Fertility control Flashcards
COCP that does not follow the 7d additional precautions rule?
Qlaira® requires 9 days of additional contraceptive precautions
COCP that does not follow the d1-5 with no additional precautions rule?
Estradiol-containing combined oral contraceptives (Qlaira and Zoley) require additional precautions if started after Day 1
Problematic bleeding on hormonal contraception: investigations
STI test
Cervical screening
UPT
Problematic bleeding on hormonal contraception: when not to examine
no risk factors for STIs,
no concurrent symptoms suggestive of underlying causes,
they are participating in an NHSCSP,
and have had no more than 3 months of problematic bleeding.
Problematic bleeding on hormonal contraception: when to endometrial biopsy
in women aged ≥45 years or in women aged <45 years with risk factors for endometrial cancer who have persistent problematic bleeding after the first 3 months of use of a method or who present with a
change in bleeding pattern
Bleeding on COC
For women using a COC the lowest dose of ethinylestradiol (EE) to provide good cycle
control should be used. However, the dose of EE can be increased to a maximum of 35 µg to provide good cycle control.
Although DONT change within the first 3 months.
Bleeding on POP
There is no evidence that changing the type and dose of POP will improve problematic bleeding; bleeding patterns may vary with different POP
preparations and this may help some individuals.
PO-injectable: mefenamic acid 500 mg twice daily (or as licensed up to three times daily) for 5 days.
PO-injectable, implant or
IUS: COC may be tried for 3 months (this can be used in the usual cyclic manner
or continuously without a pill-free interval and is outside the product licence).
Upper arm anatomy
Separated into anterior (flexor) and posterior (extensor) compartments by fascia, bones and ligaments.
Arm: Anterior compartment
contains 3 muscles:
(1) Biceps brachii:
*Flexor of the forearm at the elbow joint
*Supinator of the forearm
*Accessory flexor of arm at glenohumeral joint
*Biceps tendon reflex tests C6
(2) Brachialis:
*Flexor of the forearm at the elbow joint
(3) Coracobrachialis:
*Flexor of arm at glenohumeral joint
All predominantly innervated by musculocutaneous nerve
Brachialis has small component laterally which is innervated by the radial nerve
Posterior compartment
contains only the triceps brachii
Innervated by the radial nerve
Extensor action on the forearm at the elbow
Triceps tendon reflex tests C7
Arteries in the arm
Aortic arch -> gives rise to Brachiocephalic trunk on the right -> right subclavian and common carotid
On the left, the subclavian and common carotid arise directly from the aortic arch
**Remember ABCs – Aorta: Brachiocephalic, Common carotid, Subclavian **
The subclavian artery -> (gives rise to ) axillary artery -> (becomes the) brachial artery when passes beyond the lower border of teres major -> (becomes the) radial and ulnar arteries distal to the elbow
Brachial artery gives off profunda brachii, which passes into and supplies the posterior compartment of the arm (which it enters alongside the radial nerve)
(Profunda brachii passes along the radial groove and anastomoses with the posterior circumflex humeral artery)
Veins in the arm
Includes the superficial veins (cephalic and basilic) and deep veins (brachial and axillary)
Veins of the arm -> (become the) subclavian vein -> (joins with the jugular veins) brachiocephalic vein -> (right and left brachiocephalic veins merge) superior vena cava -> (empties into) right atria
The basilic vein passes vertically in the medial distal half of the arm
*Penetrates the deep fascia
*Becomes the axillary vein at the border of the teres major
The cephalic vein passes on the anterolateral aspect of the arm
*Proximally, it joins with the axillary vein
The paired brachial veins pass along the medial and lateral sides of the brachial artery
Nerves of the arm
Musculocutaneous (C5 - C7)
Axillary (C5, C6)
Median (C5-T1)
Radial (C6-T1)
Ulnar (C8, T1)
Nerve injury from Implant INSERTION
Ulnar nerve damage: If damaged proximally (as we would from implants) - when try to make a fist hand resembles an ‘OK sign’ as cannot bend the medial 2 digits
Nerve injury from Implant removal
median, cutaneous and ulnar nerves
Ulnar nerve damage: If damaged proximally (as we would from implants) - when try to make a fist hand resembles an ‘OK sign’ as cannot bend the medial 2 digits
Median nerve: If damaged proximally (as could occur with implant removal) when asked to make a fist - hand of benediction (unable to bend lateral 3 digits)
Study which led FSRH to change their guidance used cadaveric dissection of 40 cadavers.
In elbow flexion the ulnar nerve moves towards the sulcal line (correct position for insertion/ removal – ulnar nerve out of the way)
At 2-3cm posterior to the sulcal line basilic vein (40%), ulnar nerve (40% - though deep), MEDIAL BRACHIAL CUTANEOUS NERVE of the arm (57.5%) and medial antebrachial cutaneous nerve of forearm (17.5%) were localised with only 25% of the arms dissected being free from neurovascular structures at this location.
At the 3-5cm window no cadavers had significant neurovascular structures (only triceps muscle more deeply)
Upper limb arteries
ABCs
Ascending aorta/ aortic arch
Brachiocephalic (r) (– R common carotid and R subclavian)
Left Common carotid
L subclavian
Then another ABC
(Axillary, Brachial, Post circumflex)
Subclavian branches into 4, one of which is the…
Axillary which (after giving off 3 branches) becomes the…
Brachial which becomes the Ulnar and Radial aa, and the Profunda Brachii.
Another branch of the Axillary is the posterior circumflex humeral. This forms an anastamosis with the Profunda Brachii.
Upper limb veins
Superficial veins are the cephalic v (radial, anterolat) and the basilic (ulnar, medial BUM).
There is an anastomosis through these at the AC region called the median antecubital vein.
Deep veins are radial and ulnar veins, which come together to form the
Brachial veins (paired).
The basilar vein becomes the axillary vein. The brachial vein empties into this.
The cephalic and axillary veins feed into / form the subclavian veins.
The subclavian veins merge with the jugulars to form the brachiocephalic.
R and L brachiocephalic come together to form the SVC which feeds into the RA.
Testosterone based progestins
Levonorgestrel
Ethynodiol diacetate
Gestodene
E
Norethindrone / acetate
Norethisterone
N
Nomegestrol acetate (in Zoely)
Norgestimate à Norelgestromin
D
Dienogest* (hybrid, in Qlaira)
Desogestrel à etonogestrel
Progesterone based progestins
Medroxyprogesterone acetate
Chlormadinone acetate
Cyproterone acetate
Nestorone (segesterone acetate – male contraceptive!)
Spironolactone based progestins
Drosperinone
1st generation progestins
Norethisterone
Cyproterone acetate
Medroxyprogesterone
2nd generation progestins
Levonorgestrel (Microgynon/ other first like COCP options)
Norgestrel
3rd generation progestins
Desogestrel (Mercilon, Marvelon)
Gestodene (Femodette, Femodene)
Norgestimate (Cilest)
4th generation progestins
Drosperinone (Yasmin)
Dienogest (Qlaira)
Semen Normal values:
Ejaculate volume >=1.5ml (average 2-5ml)
>=15 millions spermatozoa/ml
> =39 million sperm/ ejaculate
pH >=7.2
Motility of 40% + (progressive motility 32%+)
58%+ live sperm (vitality)
4%+ normal sperm morphology
Fenton Millard (15 mil, 1.5/ml) was running down the motorway.
It was the M40 progressed from M32 last year (Motility of 40%+, progressive motility 32%)
Vitality peaked at 58mph (58%+ live sperm)
His running style was unpredictable, had 4+ morphologies depending on the wind! (4%+ normal sperm morphology)
He stopped at 7/1+1 for a P (pH > equal 7.2)
LA Implants
Lidocaine 1%
1% = 10mg/ml (recommended dose for SDI insertion 2-3ml, and removal 0.5-1ml).
amide type local anaesthetics
with or without adrenaline 1:200 000 (adrenaline may reduce local bleeding)
MAXIMUM safe dose is 200mg (20mls of 1%)
Lidocaine interactions
Beta blockers, cimetidine, antiviral agents and noradrenaline increase the action of lidocaine
QT prolonging drugs such as antipsychotics increase the risk of ventricular tachycardia (VT)
Hypokalaemia (care with those on diuretics) decreases the action of lidocaine
Lidocaine crosses the placenta and should not be used in early pregnancy unless the benefits outweigh the risks
Lidocaine LA SE/Precautions/risks
Adverse effects usually due to actions of CNS (low dose stimulates, high dose depresses)–nervousness, dizziness, tinnitus, tremor, drowsiness, convulsions and
CVS – bradycardia, reduced cardiac output, vasodilation (low BP), myocardial conduction block. Hypersensitivity reaction/allergic dermatitis.
