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Abstract

Cardiac disease is the main cause of maternal mortality in the UK; therefore, accurate and appropriate contraceptive advice for women with cardiac disease is an essential part of any consultation. All females should be counseled regarding pregnancy and contraception before they become sexually active, with information tailored to their diagnosis and risks of a pregnancy. In this review, we discuss current clinical recommendations and practice in a number of different cardiac conditions, including congenital heart disease, as well as highlighting future developments and challenges with contraception in women with cardiac disease.

Keywords

combined hormonal contraception congenital heart disease contraception preconception counseling progesterone-only contraception

Cardiac conditions, including congenital heart disease, cardiomyopathy, ischemic heart disease, aortic pathology and pulmonary hypertension, contribute to cardiac disease being the main cause of maternal mortality in the UK [1]. For women with heart disease, contraception may not simply be a method of convenient spacing of pregnancies, but a way in which to allow preconception planning and to avoid a high-risk or life-threatening pregnancy.

Provision of appropriate and effective contraceptive advice to all female cardiac patients is paramount and should be an integral part of each consultation even prior to a patient becoming sexually active. Medical professionals must be aware of accurate and appropriate information regarding pregnancy and contraception specific to patients with cardiac disease.

Giving appropriate contraceptive advice to women with heart disease requires a thorough understanding of which contraceptive methods are safe and efficacious for each individual's cardiac condition. Unfortunately, many contraceptive specialists lack appropriate knowledge of cardiology (especially complex congenital heart disease), and many cardiologists know little regarding the range and efficacy of available contraceptive methods. As a result, the very women who most need safe and effective contraception may either be denied it, risking pregnancy, or be given contraceptives that increase their cardiac risk.

There is little published evidence regarding contraception in patients with cardiac disease and this review summarizes current clinical recommendations and practice, as well as outlining ongoing challenges [2 –4].

General principles for young women with heart disease

The outlook for children born with congenital heart disease continues to improve as a result of advances in pediatric cardiac surgery, catheter interventions, medical and perioperative management and imaging techniques. Most patients are now expected to live to adulthood, leading to a significant increase in the population of adults with congenital heart disease [5 –7]. Half of these patients are female and may want to consider becoming pregnant at some stage.

All adolescent girls with cardiac disease should be counseled regarding sexual health, contraception and pregnancy before they become sexually active. Advice should be offered by both specialists in Adult Congenital Heart Disease and in Family Planning, and should involve a discussion regarding potential maternal and fetal risks. Discussions must be sensitive to the patient's developmental stage [8]. The presence of parents or carers may prevent any fruitful discussion so opportunities must be given to allow the patient to ask questions in their absence. Discussions and advice given must be carefully documented in patient notes.

Summary

All female patients should be counseled regarding sexual health, pregnancy and contraception before they become sexually active;

With advances in treatment, a large number of patients with congenital heart disease are surviving into adulthood and may wish to become pregnant.

Types of heart disease

Patients with cardiac disease are not a uniform group and include not only those with congential heart disease who may have undergone a number of surgical procedures but also those with cardiomyopathy, diseases of the aorta, including Marfan's syndrome, rheumatic heart disease, pulmonary vascular disease and, ever increasingly, those with ischemic heart disease. The discussions regarding the most effective and appropriate contraception should include an informed discussion regarding the risks of a potential pregnancy, which may be as high as 50% in patients with pulmonary hypertension, or no different from that of the general population, such as in a patient with mild pulmonary stenosis [2,3,9].

Types of contraception

The WHO classification places contraceptives into four groups relating to their use in clinical conditions and this can be adapted to cardiac conditions ( Table 1 ) [10].

Table 1.

WHO classification of risk from contraceptive use in cardiovascular disease.

