Long-acting reversible contraception (LARC) is the term to describe the types of contraception which involve very little user effort and, as a result, have been shown to be the most effective options for women who really want to avoid pregnancy.

In Ireland most women opt for condoms or the combined oral contraceptive pill (COCP) unless prompted to consider a LARC.¹ However, condoms and the COCP are among the least reliable alternatives as both require significant user compliance.

Barriers to LARC

Among the barriers to LARC are lack of patient knowledge about the method as an option, unavailability of LARC in particular practices, unattractive service fees for GPs and the cost to patients (although it is more cost-effective than the COCP within 12 months).

The 2008 contraceptive CHOICE project was a US prospective cohort study of 10,000 women, 14-45 years of age who wanted to avoid pregnancy for at least one year and who were initiating a new form of contraception.²

Women were asked if they would choose LARC methods over pills and condoms if given the choice and if access to LARC was facilitated. Most answered yes.

Given the choices set out, 67% of women enrolled chose a LARC method; 56% selecting an intrauterine device and 11% the subdermal implant. Interestingly among the women who chose an IUCD, almost half were nulliparous even though this is often perceived as a barrier to intrauterine contraception.

Contraceptive efficacy data

PI refers to the ‘Pearl Index’ of contraceptive efficacy. It tabulates the number of pregnancies per 100 women per year of use. The ‘perfect’ PI refers to efficacy when a product is used exactly as advised as in clinical studies, whereas the ‘typical’ PI refers to the efficacy that is seen among the average user. This contraceptive efficacy data was compiled and published by Dr James Trussell in a 2007 edition of Contraceptive Efficacy.³

If used perfectly, the COCP should allow as few as 0.3 pregnancies for every 100 women per year of use – a very small failure rate. In actuality the failure rate of the COCP is closer to 8-9 pregnancies per 100 women per year of use because of factors such as forgetting to take a tablet, vomiting or taking liver enzyme-inducing medications.

Depo-Provera 

Depo medroxyprogesterone acetate (DMPA) has been available as the 150mg deep IM injection for decades in Ireland. The large bolus of medroxyprogesterone is delivered to the gluteus or deltoid muscle and has a strong impact on the hypothalamic-pituitary-ovarian hormone axis causing complete anovulation.

It can be started at any time of the cycle with or without a period as long as a current pregnancy can be ruled out. It begins to work almost immediately and is one of the most effective contraceptives available, with a PI of 0.3 pregnancies per 100 women/years. Typical efficacy is closer to three pregnancies per 100 women/years (late attenders and not managing to find deep muscle when administering the injection are possible explanations for rare failures).

The impact on ovarian activity can sometimes be so profound that circulating oestrogen levels may drop and a transient reduction in bone mineral density can result. This phenomenon is considered benign in low-risk users and has never been linked to an increase in fracture risk. It recovers within weeks of discontinuing the DMPA but it is for this reason that women under 18 (who have yet to achieve their maximal bone density) and women over 45 (who are starting to lose bone density more rapidly) might benefit from a fracture risk assessment before commencing this product. 

If a woman is already high-risk for fracture with a multiplicity of lifestyle risks (eg. very low BMI, heavy smoking, sedentary lifestyle, high dose steroid users, etc.) then DMPA may not be the wisest option for them. Despite this, if they want to use the depo injectable then a two-yearly reassessment is recommended.⁴

For most healthy young women, the benefits of this form of contraception far outweigh any risk and it is an excellent option for women who need highly reliable contraception but aren’t prepared to commit to the cost of an implant or IUD. There is no recommendation for ordering DXA scans on DMPA users. 

The anovulation lasts for at least 12 weeks. The UK Faculty of Reproductive and Sexual Health advises that DMPA is protective for up to 13 or 14 weeks (although this is outside the product licence of 12 weekly injections). For women on liver-enzyme inducing medications there is no need to shorten the injection intervals as was previously thought (the large dose of progestagen is fully cleared by the liver in the first pass).

