15 Questions - Reproduction and Contraception Health with Lupus

(September 2011) Pregnancy and contraception health often become crucial questions for young women with lupus. For September, the LFA invites you to join us for the "Reproduction and Contraception Health with Lupus" Q&A with guest expert Dr. Lisa R. Sammaritano. This is your opportunity to ask questions and learn from an expert. 


1. What kind of birth control is safe to use and recommended for someone with SLE?  Could you please address the difference between estrogen and progesterone contraceptives, what are the pros and cons and potential side effects?  Brooklyn, NY

Contraceptive options for women with SLE depend on an individual patient’s medical history and autoantibody test results. In general, barrier methods of contraception (condoms or diaphragms) are safe for all patients and provide some protection against sexually transmitted diseases, but they are not as effective as intrauterine devices or hormonal methods and are less convenient to use.

Intrauterine devices (IUD’s) may be used by most patients with SLE. They are inserted into the uterus by the gynecologist, and may contain either copper or progesterone. Copper IUD’s can remain in place for up to 10 years and contain no hormones, but often increase menstrual cramping and blood flow. Progesterone IUD’s remain in place for up to 5 years and usually decrease cramping and blood flow: they are a good choice for patients on blood-thinning medications such as warfarin. The progesterone in the IUD tends to have only a local effect on the uterus, so common progesterone effects such as breast tenderness or mood change are rare. IUD’s available today are unlikely to be associated with infection risk, and OB-GYN’s now offer this option to younger women who have not yet completed childbearing (unlike older IUD’s, no longer available, that increased risk of uterine and tubal infections). There may still be a slight increase in infection risk with IUD placement, so SLE patients who are on aggressive immunosuppressive medications should discuss this with their rheumatology and OB-GYN doctors.

Hormonal methods of birth control vary in how they are administered, and in whether they contain both estrogen and progesterone or progesterone alone.  The estrogen-containing methods include pill, patch and vaginal ring. For patients with lupus, the concern with estrogen-containing birth control methods has centered on two risks: increase in lupus flare and risk of thrombosis (blood clots). Recent studies show that for a patient with stable, inactive lupus there is no significant risk of lupus flare with estrogen-containing birth control pills. Risk of thrombosis with oral contraceptives is related to presence of antiphospholipid antibodies (aPL): these autoantibodies are present in one-third of lupus patients and further increase risk of blood clots. Patients with aPL (or any history of blood clots) should not receive estrogen-containing medications.

The progesterones used in progesterone-only forms of birth control (including the progesterone pill, depo-medroxyprogesterone (DMPA) injection, and progesterone-IUD) are not associated with a significant increase in risk of blood clots, so these are good options for lupus patients with aPL or any history of previous blood clots. The progesterone-only pill is slightly less effective than combined oral contraceptives and must be taken the same time every day, and breakthrough bleeding is common. The DMPA injection works well and is convenient, but can lead to osteoporosis when used for prolonged periods so is not a good long-term contraceptive for lupus patients who maybe at greater risk for osteoporosis due to corticosteroid use. The progesterone-IUD is a good option: it is convenient, does not increase risk of osteoporosis, and usually decreases cramping and menstrual blood flow. 

The brief descriptions above should serve as a basis for discussion between a patient and her OB-GYN and rheumatologist: every patient is different and there may be additional factors that impact the decision-making process.

2. I have mixed connective tissue disease and have always been told in the past that plaquenil is unsafe during pregnancy and I would have to stop before trying to conceive.  My rheumatologist said at my last appointment that it is now safe to take during pregnancy. Brisbane, Australia

Your rheumatologist is in agreement with most rheumatologists worldwide – there has been a significant change in outlook on safety of hydroxychloroquine (plaquenil) during pregnancy over the last several years. In the past, rheumatologists had theoretical concerns that eye or ear toxicity could affect the developing fetus. Over the past several years, studies of pregnant women treated with hydroxychloroquine have not demonstrated abnormalities in the offspring and show that women who continue this medication during pregnancy are less likely to flare than those who discontinue it before pregnancy. Continuing hydroxychloroquine during pregnancy appears to be both safe and beneficial for patients with connective tissue disease.

