Phase 3a Louise Cloney and Lucy Rigg

Phase 3a

Louise Cloney and Lucy Rigg

Gynaecology

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• Menstruation– Physiology– Disorders: menorrhagia, dysmenorrhoea, dysfunctional

uterine bleeding.

• Infertility– Amenorrhoea (primary and secondary)– PCOS – STIs and pelvic inflammatory disease

• Contraception


Aims

• Physiology– Puberty


MenstruationHypothalamus

Anterior Pituitary

Thelarche: 9-11 years

Adrenarche: 11-12 years

Menarche: 13 years


Menstrual Cycle

• Day 1-4: Menstruation• Endrometrium and myometrium contraction

• Day 5-13: Proliferative Phase • Pulses of GnRH from hypothalamus cause release of FSH and LH which

stimulate follicle growth. • Follicles release oestradiol and inhibin – negative feedback, FSH levels

drop. Only the dominant follicle has enough receptors to continue developing under low levels of FSH.

• Levels of oestradiol continue to increase and cause positive feedback producing LH and FSH surge = ovulation.

• Oestradiol is responsible for proliferation of the endometrium: stromal cells proliferate causing it to thicken and the glands elongate.


Menstruation

• Day 14-28: Luteal/Secretory Phase• The surrounding follicular cells from the ovarian follicle becomes the

corpus luteum(theca and granulosa cells) which produces oestradiol but mainly progesterone which is responsible for maintaining the endometrial lining. Levels peak at 21 days.

• Progesterone is responsible for the secretory changes to the endometrium: stromal cells enlarge, the glands swell and the blood supply increases.

• If the egg is not fertilised, the corpus luteum breaks down along with the endometrial lining and the cycle starts again.


Menstruation

Clinical definition: excessive menstrual blood loss that interferes with the woman’s physical, emotional, social and material quality of life, and which can occur alone or in combination with other symptoms. (Objective: >80mL, never measured!)


Menorrhagia

Menorrhagia

Regular Cycle Irregular Cycle

IdiopathicFibroids (30%)Polyp (10%)

Chronic Pelvic InfectionOvarian tumours

Cervical and Endometrial malignancy

Rare: Thyroid disease, haemostatic disorders (VWB), anti-coagulant

therapy

• Check haemoglobin to assess effect of blood loss• Transvaginal Ultrasound – assess endometrial thickness,

exclude a uterine fibroid or ovarian mass and detect larger intrauterine polyps.

• Endometrial biopsy if:• Thickness >10mm• Polyp suspected• 40+ with: recent onset menorrhagia or IBS or unresponsive to

treatment

• Exclude systemic causes:• TFT and coagulation screen only if history suggests.


Menorrhagia - investigations

When possible pathologies have been ruled out:1st Line: IUS2nd Line:i. Antifibrinolytics (tranexamic acid) can

reduce blood loss by 50% with few S/E.ii. NSAIDs (mefanamic acid) inhibits

prostaglandin synthesis, can reduce blood loss by 30%.

iii. COCP 3rd Line: iv. Progestogens cause amenorrhoeav. GnRH agonists cause amenorrhoea. (unless

HRT used, limited to 6 month use) 4th Line: Surgery – endometrial ablation, hysterectomy


Menorrhagia - management

• /leiomyomata – benign tumours of the myometrium


Fibroids

• Occur in at least 25% of women. • More common near menopause, Afro-

Caribbean women, FH• Less common in parous women, COCP,

injectable progestogens • Growth is dependent on oestrogen. • During pregnancy, fibroids equally likely to

grow, shrink or stay the same. Symptoms/complications: • Asymptomatic• Menorrhagia • Dysmenorrhoea • Pain = torsion, red degeneration (particularly in pregnancy) or rarely sarcomatous change (0.1%). • Pressure effects – frequency, retention• Fertility impaired if preventing implantation • Pregnancy: premature labour, malpresentation, transverse lie, obstructed labour and PPH.


