Emergency Contraceptives

Emergency contraceptives are measures taken to prevent pregnancy occurring after unprotected intercourse has taken place.

In the UK three forms of emergency contraceptives are currently recommended^[1]:

• An oral progestogen-only emergency contraceptive (POEC) - levonorgestrel (LNG).
• A selective progesterone receptor modulator (SPRM) - ulipristal acetate (UPA)^[2].
• A copper intrauterine device (Cu-IUCD).

Historically, combined oestrogen and progestogen preparations were used (the Yupze method); however, studies showed increased effectiveness and acceptability of the POEC. The Yupze method is therefore no longer a standard emergency contraceptive (EC).

Mifepristone may also be used as an emergency contraceptive but is not licensed for this use in the UK^[3].

Important points to note about emergency contraceptives:

• They are not considered an abortifacient (a Judicial Review in 2002 ruled that pregnancy begins at implantation, not at fertilisation).
• There is no time in the menstrual cycle when there is no risk of pregnancy following unprotected sexual intercourse (UPSI), particularly in an irregular cycle. Conception has been recorded as occurring on all days in a cycle, but is most unlikely to occur in the first three days..
• A Cu-IUCD is the most effective form of emergency contraceptive and should be offered to all women, even if they present within three days after unprotected sex.

The 2017 Faculty of Sexual and Reproductive Healthcare (FSRH) guidelines for emergency contraceptives state^[1]:

• Clinicians should advise women that the Cu-IUCD is the most effective emergency contraceptive.
• Providers should be aware that a Cu-IUCD can be inserted up to five days after the first UPSI in a natural menstrual cycle, or up to five days after the earliest likely date of ovulation (whichever is later).
• Providers should advise women that UPA-EC has been demonstrated to be more effective than LNG-EC.
• Clinicians should advise women that the available evidence suggests that an oral EC administered after ovulation is ineffective.

Indications for emergency contraceptives

When no contraceptive has been used

• Following consensual sexual intercourse.
• Following rape or sexual assault.

When there is contraceptive failure or incorrect use

• Incorrect use or failure of barrier methods such as the condom, diaphragm or cap.
• Failed coitus interruptus (ejaculation into vagina or on to external genitalia).
• Miscalculation of the fertile time, or failure to abstain/withdraw/use barrier methods during this time, when using natural family planning methods.
• IUCD/intrauterine system (IUS) expulsion (if complete or partial expulsion has occurred or if it is necessary to remove the device mid-cycle and there has been UPSI within the previous five days).
• While using any form of oral hormonal contraceptive if UPSI has occurred whilst taking, or within 28 days after taking, enzyme-inducing agents such as rifampicin. (In this situation, the Cu-IUCD should be offered. If using LNG, a double dose of 3 mg should be used. UPA should not be used with enzyme-inducing drugs.)
• Following incorrect use or potential failure of hormonal contraceptive as outlined below.

Factors in choosing the type of emergency contraceptive

Before making a shared decision with the patient as to the appropriate form of EC, a full history should be taken with particular reference to^[4]:

• Discuss what time has elapsed since unprotected intercourse.
• Note what contraception was used at the time of intercourse, if any.
• Go through menstrual history:
  • What was the date of the last menstrual period?
  • Was the last period normal?
  • What is the usual cycle length?
  • Is ovulation likely to have taken place yet in this cycle? (If the normal cycle is 28 days, ovulation is thought to occur around day 14).
  • Could implantation of a fertilised ovum have occurred in this cycle? (Implantation occurs no earlier than five days after ovulation. To calculate the likely date of implantation, subtract 14 days from the date of the expected date of the next period and add five days).
• Note whether there has been any other unprotected intercourse this cycle and whether the woman might already be pregnant.
• Establish whether there has been any previous use of EC.
• Ask whether the woman is breastfeeding.
• Discuss obstetric and gynaecological history (with particular attention to history of pelvic inflammatory disease (PID), current vaginal discharge, history of ectopic pregnancy).
• Discuss current requirement for contraception.
• Note medications used - eg, enzyme-inducing agents such as phenytoin (ask about over-the-counter enzyme inducers such as St John's wort).
• Take account of general health, looking for any contra-indications - eg, liver disease, porphyria.
• Sexual history - consider the risk of sexually transmitted infection (STI).

Progestogen-only emergency contraceptive - levonorgestrel

Mode of action

• When used early in the cycle, it is thought that progestogen-only emergency contraception (POEC) inhibits ovulation. FSRH recommends that POEC not be used after ovulation.

Prescribing

• POEC should be given in the form of LNG 1.5 mg, taken as soon as possible after UPSI.
• It is now available to buy without prescription over the counter for those aged 16 years or more, in addition to being a prescribable drug.
• There are several available brands, taken as a single 1.5 mg dose (World Health Organization (WHO) recommended regimen). Some can be bought from pharmacies. Some are prescription-only medicines.