3. As most lupus patients I am on several medications just to maintain my day to day functionality (Medrol, Plaquenil, CellCept, Celebrex (prn), Nexium, Evoxac, and Coumadin).  Some of these medications would need to be discontinued prior to getting pregnant as my doctor has mentioned, but what happens if I flare and am unable to be off or lower some of the dosages I take...would that mean that I cannot have children?  New York, NY

Your question is an important one and brings up a common concern for many patients with SLE, especially those with significant disease activity requiring immunosuppressive medications or a history of blood clots requiring anticoagulation therapy. Planning and preparation for pregnancy will be more complicated and more time-consuming for you than for a lupus patient whose disease is milder and requires less medication.  This does not mean that you will be unsuccessful in your attempt to have children: most lupus patients are able to eventually have successful pregnancies. While rheumatologists often tell patients about the safety risks of medications they are on – and the need to discontinue certain medications for pregnancy – we do not always emphasize the alternatives until the time comes to make the necessary changes.

Specific options depend on the individual patient in terms of her disease activity and severity. In general, for patients unable to taper off mycophenolate mofetil (CellCept) we usually recommend substituting azathioprine (Imuran), an immunosuppressant commonly used in pregnancy. Warfarin (Coumadin) must be replaced with a safer anticoagulant, usually a form of heparin (often enoxaparin, or Lovenox) that would be injected twice daily to provide continued protection from recurrent clots. Similarly, other medications may have safer, if slightly less effective, alternatives for use during pregnancy. Because of the importance of quiet disease for at least 6 months before pregnancy, patients should change over to azathioprine and be followed carefully for 3 – 6 months on this medication before they start trying to conceive. If the lupus flares on azathioprine, then we must change back to the mycophenolate mofetil until disease stabilizes and put plans for pregnancy on hold. Cyclosporine, another immunosuppressive, is a less common alternative for pregnancy treatment in patients who flare (or do not tolerate) on azathioprine.

4. I'm 25 years old and I have systemic lupus erythematosus and I've never been pregnant. Should I be concerned about having babies before certain age to avoid complications?  Los Angeles, CA

The most important factors relating to successful lupus pregnancy are not age-related. Lupus-related factors that affect pregnancy outcome include ongoing lupus disease activity, presence of certain autoantibodies (including antiphospholipid (aPL) and anti-Ro (SS-A) and anti-La (SS-B) antibodies), level of kidney function, and medication effects.

Lupus pregnancies are more likely to be successful for mother and child if disease is quiet for at least six months prior to conceiving. Antiphospholipid antibodies increase risk of miscarriage, especially if present at high levels (or in patients with a history of previous miscarriage). Evaluation by the rheumatologist and OB-GYN will guide therapy depending on pregnancy history and antibody test results (generally daily low dose aspirin is recommended for patients during a first pregnancy).

Anti-Ro (SS-A) and anti-La (SS-B) antibodies are risk factors for neonatal lupus erythematosus (NLE), a condition in the newborn that may include low blood counts, rash, liver test abnormalities and congenital heart block (CHB). The only permanent complication is CHB and this is rare, occurring in about 2% of babies of anti-Ro (SS-A)/La (SS-B) positive mothers.

Previous kidney inflammation that has resulted in lowered kidney function may affect the course of the pregnancy:  patients with kidney function that is less than 50 – 60% normal are at greater risk for further kidney problems during pregnancy (the kidneys must work harder during pregnancy to filter the greater blood volume, which stresses previously damaged kidneys). Finally, certain lupus medications must be altered or discontinued due to issues with fetal safety.

You shouldn’t feel pressured to become pregnant at age 25 just because you have lupus. However, while lupus issues are most important in deciding on timing of pregnancy, it certainly makes sense to be aware of age-related fertility issues and factor this into your plans. Lupus patients do not have a greater risk of infertility (unless treated with cyclophosphamide), but any woman may encounter difficulty in getting pregnant. It may add another layer of difficulty to planning for lupus pregnancy if a woman is in her mid-to-late thirties when she starts trying for the first time.

5. I am getting married in 1 month and my fiancée and I are talking about trying to get pregnant within the next 6 months. I am just wondering what steps I need to take in order to do this the right way. I am currently taking CellCept (although I have been told that CellCept is not a good one to get pregnant on, so I will have to change to a different medicine) and I have an IUD.   Elmira, OR

It is important to start planning now - as you are doing - since pregnancy in a patient with lupus is best undertaken after an evaluation for disease activity, presence of certain autoantibodies, measurement of kidney function and medication review. Pre-conception discussions with your rheumatologist and OB-GYN are critical in planning for a successful pregnancy.