WHO class	Eligibility for contraceptives with medical conditions	ABCD classification
1	No restriction for use	Always usable
2	Advantages of method generally outweigh theoretical or proven risk	Broadly usable
3	Theoretical or proven risks generally outweigh advantages	Caution/counseling
4	Unacceptable health risk	Do not use

There are a number of contraceptives suitable for each cardiac condition. Each patient should have a contraceptive choice tailored to the relative importance of the following factors:

Contraceptive efficacy and the risks of a pregnancy with failure

Thrombotic and hypertensive risks of estrogen components

Bleeding risks with administration or menstrual disturbance

Insertion difficulties, including risk of infection or vasovagal with insertion

Other potential side effects

Very few women use a contraceptive ideally and the risks of failure vary between different methods [2,11]. Typical failure rates of contraceptives are shown in Table 2. Only the most reliable methods of contraception should be used by cardiac patients with increased risks of pregnancy (class 3 and 4) [12].

Table 2.

Failure rates of contraceptive methods.

Contraceptive technique	Number of women becoming pregnant within 1 year of use (%)
No method	85
Condom (male)	15
Condom (female)	21
Combined oral contraceptive pill	8
Standard progesterone-only pill	10
Cerazette®*	0.4
Depo-Provera®	3
Implanon®	0.05
Intrauterine system: copper	0.8
Mirena® intrauterine system	0.1
Female sterilization	0.5
Male sterilization	0.15

The data for Cerazette are from a different source than the other methods on the table, so its efficacy may not be directly comparable with the other methods. However, it is likely to be at least as efficacious as the combined oral contraceptive pill. Adapted from [11].

Barrier methods

These methods are safe for all cardiac patients and additionally protect against sexually transmitted diseases. However, male and female condoms should not be recommended as an effective method of contraception as they are user dependent and the failure rates may be up to 5%. Therefore, they should not be used by women in whom a pregnancy is not recommended.

Hormonal methods

Combined hormonal methods

The combined oral contraceptive pill (COC) is an effective and popular form of contraception. However, there are a number of risks to women with heart disease as a result of the arterial, venous and cardiac thrombosis risks of the estrogen component [13,14]. Any additional comorbidity, such as diabetes, smoking, hypertension, obesity or migraine with aura, increases the risk of ischemic stroke. This form of contraception is WHO class 4 for patients with cyanotic heart disease, a Fontan circulation, coronary artery disease, impaired left ventricular function (left ventricular ejection fraction < 30%), pulmonary hypertension, patients with Bjork Shiley or Starr Edwards metallic heart valves and patients with a dilated left atrium (>4 cm). COC is also contraindicated in women with right to left shunts due to cyanotic heart disease because of the risk of paradoxical embolus. Alternative methods of effective contraception should be recommended in these cases, as described below.

Therefore, these women with cardiac conditions that are prothrombotic may be at particular risk and hence should not be recommended COC ( Table 3 ). This includes patients with risk factors for ischemic stroke or heart disease, such as hypertensive patients.

Table 3.

Estrogen-containing contraceptives contraindicated as a result of thrombotic or paradoxical embolus risks.

WHO 1: always usable	WHO 2: broadly usable	WHO 3: caution in use	WHO 4: do not use
Thrombotic risk
Minor valve lesions	Most tissue prosthetic valves	Bileaflet mechanical valve	Other mechanical valves: Starr Edwards, Bjork Shiley
Mild pulmonary stenosis	Mild uncomplicated native aortic or mitral valve disease	Previous thromboembolism	Any mechanical tricuspid valve
Simple congenital lesions repaired with no sequelae		Atrial arrhythmia e.g., atrial flutter or fibrillation	Dilated cardiomyopathy or severe left ventricular dysfunction of any cause
Simple congenital lesions repaired with no sequelae			Pulmonary hypertension
Simple congenital lesions repaired with no sequelae	Hypertrophic cardiomyopathy	Dilated left atrium	Fontan circulation
Simple congenital lesions repaired with no sequelae			Previous coronary arteritis
Paradoxical embolism	Minor congenital heart defects e.g., small left to right shunts	Unoperated atrial septal defect and other left to right shunt with potential for reversal	Cyanotic heart disease Pulmonary arteriovenous malformation

Patent foramen ovale (PFO) is a normal variant, occurring in up to 20% of the population and is undiagnosed and asymptomatic in the majority [15]. Patients who have a PFO diagnosed following an embolic event should be advised against using the COC and other alternatives should be considered. For those women whose PFO is an incidental finding, there is a theoretical risk of paradoxical embolus and hence they should probably consider alternative methods. However, there is no evidence for routine screening for PFOs in patients wishing to use the COC.