Timing of use

• Licensed for use within 72 hours of UPSI.
• Use beyond 72 hours is unlicensed, but consider use between 72-120 hours if the other forms of emergency contraceptives cannot be used. It may still have some efficacy at this time, although it will be less effective than if it is taken within 72 hours^[5].
• POEC can be used more than once in a cycle if appropriate and repeated use will not induce abortion if the woman is already pregnant. However, use after ovulation is thought to have occurred is unlikely to be successful^[1].

Efficacy

• Efficacy rates are difficult to establish and compare. Comparison has to be made with the number of women who would become pregnant after a single episode of UPSI without an EC, which is variably reported as 5.5-8%. Pregnancy rates following a single episode of UPSI for women taking levonorgestrel emergency contraception (LNG-EC) are 1.1-2.6%^{[6, 7]}- ie if 1,000 women had unprotected sex once, around 60 to 80 would become pregnant. If all those women had taken Levonelle®, only around 11 to 26 would have become pregnant.
• There does not seem to be a statistically different effect in efficacy between Day 1 and Day 4, but it does decline significantly by Day 5.
• Women who are taking enzyme-inducing drugs (eg, phenytoin, rifampicin, etc) will be at risk of a higher failure rate. They should be advised that the IUCD is a more reliable method for them. If they choose to take LNG-EC, they should take 2 x 1.5 mg tablets as a single dose. This is outside the licence for the drug and they should be informed of this.

Contra-indications^{[8, 9]}

• Hypersensitivity to LNG.
• Acute porphyria.
• Severe liver disease.
• Severe malabsorption syndromes (eg, Crohn's disease) might impair the efficacy of LNG-EC.
• Rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption (preparations contain lactose).
• Caution is recommended if there is a history of ectopic pregnancy. Previous ectopic pregnancy is not an absolute contra-indication.

NB: POEC can be safely used during lactation.

Side-effects

Reported side-effects include:

• Nausea.
• Vomiting.
• Menstrual irregularities. Menses may be delayed, or there may be some spotting.
• Dizziness.
• Diarrhoea.
• Breast tenderness.

Interactions

• Liver enzyme-inducing drugs. For example:
• Anticonvulsants such as carbamazepine, oxcarbazepine, phenytoin, barbiturates, primidone, and topiramate.
• Antibiotics - rifabutin and rifampicin (potent enzyme inducers).
• St John's wort.
• Antiretrovirals - particularly ritonavir-boosted protease inhibitors.
• Ciclosporin. (LNG may increase the risk of toxicity by inhibiting metabolism of ciclosporin.)
• Selegiline. (Avoid concomitant use. May cause toxicity.)
• Tizanidine. (Monitor as may cause toxicity.)

Specific advice for women using LNG-EC

• If vomiting occurs within two hours of taking LNG-EC, a repeat dose is needed.
• Following use, women should be advised to use additional contraceptive precautions for seven days for the combined oral contraceptive (COC) pill, nine days for Qlaira®, and three days for the contraceptive progestogen-only pill (POP).
• If EC is used because of missed oral contraceptive pills, women should be advised to resume their normal pill-taking regime within 12 hours of taking LNG-EC.
• There is no current evidence that POEC affects an existing pregnancy^{[8, 9]}.

Selective progesterone receptor modulator - ulipristal acetate

This emergency contraceptive pill has been available in the UK since October 2009, as ellaOne®. It is a second-generation SPRM (mifepristone is a first-generation SPRM) and is the only licensed oral choice for UPSI between 72 and 120 hours.

Mode of action^[10]

The main mechanism of action is by inhibition or delay of ovulation. A single dose in the mid-follicular phase has been shown to suppress the further development of follicles. If given around the time of the luteinising hormone (LH) surge, the rupture of follicles is inhibited. After the LH peak, it is not effective in delaying follicular rupture.

Prescribing

It consists of one tablet (30 mg) of UPA which should be taken as soon as possible after UPSI, but within 120 hours (five days) of the event.

Timing of use

It has been shown to be effective up to 120 hours after UPSI, or failure of the normal contraceptive method.

Efficacy

Pregnancy rates with UPA are around 0.9-1.8% when taken within 120 hours^[7]- ie if 1,000 women had unprotected sex once, around 60 to 80 would become pregnant. If all those women had taken ellaOne®, only around 9 to 18 would have become pregnant.

There are data to show performance comparable to POEC and potentially more effective.

Efficacy may be reduced when the woman is taking liver enzyme-inducing medication, or medication which raises normal gastric pH.

Contra-indications^[10]

Pregnancy or suspected pregnancy should be excluded before UPA is prescribed. There is insufficient research to advise safely on breastfeeding and it is therefore recommended that breastfeeding is best avoided for one week after a dose has been taken.

Severe liver disease or uncontrolled asthma are also contra-indications to its use.

Repeated use within the same menstrual cycle is contra-indicated.

Side-effects^[10]

Reported side effects include:

• Vomiting. As with LNG, if a woman vomits within two hours of taking UPA, she should repeat the dose. If this is the case, consider an antiemetic.
• Nausea.
• Dizziness.
• Menstrual irregularities.
• Abdominal pain.
• Myalgia and back pain.
• Pelvic pain.
• Headache.
• Mood disorders.