If your disease has been quiet for 6 or more months, and you have normal or near-normal kidney function, then the next step is planning medication changes. CellCept is not considered safe for pregnancy and you will likely need to switch over to azathioprine, another immunosuppressive medication commonly prescribed in pregnancy, and be observed on that for 3 – 6 months to assure that your disease remains controlled. An alternative is discussing with your rheumatologist whether he or she feels you might safely taper off the CellCept (over about 6 months) instead of substituting azathioprine.  After that, you can arrange for removal of the IUD and begin trying to conceive.

If you have moderate or high levels of antiphospholipid antibody (associated with an increased risk of miscarriage), you may benefit from taking a low dose aspirin daily during your pregnancy and having ultrasound and fetal heart rate monitoring. If you are positive for anti-Ro(SS-A) and/or anti-La(SS-B) antibodies (about 1/3 of women with lupus are), you should have fetal echocardiograms done starting at 16 weeks to monitor for the (unlikely) development of congenital heart block.

6. I was diagnosed with SLE about a year ago, and now have been diagnosed with Polycystic Ovary Syndrome.  I was wondering if you think that there could be any connection between the two?  St. Louis Park, MN

I am not aware of any relationship between these two disorders and a quick search of the medical literature does not suggest any significant interrelationship. Your lupus (including possible presence of antiphospholipid antibodies) may influence plans for treatment of the PCOS however if estrogen-containing medications are suggested, so it is important to discuss any treatment recommendations from your OB-GYN with your rheumatologist.

7. How does Lupus affect libido and is there anything that a person with Lupus can take to help libido?  Killeen, TX

Loss of libido may be seen in association with any chronic inflammatory disease including SLE. Optimal control of disease activity may be helpful with restoring libido. There are also secondary factors that contribute to decreased libido in patients with SLE including medication effects (especially antidepressant and beta-blocker medications), depression, fatigue, and body-image issues. It is worthwhile to ask your rheumatologist to check levels of thyroid hormones and DHEA (a mild male sex hormone) to see if these are low. Studies of DHEA treatment in patients with lupus suggest improvement in lupus symptoms as well as possible improvement in libido. For post-menopausal women, estrogen therapy may help with loss of libido (this is only appropriate for patients with stable inactive SLE without antiphospholipid antibodies); this benefit, however, must be balanced against the known increased risk of cardiovascular disease and breast cancer.

8. What are some complications associated with lupus in expectant mothers? And is there a higher incidence of endometriosis with females?  Worthington, KY

There are numerous complications associated with lupus in expectant mothers, for both and mother and the child. Maternal complications include increased risk of lupus flare during and immediately after pregnancy, as well as possible worsening of kidney function in patients with abnormal kidney function pre-pregnancy. 

Pregnancy complications that may affect the fetus as well as the mother include increased risk of high blood pressure, preeclampsia / eclampsia, and placental dysfunction leading to preterm delivery or fetal loss (antiphospholipid antibodies are primarily associated with risk of placental insufficiency and fetal loss).  Preterm birth and/or growth restriction, when severe, can result in long-term neuron-developmental and pulmonary disease.

Neonatal outcome is also affected by presence of anti-Ro (SS-A) and anti-La (SS-B) antibodies in the mother: these cross the placenta and may cause inflammation in the developing fetus, a condition termed neonatal lupus (NLE). The rash, liver function test abnormalities and low blood counts disappear in 3 – 6 months when the maternal antibodies disappear, but congenital heart block is permanent and most affected babies require pacemakers.

Careful pre-pregnancy evaluation and monitoring by both the rheumatologist and OB-GYN doctors can minimize or promptly identify and treat many of these complications. For this reason, it is advisable for lupus patients to be cared for by a high-risk OB-GYN.

Although older studies suggest that endometriosis may be more common in or might be a risk factor for SLE, more recent large-scale studies do not show a relationship.

9. For a patient with lupus nephritis and SLE, is it possible to safely and successfully have a pregnancy or should pregnancy not even be considered?  Would a pregnancy damage the kidneys further?  Lansing, MI

It is possible for a patient with lupus nephritis to safely and successfully have a child, but inadequate kidney function is an important risk factor for further decline in kidney function and possible loss of the pregnancy. It is important to assess both the current activity of the nephritis (presence of active inflammation) and the extent of damage, including filtration ability and amount of urinary protein. Pregnancy is contraindicated if there is current active inflammation. Once it is confirmed that there is no active kidney disease, the level of kidney function is the most important factor in determining which patients with lupus nephritis may be able to safely proceed. If the kidneys are filtering at least 50 – 60% of normal and the amount of protein is not very high than it is reasonable to think about pregnancy.