FibroidsInvestigations• TVUS – MRI may be required to distinguish from ovarian mass or adenomyosis.

Treatment• Medical

• Tranexamic acid, NSAIDs or progestogens (often ineffective)• GnRH agonists (+HRT)

• Surgical • TCRF (hysteroscopic) – pretreatment with GnRH agonists 1-2 months to shrink• Myomectomy – preservation of reproductive function when medical treatment

failed. GnRH agonists 2-3 months prior to reduce vascularity. Vasopressin injected into myometrium to reduce blood loss. Can increase risk of uterine rupture during labour if cavity opened – caesarian indicated.

• Radical Hysterectomy – GnRH agonists 2-3 months prior. • Other

• Uterine Artery Embolisation

Intrauterine • Small, usually benign tumours that grow into the uterine cavity. • Common in women 40-50 years. • Menorrhagia, IMB, occasionally prolapse through the cervix. • Treated by resection with cutting diathermy Cervical• Benign tumours of endocervical epithelium• Most common in women >40• Asymptomatic or IMB or PCB


Polyps

• Causes most gynaecological cancer deaths – common in post-menopausal women

• Epithelial (90%), Germ Cell, Sex Cord tumours• Aetiology

• FH – BRCA1, BRCA2 or HNPCC• Related to number of ovulations - nulliparity, early menarche, late menopause increased

risk. Pregnancy and use of pill protective.

• Symptoms• Silent in early stages • 75% present in stages 3-4• Abdominal distension or pain (bloating), loss of appetite, change in bowel habit.• Urinary frequency/urgency. • Pain or vaginal bleeding• Think new onset IBS symptoms in elderly woman!


Ovarian Cancer

• Transcoelomic spread directly within the pelvis and abdomen • Risk of Malignancy Index = UxMxCA125 (ultrasound score and menopause

status)• Investigations

• USS• CA 125 - if >35 IU/mL, ultrasound of pelvis and abdomen• CT

• Alpha fetoprotien and hCG in <40 years for germ cell tumours • Staging

• 1 Ovaries only. 1a one ovary; 1b both ovaries; 1c capsule broken with malignant cells in the abdomen

• 2 Pelvis only• 3 Abdomen and Pelvis • 4 Distant, including liver , lung (Meigs’ syndrome)


Ovarian Cancer

Management• Surgery

• Total hysterectomy, bilateral salpingoophorectomy and partial omentectomy. • Retroperitoneal lymph nodes sampled/removed in stage 2+• Random biopsies of peritoneum. • To preserve fertility in ‘early’ or ‘borderline’ cases , uterus and unaffected ovary

preserved with meticulous follow up.

• Chemotherapy• Stages 1c+

• Palliative Care• Prognosis

• CA125 useful to monitor • CT scans• Death commonly from bowel obstruction or perforation • <35% 5 year survival due to late presentation.


Ovarian Cancer

• Most common gynaecological carcinoma, usually >60 years• >90% adenocarcinoma, adenosquamous carcinoma (poorer prognosis)• Aetiology

• High oestrogen:progesterone ratio: nulliparity, late menopause, PCOS, obesity. Unopposed oestrogens (HRT) and tamoxifen.

• COCP and pregnancy protective.

• Clinical Features• PMB• Premenopausal: irregular or IMB, recent onset menorrhagia. • Cervical smear showing abnormal columnar cells: cervical glandular intraepithelial

neoplasia CGIN

• Investigations• If PMB: TVUS plus, if endometrium >4mm thick or multiple episodes, biopsy by pipelle or

during hysteroscopy • If premenopausal: TVUS then biopsy if abnormal or change in periods and >40. • FBC, U&E, ECG – fitness for surgery


Endometrial Cancer


Endometrial Cancer• Staging

• Surgical and histological • FIGO

• Stage 1: Lesions confined to the uterus – A <1/2 myometrial invasion; B >1/2• Stage 2: Cervical stromal invasion, but not beyond uterus• Stage 3: Tumour invades through the uterus (A-Cii)• Stage 4: Further Spread – A in bladder it bowel; B distant metastases

• Histological grade: G1-3, G1 being a well differentiated tumour.

