Tip: If you or your spouse has multiple sclerosis and are planning to have a child, consider planning pregnancy during the spring, summer and fall and take vitamin D during pregnancy...click to read our physician blog on the risk of passing MS on to a child...
Multiple Sclerosis: Pregnancy Q&A (Source: Cleveland Clinic)
1. Does having multiple sclerosis affect my fertility?
Having multiple sclerosis (MS) does not seem to affect fertility in any significant way. Women with MS have a normal fertility rate and no increase in fetal abnormalities or spontaneous miscarriage. The standard immunomodulating agents for MS (the interferons and copolymer) do not affect fertility itself, although they are not recommended during pregnancy. Mitoxantrone (Novantrone®), an FDA-approved medication for progressive MS, may affect fertility in the same way that other chemotherapies may. It is probably a good idea to discuss fertility with your neurologist before going on such medications.
2. Does having children alter the long-term course of multiple sclerosis?
In the past doctors often advised women with MS to avoid getting pregnant. It is unclear how the doctors decided on this advice, but over the past 20 years we have learned a lot about the interaction of pregnancy and MS. We now know that having children does not have a major impact on the course of MS in the long term. One study from Sweden in the 1990's indicated that having children may, in fact, improve the course of MS in the long run. A well-designed follow-up study of pregnancy in MS (the PRIMS study) showed that while the relapse rate increased post-partum, there was no change in the overall course of MS during a three-year follow-up period.
3. How does pregnancy affect the short term course of multiple sclerosis?
There are many follow-up studies of women with MS going through pregnancy. We now know that during pregnancy there is a significant reduction in attacks, particularly in the third trimester. In the PRIMS study, the relapse rate dropped 70% during the third trimester. We don't know yet which changes during pregnancy cause this reduction, but there are many factors that are altered in pregnancy. There are elevated hormonal levels during pregnancy.One of these hormones, estriol, has been shown to reduce MRI activity in women with MS.Other hormones may also be important. We also know that levels of some immune chemicals such as IL-12 and TNF-alpha are reduced during pregnancy. In addition, cells that make interferon-gamma, an interferon that worsensMS, are reduced during pregnancy compared with the post-partum period. Finally, there appears to be an increase in certain immune cells (regulatory T cells) that may also suppress MS activity in pregnancy. These and other changes may help protect against attacks of MS.
4. What about after pregnancy?
We know that in the first three to six months after delivery there is an increased risk of MS attacks. The overall rate of attacks during the pregnancy and post-partum period does not differ from the attack rate before and after the pregnancy year. In the largest prospective study of pregnancy in MS (the PRIMS study), 72% of women followed did not experience a relapse during the first three months post-partum. There are no specific factors that predict a relapse after delivery.
5. Is the outcome of pregnancy any different for a mother with MS?
Using data from a Medical Birth Registry in Norway, Dahl and colleagues found that mothers with MS had a higher proportion of small-for-gestational age babies. They also had a higher rate of induction of labor and operative interventions during delivery. Another study of mothers who had become pregnant while on interferon therapy showed an increased rate of miscarriages and still births compared with controls. This study also found low birth weight compared with controls. In another study from Seattle, mothers with MS were twice as likely to need to be re-hospitalized compared with controls; however, in this study, there was no increase in small-for-gestational age infants, preterm infants, or infants with fetal malformations. Differences among such studies may reflect different populations, obstetrical practices,and differences in the MS disease course. In general, these differences were not major and did not appear to affect the long-term health of the baby.
6. What about breastfeeding?
Studies done in the 1980s showed that breastfeeding does not have an impact on MS. As with any medication, there is little or no information on the standard MS medicine and breastfeeding, so, in general, it is best to avoid medications during breastfeeding if possible. How long to breastfeed before restarting immune modulating medications is an individual decision.
7. Are immunomodulating medications okay to use in pregnancy?
There are a variety of registries that have reported on women using immunomodulating medications in pregnancy. The interferons as a class (Avonex®, Betaseron®, Betaferon®, Rebif®)are contraindicated in pregnancy. In animal models they cause miscarriages. In women who have become pregnant while on these agents, there is an increased risk of still birth and miscarriage as well as small-for-gestational age babies. Limited data on copolymer (Copaxone®)indicates that it has little or no impact on infant outcomes. In general, it is recommended that women stop such medications about three months before trying to become pregnant to avoid problems during pregnancy. Chemotherapeutic agents such as mitoxantrone are contraindicated in pregnancy.
