GYNAECOLOGY

GUM, FERTILITY, CONTRACEPTION, AND UROGYNAECOLOGY

 Genitourinary medicine

GUM INFECTIONS

I. A
BP falls in early pregnancy until 24

Vulval warts
I. CONDYLOMA ACCUMINATUM (VULVAL WARTS)
A. Benign wart (HPV 6, 11 spread by sexual contact)
B. HPV viral cytoplastic changes include: nuclear atypia, cytoplasmic vacuolation.
C. Not premalignant (but marker for STD see GUM.

Human papilloma virus (HPV)is usually spread by sexual contact.

Incubation:

weeks. Her partner may not have obvious penile warts. The vulva, perineum, anus, vagina, or cervix
may be affected. Warts may be very florid in the pregnant and immunosuppressed. HPV types 6 and
11 cause vulval warts and 16, 18, and 33 can cause vulval and cervical intra-epithelial neoplasia.
Warts may also cause anal carcinoma (OHCM p633). Treat both partners. Exclude other genital
infections. Warts may be destroyed in the clinic by cryotherapy, trichloroacetic acid or
electrocautery/excision/laser. Vulval and anal warts (condylomata acuminata) may be treated at home
with podophyllotoxin cream for 46 weeks, washed off after 30min (CI: pregnancy). Only treat a few
warts at once, to avoid toxicity. Self-application with 0.15% podophyllotoxin cream (Warticon 5g
tubesenough for 4 treatment coursesis supplied with a mirror): use every 12h for 3 days,
repeated up to 4 times at weekly intervals if the area covered is <4cm 2. Relapse is common. In
pregnancy, warts may grow rapidly and usually regress after delivery. Problematic warts can be
treated with cryotherapy. It is not an indication for delivery by CS.

HPV immunization and cervical cancer:

See [link]. NB: HPV types 6 and 11 may cause laryngeal or respiratory papillomas in the offspring of
affected mothers (risk 1:501:1500; 50% present at <5yrs old). Any warty lesion in a post-menopausal
woman should be biopsied to exclude vulval cancer.28

Vulvitis
Vulval inflammation may be due to infections, eg candida ([link]), herpes simplex; chemicals (bubble-
baths, detergents). It is often associated with, or may be due to, vaginal discharge.

Vulval ulcers
(fig 3.10) Causes Always consider syphilis. Herpes simplex is common in the young. Others:
carcinoma; chancroid; lymphogranuloma venereum; granuloma inguinale; TB; Behets syndrome;
aphthous ulcers; Crohns disease.
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Herpes simplex
(fig 3.8) Herpes type II classically causes genital infection, but either type can be the cause (30% type
I). It is the third most common STI in the UK. The primary infection is usually the most severe, starting
with the prodrome (itching/tingling of affected skin) and flu-like illness, progressing to vulvitis, pain, and
small vesicles on the vulva. Urinary retention may occur due to autonomic nerve dysfunction.
Recurrent attacks are usually less severe and may be triggered by illness, stress, sexual intercourse
and menstruation.

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Fig 3.8
Herpes simplex.
Reproduced from Pattman et al., OH of Genitourinary Medicine, HIV, and Sexual Health (2010) with
permission from Oxford University Press.

Treatment:

Strong analgesia, lidocaine gel 2%, salt baths (and micturating in the bath) help. Exclude coexistent
infections. Aciclovirorally shortens symptoms. Oral dose: 200mg 5 times daily or 400mg/8h for 5 days
(longer if new lesions appear during treatment or if healing is incomplete). If
immunocompromized/HIV+ve: 400mg 5 times daily for 710 days during 1st episode or 400mg/8h for
510 days during recurrent infection. If >6 outbreaks/year consider suppressive aciclovir for 612
months. Topical aciclovir is not beneficial. HSV can be transmitted during asymptomatic phases of
viral shedding, and from areas of the genitals not protected by barrier contraception. Men are usually
less symptomatic and may never have been aware of the infection, thereby unknowningly infecting
their partners months or even years later, so dont assume infidelity.

For herpes in pregnancy, see [link].

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Vaginal discharge
Discharge may be physiological (eg pregnancy; sexual arousal; puberty; COCP). Most discharges are
smelly, itchy, and due to infection. Foul discharge may be due to a foreign body (eg forgotten
tampons, or beads in children). Note the details of the discharge. Could it be a sexually transmitted
disease (STD)? See OHCM p404. If so, refer to a genitourinary clinic. Do a speculum examination and
take swabs: vulvovaginal/endocervical samples for chlamydia and gonorrhoea ([link]; OHCM p416).
Discharges rarely resemble their classical descriptions.

Thrush

(Candida) The 2nd commonest cause of discharge (1st is bacterial vaginosis), 95% is due to C.
albicans, 5% C. glabrata(harder to treat). Vulva and vagina may be red, fissured, and sore, especially
if allergic component; discharge is non-offensive, classically white curds. Her partner may be a carrier
who is asymptomatic. Pregnancy, contraceptive and other steroids, immunodeficiencies, antibiotics,
and diabetes are risk factorscheck glucose. Candida elsewhere (eg mouth, natal cleft) in both
partners may cause reinfection. Thrush is not necessarily sexually transmitted.

Diagnosis:

Microscopy (shows mycelia or spores) and culture.

Treatment:

Topical treatment (eg clotrimazole 500mg pessary + cream for the vulva) gives similar cure rates to
oral fluconazole 150mg PO as a single dose. C. glabrata may require topical nystatin or 714-day
course of an imidazole. Use topical regimen alone if pregnant or breastfeeding. Very recurrent
infection may be treated by weekly maintenance doses of treatment (unlicensed).

Trichomoniasis

Trichomonas vaginalis (TV; fig 3.18; sexually transmitted) produces vaginitis and a bubbly, thin, fish-
smelling discharge. Cervix may have strawberry appearance. Exclude gonorrhoea (often coexists).
Motile flagellates are seen on wet films (400), or cultured.

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Fig 3.18
TV.
Prof S Upton; Kansas Univ.
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(treat partner too) metronidazole 2g PO stat or 400mg/ 12h PO for 5 days (eg if pregnant).

Bacterial vaginosis

Prevalence ~10% mostly asymptomatic. Any discharge has fishy odour, from cadaverine & putrescine.
Vaginal pH is >4.5. The vagina is not inflamed and pruritus is uncommon. Mixed with 10% potassium
hydroxide on a slide, a whiff of ammonia may be detected. Stippled vaginal epithelial clue cells may
be seen on wet microscopy (fig 3.19, top). There is altered bacterial floraovergrowth, eg
of Gardnerella vaginalis, Mycoplasma hominis, peptostreptococci, Mobiluncus, and anaerobes,
eg Bacteroidesspecieswith too few lactobacillae. There is risk of preterm labour, intra-amniotic
infection in pregnancy, susceptibility to HIV,34 and post-termination sepsis.

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Fig 3.19
Clue cells.
Reproduced from Warrell, Cox, Firth, The Oxford Textbook of Medicine (2010) with permission from
Oxford University Press.

By culture.

Metronidazole 2g PO once, gel PV, or clindamycin 2% vaginal cream, 1 applicator full/night PV 7

times. If recurrent, treating the partner may help. If pregnant, use metronidazole 400mg/12h PO for 5
days. Balance Activ vaginal acidic gel can be a useful (more natural) alternative.

Discharge in children

may reflect infection from faecal flora, associated with alkalinity from lack of vaginal oestrogen
(prepubertal atrophic vaginitis). Staphs and streps may cause pus. Threadworms cause pruritus.
Always consider sexual abuse. Gentle rectal examination may exclude a foreign body.

Tests:
 Genitourinary medicine

Vulval vaginal swab (hard to know if result is normal flora). MSU: is there glycosuria? For prolonged
or bloody discharge, examine under anaesthesia (paediatric laryngoscopes can serve as specula)
US or X-rays.

Management:

Discuss hygiene. If an antibiotic is needed, erythromycin is a good choice. An oestrogen cream may
be tried (1cm strip).

Chlamydia

Chlamydia is the most common bacterial STI in the UK and is an important cause of tubal infertility.
70% cases are asymptomatic, but symptoms may include dysuria, vaginal discharge, and/or
intermenstrual or postcoital bleeding. In the UK, the National Chlamydia Screening Programme tests
over a million people per year, and has caused an estimated 20% drop in prevalence in those <25
years. Complications include pelvic inflammatory disease ([link]) in 1040% of those infected,
perihepatitis (Fitz-HughCurtis syndrome), Reiters syndrome (arthritis, conjunctivitis, and urethritis,
more common in men), tubal infertility and increased risk of ectopic pregnancy. Diagnosis is by
vulvovaginal or endocervical swab for nucleic acid amplification test (NAAT) using a special medium.
Swabs may be self-taken.

Treatment:

Azithromycin 1g single dose or doxycycline 100mg BD for 7 days (>95% cure). It is essential to treat
partners and abstain from intercourse until this happens. Chlamydia in pregnancy is treated with
erythromycin 500mg BD for 1014 days; untreated, there is an increased risk of preterm rupture of
membranes and premature delivery, and neonatal conjunctivitis and pneumonia.

Gonorrhoea

Full name Neisseria gonorrhoeae, a Gram ve diplococcus. It is the fourth most common STI in the
UK, and there is increasing antibiotic resistance. There are often no symptoms, but may present with
lower abdominal pain, vaginal discharge, intermenstrual or postcoital bleeding. Complications include
PID (10% of those infected), Bartholins or Skenes abscess, tubal infertility and increased risk of
ectopic pregnancy. Disseminated gonorrhoea leads to fever, pustular rash, migratory polyarthralgia,
and septic arthritis. Diagnosis is by vulvovaginal or endocervical swab for NAAT using a special
medium. Swabs may be self-taken. Urethral, pharyngeal, and rectal swabs should be taken if
appropriate. If NAAT +ve, take further swabs for culture for sensitivities prior to treatment due to high
rates of antibiotic resistance (35% strains resistant to ciprofloxacin and 70% to
tetracyclines). Treatment is with ceftriaxone 500mg IM stat, plus azithromycin 1g PO stat. If severely
penicillin-allergic, spectinomycin 2g IM plus azithromycin 1g PO stat. Treat partners and contact trace.
Treatment is the same in pregnancy (untreated, gonorrhoea in pregnancy is associated with preterm
rupture of membranes, preterm delivery, and chorioamnionitis, and to the baby, ophthalmia
neonatarum).
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Pelvic inflammatory disease

Pelvic inflammatory disease (PID) is defined as infection of the upper genital tract. Many cases
probably go undetected due to lack of symptoms, so prevalence is difficult to ascertain.

Causes

Usually from ascending infection from the endocervix:

o STIs
o Uterine instrumentation eg hysteroscopy, insertion of IUCD, TOP
o Post-partum
Can descend from other infected organs, eg with appendicitis
25% due to chlamydia and gonorrhoea
Remainder may be due to anaerobes and endogenous bacteria.
Age <25 years, previous history of STIs and new or multiple sexual partners increase risk. Protective
factors are use of barrier contraception, Mirena IUS and the COCP.

History and examination

The woman may give a history of lower abdominal pain which may be uni- or bilateral, which is
constant or intermittent. There may be deep dyspareunia, vaginal discharge, intermenstrual or
postcoital bleeding, dysmenorrhoea, and/or fever. On examination, vaginal discharge may be evident.
There is cervical motion tenderness (cervical excitation) on vaginal examination, with or without
adnexal tenderness. In mild or chronic PID she will be afebrile.

Investigations

Take vulvovaginal/endocervical swabs for chlamydia and gonorrhoea, and MC&S. If the woman is
acutely unwell, check FBC (elevated WCC) and CRP and take blood cultures if sepsis. If tubo-ovarian
abscess is suspected, arrange TVS. Laparoscopy is not indicated unless diagnosis is uncertain, for
example right iliac fossa pain and possible appendicitis or drainage of tubo-ovarian abscess is
required.