• Management• 75% present at stage 1: hysterectomy and bilateral salpingo-oophorectomy • External beam radiotherapy: for patients following hysterectomy at ‘high risk’ of lymph

node involvement. • Vaginal vault radiotherapy: stage 2, reduces local recurrence but doesn’t prolong

survival.

• Prognosis• 85% 5 year survival rate at stage 1.

• Cervical Intraepithelial Neoplasia: the presence of atypical cells within the squamous epithelium.

• Dyskaryotic: large nuclei and frequent mitoses• CIN I: mild dysplasia.

• Atypical cells found in the lower 1/3 of the epithelium• Can become CIN II/III but usually regresses on own

• CIN II: moderate dysplasia• Atypical cells in the lower 2/3 of the epithelium

• CIN III: severe dysplasia • Atypical cells occupy the full thickness of the

epithelium.• Carcinoma in situ: similar in appearance to malignant lesion but there is no invasion.

Malignancy ensues if they invade through the basement membrane.

• If untreated, one third of women with CIN II/III will develop cervical cancer over next 10 years


CIN

• 90% cases in <45 years old, peak incidence 25-29 years.

Aetiology:• HPV – 16, 18, 31 and 33.

– Vaccination (16 and 18) reduces risk of pre-cancerous lesions. • Number of sexual contact, especially at an early age. • Oral conraceptives• Smoking • Immunocompromised more at risk of early progression to malignancy.

Pathology:• Columnar epithelium undergoes metaplasia at the transformation zone to squamous

epithelium.• Presence of HPV results in incorporation of vial DNA into cells – inactivate key cell tumour

suppressor gene products and push cells into cell cycle. Mutations occur over time = carcinoma.• Viruses also hide cells from immune response so aren't destroyed, similar in

immunosuppressed.


CIN

CIN causes no symptoms and is not visible on the cervix. Diagnosis identifies women at high risk of developing carcinoma of the cervix that could be treated before the disease develops.• Cervical Smears

• All women from 25 years old, or after first intercourse if later, every 3 years until 49. • Between 50 and 65, 5 yearly.• From 65, those who have not been screened since 50 or who have had recent abnormal

tests are screened. • Brush scraped around external os of cervix to pick up loose cells over transformation

zone for Liquid Based Cytology. • Cellular abnormalities as only superficial cells sampled. Graded mild, moderate,

severe dyskaryosis – relates to likely CIN to be found on biopsy.


CIN - Screening

Results:


CIN - Screening

Mild•Test sample for HPV •If high risk strain +ve, colposcopy arranged•If negative, returned to routine programme

Moderate •Colposcopy

Severe •Urgent colposcopy

CGIN •Colposcopy•If abnormality not found, hysteroscopy

Colposcopy• Acetic acid turns white on CIN • Diagnosis can only be confirmed with biopsy and histology • If CIN II or III is present: LLETZ – large loop excision of transformation zone with

cutting diathermy. • Occasionally malignancy is diagnosed • ‘See and treat’ when don’t wait for histology of colposcopy more common. • S/E LLETZ – postoperative haemorrhage, uncommon. Risk of subsequent preterm

delivery increased.• Significant false negative rate with cervical smears, dependent on both sampling and

interpretation techniques.


CIN - Screening

• 90% squamous cell carcinomas, 10% adenocarcinoma (worse prognosis) • Same risk factors as CIN as it is the preinvasive stage• Clinical Features:

• None, found on LLETZ• PCB• Offensive vaginal discharge• IMB or PMB • Later stages: involvement of ureters, bladder, rectum and nerves, get uraemia, haematuria, rectal

bleeding and pain. • On Examination: ulcer or mass may be visible or palpable on cervix.