Interactions

• Medication which increases gastric pH - for example, antacids, proton pump inhibitors (PPIs), H2-receptor antagonists. They may reduce concentration of UPA and therefore reduce its efficacy.
• Liver enzyme-inducing drugs. For example:
• Anticonvulsants such as carbamazepine, oxcarbazepine, phenytoin, barbiturates, primidone and topiramate.
• Antibiotics - rifabutin and rifampicin (potent enzyme inducers).
• St John's wort.
• Antiretrovirals - particularly ritonavir-boosted protease inhibitors.
• Contraceptives. UPA may compete with progestogens in contraceptive pills for progesterone receptors, and therefore reduce efficacy of ongoing contraception. Therefore, if starting or continuing oral contraception after using UPA, women should be advised:
• To wait five days (at least 120 hours) after taking UPA before continuing or starting combined hormonal contraception (CHC), with a pregnancy test 21 days later to exclude pregnancy resulting from EC failure.
• To use additional contraception (such as a condom) or avoid sexual intercourse until the CHC becomes effective:
  • Before continuing or starting the progestogen-only contraception, she should wait five days (at least 120 hours) after taking IPA with a pregnancy test 21 days later to exclude pregnancy resulting from EC failure.
  • She should use additional contraception (such as a condom) or avoid sexual intercourse until the progestogen-only contraception becomes effective.

Copper intrauterine contraceptive device

Most devices are plastic with copper wire wrapped around some sections. The total surface area of copper varies between devices but IUCDs containing at least 380 mm²of copper are more effective than those containing less copper. The clinician chooses a device based on uterine length and desired length of contraception needed for the woman.

Mode of action

• It is thought that IUCDs have an inhibitory effect on both fertilisation and implantation.
• Fertilisation inhibition occurs through direct toxicity effects of the copper on both ovum and sperm.
• Copper can also have the effect of inhibiting sperm penetration of cervical mucus.
• Inflammatory reaction effects on the endometrium due to the Cu-IUCD being in situ can also prevent implantation. If fertilisation has occurred, the mode of action is by preventing a fertilised egg implanting. Women should be aware of this, as some may have a moral view about this, although by law pregnancy begins at implantation, not at fertilisation. To ensure that an IUCD is inserted before the process of implantation begins, the IUCD should be fitted within the first five days (120 hours) following first UPSI in a cycle or within five days from the earliest estimated date of ovulation.

Timing of use

• Can be used up to five days after UPSI.
• If the timing of ovulation can be estimated, insertion can be beyond five days after UPSI, (ie day 19 of a regular 28 day cycle) as long as insertion does not occur beyond five days from ovulation:
• An IUCD should ideally be fitted at first presentation as a method of emergency contraception. It may be appropriate to delay the insertion in certain circumstances - eg, until the next-day sexual health clinic service is available. In such cases, POEC should be given in the interim.

Efficacy

• Pregnancy rates are significantly less than 1% when the IUCD is used as an EC - ie less than one woman in a hundred would become pregnant after a single episode of UPSI if the IUCD was used within five days.
• It is the most effective form of EC, and the only one to provide ongoing protection if left in situ.

Contra-indications

These are the same contra-indications as for insertion of a Cu-IUCD under other circumstances:

• Puerperal sepsis and septic abortion.
• Current PID.
• History of copper allergy or Wilson's disease.
• Markedly distorted uterine cavity.
• Gestational trophoblastic disease with persistent elevated beta-hCG levels, or malignant disease.
• Cervical or endometrial cancer.
• Active infection with chlamydia or gonorrhoea.

Risk of PID

• There is a potential risk of PID when inserting an IUCD in a woman who has had UPSI.
• It is recommended that, as a minimum, women at higher risk of STI (age ≤25 years, new sexual partner or ≥1 sexual partner in the previous year) should be offered testing for chlamydia.
• For such high-risk women, the use of prophylactic antibiotics should also be considered when the IUCD is inserted.

Other points

• Previous ectopic pregnancy is not a contra-indication to emergency IUCD use.
• Non-copper-containing IUCDs (including the IUS) are not recommended as emergency contraceptives, as there is currently no available evidence of their effectiveness.
• The IUCD may be removed following the next menstrual period if not required as long-term contraception.
• It may also be removed if hormonal contraception is started within the first five days of the next cycle.

General points for women receiving emergency contraception

• Discuss information about the failure rate, and document this.
• Give a written advice sheet about emergency contraceptives.
• Explain that their next period may be on time, early, or late.
• Explain that they should return for a pregnancy test if they have not had a normal period within seven days of their expected next period or if they have irregular bleeding.
• Advise that they should see a doctor immediately if they develop lower abdominal pain (consider the possibility of ectopic pregnancy).
• Advise about an effective method of contraception for the future. Written information is helpful.
• Discuss the risk of STI. They have all had unprotected sexual intercourse. They should be referred for a full sexual health screen as appropriate.
• Examine and document Fraser-ruling competence if appropriate.