Complications

Tubo-ovarian abscess
Fitz-HughCurtis syndrome (liver capsule inflammation with perihepatic adhesions)
Recurrent PID (can be instigated by gynaecological procedures)
Ectopic pregnancy
Subfertility from tubal blockage (8% after 1 episode; 40% after 3 episodes).
Management

Prompt treatment and contact-tracing minimizes complications. Start treating with antibiotics before
culture results are available. Well patients can be treated as outpatients and should be reviewed 72h
later to check response. Admit for IV antibiotics if symptoms severe, there is sepsis or symptoms fail to
respond.

Outpatient management

Ceftriaxone 500mg IM stat or azithromycin 1g PO plus doxycycline 100mg PO BD for 14 days and
metronidazole 400mg PO BD for 14 days.
If gonorrhoea suspected, discuss with microbiologist due to high rates of antibiotic resistance.
Inpatient management

Ceftriaxone 2g IV OD plus doxycycline 100mg IV BD, followed by oral doxycycline 100mg BD for 14
days + metronidazole 400mg PO BD for 14 days.
Chronic PID
 Genitourinary medicine

Unresolved, unrecognized, or inadequately treated infection. Inflammation leads to fibrosis, so

adhesions develop between pelvic organs. The tubes may be distended with pus (pyosalpinx) or fluid
(hydrosalpinx).

Pelvic pain, menorrhagia, secondary dysmenorrhoea, discharge, and deep dyspareunia are some of
the symptoms. Look for tubal masses, tenderness, and fixed retroverted uterus. Laparoscopy
differentiates infection from endometriosis. Difficult to manage pain; antibiotics are generally not
helpful.

Cervicitis
This may be follicular or mucopurulent, presenting with discharge.

Causes:

Chlamydia (up to 50%), gonococci, or herpes (look for vesicles). Chronic cervicitis (see fig 3.12) is
usually a mixed infection. Cervicitis may mask neoplasia on a smear.

I. CERVICITIS
A. Inflammation resulting in a spectrum of changes from squamous metaplasia to Nabothian
cyst formation.
1. Nabothian cysts = mucus retention cysts found on cervix. They are harmless.
B. These are non-sepcific changes unless specific organisms identified common one being
Trichomonas and Herpes.
Can be chronic or acute.
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Human immunodeficiency virus (HIV)

HIV1, a retrovirus ([link]), is responsible for most HIV infections. HIV2 causes a similar illness (?longer
latent period). Over 30 million people are HIV +ve (2.5 million/yr; 2 million deaths/yr; most are in Africa
(Africa has 25% of the world's disease burden, 3% of total health workforce, and 1% of wealth)). 194 In
many areas, incidence is falling as using antivirals infectivity by 96%.195 There is
increasing HIV transmission in eastern Europe & Middle East, where homosexuality is less accepted
and driven underground. UK prevalence: 100,000.196 UK incidence: 6280/yr (in 2011); : 3:1197
heterosexual : gay or bisexual=42% vs 44%;198 IV drug abusers: 2%; motherbaby: 3% (600,000
child deaths/yr globally). Oral sex: 37%.199,200

Immunology

HIV binds, via its gp120 envelope glycoprotein, to CD4 receptors on helper T lymphocytes, monocytes,
macrophages, and neural cells. CD4 +ve cells migrate to the lymphoid tissue where the virus
replicates, producing billions of new virions. These are released, and in turn infect new CD4 +ve cells.
As infection progresses depletion or impaired function of CD4 +ve cells immune function.

Virology

RNA retrovirus; HIV1 has 9 subtypes or clades. After cell entry, viral reverse transcriptase enzyme
makes a DNA copy of the RNA genome. The viral integrase enzyme then integrates this into host DNA.
The core viral proteins are initially synthesized as big polypeptides that are cleaved by
viral protease enzymes into the enzymes and building blocks of the virus. The completed virions are
then released by budding. The number of circulating viruses (viral load) predicts progression to AIDS.

Stages

Seroconversion (primary infection) may be accompanied by a transient illness 26wks after exposure:
fever, malaise, myalgia, pharyngitis, maculopapular rash or meningoencephalitis (rare). A period
of asymptomatic infection follows but 30% have persistent generalized lymphadenopathy (PGL),
defined as nodes >1cm diameter at 2 extra-inguinal sites, persisting for 3 months or longer. Later,
constitutional symptoms develop: T, night sweats, diarrhoea, weight, minor opportunistic
infections, eg oral candida, oral hairy leucoplakia, herpes zoster, recurrent herpes simplex,
seborrhoeic dermatitis, tinea. This collection of symptoms and signs is referred to as the AIDS-related
complex (ARC) and is regarded as a prodrome to AIDS. AIDSHIV + an indicator disease
([link]). CD4 usually 200 106/L.

Time-scales:

HIVAIDS 8yrs; ARCAIDS 2yrs; AIDSdeath 2yrs (without HARRT).201

Which signs correlate best with HIV progression?

Chronic fever (odds ratio 5.6 vs those in whom HIV is not progressing); PGL (4.7); cough for >1 month
(3.5); chronic diarrhoea (3.3); oral thrush (3.2); weight by 10% in < 1 month (2.9); TB (2.8); zoster
(2.5).

Diagnosis

Serum (or salivary) HIV-AB by ELISA, eg confirmed by Western blot. In recent infection, HIV-AB might be
ve (window period 13wks after exposure); here, checking HIV RNA (PCR) or core p24 antigen in
plasma, or repeating ELISA at 6wks and 3 months confirms diagnosis. 4th-generation kits can test
for HIV-AB and p24-Ag. Rapid test kits give results in 30min; but +ve results must be confirmed
by ELISA. Ora-Quick ADVANCE uses oral fluid, and may be bought over the counter, eg in UK/USA
sensitivity of 97.4%; specificity of 99.9% (untrained vs trained testers). 202

HIV sub-types
 Genitourinary medicine

A and B predominate in the UK; D is commoner in Africa; hybrid/recombinant types have a worse
prognosis as they bind to immune cells more readily.

Prevention

Blood screening; disposable equipment; antenatal antiretrovirals if HIV+ve Caesarean birth bottle-
feeding (may mortality if hygiene poor); PEP ([link]).

A stop-HIV sexual manifesto:

Good HIV information (TV, wind-up radios, eg in Africa; HIV issues in soap operas are influential).203
Accessible HIV tests with opt-out not opt-in when done in clinics204 (expensive counselling just if
+ve).
Good sexual negotiation skills.
Condoms for all sexual contact, or abstinence (very unreliable!205also I'd rather be dead
than abstain206).
Reframing of our bodies as a route to intimacy rather than as instruments of gratification always
entailing penetration.
Fewer sexual partners. NB: 3 simultaneous partners is much riskier than 6 serial partners.
Alcohol use (to avoid risky behaviour).
Good trials find that circumcision prevents 65% of HIV (and herpes207) over 1 yrs.208 It is not a
reliable preventive: circumcised men must not behave as if they are safe.

Complications of HIV infection

Most complications are either psychological or the result of suppression of T-cell-mediated
immunity. Test all with newly diagnosed HIV for toxoplasma, CMV, hepatitis B/C, and syphiliseg
serology; tuberculin test.

For TB see [link]; HHV-8/Kaposi's sarcoma1 see [link]; for Leishmaniasis see [link].

Pulmonary

The lung is the most vulnerable organ; in developed countries bacterial pneumonia (esp.
pneumococcal)229 is commonest; elsewhere it is TB ([link] & [link]) and Pneumocystis
jiroveci pneumonia (PCP, fig 1)the chief life-threatening fungal opportunistic infection (others:
aspergillus, cryptococcus, histoplasma). Suspect it in anyone with cough/breathlessness or
pneumothorax. CXR may be normal; CT: diffuse ground-glass opacity, consolidation, nodules,
cysts.230 : Sputum (eg induced or via bronchoscopy and bronchoalveolar lavage. 231 : high-dose co-
trimoxazole (see BOX); special monitoring must be available; precede each dose by prednisolone
50mg (reduce after 5d, and tail off). Primary prophylaxis: If CD4 <200106/L: co-
trimoxazole 480mg/24h PO or 960mg 3/wk. Prophylaxis is essential after 1 st attack
until CD4 >200106/L.232 Other pathogens: M. avium intracellulare (MAI); CMV. Also: HHV-8 (Kaposi's
sarcoma, lymphoma)1 and lymphoid interstitial pneumonitis.

Gut

Oral pain may be caused by candidiasis, HSV or aphthous ulcers, or tumours. Oral candida
: Nystatin suspension 100,000U(1mL swill and swallow/6h). Oesophageal involvement causes
dysphagia retrosternal discomfort: fluconazole, ketoconazole, or itraconazole PO for 12wks.
Relapse is common. HSV and CMV also cause oesophageal ulcers (similar
to Candida). Anorexia/weight loss is common, also LFT and hepatomegaly from viral hepatitis,
sclerosing cholangitis, drugs or MAI. MAI causes fever, night sweats, malaise, anorexia, weight,
abdominal pain, diarrhoea, hepatomegaly, and anaemia.
 Genitourinary medicine

Blood cultures, biopsies (lymph node, liver, colon, bone marrow).

: ethambutol + clarithromycin + rifabutin (BOX). Chronic diarrhoea may be caused by bacteria
(Salmonella, Shigella, Campylobacter, atypical mycobacteria, C. difficile), protozoa
(Cryptosporidium [link], Microsporidium, Isospora belli, cyclospora), or viruses (CMV,
adenovirus). Perianal disease may be from recurrent HSV ulceration, perianal warts, squamous cell
cancer (rare). Kaposi's sarcoma ([link]) and lymphomas can also affect the gut.

Eye

CMV retinitis

(acuity blindness) may affect 45% of those with AIDS. Fundoscopy: characteristic mozzarella pizza
signs, fig 5 [link]. Treatment: see BOX. Ganciclovir-containing intra-ocular implants, where available,
can improve quality of life.233 (NB: risk of post-op retinal detachment, one implant does not prevent
disease in the other eye.) The need for maintenance therapy may be reviewed if CD4 100106/Leg
after immune restoration by HAART ([link]), if retinitis is inactive.234

CNS

Acute HIV

is associated with transient meningoencephalitis, myelopathy, and neuropathy.

Chronic HIV-associated neurocognitive disorder (HAND)

143 comprises dementia and various encephalopathies (PML, [link]).

Toxoplasma gondii

([link]) is the main CNS pathogen in AIDS, presenting with focal signs. CT/MRI shows ring-shaped
contrast enhancing lesions. Treat with pyrimethamine (+folinic acid)
+ sulfadiazine or clindamycin for 6 months. Lifelong secondary prophylaxis is needed. Pneumocystis
prophylaxis also protects against toxoplasmosis.235

Cryptococcus neoformans

(fig 2; and [link]) causes a chronic meningitis, eg with no neck stiffness.

See BOX.

Tumours

affecting the CNS include primary cerebral lymphoma, B-cell lymphoma. CSF JC virus PCR is useful in
distinguishing PML from lymphoma.

Psychological complications

HIV is the paradigm of a biopsychosocial illness. HIV is 100% preventable, yet very prevalent.
Asking why tells us more about ourselves than about HIV.236 Shame, sexual imperatives, pride and
prejudice237 keep HIV underground and multiplying. Imagine you are pregnant and HIV+ve, eg as a
result of rape, and you will appreciate some of the psychological problems ([link]). Being HIV+ve is
associated with dissociation during sex (I had no connection to what was going
onnumbunfeelingI would try to say something but couldn't).237 Appreciating some of these
psychological complexities helps us realize why simplistic messages about safe sex so often fail.
 Genitourinary medicine

ward. 2 rapid tests done in parallel accuracy (blood is more sensitive than saliva: 98% vs 99.7%).252

Home-use HIV tests are starting to be used by sex partners to inform sexual decisions. Absence of
counselling is a problem (or failure to use the post-test counselling phone number if one is
provided),253 as is delayed entry into HIV care. Research must be done to determine the best context
for their use.254

Counselling throughout life/safe sex: Issues arise if sexual partners are HIV-discordant. If the
woman is HIVve, the HIV+ve man is required to use condoms. If pregnancy is wanted, sperm washing
to remove HIV can be successful.255n=635

Legal help may be needed on housing, next-of-kin, employment, and guardianship of children, and
making a will. Making advance directives needs special skill. Domiciliary genitourinary teams, GP, and
hospices all have a role.