8. Will pregnancy affect my MS symptoms?
There are no well-designed studies of symptoms of MS during pregnancy outside of attack rate and progression of MS. Anecdotally, women often feel well during pregnancy, but there are no good measures of this. One study looked at urinary function during pregnancy in MS and showed no effect of vaginal delivery on urinary function after pregnancy in women with MS.
9. Can I have an epidural if I need it?
In the past there were concerns that various anesthetic agents might affect MS negatively, and women were often encouraged to avoid anesthetics such as an epidural. However, the best evidence we have indicates that there is no special risk for an epidural in women with MS. It is an individual choice as to whether or not to have an epidural.
10. What about having a caesarean section?
Prospective studies have shown that in general women with MS are more likely to have a caesarean section than other women.It is unclear why this is. It may reflect a delay in labor in women with muscular weakness. It may reflect heightened concerns by physicians and nurses when caring for a woman with MS. However, what is known is that a caesarean section does not have an impact on the MS course. There is no evidence that having a caesarean section will cause a relapse or progression of MS beyond the already established course of the disease. In addition, there is no evidence for a benefit of caesarean section over vaginal childbirth;each birth decision is an individual one.
11. What are my children's chances of getting MS?
It is known that MS has some genetic features. Children of women with MS have a 3% to 5% lifetime chance of developing MS. In other words, they have an approximately 96% chance that they won't develop MS, or 24 to one odds against having MS.
12. Can I breast-feed after pregnancy?
There is no evidence that breast-feeding is a problem for patients for MS or their children. Breast-feeding may be important for many reasons for the developing child. A major question in women with MS is when to start back on immunomodulating medications. There is no specific timeline for weaning.
13. Can I take steroids if I have a relapse during pregnancy?
The best evidence we have shows that steroids can be used during pregnancy without a major risk to the mother or baby. In general, we try to avoid using steroids during the first trimester,and then use them only when necessary during the rest of pregnancy. Usually they will be needed only when the mother has an attack that affects her ability to function.
14. Should I take anything else after pregnancy?
In general, women who have needed immunomodulating medication before pregnancy are started back on their medication after they finish breastfeeding. One study showed that using IV steroids once a month for the first six months after delivery seemed to reduce the relapse rate compared with controls. However, there was no difference in neurological function or progression, and steroids have their own side effect profile. Using IV steroids or other medications such as IV immunoglobulin after delivery are at present not standard approaches in the United States in the postpartum period.
© Copyright 1995-2009 The Cleveland Clinic Foundation.All rights reserved.
1. Does having multiple sclerosis affect my fertility?
Having multiple sclerosis (MS) does not seem to affect fertility in any significant way. Women with MS have a normal fertility rate and no increase in fetal abnormalities or spontaneous miscarriage. The standard immunomodulating agents for MS (the interferons and copolymer) do not affect fertility itself, although they are not recommended during pregnancy. Mitoxantrone (Novantrone®), an FDA-approved medication for progressive MS, may affect fertility in the same way that other chemotherapies may. It is probably a good idea to discuss fertility with your neurologist before going on such medications.
2. Does having children alter the long-term course of multiple sclerosis?
In the past doctors often advised women with MS to avoid getting pregnant. It is unclear how the doctors decided on this advice, but over the past 20 years we have learned a lot about the interaction of pregnancy and MS. We now know that having children does not have a major impact on the course of MS in the long term. One study from Sweden in the 1990's indicated that having children may, in fact, improve the course of MS in the long run. A well-designed follow-up study of pregnancy in MS (the PRIMS study) showed that while the relapse rate increased post-partum, there was no change in the overall course of MS during a three-year follow-up period.