The relatively high dose of synthetic progestagen may have some unwanted side-effects. Some women complain of acne, bloating, headache, alopecia, flushes, decreased libido or moodiness, but causation has never been established. A small but significant proportion of women experience rapid weight gain which is very distressing (DMPA is the only form of contraception shown to do this). Weight gain is more likely to be an issue for women under 18 years of age with a body mass index (BMI) ≥ 30kg/m² and if this is an issue it is likely to get worse so alternatives should be considered.

Use of DMPA usually results in a much lighter or non-existent PV bleed after the first or second injection. While this is reversible it may interfere with conception for the 6-12 months after the injections are discontinued so forward planning is suggested. Being amenorrhoeic on DMPA does not imply low fertility. The amenorrhoea may be a blessing for women who suffer from menorrhagia or endometriosis, are HIV-positive, suffer from severe dysmenorrhoea or who struggle to maintain menstrual hygiene. 

Before becoming amenorrhoeic, some users experience unscheduled bleeding in the first three to six months. For those who are medically eligible, a three-month prescription of the COCP may be offered to help resolve this annoying side-effect. The pill can be taken in the usual cyclic manner or continuously without the pill-free interval (outside the product licence). Longer-term use of the DMPA with additional COCP has not been studied and is a matter of clinical judgement. Alternatively, unscheduled bleeding can be controlled with 500mg mefenamic acid up to three times daily for five days. Persistent unscheduled bleeding should be investigated and STIs and other pathologies ruled out.

DMPA is suitable for breastfeeding mothers and women who have been told to avoid the oestrogen-containing pills because of obesity or smoking. It is UKMEC Category 2 (benefits outweigh risks) for women who currently have or have had a DVT (deep vein thrombosis) or suffer from migraine with aura.  

Intrauterine systems

Mirena 

The Mirena IUS comprises a plastic membrane reservoir containing 52mg of levonorgestrel (LNG) wrapped around a T-shaped, polyethylene frame. The membrane only allows 20µg of the hormone to escape over 24 hours in the first few years, dropping down to 12 and then 10µg in the fourth and fifth years of use respectively. This gives the device long-term effectiveness for at least five years. There is evidence to suggest that the term might be safely extended to seven years for all users. 

As a result of the Covid pandemic, the UK Faculty of Sexual and Reproductive Health (FSRH) has recommended a six-year contraceptive efficacy for current Mirena wearers, although this is outside the licence.

When inserted into a woman 45 or older the FSRH says there is no need to change the device for contraceptive protection (although control of menorrhagia may be lost as a result of the depleted reservoir and placement of a new Mirena may be warranted). 

If a woman with a Mirena that is less than five years in- situ chooses to take HRT, she need only use an oestrogen product, as the Mirena’s LNG will protect her endometrium from any negative impact that the oestrogen might cause. If a woman using oestrogen-only HRT is keeping her Mirena beyond the five-year licence for contraception, she must then change to a combined oestrogen and progestagen HRT product. Sometimes a new device may be inserted in women over 50 either for HRT or if menorrhagia is starting to return but this entirely up to the patient and rarely necessary.

Mirena has a good ‘period improving’ effect and helps ease menorrhagia and dysmenorrhoea. LNG hormone is a great contraceptive as it alters cervical mucus, rendering it hostile to sperm. It alters the endometrium, making it less receptive to implantation and these, among other contraceptive effects, prevent pregnancy. Occasionally, enough of the LNG is absorbed into the uterine vasculature (and then on into the systemic circulation) causing anovulation. This also accounts for the not uncommon issue of LNG side-effects that may complicate the use of Mirena. Some women experience systemic LNG effects (acne, bloating, mood changes, etc.) after insertion of a new Mirena device. These are usually mild and transient but can cause significant distress for some Mirena wearers and should be discussed at counselling. 

The most novel effect of IU LNG is that it causes significant endometrial depletion. The microscopic features seen within the endometria of Mirena users are similar to those expected to be seen in the presence of a foreign body (eg. surface undulations, inflammatory cell infiltrate, and stromal haemosiderin deposition) as well as features seen as a result of progestagen exposure (eg. glandular atrophy and stromal decidualisation).⁵

Initially this may create longer or more frequent PV bleeding (while the womb lining is being shed) but eventually the thinner, lighter endometrium should mean shorter, lighter periods for most women. It is the only IUCD available in Ireland that has a licence for the treatment of heavy menstrual bleeding.