Aims of HAART (highly active antiretroviral therapy)

HAART aims to suppress plasma HIV RNA concentrations below the limit of detection and restore
immune function. This is not a cure as latent replication-competent provirus exists in resting CD4+
T lymphocytes and persistent (but cryptic) viral replication remains intact. 256 Lifelong suppression of
plasma HIV RNA is problematichence the need for strategies to eradicate HIV.
In theory, these effects can be helped by any therapy that blocks histone deacetylase 1
(HDAC1 mediates virion production). This is the rationale behind studies of HDAC1 blockers such as
valproic acidwhich has been shown to frequency of resting cell infection (mean reduction 75%). 257

HAART must be part of a holistic, integrated, individualized care plan, proceeding with managing
comorbidities, eg malnutrition, malaria, etc.258

Monitoring HIV infection259

Routine tests

CD4 T cell count (every 36 months). CD4 counts are expensive. A reasonable alternative is
the TLCthe total lymphocyte count: a TLC of 1400/L a CD4 count of 200/L as far as risk of
mortality from HIV goes.260
HIV RNA (every 36 months).
Serum U&E, HCO3, Cl, creatinine, bilirubin (total + direct)/LFT (every 612 months).
FBC differential (every 36 months).
Fasting lipid profile and glucose (annually).
Other tests

Pregnancy test; drug resistance testing.

Indications for initiating antiretroviral therapy259

History of an AIDS-defining illness or with a CD4 count 350 cells/L.261

Antiretroviral therapy should also be initiated in the following groups of patients regardless
of CD4 count: pregnant women; patients with HIV-associated nephropathy; and patients co-infected
with HBV when treatment is indicated for hepatitis B.
Antiretroviral therapy may be considered in some patients with CD4 counts >350 cells/mm 3 (high viral
load, or when CD4 count is falling rapidly).
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Antiretroviral agents
(HAART=highly active antiretroviral therapy)
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Seek expert help early. Ask if a once-daily regimen (below) is possible. Nonspecialists need to be
aware of 4 things:

1. 1 Drug interactions are important, so don't co-prescribe without computerized decision support
(or prolonged reading of drug data).
2. 2 Any new sign in your patient may be a side-effect or an effect of HIV itself.
3. 3 Know baseline viral load, eg >100,000 vs 50 copies/mL now. Is the CD4 count rising?
4. 4 Monitor: BP, U&E, glucose/lipids. HAART may cause renal failure insulin resistance.
Nucleoside reverse transcriptase inhibitors (NRTI)

Zidovudine (AZT)

was the 1st anti-HIV drug. Dose: 250300mg/12h PO or 1mg/kg/4h IV. SE:
anaemia, WCC, GI disturbance, fever, rash, myalgia. Stop if LFT, hepatomegaly, lactic acidosis. CI:
anaemia, neutropenia, breastfeeding.

Didanosine (DDI; Videx EC)

250mg/24h PO if eGFR >80 and wt <60kg; 400mg/24h if 60kg. SE: pancreatitis, neuropathy,
urate, GI disturbance, retinal and optic nerve changes, liver failure. Stop if significant rise in LFT or
amylase. CI: breastfeeding.

Lamivudine (3TC)262

is well-tolerated. Dose: 150mg/12h PO, take without food. SE: see zidovudine, but less common. Stop
if: LFT; big liver; lactic acidosis; pancreatitis.

Emtricitabine (FTC)

It is like lamivudine but is also active against hepatitis B.263

Stavudine (D4T)

40mg/12h PO if 60kg; 30mg/12h if <60kg; stop if neuropathy or LFT.

Tenofovir

245mg/24h PO. SE: see lamivudine.

Abacavir

600mg/24h PO. SE: hepatitis, lactic acidosis, hypersensitivity syndrome (35%)rash, fever, vomiting;
may be fatal if rechallenged.

Protease inhibitors (PI)

slow cell-to-cell spread, and lengthen the time to the first clinical event. PIs are often given with low-
dose ritonavir (100mg/12h PO), which appears to enhance drug levels. All PIS are metabolized by the
cytochrome p450 enzyme system so increase the concentrations of certain drugs by competitive
inhibition of their metabolism.264 PIS can cause dyslipidaemia, hyperglycaemia/insulin resistance.

Lopinavir/ritonavir (Kaletra)

400mg (+100mg ritonavir)/12h PO. SE: see saquinavir.

Saquinavir
 Genitourinary medicine

1g/12h PO within 2h of a meal. SE: oral ulcers, paraesthesiae, myalgia, headache, dizziness, pruritus,
rash, pancreatitis.

Fosamprenavir; tipranavir; darunavir; atazanavir; indinavir.

Fosamprenavir; tipranavir; darunavir; atazanavir; indinavir.

Non-nucleoside reverse transcriptase inhibitors (NNRTI)

These also may interact with drugs metabolized by the cytochrome p450 enzyme system. 265

Nevirapine

200mg/24h for 2wks, then 200mg/12h PO. Resistance emerges readily. SE: StevensJohnson
syndrome, toxic epidermal necrolysis, hepatitis.

Efavirenz

Dose: 600mg/24h PO. SE: rash, insomnia, dizziness. Avoid in pregnancy.

Rilpivirine

A new NNRTI. Resistance may develop (+ cross resistance to other NNRTI).

Integrase strand transfer inhibitors (INSTIS)

Raltegravir; elvitegravir; dolutegravir266

May be combined with tenofovir lamivudine.267 SE: GI upset; insomnia.

CCR5 antagonists

(CC-chemokine receptor 5) Maraviroc 300mg/12h PO.

Once-a-day tablets

On an empty stomach at night; those with INSTI may be best, eg

Kivexa/Epzicom = abacavir + lamivudine;268 may be given with dolutegravir. Others include:

Atripla=tenofovir, emtricitabine + efavirenz (causes psychiatric symptoms in 4%).
Stribild=elvitegravir + cobicistat + tenofovir + emtricitabine.
Eviplera=tenofovir, emtricitabine + rilpivirine. Availability depends on location.

It's not all about drugs! There is no point in what we do if negatives outweigh positives, eg endless
rounds of appointments; low/suicidal mood; poor body image; low self-esteem; guilt; discrimination;
stigma; safe-sex conundrums; intercurrent infections; financial/insurance headaches; family conflict
with soon-to-be-orphaned children. Enable patients to become people in charge of their own
destiny. Treat low mood holistically. Make symptoms less intrusive. Randomized trials show that even
one session of art therapy can achieve these ends.269 Phone-delivered support270 and conflict
resolution workers canhelp. HIV+ve people can be involved in caring for other HIV people to mutual
advantage. This may help bridge cultural phenomena known to inhibit access to HIV services, eg
machismo and marianism in Latino and other cultures. 271 (Marianismis excessive humility and
willingness of women to sacrifice themselves, and to be submissive to their sexually wayward
husbands; machismo is its hypermale homophobic counter-stereotype.)

Golden rules in HAART (highly active antiretroviral therapy)

 Genitourinary medicine

Start HAART early, ideally before CD4 count <200 x 106/L.

Negotiate strict adherence; try to use once-daily regimens where available (eg Atripla, Stribild).
Harmonize pills with the patient's expectations and lifestyle.
Is the patient suitable to include in an ongoing research trial?
Aim for no more than twice-daily dosing, if possible.
Use 3 drugs (minimizes replication and cross-resistance). No dual therapies.
Monitor plasma viral load & CD4 count; what seems like elimination of HIV often turns into
reactivation when treatment stops. Aim for undetectable viral loads 4 months after starting HAART.
Suspect poor adherence if viral load rebounds.
If viral loads remains high despite good adherence, if there is a consistent fall in CD4 count, or if new
symptoms occur, change to a new combination of anti-HIV drugs and request resistance tests, eg
genotyping for HIV reverse transcriptase/protease mutations (if available).
Stay informed about new drugs, and emerging classes of drugs.
Examples and problems with HAART regimens

Typical regimen for HIV-1: efavirenz 600mg/24h PO with 2 NRTIs (eg lamivudine 300mg/24h PO +
tenofovir disoproxil fumarate 245mg/24h PO). Monitor U&E, eg tenofovir 245mg/2d if eGFR 3050;
245mg/34d if eGFR 1030.
To avoid NRTI SE (eg lipoatrophy) non-NRTI regimens may be tried, eg efavirenz + lopinavir +
ritonavir.272,273
Comorbidities: no DDI if pancreatitis. If polyneuropathy, avoid using D-drugs (DDI,
DDC/dideoxycitidine, D4T). Type 2 DM may need insulin with PIS.
Common initial regimens consist of two nucleoside analogues, combined with either a protease
inhibitor, an NNRTI or a third nucleoside analogue.274
In older patients (5060yrs) getting a good immune response (IR=CD4 by >100/L) is 30% less
likely vs those <25yrs starting HAART; survival is also lower.275
Managing highly antiviral-experienced patients is complicated by drug resistance (BOX 3), SEs, drug
interactions and quality-of-life issues. So potent regimens need expert input to maximize activity
against resistant virus.276
Attempts to extend HAART are experimental, and non-standard (MEGAHAART, eg tenofovir +
emtricitabine + efavirenz + raltegravir + maraviroc).277
 Genitourinary medicine

FERTILITY

I. SUBFERTILITY
A. Devastating to both partners and its Ix a great strain. Sympathetic management crucial.
B. 84% having regular intercourse conceive within a year, and 92% by 2 years.
C. Fertility decreases w age (girl born with 300,000 eggs 12% left by 30 y 3% by 40 y).
D. Offer Ix after 1 year of trying
E. Earlier offer if:
1. aged 35 years
2. Amenorrhoea
3. Oligomenorrhoea
4. Past PID
5. Undescended testes or cancer treatments which may affect fertility
F. List of causes:
1. Unexplained (28%)
2. Male factor! (25%)
3. Anovulation (21%)
a. May be due to premature ovarian failure; Turners; surgery or chemo, as well as
PCOS (MCC), excessive weight loss or exercise, hypopituitarism, Kallmans
syndrome, and hyperprolactinaemia.
Kallmans syndrome is characterised by (1) anosmia and (2)
infertility/delayed puberty. It is a hypogonadotropic hypogonadism. There is
disruption in production of GnRH due to embryonic developmental disorder
where GnRH releasing neurones fail to migrate from nasal region into
hypothalamus, secondary to failed development of olfactory nerve fibres.
4. Tubal factor (15-20%)
5. Endometriosis (6-8%)
G. History taking
1. It takes 2 to be infertile ( causes 67%); see both partners.
2. Note age and duration of subfertility.
3. Have they had any previous pregnancies and does either partner have children?
4. Menstrual history, regularity, pelvic pain, history of STIs, previous surgery (tubal or for
ectopic pregnancy).
5. Smoking reduces fertility, as does drinking more than the recommended amount of
alcohol per weekin both partners.
6. Check the medical history and drugs to optimize both.
7. Ask about frequency of sexual intercourse and any problems during sex including
erectile dysfunction.
8. Ask the man about history of undescended testes, mumps as an adult, and check his
medical, drug history, and smoking and alcohol use.
H. O/E:
1. BMI (obesity has an adverse effect on fertility, and there are BMI ranges above which
treatment cannot be started).
2. Are there signs of endocrine disorder e.g. PCOS?
3. Exclude pelvic pathology e.g. endometriosis or fibroids, take a cervical smear if due, and
high vaginal and chlamydia swabs.
4. Surgical treatment of a varicocele has no effect on pregnancy rate.
I. Investigations
1. Primary care:
a. Chlamydia screen!
b. Baseline hormonal profile (d2-5 FSH should be < 10) and LH
 Genitourinary medicine

c. TSH, prolactin, and testosterone.

d. Rubella status (vaccinate if non-immune)
e. Mid-luteal progesterone to confirm ovulation (T minus 7 days before expected
period e.g. 21 in 28-day cycle). If > 30 ovulating.
f. Semen analysis. Repeat in 3m if abnormal, after making lifestyle change + start
multivitamin e.g. Se, Zn, vitamin C.
2. Secondary care:
a. TVS to rule out adnexal masses, submucosal fibroids, or endometrial polyps. It can
also help confirm PCOS.
b. Hysterosalpingogram (HSG) uses XR and contrast injected through small cannula in
cervix. It demonstrates uterine anatomy and tubal patency. May cause period-like
cramps and tubal spasm, giving a FP. Only perform once chlamydia swabs ve and
give azithromycin 1g PO STAT.
c. Hysterosalpingo-contrast sonograph (HyCoSy) similar to above but uses US
contrast and TVS.
d. Laparoscopy and dye test a day-case and gold-standard for assessing tubal
pregnancy. Methylene blue dye is injected through the cervix, while tubes
visualised w laparoscope. Used first-line if strong clinical suspicion of tubal
abnormality, or needs laparoscopy for whatever other reasons. 2nd-line if HSG or
HyCoSy abnormal. Pelvic path can be Tx at same time.
J. Management:

Treat the cause!