Even in quiet kidney disease with good function there is a 10 – 20% chance that kidney function will worsen during pregnancy, although this is not usually permanent. Any history of renal disease or dysfunction also puts patients at greater risk for high blood pressure and preeclampsia / eclampsia, which may lead to renal failure and seizures.

For patients with poor kidney function for whom carrying a pregnancy is not safe, it may be possible to undergo in vitro fertilization and implant the embryo in a surrogate. This poses minimal risk to the kidneys and still allows for a biological child.

10. How are lupus flares affected during pregnancy and postpartum?  Does the lupus actively affect the fetus?   I am not speaking genetically, more environmentally ...while in utero.  Delaware, OH

Fear of flare during pregnancy was been the reason that lupus patients were told to avoid pregnancy in past years. Many studies have tried to address how great a risk this really is, with widely varying results: risk of flare in lupus pregnancy ranges from 13 to over 80% depending on the study. Most recent studies suggest a low risk of flare which is less if patients have quiet disease for at least 6 months prior to conception. The postpartum period should be considered an extension of the pregnancy in many ways, as it takes 3 – 6 months for hormone and other changes to return to baseline. Risk of flare is still present during this period. 

The recommended approach is wait to try to become pregnant until lupus has been quiet, and then to follow frequently with the rheumatologist for any manifestation of disease activity during pregnancy. If necessary, patients may be treated with corticosteroid during pregnancy.

Lupus may affect the fetus in several ways. Severe lupus flares have been shown to increase risk of pregnancy loss, so control of disease activity is important for both mother and baby. Kidney disease may also increase risk of pregnancy loss.

Autoantibodies present in some patients may affect the fetus: antiphospholipid antibodies predispose to miscarriage, as well as fetal growth restriction and preterm birth due to placental insufficiency. Prematurity may lead to long term health effects for the neonate including pulmonary, visual and neuro-developmental deficits.  Anti-Ro(SS-A) and anti-La (SS-B) can lead to neonatal lupus which may have long term effects for the 2% of infants in whom congenital heart block develops.

11. I'm not planning on having any children anytime soon as I'm only 18 but I want to know how likely it is that I will have a hard time becoming pregnant/having a healthy child when I do decide to have children. I am anti-Ro positive and my rheumatologist has told me several times that I will have to be very careful when I decide I want to have kids. How likely is it that I will have complications because I am anti-Ro positive?  Edgewood, KY

Lupus doesn’t affect directly fertility, although treatment with cyclophosphamide can decrease fertility and lead to premature menopause (other common immunosuppressives used in SLE such as mycophenolate mofetil and methotrexate do not have this irreversible effect). The impact of cyclophosphamide is greatest in patients who are over age 30 and those who receive higher cumulative doses. Unless treated with cyclophosphamide (or if you have other unrelated fertility problems) your likelihood of conceiving should be about the same as other women of your age.

The presence of anti-Ro (SS-A) is important to be aware of during pregnancy: only women with these antibodies are at risk for having a child with neonatal lupus, a syndrome of inflammation in the fetus and baby resulting from passage of these antibodies through the placenta with resulting effects on the blood counts, liver, skin and heart.

Symptoms associated with the syndrome develop in 15-25% of children born to mothers with anti-Ro (SS-A) antibodies, but are most often temporary. The rash, low blood counts and abnormal liver function tests go away with time as the antibodies are cleared from the baby’s system over the first 3-6 months of life, but the congenital heart block (CHB) is irreversible.

Congenital heart block is the result of damage to the conduction system in the fetal heart caused by inflammation. Electrical impulses are not transmitted properly from the upper part of the heart to the lower part; as a result, the heart beat is too slow to maintain adequate circulation and most babies born with this condition require placement of a pacemaker and the mortality rate is 19%. Fortunately CHB is a rare manifestation of NLE, occurring in only 2% of babies born to anti-Ro (SS-A)/La (SS-B) positive mothers. Although there is not yet a proven preventative treatment for CHB, anti-Ro (SS-A)/La (SS-B) positive mothers are monitored with fetal echocardiograms every 1-2 weeks from 16 weeks onward: if evidence of developing heart block is found, the mother will be treated with a steroid that passes through the placenta (dexamethasone or betamethasone) in an attempt to calm the inflammation and prevent the progression of tissue scarring that leads to the heart block.