3. How does pregnancy affect the short term course of multiple sclerosis?
There are many follow-up studies of women with MS going through pregnancy. We now know that during pregnancy there is a significant reduction in attacks, particularly in the third trimester. In the PRIMS study, the relapse rate dropped 70% during the third trimester. We don't know yet which changes during pregnancy cause this reduction, but there are many factors that are altered in pregnancy. There are elevated hormonal levels during pregnancy.One of these hormones, estriol, has been shown to reduce MRI activity in women with MS.Other hormones may also be important. We also know that levels of some immune chemicals such as IL-12 and TNF-alpha are reduced during pregnancy. In addition, cells that make interferon-gamma, an interferon that worsensMS, are reduced during pregnancy compared with the post-partum period. Finally, there appears to be an increase in certain immune cells (regulatory T cells) that may also suppress MS activity in pregnancy. These and other changes may help protect against attacks of MS.
4. What about after pregnancy?
We know that in the first three to six months after delivery there is an increased risk of MS attacks. The overall rate of attacks during the pregnancy and post-partum period does not differ from the attack rate before and after the pregnancy year. In the largest prospective study of pregnancy in MS (the PRIMS study), 72% of women followed did not experience a relapse during the first three months post-partum. There are no specific factors that predict a relapse after delivery.
5. Is the outcome of pregnancy any different for a mother with MS?
Using data from a Medical Birth Registry in Norway, Dahl and colleagues found that mothers with MS had a higher proportion of small-for-gestational age babies. They also had a higher rate of induction of labor and operative interventions during delivery. Another study of mothers who had become pregnant while on interferon therapy showed an increased rate of miscarriages and still births compared with controls. This study also found low birth weight compared with controls. In another study from Seattle, mothers with MS were twice as likely to need to be re-hospitalized compared with controls; however, in this study, there was no increase in small-for-gestational age infants, preterm infants, or infants with fetal malformations. Differences among such studies may reflect different populations, obstetrical practices,and differences in the MS disease course. In general, these differences were not major and did not appear to affect the long-term health of the baby.
6. What about breastfeeding?
Studies done in the 1980s showed that breastfeeding does not have an impact on MS. As with any medication, there is little or no information on the standard MS medicine and breastfeeding, so, in general, it is best to avoid medications during breastfeeding if possible. How long to breastfeed before restarting immune modulating medications is an individual decision.
7. Are immunomodulating medications okay to use in pregnancy?
There are a variety of registries that have reported on women using immunomodulating medications in pregnancy. The interferons as a class (Avonex®, Betaseron®, Betaferon®, Rebif®)are contraindicated in pregnancy. In animal models they cause miscarriages. In women who have become pregnant while on these agents, there is an increased risk of still birth and miscarriage as well as small-for-gestational age babies. Limited data on copolymer (Copaxone®)indicates that it has little or no impact on infant outcomes. In general, it is recommended that women stop such medications about three months before trying to become pregnant to avoid problems during pregnancy. Chemotherapeutic agents such as mitoxantrone are contraindicated in pregnancy.
8. Will pregnancy affect my MS symptoms?
There are no well-designed studies of symptoms of MS during pregnancy outside of attack rate and progression of MS. Anecdotally, women often feel well during pregnancy, but there are no good measures of this. One study looked at urinary function during pregnancy in MS and showed no effect of vaginal delivery on urinary function after pregnancy in women with MS.
9. Can I have an epidural if I need it?
In the past there were concerns that various anesthetic agents might affect MS negatively, and women were often encouraged to avoid anesthetics such as an epidural. However, the best evidence we have indicates that there is no special risk for an epidural in women with MS. It is an individual choice as to whether or not to have an epidural.
10. What about having a caesarean section?
Prospective studies have shown that in general women with MS are more likely to have a caesarean section than other women.It is unclear why this is. It may reflect a delay in labor in women with muscular weakness. It may reflect heightened concerns by physicians and nurses when caring for a woman with MS. However, what is known is that a caesarean section does not have an impact on the MS course. There is no evidence that having a caesarean section will cause a relapse or progression of MS beyond the already established course of the disease. In addition, there is no evidence for a benefit of caesarean section over vaginal childbirth;each birth decision is an individual one.
11. What are my children's chances of getting MS?
It is known that MS has some genetic features. Children of women with MS have a 3% to 5% lifetime chance of developing MS. In other words, they have an approximately 96% chance that they won't develop MS, or 24 to one odds against having MS.