Additionally, patients taking warfarin require careful monitoring of their INR because of the combined effect of estrogens and progestogens on warfarin metabolism. Careful INR monitoring is recommended, particularly when initiating any hormonal contraception since the effect of warfarin is antagonized by estrogen and progestogens.

If patients on anticoagulants develop breakthrough bleeding, close collaboration between cardiologists and family planning physicians is important to enable safe discussion regarding alternative therapies.

More recent combined non-oral contraceptives include EVRA®, a skin patch, and Nuva Ring®, a vaginal ring. They are not widely available but are licensed worldwide [16 –18]. With the combination of hormonal therapy, the same risks will apply as for the COC.

Progestogen-only methods Progestogen-only contraceptive methods are the method of choice in women with conditions that carry an increased risk of venous or arterial thrombosis or of paradoxical embolism because they are not associated with a significantly increased risk of arterial or venous thrombosis. They are generally safe for all patients with cardiac disease ( Table 4 ). However, progestogens can interact with warfarin metabolism and hence careful INR monitoring is recommended to ensure that it remains therapeutic.

Table 4.

Summary of progestogen-only preparations.

Contraception	Efficacy	Menstrual effects	Cardiac risks
Progestogen-only pill ‘mini pill’	+	Variable: irregular bleeding <=> amenorrhorea	Safe, but not very effective
Cerazette®	++++	Variable: irregular bleeding <=> amenorrhoea	Safe
Levonelle®	+++	–	Safe
Depo-Provera®	++	Irregular bleeding then often amenorrhea	Safe
Mirena® intrauterine system	+++++	Irregular bleeding then often amenorrhea	Risk at insertion
Implanon	++++++	20% amenorrheic, irregular bleeding	Safe

++++++; Very effective; +: Less effective.

Some progestogen-only methods cause irregular menstrual bleeding, which may be prolonged, making the method unacceptable. Others ultimately induce oligomenorrhea, which is often an advantage for women on warfarin. These methods include:

Oral preparations, such as progestogen-only pills (POPs), ‘mini pill’, the new progesterone-only pill Cerazette®, and emergency contraception (e.g., Levonelle®);

Long-acting preparations, such as the depot injection Depo-Provera® (medroxyprogesterone acetate), the Mirena intrauterine system (IUS; levonorgestrel) and Implanon® subcutaneous progestogen implant (etonogestrel).

Progestogen-only pills: ‘mini pill’

Although safe in cardiac patients, this form of contraception should not be recommended for patients with classes 3 and 4 cardiac disease because POPs have a low efficacy; they do not inhibit ovulation and must be taken at the same time each day. If taken more than 3 h after the required time, the risk of contraception failure increases (WHO class 3 and 4).

New progesterone-only pill: Cerazette

Cerazette (Organon, Cambridge, UK; desogestrel 75 μg) is a newer highly effective POP that results in anovulatory failure and the risk of contraceptive failure does not increase until 12 h after due time. Hence it is appropriate for patients with cardiac disease [19]. Cerazette is the prodrug for the progestogen released by the Implanon implant, and can be utilized as a trial for the nonbleeding side effects prior to implant insertion. It is at least as effective as the COC and is an ideal method for patients wishing to use an oral method.

Emergency contraception: Levonelle

This form of emergency ‘morning after’ pill can be used by all cardiac patients. The failure rate is up to 1% if used within 72 h of unprotected sexual intercourse. Side effects include nausea, vomiting and dizziness. Patients taking warfarin should have an INR checked within 48 h of taking levonelle because of the enhancing effects on warfarin.