Lifestyle Lose weight if necessary, eat a healthy diet, stop smoking recreational drugs,
reduce EtOH, take regular exercise, folic acid (the woman)
Aim to have regular intercourse every 23 days (avoid timed intercourse), and avoid
ovulation monitors (they increase stress and there is no evidence of benefit).
Couples who time intercourse for the day of ovulation may be too lateideally there
should be some sperm available for fertilization whenever ovulation occurs.

Ovulation PCOS is the most common cause of anovulatory subfertility, accounting for 80%.
induction Weight loss or gain
Clomifene citrate SERM (anti-E = increase endogenous FSH via negative feedback
to pituitary).
o 10% multiple pregnancy rates.
o Can cause menopausal Sx (hot flushes, labile mood; if severe headache or
visual disturbance = stop immediately).
o Should only be used for 6-12 cycles (associated w ovarian CA)
o Needs follicular monitoring by USS (risk hyperstimulation)
o Should be Rx by specialist, ideally after tubal patency confirmed + semen
count normal/near-normal & BMI <30 35.
Laparoscopic ovarian drilling in PCOS small holes using needlepoint diathermy aims
to reduce LH and restore feedback mechanisms.
Gonadotrophins if clomifene-resistant PCOS, or low E with normal FSH. Injected,
expensive, need USS monitoring.
Metformin (controversial; weight loss more effective)

Surgery Tubal
Proximal blocks = tubal cath or hysteroscopic cannulation
High rates of ectopics.
 Genitourinary medicine

Endometriosis
COCP (cyclical or continuous) or progestogens PO/IM/SC, IUS Mirena
NSAIDs
GnRH analogues (goserelin) can be used prior to IVF to increase success rate. Have
to be short-term (< 6m) due to BMD reduction; minimised via add-back HRT
(tibolone).
Surgery if medical Tx failed (laparoscopic ablation, excision, coagulation). Increased
spontaneous pregnancies after surgical removal (mild-moderate disease).
Hysterectomy is last resort, and lose fertility.

IU adhesions
Hysteroscopic adhesionlysis

IVF Indications
Tubal disease
Male factor subfertility
Endometriosis
Anovulation not responding to clomifene
Subfertility due to maternal age
Unexplained subfertility >2yrs.

Prognosis
Success depends on many factors including age, duration of subfertility, previous
pregnancy (higher success rate), smoking, and high BMI (lower success).
Low anti-Mullerian hormone (AMH) levels predict poorer response.
Women with hydrosalpinges should have salpingectomy prior to IVF to chance of
live birth.

Screening
Screen couple for HIV, hepatitis B & C.

Process
Ovaries are stimulated (see Ovarian hyperstimulation syndrome
Ova collected (by transvaginal aspiration under transvaginal US guidance)
Fertilized
35 days later, 12 embryos returned under US guidance to the uterus as an
outpatient procedure.
Luteal support is given in the form of progestogens
2 weeks later the woman should do a pregnancy test.

NHS funded assisted conception

Inclusion criteria: varies but limited to couples with no children, non-smokers, BMI < 30, <
42y (35 y in some counties), and dont require gamete donation.

Donor DI used when the male partner has azoospermia with failed surgical sperm retrieval, in those
insemination at high risk of transmitting a genetic disorder and those at high risk of transmitting HIV.

It is also used for women with no (male) partner.

 Genitourinary medicine

Intra- ICSI directly into an egg. Sperm may be taken from the ejaculate, or surgically from the testis
cytoplasmic or epidydimis.
sperm injection
This technique is used when the semen parameters are severely abnormal or failed
fertilization has occurred with IVF cycles.

There is some concern that genetic mutations (especially Y chromosome deletions) will be
propagated by transmission to the offspring.

Intrauterine IUI useful in mild male factor subfertility, coital difficulties, unexplained subfertility, and
insemination same-sex couples.

It can be combined with ovarian stimulation, but if >3 follicles develop, the treatment cycle
should be cancelled due to a high chance of multiple pregnancy (>25%)

In vitro IVM = where immature eggs are collected from the ovaries, matured in the lab before sperm
maturation injection (ISCI).

Avoids expensive ovulation-inducing drugs and risk of ovarian hyperstimulation, it may be

especially suitable for women with polycystic ovaries.

Ooplasmic OT/NT(P) = the baby has 2 mothers: one (too old to conceive normally) gives a nucleus; the
transfer/ nuclear other gives fresher cytoplasm (+mitochondrial DNA) for the ovum.
transfer
procedure This is an example of human germline modification. 15 babies were born using this
technique in the USA (2 had Turners syndrome).

P/C epididymal PESA uses a needle inserted into the epididymis, so scrotal exploration is not needed.
sperm aspiration

Pregnancy by POT has been reported (autologous transplant, 1 between identical twin sisters, another
ovary transplant between sisters).

Egg donation Can offer women change of pregnancy when previous IVF failed, or in ovarian failure, or in
women >45.

Adoption and
fostering
* The above method highlighted in gold allows embryos to be sexed and screened for genetic
diseases w implantation only for those w desired characteristic e.g. offering perfect match for stem-
cell TXP in older sibling w Fanconis anaemia. Controversial.
** Note: ethical issues.
 Genitourinary medicine

II. OVARIAN HYPERSTIMULATION SYNDROME (OHSS)

A. OHSS is a complication of ovulation induction or superovulation.
B. This is a systemic disease and vasoactive products (particularly vascular endoethelial
growth factor, VEGF) are central to its pathophysiology.
C. It has an incidence of up to 33% in mild forms, and in 1:200 it is severe, requiring
hospitalization.
D. Characteristics
1. Ovarian enlargement
2. Fluid shift from intravascular to extravascular space:
a. This leads to the accumulation of fluid in peritoneal and pleural spaces
b. Intravascular volume depletion causes haemoconcentration and hypercoagulability.
E. Risk factors
1. Young age
2. Low BMI
3. Polycystic ovaries
4. Previous OHSS
F. Presentation
1. Abdominal discomfort, N+V, and abdominal distension dyspnoea.
2. Presentation is usually 37 days after hCG administration, or 1217 days, if pregnancy
has ensued.
G. Prevention
1. Prediction and prevention are the key.
2. Women should be given the lowest effective regimen of gonadotrophins.
3. Cycle cancellation may be necessary, or elective embryo cryopreservation, for use in a
further frozen-thawed cycle.
4. In women with PCOS, in vitro maturation (IVM), where immature eggs are collected,
avoids ovarian stimulation and the risk of OHSS.

H. Management
1. Mild and moderate OHSS (Abdominal bloating, mild to moderate pain, US evidence of
ascites, and ovarian size usually 812cm):
a. Outpatient management
b. Analgesia (paracetamol and/or codeine)
c. Avoid NSAIDs (C/I in pregnancy; will worsen fluid shift and renal impairment)
d. Drink to thirst, not to excess
e. Avoid strenuous activities and intercourse due to risk of ovarian torsion
f. Continue with progesterone luteal support, and avoid hCG.
g. Review by the assisted conception unit every 23 days.

2. Severe OHSS (Clinical ascites, oligouria, haematocrit is >45%, hypoproteinaemia, ovarian

size >12cm):
a. Admit to hospital
b. Analgesia and anti-emetics (avoid NSAIDs)
c. Daily FBC, U&E, LFTS, albumin
d. Strict fluid balance
e. Daily assessment of girth (ascites), weight, and legs (thrombosis)
f. VTE PPx with compression stockings and LMWH
g. Paracentesis for symptomatic relief ( IV replacement albumin)
h. Urinary catheter.
 Genitourinary medicine

3. Critical OHSS (Tense ascites, haematocrit >55%, WCC >25109/L, oligo- or anuria,
thromboembolism, ARDS):
a. Get senior help early.
b. Admit to ITU.
c. Symptomatic pleural effusions may need drainage.
d. Use antiembolic measures as above.
e. Pay meticulous attention to fluid balance.
f. Aim to maintain intake at 3L/24h using normal saline if unable to tolerate oral
fluids.
g. Beware hyponatraemia.

Other IVF problems

Multiple birth
1 in 4 IVF pregnancies.
Monozygotic twins commoner
Rate of triplets was 5X pre-IVF (but are now only twice, as only 2 embryos are implanted into
women < 40 y).
1 fresh embryo transfer with frozen embryo months later, if unsuccessful gives as good result
as 2 embryos transfer.

Older mum effects

So more pre-eclampsia, pregnancy-induced HTN, C-section delivery, and DM in the mothers
(all of which have implications for offspring).

Donor egg problems

Pregnancy-induced HTN is 7.1X more common if nulliparous women receive donated eggs
than for standard IVF.

Genetic defects
Beckwith-Wiedemann syndrome is 6X more common in IVF babies, and there is concern that
intracytoplasmic sperm injection (ICSI) could encourage chromosomal abnormalities or CF in
offspring of men with azoospermia or oligospermia.
Men w low sperm counts are now screened for CF carrier status and chromosomal
abnormalities before referral for ICSI.

Low birthweight (LBW)

1.75 X commoner for singleton IVF babies compared to naturally conceived babies (and very
low birthweight 2.73 X commoner).
Part of this is due to prematurity, part to growth restriction.
Interestingly LBW is particularly correlated to the number of gestation sacs at earliest scan,
even if a baby ends up as a singleton.
IVF twins are less commonly low birthweight compared to naturally conceived twins.
There is also some evidence to suggest a slightly higher rate of stillbirth.

Vasa praevia
Rates increased, possibly up to 1:300.
 Genitourinary medicine

Prematurity
2X as common in IVF singleton babies compared to those naturally conceived, 3X more
common for prematurity <32 weeks.
Again it is commoner if there was originally >1 gestation sac.
There is less difference between IVF and naturally conceived twins.

Perinatal mortality
Is 60% in IVF conceived singletons (but natural conception after delay mortality 3
compared to quick conception).

Abnormality rates (even in IVF singletons)

Bringing up one child is difficult: twins are often very very difficultbut triplets is more than
very very very difficultand are frequently a source of significant psychopathology. Even 4
years after their birth, all mothers in 1 triplets study suffered from exhaustion and emotional
distress.
The relationship with the children was often difficult (aggression and conflicts).
1/3 of mothers had sufficient depression to require psychotropic medication, and 1/3
spontaneously expressed regrets about having triplets.
If triplets are reduced to twins in utero, subsequently 1/3 of mothers will suffer emotional
problems (persistent sadness and guilt) up to 1 year.
However, adjustment had occurred in ~90% by 2 years after birth.