CI: complete heart block. Hypovolaemia,
Caution: cardiac rhythm disturbance/congestive cardiac failure, liver or renal impairment, porphyria, myasthenia gravis, epilepsy,
Avoid injection into infected/inflamed tissues → wont work as well.
Crosses placenta, use if benefits outweigh risks. large doses can cause fetal bradycardia. Ok in breast feeding.
Toxic from 5-10mg/L and lethal range from 6-33mg/L.. Accidental IV injection can result in excessive concentrations and acute toxicity→needs ABC/999→IV fluids to prevent Local anaesthetic systemic toxicity (LAST)
LA pharmacodynamics
Decreased excitability of neurons by preventing sodium conduction/permeability and therefore blocking the initiation and propagation of action potentials
At low concentrations they decrease rate of action potential increasing duration and reducing firing rate, at higher concentrations they prevent action potential firing at all
Enters the open sodium channel and physically blocks it. Use-dependant → effect is greater when actional potential frequency increases as has better access to channels when they are already open.
Strongly pH dependant – increased activity in higher (alkaline) pH. Clinically important as means that inflamed tissues usually more acidic and therefore may not response as well to local anaesthetic.
In general block conduction in small diameter nerve fibres>large fibres which is why pain is blocked more readily than touch and why large motor axons are relatively resistant.
Implant whats it made of and size
4cm long, 2mm wide
68mg Etonogestrel (EMP-IMP), Nexplanon
Implant failure rate
0.05% failure rate
Implant concentration and it after 3 years
Maximum concentration reached within 2 weeks
average of 156 pg/ml (111−202 pg/ml) after 3 years
(over 90 inhibits ovulation)
Fitting / Switching to IMP
No extra precautions: By day 1-5 of cycle, up to day 21 after childbirth, day 5 after abortion
Condoms 7 days: outside above timeframes
If UPSI since LMP, PT negative; consider EC and Quickstart immediately after LNG-EC, wait 5 days after UPA-EC. PT in 21 days
From CuIUD
If UPSI >7d – retain Cu-IUD for 7 days OR condoms 7/7
If UPSI <7d - retain Cu-IUD for 7 days AND condoms 7/7
The only time you can’t fit an implant immediately is after UPA-EC
Switching imp <3 years; 3-4 years; >4 years
IMP <3yrs – CHC/ POP/ IMP/ DMPA/ LNG-IUS/ Cu-IUD – start immediately, no extra precautions
IMP 3-4 years – PT negative, no UPSI in last 21 days
start immediately, condoms 7 days (or 2 for POP)
IMP 3-4 years – PT negative, UPSI in last 21 days
start immediately, condoms 7 days (or 2 for POP), PT 21 days
> 4 years PT negative, no UPSI in last 21 days
start immediately, condoms 7 days (or 2 for POP)
> 4 years PT negative, UPSI in last 21 days
consider EC, start immediately (or after 5/7 if UPA-EC), condoms 7 days, PT 21 days
DMPA consider bridging
Cu-IUD If all UPSI either ≥21 days ago or <5 days ago then insert immediately. If UPSI between 5 and 21 days ago, delay insertion until pregnancy excluded by negative PT 21 days after last UPSI, consider bridging
P450 inducers:
Sulfonylureas
Carbamazepine
Rifampicin
Alcohol (chronic)
Phenytoin
Griseofulrin
Phenobarbital
St johns wort
Some (but not all) of the non-nucleoside reverse transcriptase inhibitors (NNRTIs) are enzyme inducers.
Which ones and what are the clinical relevance?
May reduce the effectiveness of LNG-EC and UPA-EC.
The enzyme inducing NNRTIs include:
Efavirenz
Nevirapine
Etravirine
Implant UKMEC 3
IHD (cont 3, initiation 2)
Hx stroke (cont 3, initiation 2)
Unexplained vag bleeding (not ix)
Liver cirrhosis severe decomp
Liver cancer
Past breast ca
Implant UKMEC 4
Current breast ca
Bleeding pattern on Impl
20% amen
30% infreq
7% freq
40% Normal
20% prolonged
Starting COCP >40
1st line – start with ≤30 μg ethinylestradiol
Advise to stop age 50
Smokers – stop CHC age ≤35
CHC can be used <50 as an alternative to HRT for relief of menopausal symptoms and prevention of loss of BMD.
DMPA >40
DMPA - can be used until menopause, BUT assess risk at age 50
Review every 2 years for everyone
Risk of BMD loss is not worsened by DMPA + menopause
Stopping contraception >40yrs
Can stop contraception age 55 (even if still periods)
Can continue implant/POP/IUS until age 55
52mg LNG-IUS 5 years for endometrial protection
52mg LNG-IUS for contraception:
If inserted ≤age 45, can keep until menopause (or age 55)
FSH not routinely measured. Can measure if on hormonal contraception and want to stop: Inaccurate if on CHC or HRT (suppressed estradiol and gonadotrophins)
If wish to stop, in amenorrhoeic individuals on IMP/POP/LNG-IUS, can check FSH, if >30 IU/L then can stop in 1 year, if peri-menopausal range, check FSH in 1 year
(non hormonal if aged 40-50 stop after 2 years ammen, if >50 1 year)
Qlaira
(estradiol valerate/dienogest)
good COCP for HMB (also can be used in endometriosis).
Remember 9 day starting window (rather than the usual 7!)
BMI and contraception
BMI 30-34
UKMEC 2:
CHC (if BMI only RF, if more then 3)
POP/IMP/LNG IUS (if BMI PLUS other RF CVD)
UKMEC 3:
CHC/DMPA (if BMI PLUS other RF CVD)
BMI > equal 35
UKMEC 2
POP/IMP/LNG IUS (if BMI PLUS other RF CVD)
UKMEC 3
CHC (if BMI ONLY RF, if more then 3)
CHC/DMPA (if BMI PLUS other RF CVD)
Hx of bariatric surgery = same as BMI only RF
DMPA and obesity
DMPA can cause weight gain, esp in age<18 and BMI >30
If obese and on depo, consider injection in deltoid rather than gluteal
Obesity and patch
The patch may be less effective if weight >90kg
Obesity and EC
LNG-EC – double dose if BMI>26 or >70kg
In-hospital insertion for IUD and cardiac disease:
Fontan’s circulation
Eisenmenger’s physiology
Tachycardia
Pre-existing bradycardia
cardiac drugs and contraception
Most statins and anti-hypertensives are fine
Bosentan (ERA – endothelial receptor antagonist) – decreases prog and eostro levels in contra
VTE risk with CHC
Doubles the risk (9-10 in 10,000)
Baseline VTE risk = 2 in 10,000
Pregnancy & puerperium = 20 in 10,000
Lower risk progestogens =
6 in 10,000
Levonogestrel
Norethisterone
Norgestimate
Moderate risk progestogens = 8 in 10,000
Etonogestrel
Norelgestromin
Higher risk progestogens = 10 in 10,000
Desogestrel
Gestodene
Drospirenone
Resus drugs for IUC
Adrenaline 1 mg (= 10 ml 1:10 000) as a prefilled syringe
Atropine 500 or 600 mcg IV/IM (two doses) for the treatment of symptomatic bradycardia
Oxygen.
GCS
Best eye response (4)
No eye opening
Eye opening to pain
Eye opening to sound
Eyes open spontaneously
Best verbal response (5)
No verbal response
Incomprehensible sounds
Inappropriate words
Confused
Orientated
Best motor response (6)
No motor response.