Depot injection: Depo-Provera

Depo-Provera is a deep intramuscular injectable contraceptive that lasts 12 weeks and is very effective. However, after a short period of usage there may be a rapid return to fertility if injections are not continued. Patients on anticoagulants may suffer hematomas at injection sites. Women may become amenorrheic with continued use, which may be beneficial in those patients with menorrhagia who take warfarin or have cyanotic congenital heart disease. Long-term use of Depo-Provera may result in a hypoestrogenic status and have implications for patients at risk of bone mineral density and ischemic heart disease [20].

Mirena intrauterine system

The Mirena intrauterine hormone-releasing device is inserted into the uterus using cervical dilatation and is extremely effective, being superior to sterilization and requiring replacement every 5 years. Most women become amenorrheic, which may be advantageous. It may be inserted in nulliparous women but up to 5% of patients suffer a vasovagal reaction with insertion, which may result in serious cardiovascular collapse. As a result, the use of the IUS is not recommended in patients with pulmonary vascular disease or a Fontan circulation, where a vasovagal reaction may prove fatal (WHO class 3 risk). It is also not recommended in patients who have a high risk of endocarditis, although the risk appears to be confined to the time of insertion and is lower than that associated with the traditional copper coil. Women should be screened for sexually transmitted infections before insertion or treated empirically. Prophylactic antibiotics should be administered for insertion to minimize the risk of infection and the device should be replaced after 5 years.

Implanon subcutaneous progestogen implant: Implanon

The Implanon subdermal implant is as effective as sterilization, is well tolerated and has no cardiac contraindications. It is inserted subdermally in the nondominant arm by experienced operators using local anesthetic. There is less risk of hematoma formation and fewer side effects than with the Depo-Provera. Approximately a fifth of patients become amenorrheic. Removal and replacement is required after 3 years.

Bosentan effects on hormonal contraception

Patients with pulmonary hypertension carry the highest risk of pregnancy and hence effective contraception is essential [2,3]. Bosentan, an endothelin antagonist and enzyme inducer that is used in such patients may reduce the efficacy of the POP mini pill, Cerazette, Levonelle and Implanon contraceptives [21]. There is no effect of bosentan on Depo-Provera or the Mirena IUS. Patients on bosentan who are unable to use Depo-Provera or the Mirena IUS should use double-dose Cerazette or Levonelle, respectively, and additionally take Cerazette to improve efficacy when using Implanon. These patients should not use the POP mini pill.

Summary

Combined hormonal methods are not recommended for patients with heart disease;

Progesterone-only forms of contraception are safe for all cardiac patients;

Warfarin therapy metabolism is affected by progestogens;

Bosentan may affect some forms of hormonal contraception.

Copper intrauterine systems

Copper intrauterine coils are inserted after cervical dilatation but only require replacement after 5–10 years and hence may be appropriate for some patients with cardiac disease. Although the risk of vasovagal syncope is less than with the Mirena IUS, there is a risk of cardiovascular collapse with cervical dilatation and also a risk of menorrhagia.

There is also a risk of infection with insertion, which is higher than with Mirena, and patients must receive prophylactic antibiotics. Women should be screened for sexually transmitted infections before insertion or treated empirically.

Thus, this method of contraception is not recommended for patients with a high risk of cardiovascular collapse with vasovagal syncope (e.g., a Fontan circulation), a high risk of endocarditis or those receiving warfarin for risks of menorrhagia (e.g., prosthetic metallic heart valve).

Sterilization

There are a number of risks associated with sterilization, including the surgical procedure per se, the potential failure rate, as well as the psychological effect on the patient (WHO class 2). The surgical and anesthetic risks include those from the general anesthetic, laparoscopic techniques using positive-pressure ventilation, abdominal inflation with risks of paradoxical emboli and head-down tilt and vagal reactions with local anesthetic. Although sterilization may be performed simultaneously with cesarean section, failure rates are higher than when performed at a separate sitting [22].