Kyleena 

In the past few years a new smaller, slimmer IUS has been available in Ireland. The Kyleena IUS only has 19.5mg of LNG in its reservoir (less than half of what is in Mirena)  but still provides five years of contraception that does not depend on user compliance. Kyleena releases less LNG progestin hormone on a daily basis than Mirena, which may not provide significant menstrual reduction although there may be some benefit; however it should be less likely to provoke LNG hormone side-effects. 

The main advantage of Kyleena over Mirena is the ease of placement. The thinner, slimmer Kyleena insertion tube can ease placement for many nulliparous women, women who have never delivered vaginally or women who have had LLETZ procedures. Mirena is licensed for the treatment of menorrhoagia but Kyleena is not.

Jaydess

The third member of the IUS family is Jaydess. Jaydess uses the same slim introducer tube as employed by Kyleena but the Jaydess is unique in that it only contains a reservoir of 13.5mg of LNG. It only conveys three years of contraception – so obviously Mirena or Kyleena would be the preferable choice for women who are hoping to delay pregnancy for more than three years. 

Insertion and removal

IUCD insertions are usually uncomfortable but tolerable when performed in the GP surgery. If pre-insertion analgesia is offered and some ‘vocal local’ is employed, most office insertions go smoothly. Irish doctors do not routinely offer intra-cervical, injected local anaesthetic as might be on offer in hospital-based IUCD insertion services. Traditionally, placement was arranged to be done during a period (to exclude the possibility of a current pregnancy) but in fact placement can be offered at any time of the cycle as long as pregnancy can be reasonably outruled. 

Some studies have shown that the cervical canal is more likely to spasm during menses and ideally IUCDs should be inserted any time after the period is over as long as the patient is not at risk of pregnancy. The Royal College of Obstetricians and Gynaecologists FSRH has guidelines on how this can be established.⁶ The ICGP LARC insertion counselling and fitting protocols include information on many aspects of LARC insertion. They can be downloaded from the ICGP website.

Counselling points

Contraindication to IUS use include: recent septic abortion; CVA; MI; current breast, ovarian or endometrial cancer; uterine fibroids that distort the uterine cavity; current PID; chlamydia or gonorrhoea; pelvic TB; severe liver disease; SLE with antiphospholipid antibodies and/or severe thrombocytopaenia.

In some situations (recent breast cancer diagnosis, MI, CVA, etc) copper-bearing devices are recommended over IUS. 

Complications of IUS insertion include: pain on insertion; insertion failure; vasovagal reactions; bleeding; perforation; migration; infection; systemic effects; and expulsion and failure of the device. These should all be discussed prior to prescribing an IUCD. Using a proforma counselling guide will help with this. 

Overall, ectopic pregnancy rates are reduced by using efficacious contraception including IUCDs. Unfortunately though, when a rare failure with an IUCD in situ does occur, that pregnancy may well be ectopic because no IUCD is as effective at preventing tubal implantation as they are at preventing uterine implantation. Ectopic pregnancies should always be considered if a woman with an IUCD has a positive pregnancy test.

Infection is a rare complication of IUCD placement. Perforation of the uterus is a rare but an important known risk and is much more likely to occur with inexperienced inserters and if performed on women who are in the recent post-partum period. It is also more likely when IUCDs are placed under general anaesthesia or in women who are breastfeeding. Women should wait at least 6-8 weeks after spontaneous vaginal delivery and 8-12 weeks after uncomplicated C section before getting an IUCD inserted; even longer if they are also breastfeeding. Bridging contraception with non-oestrogen contraceptive hormones like the POP or DMPA can be offered immediately post partum while arranging IUCD insertion.

Return to fertility is immediate after any IUCD is removed.