12. Can I breast-feed after pregnancy?
There is no evidence that breast-feeding is a problem for patients for MS or their children. Breast-feeding may be important for many reasons for the developing child. A major question in women with MS is when to start back on immunomodulating medications. There is no specific timeline for weaning.
13. Can I take steroids if I have a relapse during pregnancy?
The best evidence we have shows that steroids can be used during pregnancy without a major risk to the mother or baby. In general, we try to avoid using steroids during the first trimester,and then use them only when necessary during the rest of pregnancy. Usually they will be needed only when the mother has an attack that affects her ability to function.
14. Should I take anything else after pregnancy?
In general, women who have needed immunomodulating medication before pregnancy are started back on their medication after they finish breastfeeding. One study showed that using IV steroids once a month for the first six months after delivery seemed to reduce the relapse rate compared with controls. However, there was no difference in neurological function or progression, and steroids have their own side effect profile. Using IV steroids or other medications such as IV immunoglobulin after delivery are at present not standard approaches in the United States in the postpartum period.
© Copyright 1995-2009 The Cleveland Clinic Foundation.All rights reserved.
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INFERTILITY AND MS
The widespread availability of Assisted Reproductive Technologies (ART) has led many women with MS to consider pregnancy when unable to conceive in the usual manner. Perhaps no other decision is more difficult and complicated in women with MS, and yet I am surprised by the number of women and reproductive specialists who are unaware of the issues involved.
First, some background information is in order. Almost all assisted reproductive technologies require hormonal manipulation. The most common drugs used to control ovulation are called Gonadotrophin releasing hormone agonists (GHrh agonists) such as clomiphene. This class of drugs is also used to treat endometriosis (think Lupron), and some forms of breast and prostate cancer. Scattered case reports have suggested for many years that the use of these drugs may be associated with an increased risk of relapse in MS patients. I first noticed this issue in patients taking lupron for endometriosis. More recently a study of 16 MS patients undergoing ART reported a 7 fold increase in the risk of relapse and a 9 fold increase in new MRI lesions during the 3 month period following ART. All of the patients in this study were taking GHrh agonists to help them become pregnant and none were taking disease modifying drugs (examples include avonex, betaseron, rebif, copaxone, tecfidera) to help prevent relapses during the ART period.
So what are you to do with this information if you want a baby and are unable to conceive? First, consider adoption or the use of a surrogate who uses their own eggs fertilized by your partner’s sperm. Neither option will require you to undergo hormonal manipulation. If these options are unacceptable to you, begin a dialogue with your neurologist and reproductive specialists concerning the safest ART option. You will most likely need to educate them about the risks of hormonal manipulation in MS patients. I suggest that you begin by asking them to read the following paper written by Jorge Correale from Argentina, if they have not already done so:
Increase in Multiple Sclerosis Activity after Assisted Reproductive Technology
Annals of Neurology 2012; 72: 682-694
Next you and your neurologist will need to consider if you should be on a MS treatment before, during and after the period of hormonal manipulation and possibly well into pregnancy. This is a very difficult decision but certain features of your MS may suggest a higher risk of relapse during the 3 month period following hormonal manipulation including a high rate of relapses in the past, especially those with incomplete recovery, or a high rate of developing new MRI lesions in the past. Those patients on tysabri are a particular concern since stopping this drug for any reason is associated with a return of prior MS disease activity within 6 months. Strong consideration should be given to continuation of an MS treatment during the ART period to reduce the risk of relapse. The safest option is copaxone which is listed as safe in pregnancy (category B). If this is not acceptable or did not work for you in the past, any interferon treatment (Avonex, betaseron, rebif) is a reasonable option, although they are still listed as pregnancy category C ( Defined as: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks). For those in which both interferons and copaxone are not an option, even less is known about the risks of Tecfidera, Gilenya and Tysabri and all are listed as pregnancy category C. Aubagio, which is pregnancy category D, should never be used prior to or during pregnancy. If you and your neurologist decide it is best to take you off your MS treatment during the ART period, I usually recommend an MRI of the brain with and without contrast before stopping your MS drug therapy and 3 months after starting ART, if you are not pregnant by this time. A significant return of MS disease activity 3 months after starting ART would be reason to consider treatment with corticosteroids, starting or restarting an MS drug and possibly stopping the ART.