Legislation in most developed countries is trying to limit the numbers of embryos that may be
implanted at IVF in order to reduce higher-order pregnancies (already there has been a reduction by
25% since 1998). The UK current practice is moving to single embryo transfer in mothers <35yrs.
 Genitourinary medicine

III. MALE SUBFERTILITY

A. Physiology:
a. Spermatogenesis takes place in the seminiferous tubules.
b. Undifferentiated diploid germ cells (spermatogonia) multiply and are then
transformed into haploid spermatozoa, a process taking 74 days.
c. FSH and LH are both important for initiation of spermatogenesis at puberty.
d. LH stimulates Leydig cells to produce testosterone.
e. Testosterone and FSH stimulate Sertoli cells to produce essential substances for
metabolic support of germ cells and spermatogenesis.
f. Spermatozoa
i. Dense oval head (containing the -haploid chromosome complement) capped
by an acrosome granule (contains -enzymes essential for fertilization)
ii. Propelled by the motile tail.
iii. Seminal fluid forms 90% of ejaculate volume and is alkaline to buffer vaginal
-acidity.

B. Normal semen analysis

a. VOL > 1.5 mL
b. CONC > 15 million
c. Progressive MOT > 32%
d. Total MOT > 40%
e. NORM forms 4%

C. Male factors:
a. Semen abnormality (MCC 85%):
i. Idiopathic oligo-astheno-terato-zoospermia (low; reduced motility; abnormal
morphology sperm)
ii. Testicular CA
iii. Drugs e.g. EtOH and nicotine
iv. Varicocele
b. Azoospermia (5%)
i. Pre-testicular anabolic steroid use, hypogonadotrophic hypogonadism,
Kalmanns.
ii. Non-obstructive cryptorchidism, orchitis, 47XY (Klinefelters), chemo
iii. Obstructive congenital bilateral absence of vas deferens (CBAVD),
vasectomy, chlamydia, gonorrhoea
c. Immunological (5%)
i. Anti-sperm AB
ii. Idiopathic
iii. Infective
d. Coital dysfunction (5%)
i. ED w normal sperm function (remember drugs causes e.g. BB and
antidepressants!)
ii. Hypospadias (urethral opening wrong place), phimosis, disability
iii. Retrograde ejaculation (e.g. after TURP)
iv. Failure in ejaculation (MS, SCI)

D. Examination
a. Look at body form and secondary sexual characteristics.
b. Any gynaecomastia?
 Genitourinary medicine

c. Normal testicular volume is 1535mL (compare with Prader orchidometer).

d. DRE may reveal prostatitis.
E. Tests
a. Plasma FSH is raised in testicular failure.
b. Testosterone and LH levels are indicated if you suspect androgen deficiency.
c. Karyotype to exclude 47XXY and cystic fibrosis screen (associated with CBAVD).
F. Tx
a.Address lifestyle issues, such as alcohol and smoking.
b.Optimize underlying medical conditions and consider stopping or changing
medication.
c. Consider starting a multivitamin containing zinc, selenium, and vitamin C.
d. Repeat the semen analysis 3 months after making changes.
e. ICSI = intracytoplasmic sperm injection (direct into egg), the main tool for most male
subfertility.
i. The source of sperm is the epididymis or testis in men with obstructive
azoospermia
ii. Even if the problem is non-obstructive, sperm can be retrieved in ~50%.
 Genitourinary medicine

H-P-O AXIS PROBLEMS (MALES AND FEMALES)

I. ASHERMAN SYNDROME
Secondary amenorrhoea
 Genitourinary medicine

SEXUAL HEALTH AND DYSFUNCTION

I. HYPOACTIVE SEXUAL DESIRE DISORDER (HSDD)

A. Loss of libido, affecting r/s and causing distress.
B. Can be psychosexual or organic (menopause, depression, chemo, XRT).
C. Hx: when did it start? What is normal to her? Is it realistic/ at odds w partners beliefs? R/S
problem?
D. Testosterone supplement (if Sx started after oophorectomy). Psychosexual counselling
recommended.

II. SEXUAL PAIN

A. Dyspareunia (see above) can be superficial or deep.
1. Superficial infections or skin condition e.g. lichen sclerosis.
2. Tx underlying cause. But pain may start cycle of fear lubricants + LA gel helps.
B. Vaginismus difficulty to allow penetration despite wanting to.
1. Due to involuntary pelvic floor muscles + thigh adductors contraction. It is a SiSx, not a
Dx.
2. May be precipitated by physical, psychological causes, or combination.
3. R/O anatomical problems e.g. vaginal septae so severe that penetration not possible.
4. Vaginal dilators may help eliminate pubococcygeal reflex, but encourage woman to use
her own fingers + combination with relaxation exercises may be more useful.
C. Vulvodynia burning pain occurring in absence of visible finding. Neurological.
1. Difficult to Tx. Need MDT PT, psychosexual medicine, pain management.
2. Explain Dx.
3. 1st-line = pelvic floor exercises, internal + external perineal massage, and topical
anaesthetics
4. TCAs or gabapentin may help.

III. SEXUAL DYSFUNCTION: MANAGEMENT

A. What does the woman want? Motivation is important, so is the non-sexual component of
r/s.
B. Lifestyle diet, exercise, stress reduction, exploration of r/s problems or body image
issues.
C. Education about body function, encourage exploration, sex ed material, and lubricants.
D. Hormonal oestrogen replacement in menopausal women; testosterone if oophorectomy
and HSDD
E. Behavioural therapy.
F. Devices e.g. anorgasmia or vaginismus such as dilators or clit stimulators.
 Genitourinary medicine

CONTRACEPTION

I. INTRODUCTION
A. Ideal = 100% effective, no S/E, readily reversible, without supervision.
B. Any method is better than none.
C. W/o contraception 85/100 will be pregnant, and 1 in 3 pregnancies are unplanned.
D. When dealing with under 16s use Fraser guidelines
1. Rx contraeption without parental consent if:
a. Understand doctors advice
b. Young person cant be persuaded to inform parents that they are seeking
contraceptive advice
c. They are less likely to begin or continue intercourse w or w/o contraception
d. Unless young person receives contraception, their physical or mental health is likely
to suffer.
e. Young persons best interest require doctor gives advice and/or Tx w/o parental
consent.
2. Note: Fraser guidelines and Gillick competence are not the same. Fraser guidelines are
narrower than the latter, as they only relate to contraception whereas Gillick
competence refers to children < 16 who have legal capacity to consent to medical
examination and Tx.
E. After menopause, stop contraception 2 years after amenorrhoea if < 50, 1 y if > 50y.
F. Is she already pregnant again? If yes to any of the Q pregnancy is unlikely.
1. Have you given birth in past 4 weeks?
2. Are you < 6 m postpartum and fully breastfeeding, and free from menstrual bleeding
since you had child?
3. Did your LMP start within last 7 d?
4. Have you been using reliable contraceptive consistently and correctly?
5. Have you had sex since your last period?

II. BARRIER METHODS

A. The main reason for failure is not using them.
B. Condoms reduce transmission of most STDs but not those affecting the perineum.
C. When failure has occurred (e.g. split condom), remember post-coital emergency
contraception.
D. Condoms
1. Effective when properly used, unroll onto the erect penis with the teat or end (if
teatless) pinched to expel air. This prevents bursting at ejaculation.
2. Use a new condom with each episode of sexual intercourse.
3. Do not use with oil-based lubricantsthis destroys the latex.
4. Method failure rate 5%, typical user failure rate 15%/yr.
E. Caps come in several forms.
1. Diaphragms stretch from pubic bone to posterior fornix. Check after insertion that the
cervix is covered.
2. Cervical caps fit over the cervix (so need a prominent cervix). Insert <2h before
intercourse (keep in place >6h after sex). Use with a spermicide.
3. Problems: UTIs, rubber sensitivity. They need professional fitting. 9299% effective if
perfect use.
F. Cervical sponges
1. Simple to use: spermicide- impregnated: unavailable in UK.
G. The female condom (e.g. Femidom)
1. Prescription and fitting are not needed. It has not proved popular.
2. One reason for failure is that the penis goes alongside it, rather than in it;
 Genitourinary medicine

3. Another reason: it gets pushed up in the vagina or may fall out.

4. They can be noisy.
5. Uses lubricant, not spermicide. 95% effective.
H. Spermicide*
1. Unreliable unless used with a barrier.
2. Nonoxinol-9, the only spermicide available in UK is not recommended for those with or
at high risk of HIV as it irritates vaginal epithelium and chance of HIV transmission.

III. NATURAL METHODS (FERTILITY AWARENESS)

A. Involve physiological monitoring to find fertile times (6 days prior to ovulation; the life of a
sperm) to 2 days afterwards (the life of the ovum).
B. Cervical mucus becomes clear and slippery prior to ovulation, and then abruptly thicker and
tacky.
C. No intercourse from the day mucus becomes slippery to 3d after if it becomes tacky.
D. Basal body temperature ~0.3c after ovulation (affected by fevers, drugs, recent food, or
drink).
E. Additional observations (mittelschmerz cervix changes) improve accuracy.
F. Success is common if:
1. Regular cycles
2. Dedication
3. Self-control.

IV. HIGH-TECHNOLOGY NATURAL METHODS

A. Devices e.g. Persona use urine test sticks to measure oestrone-3-glucuronide (E3Gpeaks
24h pre-ovulation) and luteinizing hormone (LHovulation occurs within 36h of LH surge
and sperm penetration of cervical mucus drops after surge).
B. Microtechnology builds a database of the womans natural variability over time, to give her
a green light (almost infertile), a red light (fertiletypically days 610), or an orange light
(test early-morning urine for E3G and LH).
C. Usually, only 8 urine tests are needed per cycle. She purchases sticks and monitor. A button
is pressed the morning her period starts: she checks the monitor lights before passing urine
each morning, in case a test is needed.
D. 9395% (manufacturers data, in motivated patients; it may be less in practice; results
should be regarded as only preliminary; explain uncertainty)
E. C/I:
1. Cycle < 23 or >35 days or variation >10 days
2. Breastfeeding;
3. If already on hormones or tetracycline (minocycline is OK)
4. Menopausal
5. Liver or kidney disease; polycystic ovaries
6. If pregnancy is definitely undesired.
 Genitourinary medicine

V. EMERGENCY CONTRACEPTION
A. This is for use after isolated episodes of unprotected intercourse (UPSI), e.g. the split
condom, and should not be used regularly. Use if the following failed:
1. COCP if > 3X 30-35 mcg pills or > 2X 20mcg pills forgotten in 1st week of pack and UPSI
occurred in those days or pill-free week.
2. POP if > 1X POP missed or taken > 3h late (>12 h late if desogestrel in Cerazette), and
UPSI occurred 2 days following this.
3. IUCD IUS - if complete or partial expulsion identified or midcycle removal necessary,
and UPSI in the 1 week preceding this.
4. Progesterone injection - if > 12 weeks 5 days from last Depo-Provera, or > 8 weeks from
Noristerat, and UPSI occurred.
5. Barrier method failure (split, slip) during sex.
B. Tablets cover that UPSI only.
C. Although usually given after UPSI, advance issue does not increase use and it may be
sensible to be prepared. However, advance issue has not been shown to reduce
pregnancy rates.
D. Management:
1. Hx LMP; normal cycle; # hours since UPSI.
2. Any C/I to later COCP use?
3. Check BP.
4. Explain that teratogenicity has not been demonstrated.
5. Discuss future contraception
6. Give supply of oral contraceptives if day 1 start at next period if planned
7. If started immediately advise precautions as below.
8. Offer infection screen (and cover HIV)
9. Offer F/U 3-6 weeks if coil is inserted; or pregnancy or STI test desired; or if she has
contraceptive concerns.

Emergency IUCD More effective than tablet contraception (prevents 99% of expected
pregnancies)
A copper IUCD can be inserted within 120h of unprotected sex.
If exposure was >5 days previously it can be inserted up to 5 days
after likely ovulation, so is useful in women who present later.
Screen for infection. Insert under antibiotic cover,
e.g. azithromycin 1g PO if screening results unavailable.
MODA: It is thought to inhibit fertilization by toxic effects and to
inhibit implantation.
If for long-term use, coils with 380mm2 Cu have the lowest failure
rates so should be used.
Unaffected by enzyme inducers, it is the method of choice for those
taking them (but see below).

EllaOne = Initiate within 120h of unprotected sex.