In addition to counselling, women considering an IUCD insertion should have a bimanual and speculum exam by the GP who is prescribing the device. 

Training

Insertion technique can be observed and acquired during gynae training or by GP trainees in a training practice where IUCDs are offered. GP colleagues may offer training to one another. The ICGP has been working in conjunction with  some of the maternity hospitals to develop IUCD training clinics but unfortunately Covid precautions have halted that programme for 2020.

The Ballerine copper IUCD

Throughout the world the most popular choice of intrauterine contraception is still a copper coil. The majority of fertile, sexually active Chinese women use a copper device.⁷

In Ireland, copper IU contraceptive devices were reasonably popular until the arrival of Mirena. Copper-bearing devices are the only LARC option that can be inserted as a form of emergency or post-coital contraception and are much more efficacious than either oral ulipristal acetate or levonorgestrel for this purpose. They maintain this high post-coital efficacy for more than five days after the episode of unprotected sex.

Ballerine is an innovative development in IUCD contraception. Unlike traditional framed IUCDs, this device comprises a thin length of ‘Nitinol’ wire with 17 tiny copper beads along its length. The tensile wire is stretched straight inside a very slim introducing tube. Once the tube and device are placed at the fundus, the tube is gently removed and the tensile wire rolls up into a little ball – adapting to the shape of the intrauterine cavity. 

The copper beads provide contraception for five years. Placement should be much kinder as the width of the introducing tube is significantly slimmer than that employed by typical IUCDs. Unlike all other copper IUCDs used in Ireland, the new copper bead device will have an Irish licence and hopefully be available on both the GMS and Drugs Payment schemes. 

Copper as a contraceptive

Copper is toxic to both ovum and sperm, therefore a copper coil works primarily by inhibiting fertilisation.⁷ In addition, the endometrial inflammatory reaction has an anti-implantation effect. The copper ions in the cervical mucus inhibit sperm penetration. The efficacy of copper devices are similar to that of Mirena and Jaydess. 

One Cochrane review, which included 35 randomised controlled trials, concluded that the TCu380A (& the TT380 Slimline) appear to be more effective than other copper devices. The TCu380A has been shown to be highly effective in up to 12 years of use. In contrast there were twice as many pregnancies with the Nova-T 380 as with the TCu380A and so counselling should include this information, bearing in mind that any correctly placed IUCD provides much better contraception than any COCP when the latter is used 21 days on and seven days off.⁸

The Flexi-T 380 has not been assessed in randomised controlled trials. The smaller version of the TT380 Slimline is the MiniTT380 Slimline but it also has yet to be adequately assessed. The placement of copper on the arms of framed devices (banded devices such as TCu380A and TCu380S) improves efficacy. The Cochrane review found that the failure rates for Mirena were similar to that for TCu380A, but preliminary results from the WHO trial suggests that the LNG-IUS may be more effective at five years of use.

The pre-insertion counselling and assessment are the same for IUCD as Mirena/Kyleena/Jaydess but some eligibility criteria are different. Unlike a hormone-containing coil, a copper coil is recommended for use in women with current VTE (on anticoagulants), ovarian cancer, ischaemic heart disease, current or past history of breast cancer, active viral hepatitis, severe decompensated cirrhosis or liver tumours (benign or malignant).Some women prefer a non-hormonal version of an IUD even though they have no medical reasons to avoid an IUS, and that should be their choice. 

Those women who should not routinely be offered a copper device (but may be offered an IUS) include those with heavy or prolonged bleeding; endometriosis; severe dysmenorrhoea; or anaemias such as thalassaemia, sickle cell disease and uncorrected iron deficiency anaemia. Wilson’s disease and copper allergy are also contraindications for copper devices.

Placement procedures are identical for hormone coils and copper coils but most copper devices require a two-handed technique to get the device out of the insertion tube (as opposed to the innovative, one-handed ‘evo-inserter’ device used with Mirena, Kyleena and Jaydess).

