night and can wake the woman
60-80% will experience hot flashes at some point during transition
Lasts several months – 5 years (small proportion up to 30yrs)
Starts during perimenopause, highest in 1st 2 years postmenopause, then decreases
Negatively effect quality of life
Fatigue, irritability, forgetfulness, physical discomfort
Mechanisms unknown – possibly increased sympathetic nervous system drive? Hormone changes?
Dry Vagina
Secretions are oestrogen dependent
Vaginal epithelium atrophy
Less elastic, reduced blood supply
Painful sexual intercourse (dyspareunia) can result
Vaginal lubricants and topical oestrogens
Irritation/Itchy Vulva
Urinary
Transition associated with stress urinary incontinence
Increased urgency and frequency
May be confused with urinary tract infection – antibiotics won’t help
Weakness in muscle layers and ligaments of the pelvic floor - prolapse
Dyspareunia
Decreased desire (libido) – starts during transition phase
Linked to decreased testosterone due to decreased ovarian function
Decreased desire due to lower sex hormone binging globulins (SHBG)
Osteoporosis
CVD:Premenopause: CHD prevalence low in women (smoking main cause)
Menopause transition is associated with a worsening CHD risk
Change in body fat distribution – gynoid to android
Higher presence of comorbid factors – metabolic syndrome, hypertension
Total cholesterol increases by 10%, LDL increases by 14%
Age-independent effects of menopause on cognition
Short-term memory and learning shown to be affected in late transition phase (returns after menopause)
Menstrual migraines peak during transition
Mood swings
Depression
Irritability
Loss of concentration ….
Skin changes:Loss of elasticity – reduced collagen
Dry, thinner skin
Adult acne
Itchy skin and formication (feeling of insects crawling)
Increased hair growth
Premature Menopause
Premature loss of oocytes (premature ovarian insufficiency/failure)
< 40 years old, amenorrhea > 4 months, x2 increased FSH
Incidence: 1% <40yrs, 5% <45yrs
Causes mostly unknown; familial, autoimmune, mosaic Turner syndrome, induced
Loss of fertility – psychological consequences, feelings of femininity
Long term effects – 2-3 fold increased risk of MI, bone loss increased
Induced Menopause
A medical intervention that results in menopause
Occurs at any age after puberty but before natural menopause
Surgical removal of ovaries (oophorectomy) often in conjunction with a hysterectomy
Chemotherapy/Radiotherapy
No transition period
Ejaculation and sperm changes
Semen expelled from posterior urethra
Within the vagina, onto the cervical os
Coagulation – during / just after deposition
Retain spermatozoa in the vagina, buffers against vaginal fluids (acidic)
Coagulating enzymes (prostate derived) combine with fibrinogen-like substrate (seminal vesicle derived)
Coagulum dissolves in 20-60 mins
99% still lost – vaginal leakage
Gamete movement and transport - spermatozoa (sperm)
Cervix lined by folds and crypts – spermatozoa can survive here before moving onwards
Further movement dependent on phase of menstrual cycle
Rising levels of oestrogen promote secretion of watery mucus
Following ovulation, high levels of progesterone promote highly viscous mucus
Movement through uterus – various methods
Own propulsion
Cervical and uterine contractions often present in preogasmic and orgasmic phases
Uterine cilia action
Enter uterine tube and ‘wait’ – become immotile & temporarily bind to epithelial cells
Detach and re-acquire motility at ovulation: travel to ampullary-isthmic junction
Dependent on chemoattractant release by oocyte and cumulus mass
Sperm chemotaxis, chemokinesis (increased swimming speed) & hyperactive flagellar beating
Where does fertilisation most commonly occur?