Abnormal extension to pain
Abnormal flexion to pain
Withdrawal from pain
Localizing pain
Obeys commands
Atropine: when, how much and how to give
Bradycardia <60
The Resuscitation Council (UK) lists shock and syncope as “adverse features” of bradycardia, for which atropine should be administered. It may be given in repeated doses to a maximum of 3 mg.9 Oxygen should also be administered.
For those trained
in gaining rapid intravenous (IV) access (by whatever means), give
IV atropine as a single dose of 500-600 micrograms (followed by a
saline flush). The heart rate will usually increase within a few minutes.
If there is no improvement in the patient’s condition emergency
assistance must be summoned and a further IV dose of 500-600
micrograms atropine given.
Although evidence for its use in this manner is minimal, a dose of
atropine (500-600 micrograms) may be given intramuscularly (IM).
This recommendation is NOT part of the Resuscitation Council (UK)
Bradycardia Algorithm.
The atropine should be given
anterolaterally in the mid-thigh with a long enough needle to ensure
correct intramuscular placement. The increase in heart rate following
IM atropine is significantly slower than after IV atropine and can take
many minutes.
Atropine MOA
Atropine is an alkaloid from the plant Atropa belladonna and is a competitive antagonist to acetylcholine.
It blocks muscarinic receptors in the autonomic nervous system, thus counteracting the effects of vagal stimulation.
In healthy individuals this results in a modest tachycardia, since it is the parasympathetic nervous system that is blocked, rather than the sympathetic stimulated.
In therapeutics it is a relatively safe and straightforward drug, which is why several doses may be administered.
Key lidocaine points
Blocks fast voltage gated sodium channels
Anti-arrhythmic
Half life 2 hours
Safe to use in pregnancy
Hepatic metabolism
Max dose is 3mg/kg (7mg/kg with adrenaline)
COCP types of oestrogens:
Most combinations use ethinylestradiol as oestrogen component (range from 20mcg to 35mcg)
Newer pills in development using body identical 17-beta-oestradiol
Zoely oestradiol valerate, metabolized -> 17-beta-oestradiol; paired w Nomegestrol acetate progestin
Qlaira uses oestradiol valerate, metabolized -> 17-beta-oestradiol; paired w Dienogest progestin
First line choice COCP contains 30mcg of ethinylestradiol with levonorgestrel (2nd gen) or norethisterone (1st gen)
Selected due to evidence suggesting these combinations have the lowest associated VTE risk
VTE risk with CHC
In 10, 000 risk of developing within one year
NOT using hormones/preg: 2
PREG: 20
CHC levonorgestrel (2)/ norethisterone (1) / norgestimate (3): 6
CHC etongestrel/ norelgestromin: 9
CHC drosperinone (4) / gestodene (3)/ desogestrel (3): 11
Rigevidon, Microgynon, Ovranette and Levest
30mcg ethinylestradiol and 150mcg levonorgestrel
COCP primarily for acne
Dianette
Ethinylestradiol 35
Cyproterone acetate 2000
Components of Qlaira
Quadraphasic combined oral contraceptive
Estradiol valerate 3 mg x 2, 2 mg x 22, 1 mg x 2
Dienogest 2 mg x 5, 3 mg x 17
Good for HMB
COCP and ovarian ca
Estimated ~20% reduction in ovarian cancer risk for every 5 years of COCP use
COCP and endometrial ca
The risk of endometrial cancer is estimated to be reduced by 50% in ever-users of the COCP
Risk reduction for both persists for ‘several decades’ following cessation of use
COCP and breast Ca
Breast cancer risk is increased in current users of COCP
Declines gradually following cessation of use, with no increase in risk found after 10 years from stopping
Known BRCA1/2 mutation is a UKMEC 3 for CHC use; UKMEC 2 for all other hormonal methods
Ethinylestradiol (EE)
Synthetic steroidal oestrogen (long acting; 24 hours)
Binds to both isoforms of oestrogen receptor (alpha> beta) with a higher affinity for oestrogen receptors than endogenous oestrogen
Binding to ER alpha -> anti-gonadotropin effects
Inhibits ovulation by inhibiting LH and FSH release from anterior pituitary
No LH surge; no ovulation
Reduces sensitivity of pituitary to GnRH
Also acts to increase SHBG levels -> lower levels of circulating /active sex hormones, including testosterone -> anti-androgenic activity /reduced androgenic symptoms i.e. acne
Changing EE dose in COCP impacts
VTE
Unscheduled bleeding (better control with vaginal ring»_space; oral or patch)
Libido lower may have less effect on libido
Which COCP contain oestradiol valerate
Qlaira and Zoely
Require 9 days additional precautions if started after d1.
TD CHC patch
Releases an average of 33.9 ug EE and 203 ug Norelgestromin / 24 hours
Efficacy may be reduced if weigh >90kg – consider alternative method
No alteration in VTE SE.
CHC Vag ring
Nuva ring (older) -> Syreni ring
Both release an average of 15 μg EE and 120 μg etonogestrel at daily rates.
For Nuva ring refrigeration is required; limited shelf life/ storage options for patients -> Syreni ring (unrefridgerated)
Better bleeding control.
CHC UKMEC 4
Postpartum 0-3 weeks if also has another risk factor for VTE (UKMEC 3 if not other risk factors)
OR post-partum 0-6 weeks if breastfeeding
Age >=35 years AND smoker >=15/day
(Note if stops smoking for >1 year risk falls back to UKMEC 2 )
CVD risk falls significantly within 1-2 years of cessation; all cause mortality takes 20 years to fall
Hypertension systolic >=160, diastolic >=100
Vascular disease
History of ischaemic heart disease/ stroke
Atrial fibrillation (think concurrent clot risk factors)
Migraine with aura (Unless last episode >=5 years ago in which case UKMEC 3)
Current / past VTE
Major surgery (or any surgery to lower limb) with anticipated prolonged lower limb immobilisation (Switch method 4 weeks prior and can switch back at + 2 weeks from recovered mobility )
Known thrombophilia
Lupus with + APLS antibodies (Lupus with negative APLS UKMEC 2)
Complicated valvular / congenital heart disease
Cardiomyopathy with impaired cardiac function
Current breast cancer
Severe/decompensated liver cirrhosis
Hepatocellular adenoma or carcinoma
Hepatocellular adenoma and CHC
Benign, well vascularised and often solitary liver tumours, associated small risk of malignant transformation
Typically occur in young women who are taking exogenous oestrogen containing medicines (CHC primarily)
More rare in recent years as oestrogen content of modern CHC is low
Up to 50% asymptomatic with normal LFTs in most cases
If oestrogen is withdrawn they usually spontaneously resolve
CHC should be withdrawn and use with a known hepatocellular adenoma is a UKMEC 4
Occasionally require surgical intervention if persistent or very large
Large range in size; 2- 15cm (larger tumours may be at risk of rupture à heamoperitoneum)
CHC use and thyroid axis
Oestrogen -> increased thyroid binding globulin
Can increase thyroxine requirements for those with hypothyroidism on treatment/ replacement
Thyroid function should be checked within + 6 weeks from commencing CHC in those with hypothyroidism
CHC and altitude
Women trekking to high altitudes (above 4500 m or 14 500 feet) for periods of more than 1 week may be advised to consider switching to a safer alternative contraceptive method.