Side-effects of copper

The most common side-effect of a copper coil is extra bleeding. This is occasionally a reason for discontinuation so must be addressed at counselling. Although copper IUDs do not have any effect on ovulation they can be associated with shorter luteal phases and therefore shorter cycles. Heavier or longer menstrual periods are common in the first three to six months following Cu-IUD insertion but additional dysmenorrhoea doesn’t seem to be an issue. These longer and heavier bleeding patterns are not harmful unless they are so severe as to cause distress or anaemia. They usually decrease with time. Discontinuation due to bleeding is similar for the different types of Cu-IUDs.  

Implanon NXT

The subdermal Implanon NXT has been available in Ireland since 1999 – although originally it was not radiopaque and was marketed under the name Implanon. During the past 17 years Implanon NXT has proven to be an effective and popular LARC, particularly among younger, nulliparous women. It is a 4cm radiopaque, non-biodegradable implant that contains 68mg of a progestagen called etonogestrel. 

The silastic membrane only allows approximately 65µg/day in week five to six, which quickly decreases to approximately 40µg/day at the end of the first year. It drops again to approximately 35µg/day at the end of the second year and to approximately 25µg/day at the end of the third year.

Etonogestrel is a strong anovulant progestagen and so its primary mode of action is prevention of ovulation; thickening of the cervical mucus and alteration to the endometrium are also observed, adding to its contraceptive activity.⁹

Implanon NXT is licensed for three years contraception but the FSRH issued a Covid guideline earlier this year that suggested the implant could be left in situ for a fourth year when replacement visits were unavailable or ill-advised.⁴

The implant is the most effective contraceptive choice in the world today, ranking above both vasectomy and tubal ligation. Because of etonogestrel’s suppressive action on ovulation and endometrial development it offers non contraceptive benefit for dysmenorrhoea and to some degree endometriosis.

Counselling points for Implanon NXT

The impact of etonogestrel on the endometrium is variable and as a result so are the PV bleeding patterns that emerge. This may be the biggest challenge for Implanon NXT users and the doctors who care for them. On the one hand you are offering a supremely reliable and fully reversible contraceptive product, but on the other hand you must be content to accept a wide variety of possible bleeding patterns. 

Approximately 25% of users will become mostly amenorrhoeic but this may take up to six months to establish and irregular, unscheduled bleeding is not uncommon immediately after insertion. For an unfortunate 33% or so of users, this troublesome bleeding won’t settle on its own and may need further medication to control it.

Medications to control bleeding

Various treatments have been investigated for the management of bleeding problems with progestogen-only implant users. Mefenamic acid and/or the combined pill have been shown to reduce bleeding and the FSRH guidelines recommend a three-month trial of the combined pill (where not contraindicated) taken either as usual or continuously (ie. omitting the pill-free interval). 

Doxycycline alone or in combination with the combined pill has also been shown effective at resolving this spotting, but it may return quickly after discontinuing the support medication. For women who are not eligible to use the combined pill, other remedies have been suggested such as oral progestagens (eg. Cerazette or Azalia) but this is a matter of clinical judgement and off-licence.  

Contraindications

Very few conditions prevent the use of an implant because  etonogestrel does not appear to have any impact on the cardiovascular system. Age is not an issue; it can be offered from menarche to menopause and can be used by smokers or women who are breastfeeding. Women who experience migraine with aura may use the implant (as they can any other non-oestrogen product) but should discontinue if the migraines worsen.

Reasons to avoid Implanon NXT include current or recent breast cancers and serious liver disease such as severe cirrhosis, malignant hepatomata and benign hepatocellular adenomata. Systemic lupus erythematosus with positive or unknown antiphospholipid antibodies is also a precaution. The most common conflict arises from the impact that liver enzyme inducers (LEI) inflict on the metabolism of Implanon NXT. Women using rifampicin, some anticonvulsants (including topiramate as used for migraine) or taking certain antiretrovirals, must avoid the implant until they are 28 days free from the LEI. 