Oocyte meets spermatozoa at the ampullary-isthmic junction
Ampulla
Gamete Transport - Oocyte
Infundibulum of the uterine tube moves towards the ovary
Fimbriated ostium envelops the ovulated oocyte with enclosing cumulus cells
Cilia and smooth muscle contraction move oocyte into ampulla
Meets spermatozoa at the ampullary-isthmic junction
Spermatazoa Capacitation - why and what
Spermatozoa are not capable of fertilisation at the time of ejaculation
Hyperactivated motility: increased strength and amplitude of flagellar beats
Surface membrane changes: allow acrosome reaction:
Removal of surface glycoproteins such as EPPIN
Increased cytoplasmic pH leads to increased calcium permeability (motility)
Loss of cholesterol
cAMP generation leads to PKA activation and subsequently phosphorylation of tyrosine
Needs to find an oocyte fairly rapidly after capacitation is complete
Fertilisation process (sperm into ovum)
1) Cumulus cells are held together by an extracellular matrix rich in hyaluronic acid - Spermatozoal acrosome is a source of hyaluronidase – the zona pellucida is exposed
2) Spermatazoal binding to ZP3 (ZP1-4 in humans) induces the acrosomal reaction
3) Acrosome swells, and its membrane binds with the plasma membrane causing exocytosis of the acrosome contents - Inner acrosome membrane exposed
4) Proteolytic enzymes digest a path through the zona
Penetration of the zona takes 5-20 mins
5) Spermatozoa enters the perivitelline space and lies along side the oocyte membrane
Microvilli on the oocyte surface envelop the sperm head – bind and fuse
6) Nucleus, various mid-pieces and tail of the spermatozoa pass into the oocyte
7) Within 1-5 mins after fusion – dramatic increase in free calcium. Followed by calcium spikes (important for later events)
- Cortical reaction:
Calcium causes cortical granules to fuse with the oocyte membrane and release their contents
Enzymes destroy ZP receptors
Tyrosine residues on adjacent ZPs are cross-linked – zona becomes non-dissolvable by proteolytic enzyme
Reduction in sperm-binding properties of the oolemma – mechanisms unknown
8) No additional sperm can attach to zona pellucida – prevents polyspermy
Preparation for syngamy - DNA change
The oocyte has been suspended in metaphase of meiosis II since ovulation occurred
Cytostatic factor stabilises M-phase promoting factor which stabilises the oocyte in M-phase
Calcium inhibits cytostatic factor
Meiosis II is completed and a 2nd polar body is released
Cytoplasmic contributions to zygote
Cytoplasmic Contributions:
Spermatozoa – centriole
Oocyte – pericentriolar material, cell membrane, cytoplasm, cell organelles (mitochondria)
Syngamy process
Sperm nuclear membrane breaks down & highly condensed chromatin becomes filamentous strands in the oocyte cytoplasm
Both sets of haploid chromosomes become surrounded by membranes – pronuclei (4-7 hrs after fusion)
Both move centrally & synthesise DNA
Pronuclear membranes break down & all chromosomes line up on a mitotic spindle (18-24 hrs after fusion) – syngamy
Undergo anaphase & telophase
A cleavage furrow forms and this leads to one-cell zygote become two-cell conceptus
Pre-implantation embryo changes
Conceptus moves through the uterine tube to the body of the uterus
Conceptus undergoes cleavage (mitotic divisions) along the way
At approx. day 4 the morula stage is reached (16 cells) and the cells lose totipotency
When the pre-embryo reaches the uterine cavity (~day 5) it is a blastocyst – inner cell mass and trophoblast cell wall
The surrounding zona pellucida is degraded via proteolytic enzyme action – blastocyst hatches
What structures prevent implantation outside the optimal window
Long apical microvilli, high surface charge, thick glycocalyx normally present to impair attachment
What follows blastocyst attachment
Stromal reaction follows attachment – primary decidualisation
Implantation – Invasion
Trophoblast cells become one of 2 types
syncytiotrophoblast – cells fused together & lose cell membranes
cytotrophoblast – retain cellularity, serve as a proliferative source of trophoblasts
Proteases secreted by syncytiotrophoblasts break down the uterine endometrium
The blastocyst invades the tissue and is eventually completely surrounded by it
Implantation Prolongation of Luteal Phase
The blastocyst produces a luteotropic factor – human chorionic gonadotrophic (hCG)
Produced from approx. day 6-7 & released to pass into the maternal blood circulation
hCG binds to LH receptors on luteal cells
Progesterone release is maintained
Progesterone also actively promotes luteal survival by autocrine stimulation – positive feedback
Luteal relaxin also increased in response to hCG – linked to pregnancy-related renal and systemic vasodilation
Most common site of embryo implantation is the ….
Most common site of implantation is the upper posterior wall of the body of the uterus
Common abnormal sites of implantation are….