IUD: UKMEC 3 AVOID
A:
Advanced HIV (CD4 <200)
Asymptomatic chlamydia
Anatomical abnormalities distorting uterine cavity
V: Very Long QT syndrome known,
pelVic tuberculosis (continuation)
O: Organ transplant with complications,
Oncological Background of Breast Cancer (LNG-IUS Exclusive)
I: In between 48 hours and 4 weeks post partum,
Ischemic heart disease new diagnosis (LNG-IUS only)
D: Decreasing hCG levels with Gestational trophoblastic neoplasia
Decompensated cirrhosis or liver tumors (benign or malignant) (LNG-IUS only)
S: Surgery to cervix
IUD: UKMEC 4 NEVER
Neoplasia
- Endometrial and cervical (initiation),
- Current breast cancer (LNG-IUS only)
Elevated serum hCG persistently Gestational trophoblastic neoplasia
Vaginal - Unexplained vaginal bleeding (initiation)/
Known pelVic tuberculosis (initiation)
Exudate - Current pelvic inflammatory disease (PID), purulent cervicitis, gonorrhoea or symptomatic chlamydia (initiation)
Recent sepsis with abortion/ birth
Traditional POP
levonorgestrel (30mcg) OR norethisterone (350mcg)
3h window only
Desogestrel POP
75mcg – now largely replaced traditional POPs
Mechanism = inhibition of ovulation primarily
UKMEC 3 POP
IHD (cont 3, initiation 2)
Hx stroke (cont 3, initiation 2)
Liver cirrhosis severe decomp
Hepatocellular adenoma/ carcinoma
Past breast ca
UKMEC 4 POP
Current breast ca
Unexplained vag bleeding (not ix)
UKMEC 2 for CHC/POP
UKMEC 3 for DMPA/Imp
UKMEC 4 for IUS/IUD for I (but 2 for C)
Drosperinone
24 active pills followed by 4 day pill free interval (and withdrawal bleed)
24 hour window for pills
Anti-mineralocorticoid effects
- Potassium sparing diuretic effect; reduced reabsorption of sodium and water
-> May be beneficial for bloating and mastalgia symptoms
-> Theoretical BP reducing effect (no evidence yet to back this up)
Additional UKMEC precautions for DRSP POP due to action as aldosterone antagonist
(1) Severe renal insufficiency/acute renal failure
(2) Hyperkalaemia or hypoaldosteronism (Addison’s)/use of potassium sparing medications
SDI
Etonogestrel
Total amount contained in implant = 68 mg
Reaches ovulation inhibitory levels within first day (90pg/ml)
7 days to become effective (fully inhibit) unless fitted within day 1-5 of cycle/ up to 21 days post-natal
Maximum serum concentration within 2 weeks
Then declines rapidly
Mean serum concentration at 1 year = 200pg/ml
Mean serum concentration after 3 years = 156pg/ml
Time from insertion /Release rate
5-6 WEEKS: 60-70 mcg/ day
End of year 1: 35 mcg/day
End of year 2: 30 mcg/day
End of year 3: 25 mcg/day
LA: Lidocaine
Amide type local anaesthetic agent
1% = 10mg/ml
Recommended dose for SDI insertion is 2-3ml 1% (20-30mg) and removal 0.5-1ml (5-10mg)
Maximum safe dose 200mg (20mls of 1%)
LA: Emla
5% cream
Mixed content – lidocaine and prilocaine
Apply 1-2 hours prior to procedure
Safe to use in pregnancy
Note prilocaine generally not used in obstetrics due to risk of methaemoglobinaemia however topical use of EMLA is widely accepted as safe within obstetric practice
Should only be used on intact skin
Progesterone only injectable contraception (depot)
IM = Depo Provera
150mg in 1ml
Given by healthcare professional only, into gluteal muscle U/O/Q buttock
SPC says should be given every 12 weeks - FSRH recommend can be given up to every 14 weeks
SC = Sayana Press
104mg in 0.65ml
Can be given into abdomen or upper thigh by HCP or by patient (if trained)
SPC says should be given every 13 weeks - FSRH recommend can be given up to every 14 weeks
Reduces circulating oestrogen (most suppressive of all progestogen contraceptives) -> reduced BMD
Can be given early (from 10 weeks interval) if desired i.e. to achieve amenorrhea in irregular or HMB
Absorption rates:
DEPO PROV
Immediately after injection of 150 mg/ml Depo Provera, plasma levels = 1.7 nmol/L
—> Two weeks after 150mg/ml Depo Provera levels = 6.8 nmol/l
SAYANA
Lower peak plasma concentrations following Sayana > Depo
Peak ~1 week from administration
Average peak plasma concentration 1.5ng/ml (0.5 – 3.0ng/ml)
Concentrations fall to the initial levels for both options by the end of 3 months
For IM injectables and patients with high adipose tissue
Administration here likely to result in effective SC administration
FSRH recommend alternative IM administration site into DELTOID
OR use of intentional subcutaneous injectable (Sayana press) into thigh or lower abdomen
Ventrogluteal site IM
The ventrogluteal site provides access to the gluteus medius and minimus muscles whilst avoiding nerves and blood vessels.
- The patient can be positioned prone, semi-prone or supine for this procedure, so choose whichever is most comfortable for the patient.
- Place the palm of your hand over the greater trochanter of the patient’s hip, with your thumb pointing anteriorly.
- Extend your index finger to touch the anterior superior iliac crest and point your middle finger towards the iliac crest to form a V-shape.
- Insert the needle between your index and middle fingers (i.e. within the V-shape).
Deltoid site IM
- Position the patient sitting on a chair with their arm relaxed.
- Expose the patient’s upper arm and shoulder.
- Palpate the lower edge of the acromial process and administer the intramuscular injection approximately 2.5cm below this.
Vastus lateralis site IM
The vastus lateralis muscle is relatively easy to locate and access making it an ideal site for intramuscular injections.
To locate the site, divide the front thigh into thirds vertically and horizontally to make six squares and inject into the outer middle square.
Cu-IUD
The most effective copper coils contain 380mm2 of copper
5 years = Nova T (380 unbanded),
10 years = T Safe (380 banded),
prevention of fertilization via direct toxic effect on both sperm and ovum
Extended contraceptive use recommended by FSRH if device with >300mm2 copper inserted when >=40 years –> May be retained and used until age 55 years
EC assessment
Earliest possible day of implantation of 6 days post-fertilisation (later on days 8-10 in majority)
5 day rule ensures that any existing implanted pregnancies are not disrupted (would be abortive not contraceptive here)
LNG-IUD
Mirena
32x32mm frame with 4.4mm insertion tube diameter
BROWN threads
Licensed for 8 years for contraception, or can be kept until age 55 if fitted on/ after 45th birthday
Licensed for 4 years for endometrial protection / FSRH recommend any 52mg device be used for 5 years for endometrial protection
1st year releases ~ 20mcg/ 24 hours LNG –> reduces to 7mcg/ 24 hours LNG by end of 8 year licence
Circulating plasma LNG concentrations:
276 pg/ml in year 1
196 pg/ml in year 2
177 pg/ml in year 4
Benilexa
One handed insertion with 52mg total LNG content
Blue threads
32 x 32mm frame with 4.8mm insertion tube diameter (insertion tube slightly wider than Mirena)
Licensed for treatment HMB; recommended but not licensed for 5 years of endometrial protection
6 year contraceptive licence and recommended duration of use
SPC specifies a minimum cavity length for insertion of 5.5cm
Initial LNG release 20 mcg/24 hours in 1st year –> 8.6 mcg/24 hours by end of 6 year licence
Similar circulating levels to Mirena as above
NB Levosert also available; exactly the same product as Benilexa but with 2 handed inserting device
Kyleena
One handed ‘EvoInserter’ with 19.5mg total LNG content
Blue threads with silver ring for improved ultrasound visibility
28 x 30mm frame with 3.8mm insertion tube diameter (same as Jaydess)
Licensed and recommended for 5 years for contraception
Not recommended for use for HMB treatment or endometrial protection
LNG release:
Initial – 17.5 mcg/24 hours
Average release over 1st year – 12.6 mcg/24 hours
By end of 1st year – 9.8 mcg/24 hours
At end of 5 year licence – 7.4 mcg/24 hours
Average release over 5 year licence – 9.0 mcg/24 hours
Circulating plasma LNG concentrations:
162 pg/ml in 1st week
91 pg/ml at 3 years
83 pg/ml by end of 5 year licence
Jaydess
Lowest hormone device with only 13.5mg total LNG content
Brown threads
Same size as Kyleena – 28x 30mm frame with 3.8mm insertion tube diameter and silver USS band
Only 3 year licence / recommended duration of use as contraception
Not recommended for HMB treatment or endometrial protection
LNG release:
Initially 14 mcg/24 hours
Average release over 1st year = 8 mcg/ 24 hours
By end of 1st year = 6 mcg/24 hours
By end of 3 year licence = 5 mcg/24 hours
Average release over 3 year licence = 6 mcg/24 hours
Circulating plasma LNG concerntrations:
162 pg/ml in 1st week
59 pg/ml by end of 3 year licence
Which IUS have brown threads
Mirena
Jaydess
Risks from fitting ius
Background perforation risk from fitting 1-2/1000
If breast/chest feeding significant increase in risk to ~6/1000
Expulsion risk in general population is accepted as 5% or 1:20 patients
Factors that increase risk of expulsion following fitting:
Adolescence
History of previous expulsion
Heavy menstrual bleeding
Uterine abnormality i.e. fibroids
Menstrual cup use
Insertion immediately post-partum (vaginal delivery»_space; LSCS)
Insertion immediately following late first trimester or second trimester termination
Management of cervical shock and bradycardia associated with IUC insertion
Can occur due to vagal stimulation via the cervix (Most common in nulliparous patients)