• Investigations:• Biopsy • Rectal and vaginal examination to assess size of lesion and parametrial or rectal invasion (under

anaesthetic)• Cystoscopy detects bladder involvement• MRI detects tumour size, spread and LN involvement


Cervical Cancer

• Staging:• 1 Cervix: a(i) <3mm depth, <7mm across; a(ii) <5mm depth, <7mm across; b larger than 1a• 2 Upper Vagina also: a not parametrium; b in parametrium• 3 Lower vagina or pelvic wall, or ureteric obstruction • 4 Into bladder or rectum, or beyond pelvis.

• Treatment


Cervical Cancer

1a(i) •Cone biopsy•Simple hysterectomy

1a(ii)-1b(i) •Laparoscopic lymphadenectomy and radical trachelectomy to preserve fertility

1a(ii)-2a •LNs negative: Wertheim’s hysterectomy (pelvic node clearance and removal of parametrium and upper 1/3 vagina too) or chemo-radiotherapy if older/medically unfit. •LNs positive: Chemo-radiotherapy without surgery

2b-4 •Chemo-radiotherapy wihtout surgery


DysmenorrhoeaDysmenorrhoea

No Organic Cause

Pain precedes and is relieved by

menstruation

PRIMARY(50% women, 10% severe)

SECONDARY

NSAIDSOvulation Suppression - COCP

Pain starts with menstruation

Deep dyspareunia, menorrhagia, irregular

menstruation

Pelvic Pathology

• Growth of tissue similar to endometrium outside the uterus• Particularly found in uterosacral ligaments, pouch of douglas and

on/behind the ovaries. • Endometrioma/’chocolate cysts’ due to accumulated blood• Causes inflammation with progressive fibrosis and adhesions –infertility• Theories:

• Retrograde menstruation• Lymphatic or haematogenous spread• Metaplasia of coelomic cells

Clinical Features:• Dysmenorrhoea • Dyspareunia• Cyclical or chronic pelvic pain• Subfertility


Endometriosis

Less common symptoms include: • Cyclical rectal bleeding• Menorrhagia• Diarrhoea• Haematuria

Investigations• Laparoscopy is the gold standard. Management • Medical:

• COCP• Pain management • GnRH agonist• Mirena

• Surgical:• Laparoscopic ablation/excision of cysts and adhesions• Bilateral oophorectomy, often with hysterectomy


Endometriosis

• Presence of endometrium and its underlying stroma within the myometrium.

• Associated with endometriosis and fibroids Clinical Features:• Painful, regular, heavy menstruation• Uterus mildly enlarged and tenderInvestigations:• MRIManagement:• IUS• COCP• NSAIDs• Hysterectomy often required


Adenomyosis


Amenorrhoea Hypothalamus

GnRH

Anterior PituatryFSH & LH

Ovary- Theca cellsAndrogens

Ovary – Granulosa Cells

OestrogenInhibin


Amenorrhoea Primary: failure to start menstruating by age 16 or 14 with no breast development Causes:• PCOS• Delayed puberty• Turners Syndrome (45xo) – short stature,

amenorrhoea and infertility• Gonadal Agenesis • Testicular Feminisation


Amenorrhoea Secondary = previously normal menstruation which ceases for >6 months, not due to pregnancy• Hypothalamic Hypogonadism (stress, anorexia),

reduced secretion of GnRH subsequently low FSH, LH and oestrogen.