12. I am 27 year old female with only blood markers for lupus and have never had any of the physical signs with are present with most patients.  When I was about 22 my original rheumatologist had said that most likely I would be on some form of injectable blood thinner based on my blood ranges for anti-phospholipid antibodies, for that reason I am currently on a baby aspirin a day regimen.  My new rheumatologist, my other quit practicing, said that I would probably be fine just continuing with an increased aspirin dose and not get on an injectable blood thinner. She said that she had seen studies where that higher dose would do the trick. At that time and now I was not pregnant but we are considering it now.  I would just like to know your thoughts on this, whether an increased dose of aspirin will work or injectable blood thinners are better for clotting conditions?  Austin, TX

Recommended treatment of antiphospholipid antibodies (aPL) during pregnancy depend on the individual patient’s clinical history, but there are general treatment guidelines. Risk of fetal loss is greatest with presence of persistent lupus anticoagulant and/or high titer IgG anticardiolipin antibodies. Lower levels or fluctuating levels of aPL confer less risk. 

Treatment recommendations depend on whether a patient has had previous miscarriages (either a single loss after 10 weeks gestation or 3 or more losses at less than 10 weeks gestation). For patients with positive aPL but no history of pregnancy loss (including those in their first pregnancy) most rheumatologists recommend low dose aspirin only. Injectable blood thinners such as heparin are generally used only for patients who have already had a fetal loss.

If a patient has already had a blood clot related to aPL, she must be on heparin throughout pregnancy. Rarely, other factors may lead the rheumatologist or OB-GYN to add heparin even in patients without a history of fetal loss, for example presence of an additional blood clotting risk factor such as factor V Leiden (an inherited clotting risk factor).

Most studies on prevention of antiphospholipid-related pregnancy loss have used low-dose aspirin alone or in combination with a form of heparin: these are the best-studied and most commonly recommended treatments.

13. I have two daughters that should be on birth control, but when I was in my twenties and on birth control. I was diagnosed with lupus.  The doctor said that it had something to do with activating the Lupus.  I am afraid that if they are put on birth control it could activate lupus in my daughters.  Has any research been done in this area?  Tarpon Springs, FL

Use of oral contraceptives has been associated with a very small increase in risk in developing SLE in several studies. However, given the multiple genetic and environmental factors we associate with development of SLE, the risk of SLE in your daughters is quite low. It is unlikely (but not impossible) that oral contraceptives would trigger onset of SLE in your daughters.

It might make sense to have them to be evaluated by their physician for presence of autoantibodies such as ANA and aPL. If the ANA is positive (this occurs in up to 10% of first degree relatives of lupus patients) it may suggest a slightly greater risk for eventual development of SLE, and might weigh against starting oral contraceptives (still a decision for your daughters to make by weighing the risks versus benefits). If any of the aPL tests were positive (anticardiolipin, anti-beta 2 Glycoprotein I or lupus anticoagulant antibodies) then estrogen-containing oral contraceptives should not be given due to increased risk of blood clotting.

14. After 3 1/2 years of trying to conceive, working with specialists and now headed for IVF-my diagnosis is Unexplained Infertility. Is there any way doctors can tell if Lupus may be the cause of this?  Nashville, TN

Lupus patients appear to have normal fertility when compared to the general population unless they have been treated with cyclophosphamide (an immunosuppressive medication most commonly used for kidney or neuropsychiatric disease).  It is unlikely that your lupus is the cause of your fertility problems. There is a higher than usual number of positive ANA and aPL antibodies in otherwise healthy patients with infertility but a causative relationship has not been determined.

15. Can women with lupus take hormone replacement therapy?  Woodbridge, VA

Yes, many (but not all) women with SLE are able to take hormone replacement therapy (HRT). Although widely avoided in the past due to presumed risk of flare, recent studies have found only a small increase in risk of mild flare in SLE patients treated with HRT. The patients in the study had stable inactive disease and did not have antiphospholipid antibodies (aPL), which are a contraindication to use of HRT. 

In the general population, HRT is being used less frequently in the past due to recognition of increased risks of cardiovascular disease and breast cancer. For any peri- or post-menopausal woman it is best to be cautious and use HRT for a limited period of time only if necessary to treat vasomotor symptoms like hot flushes. Vaginal atrophy or dryness can be addressed with local estrogen therapy. Women with SLE who have inactive, stable disease and low or negative aPL are the best candidates for short-term HRT for relief of vasomotor symptoms.