Uterine tube (majority of ectopic pregnancies occur here – tubal pregnancy)
Rectouterine pouch (pouch of Douglas)
Intestinal mesenteries
Ovary
Implantation in the region of the cervical internal os: may result in placenta praevia
Ectopic pregnancy definition and s&s and tests
Any pregnancy implanted outside of the uterine cavity
Estimated UK incidence of 1 in 90 pregnancies (RCOG)
~1/3 of ectopic pregnancies have no known cause
Other causes include endometriosis, damage to the uterine tube and their ciliary lining e.g. pelvic inflammatory disease, tubal surgery
Risk increases with smoking and age over 40
Symptoms include lower abdominal pain, vaginal bleeding, vomiting, diarrhoea
Any patient with +ve pregnancy test and lower abdominal pain is managed as an ectopic pregnancy until proven otherwise
Serum hCG concentration monitored: >50% decrease after 48 hrs suggests pregnancy is non-viable
Abdominal examination: ruptured ectopic may present as pain/tenderness across abdomen
Transvaginal ultrasound to visualise ectopic and any free fluid e.g. in rectouterine pouch
FBC to assess current Hb levels: anaemia may indicate ruptured ectopic (haemoperitoneum)
Most ectopic pregnancies diagnosed prior to rupture
Ectopic pregnancy treatment
Conservative management if stable, no evidence of free fluid, minimal pain, low or declining serum hCG
Majority of tubal ectopic pregnancies are managed surgically
Salpingectomy: removal of uterine tube
Salpingotomy: removal of ectopic via incision in uterine tube
Some trophoblast tissue may remain
Decidualisation
changes in the endometrium to prepare for blastocyst implantation
Progesterone causes uterine stromal cells to swell up and accumulate glycogen & lipids - decidual cells
Increased vascularisation of endometrium
Blastocyst triggers further decidualisation of uterine as the syncytiotrophoblast layer erodes the endometrium
Three layers of the decidua
Decidua basalis
Decidual layer beneath the developing embryo
Forms placenta with the trophoblast
Decidua capsularis
Decidual layer covering the embryo
Decidua parietalis
Decidual lining elsewhere in the uterus away from the embryo
Decidua capsularis and parietalis ultimately fuse together as gestational sac grows and fills uterine cavity
Fetal membranes (4)
Amnion (inner membrane)
Lines amniotic sac and protects embryo/fetus from physical damage
Secretes amniotic fluid
Oligohydramnios: low volume of amniotic fluid resulting in compression of fetus
Chorion (outer membrane)
Formed by trophoblast and extra-embryonic mesoderm
Gives rise to fetal part of placenta: chorion frondosum
Embryo suspended in chorionic cavity until amniotic sac expands and obliterates this space
Connecting stalk left behind – important for forming umbilical cord
Yolk sac and allantois
Yolk sac is an early source of embryonic nutrition
Primitive yolk sac then secondary yolk sac
Secondary yolk sac degenerates and its vitelline duct is incorporated into the developing midgut (Module 5)
Allantois helps to form urinary bladder
Amnion (inner membrane)
Lines amniotic sac and protects embryo/fetus from physical damage
Secretes amniotic fluid
Oligohydramnios: low volume of amniotic fluid resulting in compression of fetus
Chorion (outer membrane)
Formed by trophoblast and extra-embryonic mesoderm
Gives rise to fetal part of placenta: chorion frondosum
Embryo suspended in chorionic cavity until amniotic sac expands and obliterates this space
Connecting stalk left behind – important for forming umbilical cord
Chorionic villi (3)
Primary chorionic villi
Cells of the cytotrophoblast proliferate and grow into the syncytiotrophoblast: primitive uteroplacental circulation begins
Secondary chorionic villi
Extra-embryonic mesoderm grows into the core of each primary chorionic villus
Tertiary chorionic villi
Extra-embryonic mesoderm differentiates into blood cells and small blood vessels
Uteroplacental circulation
From week 2 there is an increasing need for a circulatory system: more efficient gas and nutrient exchange
Embryonic blood vessels in the tertiary chorionic villi come into contact with the intervillous spaces supplied by the maternal spiral arteries of the uterine endometrium
Umbilical arteries start to form to allow deoxygenated blood to leave the embryo
Umbilical vein starts to form to allow oxygenated blood to return from chorionic villi to embryo
Placenta contribution from maternal and foetal
Placenta formed by both the decidua basalis and chorion frondosum
Basal plate of placenta = maternal decidua basalis
Chorionic plate of placenta = fetal chorionic frondosum
Chorionic villi at each pole
Chorionic villi at embryonic pole (near umbilical cord) increase in size and number to become the chorion frondosum
Chorionic villi at abembryonic pole (opposite side from umbilical cord) become the compressed and avascular chorion laeve (“smooth”)