• Raised prolactin • Hypo or hyperthyroidism• PCOS• Premature menopause• Cervical stenosis

• 1 in 6 couples UK• NICE definition:People who have not conceived after 1 year of regular unprotected sexual intercourse, should be offered clinical investigation:- Semen analysis - Ovulation assessment• Primary = never conceived before• Secondary = have previously conceived, but have not been

able to since


Infertility


Categorising Infertility

INFERTILITY

MALE

TUBAL UNKNOWN

ANOVULATORY

• Day 21 progesterone (>30 indicates ovulation)• Day 2 FSH & LH• Rubella Immunity• Oestrogen• Testosterone • SHBG• Prolactin • TFT• Glucose• Transvaginal US• Laparoscopy + Dye Test• Hysterosalpingogram• Vaginal US


Investigating Infertility

ADVISE ALL WOMEN ABOUT WEIGHT, SMOKING AND FOLIC ACID

OVARIAN HYPOTHALAMIC

• PCOS• Premature Ovarian failure • Gonadal Dysgenesis

• Hypothalamic hypogonadism• Kallmans Syndrome


Anovulatory Causes of Infertility

PITUATRY OTHER- Sheehans Syndrome- Hyperprolactinaemia

• Hypothyroidism• Hyperthyroidism• Diabetes• Smoking• Turners (45XO)

Rotterdam critera (2 of 3)1. Oligomenorrhoea (>35 days apart)2. Hirsutism- Clinical – acne/excess body hair (face)- biochemical – raised serum testosterone 3. PCO on US (transvaginal US showing multiple small follicles on an enlarged ovary) Increased levels of LH & Insulin (due to peripheral insulin resistance) Ovarian androgen production increases, and reduced hepatic production of SHBG increase in free androgens (testosterone) irregular/absent ovulation

O/E: obesity, acne, hirsutism, oligo/amenorrhoea subfertility, miscarriage, FH type II diabetes


PCOS -Polycystic Ovarian Syndrome

Diagnostic:• Day 2 LH (raised)• Testosterone (raised)• SHBG (reduced)• Transvaginal USOther (exclude other causes of infertility)- Day 21 progesterone (>30mmol/L = ovulating)- Day 2 FSH- Prolactin- TFT- Rubella immunity- Hba1c (may have DM II)


Investigations

1. Weight loss (diet and exercise) + smoking cessation2. CLOMIFENE = anti-oestrogen to induce ovulation, use upto 6 months. SE: endometrial thinning 3. Metformin (alone or with clomifene)4. Gonadotrophins (if resistant to clomifene)5. Laparoscopic diathermy

For those not wishing to get pregnant – Co-cyprindol for hirsutismCOCP to control mestrual irregularity and hirsutismMetformin


Treatment

Hypothalamic Hypogonadism – Reduced GNRH reduced FSH & LH reduced oestrogenCommon causes = anorexia, athleticism, stress Aim: try and maintain a good normal weight

Kallmans Syndrome – GnRH secreting neurones don’t developAlso present with anosmia Treat: Gonadotrophins/ GnRH pump


Hypothalamic Causes

Hyperprolactinaemia – Raised prolactin reduced GnRHCauses:• Pituatary adenoma • Pyschotropic drugs • Hypothyroidism• Stress• Breastfeeding Oligo/amenorrhoea, Galactorrhoea, Headache + bitemporal hemianopia (if tumour)Treat: Dopamine Agonist e.g. Bromocriptine Surgical Excision (if tumour)

Sheehans Syndrome- post-partum hypopituatarism, where GNRH is normal, but FSH and LH are low due to pituatry damage.


Pituitary Causes

•Infection: PID adhesions •Endometriosis •Previous Surgery/ sterilisation causing adhesions

Needs surgical intervention, adhesiolysis


Tubal Causes


Pelvic Inflammatory Disease

Causes:• CHLAMYDIA• Gonorrhoa• Miscarriage • Termination• Laparoscopy

Investigations:• Endocervical swabs• FBC, CRP, Blood cultures• Transvaginal US• Laparoscopy

Protective Factors:• COCP• Mirena

• Nulliparous RF: • Low social class• Sexually active • Young


Pelvic Inflammatory DiseaseACUTE CHRONIC

•Severe Bilateral lower abdo pain •Abnormal bleeding discharge•Tachycardia. Pyrexia •Cervical Excitation•Bilateral Adnexal Tenderness •Unwell patient •Treat: ABC, analgesia •IM Ceftriaxone + Doxycycline + Metranidazole (IV or PO depending on severity)•Comp: chronic pid,abcess

•Chronic lower abdo pain •Dysmenorrhoea•Deep dyspareunia•Menorrhagia•Chronic discharge•Subfertility•Investigate with Transvaginal Us/ Laparoscopy adhesions, tube obstruction, hydrosalpinx•Treat: analgesia, abx, adhesiolysis, salpingectomy?