Ullipristal acetate Failure rate is 1.6% in non-inferiority (with levonorgestrel) trials.
Efficacy is not reduced by obesity (levonorgestrel may be).
It is thought to inhibit or delay ovulation.
If vomiting 3h of taking the tablet, advise another (30mg).
MODA: progesterone receptor modulator (PRM), it is unsuitable for
use if on, or within 28 days of taking, an enzyme inducer, if on
antacids or drugs raising gastric pH, for those with severe asthma
uncontrolled by oral corticosteroids.
 Genitourinary medicine

Use with caution if liver dysfunction, hereditary galactose intolerance,

Lapp lactase deficiency, glucose-galactose malabsorption.
Avoid breastfeeding for 36h after use.
Use only once per menstrual cycle.
Periods average 2 days delay (7 days in 20%).
Advise extra contraceptive precautions for 14 days for combined pills,
16 days for Qlaira, 9 days for progesterone only pills, if started or
continued.
Starting oral contraceptive immediately after ullipristal acetate is off
licence.
Should pregnancy occur, though no harm known, register via
manufacturer.

Levonorgestrel Initiate within 72h of unprotected sex.

Failure rates are 2.6%.
Suitable for those with focal migraine and past thromboembolism,
there are no medical contraindications to its use.
Levonorgestrel preferably within 12h and no later than 72h after
unprotected sex.
If on, or within 28 days of, taking an enzyme inducer, or with post-
sexual exposure HIV prophylaxis, the dose is 3mg.
If vomiting occurs within 2h of taking the dose, take another
immediately.
The earlier taken after UPSI, the fewer the pregnancies which occur.
MODA: It is believed to inhibit ovulation.
It can be used more than once in 1 cycle; and can be used (but may be
less effective) in same cycle after ullipristal acetate.
Warn that effective contraception should be used until the next
period; and that she should return if she suffers any lower abdominal
pain or the next period is abnormal.
Advise pregnancy test if period >7 days late or unusually light, or after
21 days if quick start contraception started.
If immediate (quick start) oral contraception started, or continuing,
extra contraceptive precautions are needed for 7 days for combined
pills (avoid immediate co-cyprindiol start), 9 days for Qlaira, 2 days
for progesterone-only pills
 Genitourinary medicine

VI. INTRAUTERINE CONTRACEPTIVE DEVICES

A. IUCDs (coils) are plastic shapes ~3cm long with copper winding, and a plastic thread for a
tail.
B. MODA: They inhibit fertilization, implantation, and sperm penetration of cervical mucus.
C. Most need changing every 510 years.
D. Use those with 300mm2 copper eg T-Safe copper T380A (the most effective), for which
pregnancy rate is 2.2 per 100 woman-years.
E. Most of those who choose the IUCD (5%) are older, parous women in stable relationships,
in whom the problem rate is low.
F. They can be used for emergency contraception (as above).
G. Problems
1. May be expelled (5%) by uterus if nulliparous or distorted e.g. fibroids
2. Associated w PID up to 21d following insertion
3. May cause dysmenorrhoea and menorrhagia (MCC discontinuation)
4. Risk ectopics 1:20, if she becomes pregnant
H. C/I
1. Pregnancy
2. Current pelvic infection/STD (including TB)
3. Allergy to copper; Wilsons disease
4. Heavy/painful periods
5. Trophoblastic disease or gynaecological malignancy
6. Undiagnosed abnormal uterine bleeding
7. Distorted cavity.
8. Use with caution if anticoagulated.
I. Insertion
1. Screen for STD before insertion, or use PPx Abx (azithromycin PO) STAT following
insertion. Requires specialist training.
2. An IUCD can be inserted any time (and as emergency contraception), as long as she aint
pregnant.
3. Insert immediately after TOP/miscarriage, or > 4 weeks post-partum.
4. Advise taking simple analgesia prior to insertion; warn that this can cause cramps.
5. Uterine preforation is <1: 1000.
6. Teach her to feel threads; ask her to check after each period.
7. Insertion of IUCDs can induce cervical shock (from increased vagal tone). Tip woman
head down w leg raised. Have IV atropine and anti-epileptic (if patient epileptic), and
resus equipment at hand.
J. F/U
1. Most expulsions within 1st 3m. Expulsion rate < 1:20 in 5 years.
2. F/U after 1st period
3. Threads may be easier to feel than see.
K. Lost threads
1. IUCD may have been expelled so advise extra contraception and R/O pregnancy.
2. Seek coil on USS. If missing arrange XR to R/O extra-uterine coils (surgical retrieval
advised).
3. If present ad not due to be changed, leave in situ.
L. Infection
1. Treat w device in place, but if removed dont replace for 3m
2. Sx Actinomyces = remove coil, cut off thread, send for culture +VE = seek advice for
Tx
M. Pregnancy
1. >90% are intrauterine.
 Genitourinary medicine

2. Remove coil ASAP once pregnancy Dx to reduce miscarriage (20% if removed early, 50%
if left), and to prevent miscarriage w infection.
3. R/O ectopics
N. Removal
1. Alternative contraception started (if desired) prior to removal, or abstinence for > 7d.
2. At menopause, remove after 2 y amenorrhoea if < 50; 1 year if > 50.

O. Intrauterine systems (IUS)

1. MIRENA or JAYDESS carries levonorgestrel
2. Local effect = reversible endometrial atrophy = makes implantation less likely, and
periods lighter and less painful
3. 20% may experience reversible amenorrhoea (reliability = sterilisation).
4. Lasts 5 years (Jaydess last 3 y).
5. Risk ectopics and PID reduced vs copper coil
6. Can be used in breastfeeding, obesity, CV disease, and women taking hepatic-inducing
drugs. But not as an emergency contraception.
7. Warn about spotting + heavy bleed for 1st few weeks following insertion. Usually this
settles around 3-6 m.
8. Pregnancy rate < 1:1000 over 5 y.
9. May benefit endometriosis, adenomyosis, or simple endometrial hyperplasia w/o atypia.
 Genitourinary medicine

VII. COMBINED HORMONAL CONTRACEPTIVES (CHC)

A. CHC: vaginal ring, transdermal patch, or COCP.
B. They all contain E and a progestogen, either in fixed ratio or varying through month (phased
must take pills in right order).
C. Standard-dose pills (30 mcg E) are norm.
D. MODA: stop follicular development and ovulation by suppressing gonadotropins.
1. Progestogen negative feedback decreases the GnRH pulse frequency
2. So FSH & LH release decrease.
3. Less FSH no follicular development no rise in E2 levels.
4. Progestogen negative feedback + oestrogen positive feedback on LH secretion prevents
a mid-cycle LH surge.
5. With no follicular development and no LH surge, there is no ovulation.
E. Combined pill taken for 21 days followed by 7 days break (no pills or placebo). With the pill-
free weak withdrawal bleed.
a. I.e. the bleed is due to hormonal withdrawal, not a build-up of endometrium.
b. It has been proposed that a 4 day break has better contraceptive effect. The 24/4
rationale = prevent hormonal fluctuations by preventing FSH increase and so
prevents follicular development and E2 production.
c. A continuous administration = extended or continuous cycle COCPs (28 d)
maintains a progestogen effect = thins endometrium + suppress pituitary activity
more effectively. It is used to treat endometriosis, dysmenorrhoea, and
menstruation-associated Sx. But the S/E is breakthrough bleeding over time
(endometrium outgrows vascular support eventually)
So the 21/7 or 24/4 pills prevent breakthrough bleed.
F. COCP
1. Oestrogen content: mostly ethinylestradiol, but alternatives are estradiol valerate
(Qlaira) or mestranol (Norinyl-1). Low-strength preps contain 20 mcg ethinylestradiol
and are used if there are risk factors for CV disease, or E side effects from higher dose.
The usual strength is 30-35 mcg, and used for most women. Use phased preparation for
women who have bleeding problems w monophasic products
2. Progestogen type: most commonly levonorgestrel and norethisterone used. Consider
pills containing desogestrel, norgestimate, drosperidone or gestodene if there is Sx like
acne, headache, breakthrough bleeding. Cyproterone acetate licensed for acne
treatment but dont provide contraception. Use for 3-4 months after resolution of Sx.
Higher risk of VTE vs. levonorgestrel.

G. Contraceptive patch (Evra)

1. Transdermal patch contains 20 mcg ethinyestradiol and norelgestromin.
2. Useful if compliance with taking tablets problem.
3. Apply patch on day 1 of cycle, change on day 8 and 15. Remove on 22.
4. Apply new patch after 7d-free interval to start cycle again.

H. Contraceptive vaginal ring (NuvaRing)

1. Flexible ring that releases 15 mcg/24 h ethinylestradiol and etonogestrel.
2. It is inserted into vagina on d1 cycle, and left for 3 weeks.
3. Removed on d22 for 7d ring-free interval.
 Genitourinary medicine

I. Contra-indications:
1. Venous disease: avoid if current/past VTE or sclerosing treatment to varicose veins. Use
with caution if 1 risk factor. Avoid if >1.
a. > 35 y
b. Smoker (avoid if > 35 y, and smokes > 15/d)
c. BMI > 30 (avoid if BMI > 35)
d. FHx VTE in 1st-degree relative < 45y (avoid if known thrombophilia)
e. Immobility (avoid if bed-bound or in plaster)
f. Superficial thrombophlebitis

Risk of VTE
Carriage of factor V Leiden increase risk by 35X.
3rd gen Pills increase resistance to our natural anticoagulant, activated protein C so
increase thrombosis
Anti-thrombin III, protein C or S deficiency = 5X risk
Note while 2X relative risk, the absolute risk is RARE.

2. Arterial disease: avoid if valvular or congenital heart disease w complications, or Hx CVD

including strokes, TIA, IHD, PVD, hypertensive retinopathy. Risk factors for CVD, use
with caution if 1, avoid if > 1:
a. > 35 y
b. Smoker (avoid if smokes > 40/d)
c. FHx arterial disease in 1st-degree < 45 y (avoid if atherogenic lipid profile)
d. DM (avoid if vascular, renal, neuro, or eye complications)
e. HTN with BP > 140/90 (avoid if > 160/95)
f. Migraine w/o aura (avoid if with aura, migraine Tx w ergot derivatives, and those
lasting > 72 h).

The problem is ischaemic stroke.

2 in 100,000 @ 20; and 20 in 100, 0000 @ 40.
Migraine itself is risk factor (4X increase in both age groups).
Low-dose COCPs should be used instead.
Absolute C/I: migraine w aura (POP is fine); migraine w/o aura + > 1 RF for stroke (as
above), severe migraine lasting > 72 h, ergot derivatives treatment).
Dx migraine w aura (classical/focal migraine)
o Slow evolution of Sx over several minutes
o Duration of aura 10-30 mins (resolve within 1 h), typically before
onset of headache.
o Visual Sx (99% of auras) e.g. bilateral homonymous hemianopia,
teichopsia and fortification spectra e.g. gradually enlarging C
with scintillating edges; bright (positive) scotomata.
o Sensory disturbance (31% auras) usually associated w visual Sx; usually one arm
spreading from fingers to face (legs rarely affected).
o Speech disturbance (18% auras) e.g. dysphasia, dysarthria, paraphasia
o Motor disturbances (6% auras)
Both motor + speech disturbances usually accompanied by visual and/or sensory
disturbances.
Migraine w/o aura = simple or common migraine. Sx = blurred vision, photophobia,
phonophobia, generalised flashing lights affecting whole VF in both eyes, associated w
headache.
 Genitourinary medicine

3. Liver disease: avoid if active or flare of viral hepatitis, liver tumours, severe cirrhosis,
active GB disease, and seek advice if Hx of contraceptive-associated cholestasis. Avoid if
previous OB cholestasis.
4. Cancer: avoid if Hx breast CA. If no alternative, and breast CA > 5 y ago w no known
gene mutation, seek specialist help.
5. Previous pregnancy Cx: avoid if pruritus in pregnancy, OB cholestasis, chorea,
phemphigoid gestationis. Avoid if post-partumand breastfeeding (can be used from 6W if
other methods unacceptable.
6. Hepatic enzyme-inducing drug: avoid if rifampicin or rifabutin. For others, increase dose
to 50 mcg ethinylestradiol and shorten pill/patch/ring-free interval to 4d. No evidence
that broad-spectrum Abx decreases efficacy of COCP.