In addition to consulting your neurologist, the reproductive specialist will need to understand the risks of ART and consider different options to help you successfully become pregnant. For instance, some studies suggest that using newer GHrh antagonists, such as cetrorelix and ganirelix, may not be associated with the increased risk of relapses during the ART period of hormonal manipulation. The reproductive specialist should be made aware of these studies during your initial consultations.
-Rip Kinkel, MD (copyright 2014)
The widespread availability of Assisted Reproductive Technologies (ART) has led many women with MS to consider pregnancy when unable to conceive in the usual manner. Perhaps no other decision is more difficult and complicated in women with MS, and yet I am surprised by the number of women and reproductive specialists who are unaware of the issues involved.
First, some background information is in order. Almost all assisted reproductive technologies require hormonal manipulation. The most common drugs used to control ovulation are called Gonadotrophin releasing hormone agonists (GHrh agonists) such as clomiphene. This class of drugs is also used to treat endometriosis (think Lupron), and some forms of breast and prostate cancer. Scattered case reports have suggested for many years that the use of these drugs may be associated with an increased risk of relapse in MS patients. I first noticed this issue in patients taking lupron for endometriosis. More recently a study of 16 MS patients undergoing ART reported a 7 fold increase in the risk of relapse and a 9 fold increase in new MRI lesions during the 3 month period following ART. All of the patients in this study were taking GHrh agonists to help them become pregnant and none were taking disease modifying drugs (examples include avonex, betaseron, rebif, copaxone, tecfidera) to help prevent relapses during the ART period.
So what are you to do with this information if you want a baby and are unable to conceive? First, consider adoption or the use of a surrogate who uses their own eggs fertilized by your partner’s sperm. Neither option will require you to undergo hormonal manipulation. If these options are unacceptable to you, begin a dialogue with your neurologist and reproductive specialists concerning the safest ART option. You will most likely need to educate them about the risks of hormonal manipulation in MS patients. I suggest that you begin by asking them to read the following paper written by Jorge Correale from Argentina, if they have not already done so:
Increase in Multiple Sclerosis Activity after Assisted Reproductive Technology
Annals of Neurology 2012; 72: 682-694
Next you and your neurologist will need to consider if you should be on a MS treatment before, during and after the period of hormonal manipulation and possibly well into pregnancy. This is a very difficult decision but certain features of your MS may suggest a higher risk of relapse during the 3 month period following hormonal manipulation including a high rate of relapses in the past, especially those with incomplete recovery, or a high rate of developing new MRI lesions in the past. Those patients on tysabri are a particular concern since stopping this drug for any reason is associated with a return of prior MS disease activity within 6 months. Strong consideration should be given to continuation of an MS treatment during the ART period to reduce the risk of relapse. The safest option is copaxone which is listed as safe in pregnancy (category B). If this is not acceptable or did not work for you in the past, any interferon treatment (Avonex, betaseron, rebif) is a reasonable option, although they are still listed as pregnancy category C ( Defined as: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks). For those in which both interferons and copaxone are not an option, even less is known about the risks of Tecfidera, Gilenya and Tysabri and all are listed as pregnancy category C. Aubagio, which is pregnancy category D, should never be used prior to or during pregnancy. If you and your neurologist decide it is best to take you off your MS treatment during the ART period, I usually recommend an MRI of the brain with and without contrast before stopping your MS drug therapy and 3 months after starting ART, if you are not pregnant by this time. A significant return of MS disease activity 3 months after starting ART would be reason to consider treatment with corticosteroids, starting or restarting an MS drug and possibly stopping the ART.
In addition to consulting your neurologist, the reproductive specialist will need to understand the risks of ART and consider different options to help you successfully become pregnant. For instance, some studies suggest that using newer GHrh antagonists, such as cetrorelix and ganirelix, may not be associated with the increased risk of relapses during the ART period of hormonal manipulation. The reproductive specialist should be made aware of these studies during your initial consultations.
-Rip Kinkel, MD (copyright 2014)