Atropine 500 mcg IV should be given for patients with persistent/ unstable bradycardia
If IV access not possible then it can be given IM (outside of resus council algorithm)
Should be given into anterolateral mid-thigh with long enough needle to ensure IM administration
Takes longer to work than IV administration
Atropine is a non-selective muscarinic receptor antagonist
- Inhibition of parasympathetic activation of cardiac M2 receptors (which usually act to decrease SA node conduction velocity and therefore heart rate)
- Increased SA node firing as a result and therefore increase in heart rate
Emergency hormonal contraception: UPA (EllaOne)
1 tablet = 30mg ulipristal acetate
Selective progesterone receptor modulator
Licensed up to 120 hours (5 days) post-UPSI
Delays ovulation by at least 5 days (time for any sperm in the reproductive tract from UPSI to die)
Able to act until LH peak; later possibility of efficacy compared to Levonelle
Delays ovulation by >5 days
Ineffective beyond the LH peak/ post ovulation
Most will ovulate and therefore have pregnancy risk later in the same cycle
May not be as effective above weight of 85kg or BMI 30 - Double dose not recommended
NOT suitable for severe asthmatics requiring oral glucocorticoids
Has anti-glucocorticoid activity
Can use in breastfeeding
Not suitable to use if progestogen containing compounds used in last 1 week (7 days)
Delay any quick starting of hormonal contraceptives until 5 days post-UPA use
Emergency hormonal contraception: Levonorgestrel (Levonelle)
1 tablet = 1.5mg levonorgestrel
Progestogen
Licensed up to 72 hours post-UPSI (3 days) // FSRH recommend use up to 96 hours post-UPSI (4 days)
Delays ovulation by at least 5 days (time for any sperm in the reproductive tract from UPSI to die)
Able to act until the beginning of the LH surge and not beyond this point
Ineffective post LH surge and post ovulation
Most will ovulate and therefore have pregnancy risk later in the same cycle
If weight >70kg or BMI >26; double dose required
If taking enzyme inhibitors; double dose required
Safe to breast feed and no medical contraindications
Diaphragms
Caya – fits ‘all’ (80%)
Not recommended within 6 weeks of delivery
Must be inserted with spermicide between 0-2 hours prior to sex
Must remain in place for minimum of 6 hours after sex
If subsequent episodes of sex within the 6 hour leave in window, diaphragm should not be removed but additional spermicide should be inserted into the vagina using an applicator
Diaphragm should be removed and washed at least once/ 24 hours
Main risk of use is association with toxic shock syndrome (TSS), higher around time of menstruation
NB: Spermicide preparation nonoxinol-9 = associated with increased risks of HIV transmission
Mechanism: vaginal mucosal irritation
Individuals at higher risk of HIV infection –> advise not to use methods requiring spermicide
Fertility awareness methods
Fertile window - 8 days per cycle (1d ovum and 7d sperm life expectancy)
UPSI in the follicular phase is associated with pregnancy risk (d1-9 low risk)
UPSI in the post-ovulatory phase of the cycle has a very low risk of pregnancy
The use of a single indicator is NOT recommended: Typical use failure rate of 24%/ year (higher than condoms at 18% with typical use)
Women stopping hormonal contraception –> FAM should not reply on predictors of fertility until menstruation has re-established AND they have had a minimum of 3 cycles
When approaching menopause, natural family planning = unreliable
Individual FAM methods: Cervical secretions
The survival of sperm is dependent on the presence of alkaline cervical secretions
Secretions like raw egg white – thin/wet/stretchy – are suggestive of fertility
Alkaline in nature
Allow maximum sperm penetrance into reproductive tract
Pregnancy more likely on days when cervical secretions present
Abstinence /use of barrier method recommended from the first day that any secretions are noted, continuing until 3 consecutive ‘dry days’ after secretions noted to revert to being thicker/ absent
Individual FAM methods: Basal body temperature
Defined as the temperature measured BEFORE rising from bed, when resting for at least 3 hours
Progesterone –> increased in BBT
Post ovulatory ‘infertile phase’ confirmed once BBT on 3 consecutive days is >= 0.2 degrees higher than in the previous 6 days
Following ovulation progesterone –> increase in BBT which is maintained until menstruation
UPSI >6 days before and >2 days after the rise in BBT associated with negligible pregnancy risk
When used alone, UPSI is not recommended in the pre-ovulatory phase and abstinence is recommended for ~ 16 days per cycle
If UPSI only occurs in the identified post-ovulatory phase (PERFECT USE) failure rate of BBT monitoring alone is 6.6%/ year
If UPSI does occur in the pre-ovulatory phase as well, this rises to 19% failure rate/ year
Individual FAM methods: Calendar method
Use of the calendar method ALONE recommends women to track their cycle length for a minimum of 12 cycles before relying on the data to make predictions
First fertile day = Shortest cycle length – 20 days (i.e. 26 days – 20 = day 6)
Last fertile day = Longest cycle length – 10 = (i.e. 30 days – 10 = day 20)
Requires a long period of abstinence if using correctly
A simplified version = standard days method, often allows for less abstinence days
Suitable only if cycles between 26-32 days length consistently
Advises abstinence between days 8-19 inclusive
Individual FAM methods: Urinary hormone monitoring
Urinary LH as reliable measure to detect ovulation
100% correlation with USS evidence of ovulation
Testing utilises urine strips with antibodies to estrone-3-glucuronide and LH
This method alone recommends avoidance of sexual activity when hormone is detected
Limited in scope of evidence base, appears to have high failure rate compared to other FA methods
Testing is designed and licensed to assist with conception, not contraception, and likely under-estimates the fertile window (especially preceding LH detection/ ovulation)
When correlated with cervical secretions, secretions were noted ~2 days before test detected LH +
Individual FAM methods: Changes to the cervix
The cervix is low, firm and has a closed os at infertile times in the cycle
Around the ovulatory window the cervix becomes higher, softer and the os dilates
When using this method alone the fertile window is from the first sign of cervical change –> +3 days of the cervix resuming it’s lower/firm/os closed position
No studies demonstrating efficacy of this method in isolation, so would not be advised to use alone
Lactational amenorrhoea: minimum feeding criteria
Exclusively breast/chest feeding (small amounts of occasional water/ vitamins permitted only)
Every 4 hours throughout day
Every 6 hours throughout night
No more than 6 months post-partum
Continued amenorrhoea
98% efficacious for contraception if these criteria are fulfilled
Lactational amenorrhoea: physiology of method
Suckling disrupts hypothalamic GnRH pulsatility
Mechanoreceptors in breast alveoli -> prolactin and oxytocin release from pituitary
Prolactin -> stimulates milk production, also interrupts GnRH pulses
Oxytocin -> activates milk release (via myoepithelial contractions)
Disrupted GnRH -> reduced LH release from anterior pituitary -> Anovulation maintenance
FSH is still released so there is follicular development, but no ovulation
As suckling frequency reduces -> GnRH pulsatility resumes -> LH surge -> ovulation
The effect of expression of breast milk on efficacy of LAM is unknown, but theoretically may reduce efficacy
Vasectomy
Failure rate of approximately 1 in 2000 (0.05%) after clearance has been given
10 x more effective than female sterilisation (which has failure rate of 1 in 200 / 0.5%)
Warming anaesthetic to body temperature (37) before injection à significant reduction in pain when compared to injecting local anaesthetic at room temperature
Minimally invasive approach = using needle with no incision/ <10mm incision w no sutures required
Less perioperative bleeding
Reduced pain, both during and after vasectomy
Less post-vasectomy infections
Fewer haematomas
Cauterisation followed by division of the vas deferens à lowest likelihood of early recanalisation (failure) when compared to other occlusion techniques i.e. ligation or clips (high failure rate)
After vasectomy men should be informed of the need to use additional contraception until PVSA has been undertaken and clearance/special clearance given
Evidence suggests that 12 weeks post-vasectomy is the optimal timing to schedule the first PVSA
80% of men should have achieved azoospermia by this interval
Postal semen samples
Postal semen samples can be used for PVSA but are not be suitable for sperm motility testing (needed for special clearance measures)
In a small proportion of men non-motile sperm will persist following vasectomy -> “special clearance”
Special clearance vasectomy
In a small proportion of men non-motile sperm will persist following vasectomy -> “special clearance”
Special clearance can be given to stop additional contraception if < 100 000 non-motile sperm/ml are observed in a fresh (NOT postal) semen sample post-vasectomy
Vasectomy failure definition
If motile sperm are still observed in a fresh sample 7 months post-procedure = failed procedure
What if only one VD palpated at vasectomy?