J. S/Es (short-term, resolves within 2-3 cycles)

1. Oestrogenic breast tenderness, N, cyclical weight gain, bloating, and vaginal
discharge. Due to relative oestrogen excess.
2. Progestogenic mood swings; PMS/T; vaginal dryness; sustained weight gain;
decreased libido; and acne.
3. Headaches 3% affected; women should report (frequency or focal Sx development).
Discontinue immediately if focal Sx occur and if not typical of migraine, and last > 1h
admit to hospital (could be a stroke).
4. Breakthrough bleed
a. Most common in 1st 6 m of use
b. If persist > 3 m, check compliance, R/O persistent D+V, and check for GYN causes
c. Screen chlamydia, check cervix, check smear up-to-date
d. R/O pregnancy
e. If > 45 y refer USS and GYN for endometrial Bx
f. Increase E content of COCP if on low-dose, if not change to progestogen.

K. Starting CHCs / PoPs

1. Day 1 of cycle
2. On day of TOP
3. > 21 day post-partum (> 6 weeks if CHC and breastfeeding)
4. > 2 weeks after fully mobilising post-major operation.
5. Starting CHC on d1-5, cover is immediate = no need condoms. If start later in cycle, and
not pregnant, use condoms for 1 weeks.
6. Qlaira start day 1 + condoms for 9 days.
 Genitourinary medicine

L. Stopping the Pill

1. Stop immediately if
a. Sudden severe C/P
b. Sudden SOB + cough/bloody sputum
c. Severe calf pain
d. Unexplained leg swelling
e. Severe stomach pain
f. Unusual severe prolonged headache; sudden visual loss collapse; dysphasia; FND;
hemi-motor/sensory loss; 1st sezures
g. Jaundice, liver enlargement, hepatitis
h. BP > 160/95
i. 4 weeks before leg or major surgery
j. Any C/I

2. On stopping, 66% menstruate by 6 weeks. 98% by 6 months. Women amenorrhoeic

spot-check usually were before.

M. Missing the Pill

1. (or severe diarrhoea)
2. Consult package inserts advice varies.
3. In general: if the start delay is > 48 h, or > 48 h since last Pill, continue Pills but use
condoms too for 7 days (+ days of diarrhoea).
4. If this includes Pill-free days, start next pack w/o break
5. If 2 pills of 1st 7 days in pack forgotten use emergency contraception if UPSI since end
of last pack.
6. Vomiting < 2h post-Pill take another.
7. Non-enzyme inducing broad spectrum Abx extra precautions only if cause D+V.
8. Post-coital options (see emergency contraceptions)
9. D+V does not affect patch or ring.
N. Post-natal
1. Start 21 d after birth e.g. CHC if not breastfeeding.
2. PoP, Depo-Provera (or Nexplanon) if breastfeeding.
3. IUCD: fit 4 weeks post-partum.
O. Flying and high altitude
1. Avoid immobility (mild journey exercises + support stockings) if flight > 3h; if trekking
higher than 4500 m for > 1 wk, consider alternative

VIII. PROGESTOGEN-ONLY CONTRACEPTIVES

A. MODA: progestogen-only contraceptives thicken cervical mucus, reduce receptivity of the
endometrium to implantation, and in some women, also inhibit ovulation.
B. They have the advantage of reducing pelvic infection and are used where oestrogen-
containing contraceptives are contraindicated.
C. Why and when to avoid?
1. Current breast cancer but may be used if >5y disease free, no other alternative, and
after specialist advice
2. Trophoblastic disease
3. Liver disease; active viral hepatitis, severe decompensated cirrhosis, benign or
malignant liver tumour
4. New symptoms or diagnosis of migraine with aura, IHD, stroke/TIA when taking
progestogen-only contraception
5. Avoid if SLE with antiphospholipid antibodies
6. Any unDx vaginal bleeding should be investigated before starting P only contraception.
 Genitourinary medicine

D. PoP (Progestogen-only Pill)

1. Several brands available in the UK containing differing progestogens.
2. Pills containing etynodiol, norethisterone, or levonorgestrel have a 3h window.
3. Desogestrel-containing POPS (desogestrel 75mcg eg Cerazette) have a 12h window,
and have a stronger ovarian suppressive effect than the others.
4. Side effects:
a. Higher failure rate than COCP
b. Menstrual irregularities
c. Increased risk of ectopic pregnancy and functional ovarian cysts
d. Breast tenderness
e. Depression
f. Acne
g. Reduced libido
h. Weight change.
5. Start on day 15 of the cycle (effective immediately) or any other time (use condoms for
2d), or >3 weeks postpartum.
6. Efficacy is affected by hepatic enzyme-inducing drugs- use alternative.

E. Depot progestogen (the injection)

1. Two preparations are available:
a. Medroxy-progesterone acetate 150mg given deep IM 12-weekly; start during the
1st 5 days of a cycle (postpartum)
b. Norethisterone enantate (Noristerat) 200mg into gluteus maximus 8-weekly
licensed for short-term use only.
2. Exclude pregnancy and use condoms for 7 days after late injections >2 weeks late.
F. Advantages:
1. Can be used up to age 50y if no other risk factors for osteoporosis
2. Reduced risk of ectopic pregnancy, functional cysts and sickle cell crises
3. Reduced risk of endometrial cancer
4. May help PMS and menorrhagia.
G. Problems:
1. Menstrual disturbance usually settles with time,
2. And amenorrhoea then supervenes.
a. 33% amenorrhoeic after 6 months use; 60% after 18 months (14% and 33%
respectively for Noristerat).
3. If very heavy bleeding occurs, R/O pregnancy
4. Give injection early (but >8 weeks from previous dose) and give oestrogen if not C/I.
5. Fears of osteoporosis in users; recommend review after 2 years use and avoidance in
adolescents unless the only acceptable method.
a. Bone mass density increases when stopped.
6. Other problems include weight gain (up to 2kg in 70% of women).
7. There may be some delay in return of ovulation on stopping injections (median delay 10
months).
 Genitourinary medicine

IX. IMPLANTS
A. Progesterone implants give up to 3 years contraception with one implantation.
B. Nexplanon is a radiopaque flexible rod containing etonogestrel 68mg which is implanted
subdermally into the medial surface of the upper arm.
1. Insert on day 15 of cycle (immediately effective), or any other time but use condoms
for 7d.
2. Contraceptive effect stops when the implant is removed.
3. It has no impact on bone density.
4. <23% of users become amenorrhoeic after 12 months use.
5. Infrequent bleeding occurs in 50% in the 1st 3 months use; 30% at 6 months.
6. Prolonged bleeding affects up to 33% in 1st 3 months
7. Frequent bleeding affects <10%.
8. Effective contraception may not occur in overweight women (BMI >35kg/m2) in the 3rd
year, so consider earlier changing of implant.
9. There is reduced efficacy with hepatic enzyme-inducing drugs.

X. STERILISATION
A. Sterilization is permanent, irreversible contraception.
B. There are no absolute contraindications provided that they make the request themselves,
are of sound mind, and are not acting under external duress.
C. In the UK, funding on the NHS may depend on location; it is a low-priority procedure and
in some regions special funding needs to be agreed first and after alternative methods have
failed or are contraindicated.
D. Ideally see both partners and consider:
1. Alternative methods: Do they know about depot progesterone injections, coils, and
implants? Give written information (in relevant language) about alternative
contraception and and sterilization.
2. Consent: Is it the wish of both partners? Legally only the consent of the patient is
required but the agreement of both is desirable. Those lacking mental capacity to
consent require High Court judgment.
3. Who should be sterilized? Does she fear loss of femininity? Does he see it as being
neutered? Does the really want or need hysterectomy? Examine the one to be
sterilized.
4. Irreversibility: Reversal is only 50% successful in either sex and never funded by the NHS.
Sterilization should be seen as an irreversible step. Sterilizations most regretted (310%)
are those in the young (<30yrs), childless, at times of stress (especially relationship
problems), or immediately after pregnancy (termination or delivery). For sterilization at
CS, it should be discussed at least twice in the pregnancy (excluding the day of CS).
5. Warn of failure rates1:200 for women (1:100 at CS), 1:2000 for men. In women, it is
no better than the Mirena coil. Advise seeking medical confirmation if future pregnancy
suspected or abnormal vaginal bleeding or abdominal pain. If pregnancy occurs there is
risk of ectopic (4.376%).
6. Side effect: A women who has been on the COCP for many years may find her periods
unacceptably heavy after sterilization. Record in the notes: Knows its irreversible;
lifetime failure rate discussed, eg 1:2000 for vasectomy, and 1:200 for sterilization.
 Genitourinary medicine

E. Female sterilisation
1. The more the tubes are damaged, the lower the failure rate and the more difficult
reversal becomes.
2. In the UK, most sterilizations are carried out laparoscopically with general anaesthesia.
3. Filshie clip occlusion is recommended with local anaesthetic applied to tubes (or
modified Pomeroy operation at mini-laparotomy if postpartum or at caesarean).
4. Do pregnancy test pre-op.
5. Advise use of effective contraception until the operation and next period.
6. Remove IUCD after the next period in case an already fertilized ovum is present.
7. Alternatively, hysteroscopic sterilization using fallopian implants under local anaesthetic
or IV sedation is endorsed by NICE.

F. Vasectomy
1. This is a simpler and safer procedure than female sterilization and can be performed as
an outpatient under local anaesthetic.
2. The vas deferens is identified at the top of the scrotum and is ligated and excised or the
lumen cauterized.
3. Fascial interposition improves effectiveness.
4. Bruising and haematoma are complications.
5. No-scalpel techniques reduce these complications.
6. Late pain affects 3% from sperm granulomata, which are less common if thermal
cautery (rather than electrical cautery) is used.
7. Warn of risk of chronic testicular pain.
8. The major disadvantage of vasectomy is that it takes up to 3 months before sperm
stores are used up.
9. Obtain 2 ejaculates negative for sperm (the first 8 weeks post-op; 2nd 24 weeks later)
before stopping other methods of contraception.
10. Reversal is most successful if within 10 years of initial operation.
 Genitourinary medicine

Postpartum contraception

Lactational amenorrhoea (LAM)

Natures contraception.
Breastfeeding delays return of ovulation (breastfeeding disrupts frequency and amplitude of
gonadotrophin surges, so that although gonadotrophin rise in response to falling placental
sex steroids after delivery, ovulation does not occur).
Women who are fully breastfeeding day and night (i.e. breast milk is babys sole nutrient),
and are less than 6 m postpartum, and amenorrhoeic can expect this method to be 98%.
Average 1st menstruation in a breastfeeding mother is at 28 weeks.
Contraceptive efficacy of LAM is decreased after 6 m, if periods return, if breastfeeding f
reduces, night feeding stops, there is separation from the baby (e.g. return to work), if baby
receives supplements, or if mum or baby become ill or stressed.
Aim for additional contraception once decreased efficacy is anticipated.

POP
May be started any time postpartum
But if started after day 21 additional precautions are needed for 2 days.
They do not affect breast milk production
Low doses (<1%) of hormone are secreted in milk but have not been shown to affect babies

COCP
Start at 3 weeks if not breastfeeding.
They affect early milk production are not recommended if breastfeeding until 6m
But can be used from 6 wk if other methods unacceptable
Level of hormone in breast milk are similar to ovulatory cycles.

Emergency contraception
Use the progesterone method.
It is not needed < 21 days postpartum

Depot injections
Not recommended until 6 wks in those breastfeeding (theoretical risk of sex steroid to babys
immature nervous system + liver)
Medroxyprogesterone acetate IM 12-weekly can start 5 days postpartum if bottle feed
Norethisterone enatate IM into gluteus maximus 8-weekly (licensed short-term used, but can
give immediately postpartum when medroxyprogesterone use can cause heavy bleeding).