Male SubfertilitySPERM ANALYSIS

VOLUME >1.5 ML

SPERM COUNT >15 MILLION/ML

PROGRESSIVE MOTILITY >32%

MORPHOLOGY >4%

PH ALKALINE >7

AZOOSPERMIA = no spermOLIGOSPERMIA = <15millionSEVERE OLIGOSPERMIA = <5millionASTHENOSPERMIA = low motilityTERATOSPERMIA = reduced morphology

• Stop smoking • Stop drinking • Avoid tight fitting boxers


Causes of male subfertility

• Idiopathic• Alcohol/smoking • Anabolic Steroids• Infection – epidydimitis • Kleinfelters (XXY)• Kallmans • Hyperprolactinaemia • Retrograde Ejaculation (TURP, Diabetes)• Cystic Fibrosis


Assisted Conception

1. IUI – intrauterine insemination2. IVF3. ICSI (if male problem – intracytoplasmic sperm injection)4. Egg donation5. Surrogacy

Complications: multiple pregnancy, ectopics perinatal mortality, procedural haemorrhage


Gynaecological Infection

Girl presents in the GU clinic with a new fishy smelling grey/white discharge….



BV- bacterial vaginosis - Gardnerella & Mycoplasma Hominis- Grey/white discharge- Fishy smell- Clue cells - Raised PH- Treat: Metranidazole



36 year old diabetic woman, just finished course of antibiotics, noticed a thick white discharge and has noticed pain during intercourse and itching down below



Candidiasis (Thrush)- Candida Albicans- Cottage cheese thick white discharge- Inflamed/red vulva- Pruritis vulvae- Superficial dyspareunia - RF: abx, pregnancy, diabetes, COCP, HRT- Treat: Clotrimazole cream + pessary- Fluconazole oral tablet if reccurent



19 year old girl presents in clinic, following a drunken one night stand a couple of weeks before, she has noticed some burning when weeing, and abnormal discharge since…



Chlamydia- Chlamydia Trachomatis- More often asymptomatic than not - Discharge - Urethritis- Dyspareunia - Complications: PID, reiters, subfertilty- Treat: single dose Azithromycin 1g



28 year old man who has recently split from his partner and has been making the most of his situation presents in clinic with sore red ulcers in his groin and around his penis, he notices a burning pain when weeing, and feels generally unwell



Genital Herpes- Herpes Simplex Virus 2- Multiple painful vesicles/ulcers - Dysuria- Fever-Vesicles must be present for tranmission- Lie dormant in CNS, and can reactivate, usually related to stress/infection

- Treat: Aciclovir



Woman presents in clinic with a frothy offensive green discharge, and pain on intercourse…



Trichomonas Vaginalis- Flagella Protozoa- smelly, frothy, green discharge - Irritation- Strawberry cervix- Superficial dyspareunia - Polymorphonuclear leucocytes on wet film microscopy

- Treat: Metranidazole



Young man presents in clinic with some discharge from his penis and burning sensation when weeing, swabs reveal a gram negative diplococcus



Gonorrhoea - Neisseria Gonorrhoea- Gram negative diplococcus - Asymptomatic or- Discharge and urethritis- Treat: IM ceftriaxone 250mg or oral cefixime 400mg

• Look over breast disease in the handbook provided on Minerva!


REMEMBER…

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Phase 3a Louise Cloney and Lucy Rigg