If a vas deferens on one side cannot be palpated or located, unilateral vasectomy can be carried out, and the man advised to comply with additional contraception until sterility is confirmed as per usual PVSA
These men should be informed of the probability of ipsilateral renal agenesis and may be referred for renal ultrasound
What if no VD can be felt at vasectomy?
Refer to urology specialist if bilateral absence of vas deferens or other anomaly of vas suspected
How long to continue contraception after lap steri
Women using CHC, the POP, IUC or non-hormonal contraception should be advised to continue their contraceptive method for at least 7 days after laparoscopic sterilisation
If sterilisation scheduled for HFI the hormone-free interval should be omitted
The progestogen-only implant can be removed at the time of the procedure (or any time following) *
Lap steri; Mechanisms of tubal occlusion failure
Recanalisation
Fistula
Incomplete occlusion
Slippage of the occlusive device
Occlusive device placed on wrong anatomical structure
Lap steri failure rates
The lifetime risk of failure, using a mix of occlusion methods, is estimated to be 1 in 200 (0.5%)
Filshie clip failure rate of 2–3 per 1000 at 10 years
Lap steri: Risk factors may be useful predictors of regret:
Young age <30 at time of procedure
Nulliparous or low parity (2 or fewer children)
Being in unhappy relationship/ spousal conflict at the time of procedure
Not being in a relationship at the time of procedure
Remarriage/ change of partner – desire to have children with new partner
Death of a child
Psychological problems
Psychosexual issues
Coercion by spouse or healthcare professional
Timing of procedure in relation to pregnancy – increased incidence of regret when sterilisation performed at the time of caesarean section
Ages cut offs and contraception
IUS UKMEC 2 for <20 (Younger women
using IUC may have an increased risk of expulsion compared with older women)
DMPA <18 and >45 UKMEC 2
(women should be informed that use
of DMPA is associated with a small
reduction in bone mineral density
(BMD) but this usually recovers after
discontinuation. Evidence for any longterm effects of DMPA on BMD in women aged <18 years is lacking. LT use review every 2 years)
CHC Age >=40 UKMEC 2 (Guidance from the FSRH supports use of CHC up to age 50 years if there are no medical contraindications to use.) unless smoking …
<35 and smoking: UKMEC 2
Age >35 and <15 cig/day: UKMEC 3
Age >35 and ≥15 cig/day: UKMEC 4
Age >35 and Stopped <1yr: UKMEC 3
Age >35 and Stopped ≥1yr: UKMEC 2
BMD and women >40 and DMPA
Women using depot experience initial loss of BMD due to hypoestrogenic effects
There is no evidence that this BMD loss is repeated or worsened by onset of menopause (just experienced earlier) however that is the theoretical risk/ concern with this method
Why 35 year age cut off for smoking and contraception?
Excess mortality associated with smoking is only apparent from age 35
The mortality rate from all causes (including cancers) decreases to
that of a non-smoker within 20 years of smoking cessation.
The cardiovascular disease (CVD) risk
associated with smoking decreases within 1 to 5 years of smoking cessation.
Risk of VTE in COCP >40 years compared to those aged <30 years
Therefore what should you prescribe?
3 x higher
COCP containing levonorgestrel or norethisterone (lowest VTE risk associated) should be prioritised and used first line in women >40 years (where baseline risk slightly higher therefore of even greater importance)
Additionally using formulations <=30ug EE content (lowest associated risk VTE, CVD and stroke)
Rigevidon, Microgynon, Ovranette and Levest (30mcg ethinylestradiol and 150mcg levonorgestrel
CHC and perimenopause
CHC can protect/maintain BMD in perimenopausal women safely and provide some perimenopausal symptom relief, up to age 50, compared to non-users (similar to HRT)
It can be used as an alternative to HRT, not in addition to HRT
ALL progesterone only based contraceptive methods can be used alongside HRT safely
IUD and age >40 extended use
A Cu-IUD containing ≥300 mm2 copper inserted at >= 40 years can remain in situ until age 55 OR
2 years after the LMP if age <50 years
1 year after the LMP if age >=50 years
Any 52mg LNG-IUD inserted at >= 45 years can remain in situ until age 55 for contraception
When to check fsh in context of contraception
If women on PROGESTERONE ONLY hormonal contraception want to stop before the age of 55, consider checking FSH
If FSH >= 30 then continue hormonal contraception for 1 year, then stop safely
If FSH <30 then continue hormonal contraception for 1 year and recheck FSH level
Oestrogen containing agents (CHC methods or HRT) -> gonadotropin suppression therefore not suitable to check FSH levels for this group of women
IBD and contraception/ pregnancy planing
Possible(reversible) effect of sulfasalazine sperm quality, quantity and male factor fertility
Standard 400mcg folic acid is usually advised
Higher 5mg dosing may be recommended is concurrent use of sulfasalazine (can effect folate absorption) or previous small bowel resection
Medications:
(1) If either partner using MTX – delay conception for 3 months following completion
(2) Mycophenolate mofetil – delay conception for 6 weeks from completion (female) / 3 months (male)
(3) TNF-a inhibitors (infliximab, adalimumab) – delay conception for 6 months following completion
Contraception efficacy
(A) Efficacy of oral contraception unlikey to be reduced by large bowel disease
Unless diarrhoea >24 hours; missed pill rules to be followed
(B) Efficacy of oral contraception may be reduced by small bowel disease and associated malabsorption
Contraception after Breast ca
Lack of good data to inform on risk of breast cancer recurrence with use of hormonal contraceptives
Hormonal contraception should be avoided after breast cancer, regardless of hormone receptor status
Use of LNG-IUD may be considered on case by case basis, with involvement of breast specialist
Some evidence that LNG-IUD reduces risk of endometrial hyperplasia / polyps in Tamoxifen users
Safest methods of effective contraception:
Cu-IUD
Sterilisation (female or male) – however this is permanent
Cu-IUD is first line for EC, however both LNG and UPA oral EC can be offered in this population
Contraception and HIV and HAART
Cu-IUD, LNG-IUD and depot offer effective contraception with use of all ART agents.
CHC, POP, SDI and oral EC susceptible to enzyme inducing reactions -> reduced efficacy.
Consider BMD risk – depot use not generally advised alongside concurrent TDF tenofovir for this reason. TAF Tenofovir could be used alongside depot.
For IUC, fitting/ initiation is not generally advised if CD4 count <200 (UKMEC 3); however can be considered in exception and prophylactic antibiotic cover may be provided. EG. Emergency Cu-IUD fittings, especially if on enzyme inducing medications where PO EC less effective.