Newer hysteroscopic sterilization techniques, ESSURE™, with special intratubal stent insertion proximally in the fallopian tube resulting in tubal occlusion by an inflammatory process in 3 months, can be performed using oral analgesia and may result in fewer vagal reactions [23,24]. Further outcome data are awaited.

Vasectomy of the male partner is not ideal and may not be appropriate as he may outlive the woman and wish to father children with a subsequent partner. In addition, the procedure assumes monogamy.

The finality and psychological effect of never being able to have children may be too much, resulting in regret for some female patients and other, equally effective, contraceptive methods discussed above are advantageous in these situations.

Emergency contraception

Emergency contraception should not be used as a regular form of contraception but must be available for those who have not taken appropriate protection against an unplanned pregnancy, particularly in women with cardiac disease.

The three methods available include the combined estrogen/progestogen method (Yuzpe®), single-dose levonorgestrel (Levonelle), which can be used up to 72 h following unprotected sexual intercourse, and the copper intrauterine coil device (IUCD), which can be used up to 5 days following unprotected intercourse. In women with cardiac disease, the single-dose levonorgestrel (discussed previously) is recommended with only a 1% failure rate and better tolerance than the combined hormonal method [25]. Side effects include nausea, dizziness, fatigue and vomiting in a proportion of patients. However, patients taking bosentan (an endothelin antagonist) will need an increased dosage and those on warfarin will have an increased INR level, which should be monitored closely. The copper IUCD should not be used in cardiac patients with pulmonary vascular disease or those with a Fontan circulation for fear of cardiovascular collapse associated with insertion.

Termination of pregnancy

The availability of facilities for urgent termination of pregnancy for women with medical conditions where pregnancy puts the patient's life at risk is essential. Medical termination (oral mifepristone followed by a prostaglandin 1–2 days later) can be safely performed in cardiac patients and, if successful, avoids the need for general anesthetic. However, there may be significant bleeding and pain, which may result in cardiovascular compromise in some cardiac conditions, such as severe left-sided obstruction (e.g., mitral stenosis, aortic stenosis) or pulmonary vascular disease, and sometimes the termination may not be complete or take several days to complete.

Surgical termination of a pregnancy can be performed by suction (up to 14 week' gestation) or by dilatation and evacuation (up to 24 weeks) with prior cervical priming using a prostaglandin. Regional blockade and analgesia can be utilized but there is a risk associated with the surgery and the cervical dilatation.

It is essential that skilled operators with a knowledge of cardiac disease perform these procedures in specialist centers with support from cardiological colleagues in patients with cardiac disease.

Future perspective

More women with more complex congenital and acquired heart disease are surviving to child-bearing age and will need early and informed family planning counseling. We anticipate that further non-oral contraceptives will become licensed and more widely available, enhancing choice for some women. Further pharmaceutical developments are needed to ensure that all women have a wide selection of family planning methods, as well as minimizing drug interactions.

Executive summary

An ever-increasing number of women with congenital or acquired heart disease are reaching child-bearing age.

These women must have appropriate and informed contraceptive counseling before they become sexually active to avoid unplanned high-risk pregnancies.

Many highly efficacious contraceptive methods are available and the precise choice should be tailored to each individual patient and their needs.

Emergency contraception must be easily accessible in the event of unprotected sexual intercourse, as should facilities for termination where pregnancy places a woman's health at risk.

Footnotes

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

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Contraception in Women with Cardiac Disease

Abstract

Keywords

General principles for young women with heart disease

Summary

Types of heart disease

Types of contraception

Barrier methods

Hormonal methods

Combined hormonal methods

Progestogen-only pills: ‘mini pill’

New progesterone-only pill: Cerazette

Emergency contraception: Levonelle

Depot injection: Depo-Provera

Mirena intrauterine system

Implanon subcutaneous progestogen implant: Implanon

Bosentan effects on hormonal contraception

Summary

Copper intrauterine systems

Sterilization

Emergency contraception

Termination of pregnancy

Future perspective

Footnotes

References