Progesterone implants
Insertion not recommended until 6 wks if breastfeeding
0.2% daily dose of etonogestrel excreted in breast milk
Implant at 21-28 d if bottle feed.

IUCD
Inserted within 1st 48 h postpartum until 4 weeks
This is to minimise risk of uterine perforation at insertion
Levonorgestrel-releasing IUD inserted at 4 weeks.
 Genitourinary medicine

Diaphragms and cervical cap

Fitted at 6 weeks as different sizes may be required from previously
Alternative contraception needed from day 21 until new ones confidently handled.

Sterilisation
Unless sterilisation highly advisable at CS e.g. repeated section, family complete
Best wait an appropriate interval as immediate postpartum tubal ligation has possible
increased failure rate, and more likely to be regretted.
 Genitourinary medicine

UROGYNAECOLOGY: INCONTINENCE

I. BASIC PRINCIPLES
A. A prolapse occurs when weakness of the supporting structures allows the pelvic organs to
protrude within the vagina.
B. The weakness may be congenital, and is associated with prolonged labour, trauma from
instrumental delivery, lack of postnatal pelvic floor exercise, obesity, chronic cough and
constipation.
C. Poor perineal repair reduces support.
D. Prolapse is exacerbated by the menopause and is not a danger to healthexcept for third-
degree uterine prolapse with cystocele when ureteric obstruction can occur.

II. TYPES
A. Are named according to structure affected. Several types may coexist in the same patient.
B. Cystocele
1. The anterior wall of the vagina, and the bladder attached to it, bulge.
2. Residual urine within the cystocele may cause frequency and dysuria.
3. It is associated with urethral prolapse (cysto-urethrocoele).
C. Rectocele
1. Lower posterior wall, which is attached to rectum, may bulge through weak levator ani.
2. It is often symptomless, but she may have to reduce herniation prior to defecation by
putting a finger in the vagina, or pressing on the perineum.
D. Enterocele
1. Bulges of the upper posterior vaginal wall may contain loops of intestine from the pouch
of Douglas.
E. Uterine prolapse
1. Protrusion of the uterus downwards into the vagina, taking with it the cervix and upper
vagina.
2. If the woman has had a total hysterectomy, the vaginal vault is left and may also
prolapse.

III. GRADE
A. First degree: the lowest part of the prolapse descends halfway down the vaginal axis to the
introitus.
B. Second degree: the lowest part of the prolapse extends to the level of the introitus, and
through the introitus on straining.
C. Third degree: lowest part of the prolapse extends through the introitus and outside the
vagina.
D. Procidentia refers to fourth-degree uterine prolapsethe uterus lies outside the vagina.

IV. SYMPTOMS
A. May be asymptomatic.
B. Dragging sensation, discomfort, feeling of a lump coming down, dyspareunia, backache.
C. With cystocele, urinary urgency and frequency, incomplete bladder emptying, urinary
retention if the urethra is kinked.
D. With rectocele, constipation and difficulty with defecation. How do the symptoms affect
her quality of life?

V. PREVENTION
A. Lower parity
B. Better obstetric practices
C. Pelvic floor exercises.
 Genitourinary medicine

VI. EXAMINATION
A. Bimanual to exclude pelvic masses.
B. Examine for prolapse with the woman in left lateral position using a Sims speculum.
C. Inspect anterior and posterior walls for atrophy and descent.
D. If no obvious prolapse, ask the woman to strain or stand.
E. Arrange urodynamic studies if urinary incontinence.

VII. MANAGEMENT
A. Conservative
1. Mild disease may improve with reduction in intra-abdominal pressure, so encourage her
to lose weight, stop smoking, and stop straining.
2. Improve muscle tone with exercises or physiotherapy.
B. Pessaries
1. Useful in those who decline surgery, are unfit for surgery, or if surgery is C/I.
2. They affect sexual function.
3. They should be changed every 6 months and if the woman is post-menopausal, topical
oestrogen is useful to prevent vaginal erosion.
4. Ring pessaries are the most common and come in many different sizes. It is placed
between the posterior aspect of the symphysis pubis and posterior fornix of the vagina.
5. The Gelhorn pessary is similar in principle but is shaped like a mushroom.
6. Shelves, cubes, and doughnuts are less commonly used.
C. Surgery
1. Useful if symptoms are severe, the woman is sexually active, and pessaries have failed.
2. The type of prolapse repair depends on type of prolapse.
3. Repair operations excise redundant tissue and strengthen supports, but may reduce
vaginal width.
4. Marked uterine prolapse is treated by hysterectomy with or without sacrospinous
fixation, or by laparoscopic sacrohysteropexy.
5. Post-hysterectomy vault prolapse may be treated by sacrocolpopexy (eg with mesh).
6. Primary anterior or posterior pelvic floor repair should not use mesh due to the high
complication rate.
 Genitourinary medicine

UROGYNAECOLOGY: INCONTINENCE

I. CONTROL OF BLADDER FUNCTION

A. Continence in women is maintained in the urethra by the external sphincter and pelvic floor
muscles maintaining a urethral pressure higher than bladder pressure.
B. Micturition occurs when these muscles relax and the bladder detrusor muscle contracts.

II. URINARY HISTORY

A. Incontinence is involuntary leakage of urine, which is divided into urge, stress, and mixed
urinary incontinence.
B. The woman may have waited for over 10y to seek help.
C. Continuous urinary leakage is most commonly associated with a vesicovaginal fistula or
congenital abnormality such as ectopic ureter.
D. Ask about
1. Daytime voids (normal 47)
2. Nocturia (up to 70y, >1 night-time void is abnormal)
3. Nocturnal enuresis
4. Urgency (most frequently due to detrusor overactivity)
5. Voiding difficulties (hesitancy, straining, and slow or intermittent stream, most
commonly seen with neurological conditions).
6. Feeling of incomplete emptying
7. Bladder pain (seen with interstitial cystitis)
8. Dysuria
9. Haematuria
10. Recurrent UTI.
E. Are there any symptoms of prolapse or bowel symptoms?
F. It is important to check PMHx
G. And record current drug treatment.
H. How is the urinary incontinence affecting her quality of life?
1. Does it affect her relationship?
I. Frequency/volume charts are a simple, objective way of obtaining information about fluid
intake and voiding problems and should be filled in for a 72h period.

III. EXAMINATION
A. Check weight, BMI, BP, and signs of systemic disease
B. Note manual dexterity and mobility as this can affect which Tx options are available.
C. If Sx suggests neuro cause perform neuro exam (MS is MCC of neurogenic bladder in W)
D. R/O abdo or pelvis mass including full bladder
E. Is vulva/vaginal skin atrophic?
F. Record any prolapse.
G. Is there any urinary leakage on coughing?

IV. INVESTIGATIONS
A. Urinalysis MSU for MC&S R/O UTI; OGTT if DM suspected.
B. Check residual volume post-micturition to R/O incomplete emptying.
C. Imaging is not routinely used but may include USS to R/O incomplete bladder emptying and
define and pelvic mass.
D. Cystoscopy is used to visualise urethra, bladder mucosa, trigone, and UO. Bx can be taken.
Indicated if recurrent UTI, haematuria, bladder pain, suspected fistula, tumour, or
interstitial cystitis.
E. Urodynamics = combination of test which look at ability of bladder to store and void urine.
 Genitourinary medicine

1. Uroflowmetry = screens for voiding difficulties and the patient voids in private onto a
commode with a urinary flow meter, measuring voided volume over time and plotting it
on a graph
2. Cystometry = more invasive and involves measuring pressure and volume within the
bladder during filling and voiding, and is a test of bladder function. The bladder is filled
with saline via a catheter, and an intravesical and rectal probe measure differences in
pressure, to give the detrusor pressure. The patient is asked for first desire to void,
strong desire to void, and to cough. The results are printed onto a graph and any
detrusor contractions and/or leakage noted.

V. CLASSIFICATION OF INCONTIENNCE
A. Stress = involuntary leakage of urine on effort or exertion, or on sneezing or coughing.
Commonly due to urethral sphincter weakness.
B. Urge = involuntary leakage of urine with a strong desire to pass urine. Commonly coexists
with frequency and nocturia and forms overactive bladder syndrome.
C. Mixed = combination of stress + urge; usually 1 will predominate (treat that 1st)
D. Overflow = injury or insult (e.g. post-partum). Tx = cath.
E. Functional environment.

VI. STRESS UI (SUI)

A. Most common urinary reason for which a woman will seek help.
B. It affects up to 1 in 10, and in 50% will be pure stress incontinence.
C. It occurs when detrusor pressure exceeds the closing pressure of the urethra.
D. Pregnancy itself is a risk factor (mode of delivery much less so).
E. At the menopause, oestrogen deficiency leads to weakening of pelvic support and thinning
of the urothelium.
F. Other causes include radiotherapy, congenital weakness and trauma from radical pelvic
surgery (eg for gynaecological cancer).
G. Investigations:
1. R/O UTI (worsens Sx)
2. Frequency/volume chart = shows normal frequency and functional bladder capacity
3. Urodynamics indicated if surgery considered, in order to confirm Dx.
a. Check detrusor overactivity (which can worsen irreversibly by surgical procedures).
b. Check voiding dysfunction (woman w poor flow rate is at risk of long-term urinary
retention).
H. Management
1. Conservative measures should be tried first. E.g. optimizing control of other medical
problems such as DM, weight loss, smoking cessation, treatment of chronic cough, and
constipation. Pelvic floor exercises for at least 3 months and continued long-term (refer
to a pelvic floor physiotherapist for optimal results). Biofeedback uses a device to
convert the effect of pelvic floor contraction into a visual or auditory signal.
2. Pharmacological agents not recommended as first-line by NICE. Duloxetine is the only
licensed drug but rarely used.
3. Surgery is considered after other measures have failed.
a. Peri-urethral injections of bulking agents are successful in 2040% and have lower
morbidity than other procedures. May be better for frail, older women or younger
women yet to complete their family.
b. The tension-free vaginal tape (TVT) is the most common surgical procedure for SUI
in the UK. A polypropylene mesh tape is placed under the mid-urethra via a small
vaginal incision. The mean cure rate is 94%. Risks include bladder injury, voiding
difficulty, and tape erosion.
 Genitourinary medicine

c. The transobturator tape is an alternative to this and has a lower incidence of

bladder injury but higher risk of groin pain.
d. Burch colposuspension (paravaginal fascia attached to Coopers inguinal ligament
to suspend the prolapse urethra so that the urethrovesical junction & proximal
urethra are replaced in abdominal cavity). It is now rarely performed due to the
success of the TVT.

VII. OVERACTIVE BLADDER SYNDROME (OAB)

A. Chronic condition affecting up to 1 in 6 women, and implies underlying detrusor
overactivity (DO).
B. DO is a diagnosis made on urodynamic testing.
C. Incidence increases with age. It is mostly idiopathic, but may be found with MS, spina
bifida, or secondary to pelvic or incontinence surgery.
D. Symptoms may be provoked by cold weather, opening the front door, or by coughing or
sneezing leading to confusion with symptoms of stress incontinence.
E. It is unpredictable and the urine leakage may be significant, having a huge impact on the
womans quality of life.
F. Investigations:
1. Exclude UTI.
2. Frequency/volume chart typically shows increased diurnal frequency and nocturia.
3. Urodynamics show involuntary detrusor contractions during filling and should be
performed if there is doubt about the diagnosis, complex symptoms, or drug treatment
has failed.
G. Management:
1. Avoid excessive fluid intake, caffeinated and carbonated drinks and alcohol.
2. Bladder retraining aims to suppress the urinary urge and extend the intervals between
voiding.
3. Anticholingerics are the mainstay of pharmacological therapy, blocking the
parasympathetic nerves and relaxing detrusor. Try oxybutynin. Alternatives are
solifenacin 510mg daily, or tolterodine 2mg bd.
a. S/Es include dry mouth, constipation and nausea.
4. Intravaginal oestrogen cream can help in those with vaginal atrophy.
5. Other measures include botulinum toxin A injected cystoscopically into detrusor (90%
effective).
6. Neuromodulation can help.
7. Surgery is a last resort.