IUC remains UKMEC 2 for continuation of method at CD4 <200.
There are NO expected interactions between NRTIs or integrase inhibitors (-gravir ending agents) and contraceptives.
Boosted integrase inhibitor (with cobicistat) may specifically reduce EE dose and should not be used with 20mcg EE preparations of CHC.
Some NNRTIs are known enzyme inducers – efavirenz, etravirine and nevirapine.
Protease inhibitors (-navir ending agents) may interact with hormonal contraceptives –> increased progesterone exposure, however this is not expected to effect contraceptive efficacy, but may increase risk/rates of side effects such as irregular bleeding
When to give 3/12 of CHC on top of contraception
Irregular bleeding on implant, LNG-IUS or injectable
Risks of preg interval <12 months
Pre-term birth
Low birthweight and SGA babies
Stillbirths and neonatal deaths
WHO recommends 24 months
Earliest expected ovulation post-child birth (including losses >24 weeks gestation) is day 28 (why 21 as give 7d sperm life span)
Post partum CHC
CHC is safest to be restarted after 6 weeks post-partum as a general rule
NON BREAST FEEDING
(A) PLUS VTE RF
UKMEC 4 for first 3 weeks for non-breastfeeding mothers WITH other VTE risk factors (Peri-natal VTE risks TBA: immobility, transfusion at delivery, BMI >=30, PPH, LSCS, PET & smokers)
UKMEC 3 from 3-6 weeks for non-breastfeeding mothers WITH other VTE risk factors.
(B) PLUS NO VTE RF
UKMEC 3 for first 3 weeks for non-breastfeeding mothers WITHOUT other VTE risk factors.
UKMEC 2 from 3-6 weeks (safe) for non-breastfeeding mothers WITHOUT other risk factors
UKMEC 1 at >= 6 weeks if not-breastfeeding
BREAST FEEDING
UKMEC 4 for first 6 weeks if breastfeeding
UKMEC 2 at >=6 weeks if breastfeeding
Falls to UKMEC 1 from >=6 months
Post partum IUD
IUC can be fitted immediately following delivery of placenta -> 48 hours post-delivery (UKMEC 1)
It should not generally be fitted within 48 hours – 4 weeks post-natal (UMEC 3)
It returns to UKMEC 1 from 4 weeks post-natal
Implant/ depot and abortions
For women having medical abortions, the implant can be fitted at the time of mifepristone
Depot can also be used in this way, though evidence of slightly higher rates of continuing pregnancy when given WITH mifepristone that women would need to be counselled about
P450 enzyme inducers: name them and how do they impact contraception use including EC
Carbamazepine
Rifampicin, rifabutin, ritonavir* (both inhibiting and inducing activity!)
Alcohol (chronic)
Phenytoin
Grisofulvin
Phenobarbitone
Sulfonylueas, St John’s Wort
Plus:
TOPIRAMATE
ALL protease inhibitors
Some of NNRTI class – Efavirenz, Etravirine, Nevirapine
If using an enzyme inducing medication for <4 weeks: Can continue usual contraception as long as use condoms as well
If using an enzyme inducing medication for >4 weeks à switch to a more suitable form of contraception
Methods not impacted by enzyme inducers = Depo injection, intrauterine contraception, barrier contraception
Enzyme inducers also reduce efficacy of oral emergency contraception
Cu-IUD should be offered first line
If not acceptable/ contraindicated then double dose LNG (effectiveness unknown)
P450 enzyme inhibitors and effect on contraception
P450 enzyme inhibitors do not reduce contraceptive efficacy but may increase side effects risks/ reduce method tolerability or acceptability
Sulfonamides
Isoniazid
Cimetidine
Ketoconazole
Fluconazole
Alcohol (binging/ acute)
Ciprofloxacin
Erythromycin (clarithromycin)
Sodium valproate
Chloremphenicol
Omeprazole
Metronidazole
Also grapefruit
NB: ritonavir (protease inhibitor) unique example with both inducing and inhibiting properties
Enzyme inducer +/i teratogen
teratogen = topiramate, elfavirenz
Teratogen only: SDI/IUD/IUS
Teratogen + enzyme inducer:
IUS/IUD/DMPA AND condoms
Do not recommend CHC/POP/SDI (methods impacted by enzyme induction)
Lamotrigine and CHC
CHC can lower levels of lamotrigine and therefore seizure threshold
Higher doses of lamotrigine may be required
CHC best avoided if on lamotrigine
If needs to be used it should be used continuously on an extended regime with input/ monitoring of lamotrigine levels by the patient’s lamotrigine prescriber/provider
Lamotrigine and progestogen
Lamotrigine may reduce progestogen levels (FSRH guidance)
Desogestrel may increase lamotrigine levels (FSRH guidance)
Tenofovir (NRTI) commonly used within PrEP regimes and contraception
Evidence of interaction with progesterone injectable contraceptive on bone health
Both agents have risk of loss of BMD à combined effect
Alternative contraceptive method should be used
Important for trans-men who have historically popularly used DMPA for contraception and increasingly using PrEP
Higher dose Folic acid required when?
Maternal or paternal history of MTD
Previous pregnancy with NTD
Pre-existing diabetes, sickle cell anaemia, or thalassaemia.
BMI >=30
Epilepsy
Note: Women with sickle cell disease, thalassaemia, or thalassaemia TRAIT should take folic acid 5 mg daily throughout pregnancy. Others just the 12 weeks.
HIV and folic acid in preg
Most HIV+ women should take standard 400mcg folic acid dose
Higher dose of 5mg recommended if:
(1) Dolutegravir concurrent use (this particular integrase inhibitor increases risk of NTDs – HAART)
(2) Co-trimoxazole concurrent use
Isotretanoin and pregnancy
Isotretanoin is a retinoid agent/ potent vitamin A derivative and highly teratogenic
CNS defects
Craniofacial defects
Ocular defects
Anaemia in preg define:
Hb <110 in first trimester
Hb <105 second/third trimester
Hb <100 in post-partum period
Iron deficient if ferritin <30 (even if compensated/ non-anaemic)
If anaemia identified at 28/40 bloods, treat with oral iron and recheck levels at + 2 weeks
HbA1c in which you would advise delaying pregnancy
If HbA1c >=86 (10%) delaying pregnancy should be advised until diabetic control more optimised
Sickle cell and preconception care:
VASCULAR
VACCINATIONS
Vaccinations should be up to date
Annual influenza vaccine
Pneumococcal vaccine (if not received in last 5 years)
ANTIBX
Women with sickle cell are hyposplenic and at increased risk of infections, especially with encapsulated organisms such as H influenzae, N meningitidis and S pneumoniae
Daily antibiotics prophylaxis is recommended during pregnancy with penicillin V (phenoxymethylpenicillin)
STOP MEDS
(1) ARBs and ACEi should be stopped / converted (teratogenic – reno-protective use for CKD with SCD)
Renal function and proteinuria should be monitored monthly throughout pregnancy
(2) HYDROXYCARBAMIDE
Hydroxycarbamide should be discontinued pre-conceptually (teratogenic in animal studies)
Currently the only licensed treatment for SCD in the UK – reduces painful crises and ACS
Exception: women unable to receive transfusion due to multiple red cell alloantibodies or previous severe transfusion reaction
COUNSELLING
Women should be counselled pre-conceptually about their options – partner testing +/- PIGP (type of IVF that involves testing embryos before implantation)
U
LMWH
All women with SCD should receive prophylactic LMWH for 6 weeks post-partum
Consider prophylactic LMWH from 28 weeks gestation à 6 weeks post-partum
If any additional VTE risk factors, LMWH prophylaxis is recommended from conception
ASPIRIIN
higher risk of pre-eclampsia; consider 75-150mg/day aspirin from 12 weeks
REPEAT GROWTH SCANS MONTHLY
associated with IUGR; women should be offered monthly growth scans from 24 weeks
Sickle cell and contraception
POC assoc with reduced crisis - all 1
Cu-IUD a two only because assoc with increased blood loss
CHC 2 i think for increased VTE
Thalassaemia and conception
Fertility may be reduced in thalassaemia patients where long term chelation has been inadequate -> depositions in the anterior pituitary
Significant increase risk of IUGR and maternal cardiomyopathy due to iron overload
Women with thalassaemia should have specialist cardiac assessment at 28 weeks gestation
Women with thalassaemia should have monthly growth scans from 24 weeks gestation
Iron chelators are not recommended in pregnancy due to lack of safety data
Should ideally be stopped 3 months prior to conception and throughout pregnancy
Time without chelation can à new endocrinopathies due to iron deposition (i.e. DM)
Aggressive chelation pre-conceptually -> reduced iron burden and risk of end organ damage
If women have had a splenectomy they should receive prophylactic penicillin V (phenoxymethylpenicillin) throughout pregnancy, as well as annual influenza vaccine and pneumococcal vaccine (if not received within last 5 years)
Women with thalassaemia are associated with increased peri-natal VTE risk
(1) If previous splenectomy OR plts >600: 75-150mg aspirin from 12 weeks
(2) If previous splenectomy AND plts >600: LMWH proph AND 75-150mg aspirin from 12/40
(3) LMWH prophylaxis is recommended for 6 weeks post-partum
Antipsychotics and pregnancy
Measure prolactin levels in women planning a pregnancy taking prolactin raising anti-psychotic medications
Haloperidol, amisulpride, risperidone
Rheumatological conditions and preconception counselling
Often associated with use of NSAID or DMARD agents which can have adverse pregnancy outcomes
NSAID mechanism: cyclooxygenase inhibitors (COX) à reduced prostaglandin levels (anti-inflammatory effect)
NSAID use can be acceptable for short periods at lowest dose possible within the first trimester.
