Fertility problems in RA

Dr. Sanjay Gupte

MD,DGO,FICOG,FRCOG, 

Director- Gupte Hospital and Centre for Research in Reproduction, Pune

Rheumatoid arthritis as we know is an auto immune disease. It is characterized by chronic systemic inflammatory arthritis of multiple synovial joints. As far as fertility is concerned there are lot of misconceptions regarding association of autoimmune diseases and pregnancy. At one time it was thought that auto immune diseases, especially the SLE are so dangerous with pregnancy that the patient should not be allowed to get pregnant. Now with better understanding of all these autoimmune diseases and better treatment modalities being available the scenario has changed drastically and now we are very positive about the outcomes during pregnancy.

As far as rheumatoid arthritis is concerned there are lot of peculiarities as we know rheumatoid arthritis is more common in females than in males and the incidence in our country is 1 in 600 to 1000 cases in reproductive age group. Relatives of individuals with rheumatoid arthritis are at increased risk of rheumatoid arthritis. Even though full blown cases of rheumatoid arthritis are rarely seen during pregnancy but subtle and gradual development of symmetric peripheral polyarthritis and morning stiffness is seen commonly. Pregnancy also tends to mask the symptoms of rheumatoid arthritis. Many symptoms like fatigue, weakness, joint pains are considered as pregnancy symptoms and rheumatoid arthritis can be missed. As far as fertility issues are concerned all the autoimmune diseases including rheumatoid arthritis are blamed for recurrent pregnancy loss. Though direct causation is not proved but faults in the immune system of the body are blamed for the pregnancy loss. The difference between the rheumatoid arthritis and other autoimmune diseases is quite glaring while other autoimmune problems can deteriorate due to pregnancy in contrast; symptoms of RA show improvement.

Pregnancy considerations

The majority of women, perhaps as many as 80% to 90%, experience some improvement in their RHEUMATOID ARTHRITIS symptoms during pregnancy, although only approximately 50% have more than moderate improvement. Improvement in joint pain and stiffness generally begin in the first trimester and persist through several weeks postpartum. Women who experience symptom improvement is one pregnancy will usually observe similar improvements in subsequent pregnancies. Most women who experience an improvement in symptoms during pregnancy will relapse postpartum, typically in the first three months. It does not appear that pregnancy has any significant effects on the long term course of rheumatoid arthritis.

In fact this positive effect on rheumatoid arthritis of pregnancy was observed longtime back and it actually led to the discovery of cortisone by Philip Hench. The pregnancy hormone progesterone supposedly favorably affects the rheumatoid arthritis symptoms. Not only do rheumatoid arthritis symptoms usually improve during pregnancy but rheumatoid arthritis disease activity does not appear to significantly impact the pregnancy outcome. Women with rheumatoid arthritis generally have uneventful pregnancy without increased risk for preterm birth, preeclampsia or IUGR which are seen with other autoimmune diseases.

Unfortunately after delivery there is a relapse and rheumatoid arthritis symptoms tend to worsen temporarily.

Due to these reasons it is important that all the RA patients undergo preconceptional counseling. The preconceptional counseling helps more than one ways. First it allays the fear of the patient of pregnancy with rheumatoid arthritis. Patient is counseled regarding the cause of symptoms, especially to anticipate some relapse after apparent improvement during pregnancy. More importantly preconceptional drug management can be optimized.

Again there are lot of misconceptions even among the doctors regarding the drugs used for rheumatoid arthritis and their effects on the fetus. Most of the drugs are safe to be used during pregnancy. In the past HCQ was feared to have caused fetal ocular toxicity and oto toxicity. The research in past 15 yrs has proven the safety of HCQs during pregnancy. In fact in many situations continuation of HCQ helps in reducing the dosage of glucocorticoids. Glucocorticoids do have their own side effects with prolonged use and its always prudent to keep to the minimum dosages as far as pregnancy is concerned.

Past fears of cleft lip and cleft palate being caused by glucocorticoids have not proved to be correct. Nonfluorinated steroids such as Prednisone and Methylprednisolone are preferred in pregnancy because placenta metabolizes these agents to an inactive form which results in limited fetal exposure. Both HCQ and Prednisone are compatible with breast feeding. Certain NSAIDs though considered 1^st line of treatment for rheumatoid arthritis should be kept to the minimum dosage during the 1^st trimester as some studies have shown association with miscarriages. NSAIDs are also generally avoided in the third trimester due to the concern regarding premature closure of fetal ductusarteriosus particularly after 30 weeks of gestation.

Azathioprine which is rarely used in RA (more commonly in SLE) has now proven to be safe during pregnancy as it was discovered that the human placenta lacks the enzyme that metabolizes Azathioprine to its active metabolite. Sulphasalazine has also not found to increase congenital anomalies with its use in pregnancy².But as it may cause folic acid deficiency, folic acid supplementation before and during pregnancy is most desired. Drugs like Methotrexate and Leflunomide are known teratogens in humans and are definitely contraindicated in pregnancy³.

The data regarding the use of TNF alpha inhibitors in pregnancy is still inadequate¹ and so though considered compatible with pregnancy should only be used if absolutely required.

Management of Pregnancies Complicated by Rheumatoid Arthritis

Because the majority of women with RA have improvement in their disease during pregnancy, many can discontinue their ant-rheumatic drugs. Mild to moderate joint pain can usually be managed with Paracetamol,  Acetaminophen or low-dose glucocorticoids. Physical therapy may be helpful in some cases. No alterations to routine prenatal care are necessary for women with mild uncomplicated RA. Routine serial ultrasound to assess fetal growth and antenatal testing are unnecessary because the risk of postpartum disease exacerbation is high, it is important to asses symptoms at postpartum visits and to arrange appropriate follow up with rheumatologist. Some experts recommend reinitiating antirheumatic drug treatment after delivery in all women with RA, regardless of disease activity.  

In summary

RA should not be a feared disease for fertility and during pregnancy. Patients need reassurance in this regard. The symptoms of RA are ameliorated during pregnancy but may worsen during the post-partum period. Preconceptional counseling of patients is important to understand this. Preconceptional counseling also includes opportunity for modifications of some of the medication to better suit the pregnancy.

Reference

1. American College of Rheumatology Reproductive Health Summit 2015
2. Viktil KK, Furu K. outcomes after anti-rheumatic drug use before and during pregnancy: a cohort study among 150,000 pregnant women and expectant fathers. Scand J Rheumatol. 2010;41:196-201
3. Cassina M et al. Pregnancy outcome in women exposed to leflunomide before or during pregnancy. Arthritis Rheum. 2012;64:2085-2094