Severe obesity and Implanon NXT

Pharmacokinetic studies of progestagen-only implants have shown an inverse relationship between body weight and etonogestrel serum levels. There were concerns about the duration for which the method was effective in ‘heavier’ women. Licensed for use in women up to 149kg, the FSRH has stated that body weight/high BMI do not appear to lessen the efficacy of Implanon NXT. This is new advice.¹¹

Side-effects

As already mentioned, unscheduled bleeding is the most common side-effect after insertion. Other side-effects included in the SmPC are weight change; low mood and low libido; acne may occur, improve or get worse; and headache has been reported as a possible side-effect, but no causation was shown. 

New recommendations on insertion and removal

The device should be inserted on the inner aspect of the upper arm, 10cm proximal to the medial epicondyle; 3-5cm below the biceps groove and the structures buried in there. This is new guidance as the area just below the biceps groove may contain neurovascular structures best avoided.  A marking guide is supplied by the manufacturer to assist accurate placement. The non-dominant arm is suggested but this is a matter of patient choice. A local anaesthetic should be applied or instilled (cryogesic spray is effective as is subcutanoeus lignocaine). An aseptic but not necessarily sterile technique is required for insertion. The device should be inserted fully under the skin avoiding the fat and muscle below. 

When correctly placed it should be easily palpable under the dermis and indeed the fitting protocol recommends that the patient confirms that she can feel the device under her skin immediately after placement. Practice under supervision is required to gain confidence and although the new insertion device is designed to minimise the risk of placing the implant too deep, this may still occur. 

Placement too deep in muscle or fat doesn’t impair the efficacy of the hormone but it makes removal very difficult. Very deep placements have been reported and injury to the vasculature or nervous system is possible and should be counselled about. If a device is not palpable at any stage, even immediately after insertion, the patient must be put on, or stay on alternative contraception until the device has been located (x-ray or ultrasound).

Removal of a device requires some expertise and should not be undertaken without experience and never in cases where a device is impalpably deep.

Skin atrophy has been reported after placement, which may be an adverse effect of local exposure to the steroid hormone. All of this must be discussed during pre-insertion counselling and printable consent forms can be found on the ICGP website.

Conclusion

There are advantages around using a contraceptive that removes the need for compliance. The LARC options offer enormous benefit for the patient and for the couple, and may have multiple non-contraceptive benefits. Many suitable patients are either unaware of these options or believe themselves (wrongly) to be unsuitable. Advice on LARC should be given to patients. 

References

1. Mc Bride et al. Irish contraception and crisis pregnancy study 2010 (ICCP 2010) A survey of the general population
2. Secura GM et al. The contraceptive CHOICE project: Reducing barriers to long-acting reversible contraception. American journal of obstetrics and gynecology. 2010;203(2):115.e1-115.e7. doi:10.1016/j.ajog.2010.04.017.
3. Trussell J. Contraceptive efficacy. In: Hatcher RA, Trussell J, Stewart F, Nelson A, Cates W, Guest F, Kowal D. Contraceptive Technology: Nineteenth Revised Edition. New York, NY: Ardent Media, 2007.
4. Progestogen-only Injectable contraception Clinical Effectiveness unit December 2014 (Updated March 2015) http://www.fsrh.org/pdfs/CEUGuidanceProgestogenOnlyInjectables.pdf
5. The effects of the levonorgestrel intrauterine system (Mirena coil) on endometrial morphology V Phillips, C T Graham, S Manek, W G McCluggage J Clin Pathol 2003;56:305–307
6. http://www.fsrh.org/pdfs/CEUProductReviewJaydess.pdf
7. Wang D and Altmann Dan R. Socio-demographic determinants of intrauterine device use and failure in China Hum. Reprod. (2002) 17 (5): 1226-1232 doi:10.1093/humrep/17.5.1226
8. French R, et al. Hormonally impregnated intrauterine systems (IUSs) versus other forms of reversible contraceptives as effective methods of preventing pregnancy. Cochrane Database Syst Rev 2004; 3: CD001776.
9. National Medicines Information Centre. St James’s Hospital, Dublin 8. Volume 16, No 4, 2010 
10. FSRH.org. FSRH Guideline (April 2019) Overweight, Obesity and Contraception. April 2019