NSAID use is not recommended after 20 weeks gestation, and is contraindicated in the third trimester (from 28 weeks).
Effective contraception whilst using DMARDs.
NSAIDs and pregnancy
NSAID use can be acceptable for short periods at lowest dose possible within the first trimester.
NSAID use is not recommended after 20 weeks gestation, and is contraindicated in the third trimester (from 28 weeks) as associated with:
(1) Premature closed of fetal ductus arteriosus
(2) Renal dysfunction in the fetus and oligohydramnios
(3) Increased risk of uterine atony and PPH
If use of NSAIDs beyond 20 weeks cannot be avoided, consider additional monitoring of fetus (cardiac and amniotic fluid assessments)
Methotrexate and pregnancy
Methotrexate – folate antagonist via inhibitor of dihydrofolate reductase
Associated with reduced fertility during treatment (effects sperm and ova)
Associated with severe embryopathy
Conception not recommended within 3/12 of use (in either parent)
–> Inhibition of thymidine synthesis and inhibition of DNA synthesis
–> Increases sensitivity of T cells to apoptosis (reduced number of T cells)
–> Reduced immune response
Limited evidence about MTX and breastfeeding – bnf states should not be used whilst breastfeeding
NHS website states breastfeeding may be possible depending on dose of MTX, but is not advised within 24 hours of taking a dose of the medication
Hyperthyroidism and pregnancy
Must wait minimum of 6 months after treatment with radioactive iodine before conception
Hypothyroidism and pregnancy
Levothyroxine dose usually needs to be increased during pregnancy
Epilepsy and pregnancy
Carbamazepine and lamotrigine = safe agents during pregnancy
Little evidence around safety of levetiracetam and phenytoin use
Sodium valproate well established teratogen with long term implications for fetal neurodevelopment
Wherever possible AED treatment should be adjusted prior to conception, and valproate withdrawn
2/3 of women with epilepsy will not have seizure deterioration in pregnancy
Women with epilepsy can deliver as normal – epilepsy does not necessitate an elective LSCS
AEDs are associated with IUGR and serial growth scans are recommended from 28 weeks gestation
It is generally considered safe to breastfeed on anti-epileptic drug treatment, including sodium valproate
Warfarin and pregnancy
Warfarin exposure in the first trimester (weeks 6 – 12 especially) associated with warfarin embryopathy
Rates of ~5%/ 1 in 20 in exposed fetuses
- Hypoplasia of nasal bridge
- Congenital heart defect
- Ventriculomegaly
- Agenesis of corpus callosum
- Stippled epiphyses
**Despite association with fetal abnormality, warfarin is the safest anticoagulant for women with metallic heart valves in pregnancy **
Fetal loss (fetal mortality rate) occurs in 1 in 3 pregnancies for women with a metallic heart valve
Warfarin safe in breast feeding
Cystic fibrosis
Autosomal recessive condition caused by mutation in CFTR gene
Good pre-pregnancy lung function (>=60% predicted) = tolerate pregnancy well/ have good outcomes
Women with poor pre-pregnancy lung function (<60% predicted) have higher risk of preterm delivery and complications
Pregnancy in cystic fibrosis does NOT shorten maternal survival
TORCH infections
TORCH infections (toxoplasmosis, other organisms, rubella, cytomegalovirus, and herpes simplex) can lead to congenital abnormalities.
Toxoplasmosis
Protazoa parasite
Mat infection: cat feces, undercooked pork/lamb
Pregnant woman usually asymptomatic -> transplacental transmission to fetus in first 6 months of pregnancy can cause congenital toxoplasmosis
Treatment with Spiramycin
Neonatal sequelae worse if infection during first 10 weeks of pregnancy
Triad in neonate:
(1) Chorioretinitis
(2) Hydrocephalus
(3) Intracranial calcifications
Other (O in TORCH)
Treponema pallidum
HIV
Parvovirus B19
Varicella zoster virus (chicken pox)
Listeria monocytogenes
Parvovirus B19
Respiratory transmission
Can cause symmetrical arthritis and aplastic anaemia (absence of reticulocytes) in pregnant women
Transplacental transmission -> fetal aplastic anaemia
(1) Increased compensatory cardiac workload -> increased pressure within fetal vasculature
(2) Vessels can become ‘leaky’ -> HYDROPS FETALIS
(3) High risk of spontaneous abortion if occurring <20 weeks
No association with permanent defects/ malformations if pregnancy surpasses the infection
Listeria monocytogenes
Ingestion of contaminated food, particularly unpasteurised dairy and deli meats
Maternal gastroenteritis may occur, and in severe cases can cause sepsis
Primary risk is with amnionitis (amniotic fluid infection) and transplacental transfer to fetus -> miscarriage, pre-term birth, stillbirth or neonatal sepsis/meningitis following delivery
Varicella zoster virus (chicken pox)
Respiratory transmission or contact with skin lesions
Risk is in maternal infection (no history of previous vaccination or infection conferring immunity)
Transplacental transmission to fetus in 1st or 2nd trimester (<28/40) -> congenital varicella syndrome
Low birth weight
Limb atrophy
Microcephaly
Cataracts
Cortical atrophy and intellectual disability
If maternal infection occurs in last 4 weeks of pregnancy -> risk of neonatal varicella infection
If possible delay delivery until +7 days from onset maternal rash to allow for some antibody transfer to the fetus
Management of maternal exposure:
(1) VZV is infectious until the lesions have fully crusted; this usually takes ~5 days
(2) If non-immune maternal exposure then varicella IgG (VZIG) should be given ASAP
(3) Evidence of efficacy when given up to 10 days following exposure /first appearance of rash if continuous exposure i.e. household contact
(4) VZIG is not effective once maternal chickenpox rash has developed, and should not be used
(5) Consideration of oral aciclovir if presenting within 24 hours of onset of rash
A second dose indicated if further exposure occurs and >=3 weeks since last VZIG dose given
CMV
Most common congenital infection (usually asymp)
Neonates typically affected when primary infection in pregnancy
Clinical features
Deafness
Visual impairment (Chorioretinitis)
Seizures and neurodevelopment delay
Hepatosplenomegaly with jaundice
Petecial Rash
Periventricular calcifications
HSV
Genital HSV infection occurring in early pregnancy is associated:
Increased risk of spontaneous abortion, IUGR, preterm labour and congenital herpes (rare 2 per 100,000 live births)
Clinical features
Neonatal Herpes can lead to severe neurological impairment and death
