How do autoimmune diseases affect fertility and pregnancy?

Autoimmune diseases increase the complications risk and adverse pregnancy outcomes, and have also been linked in some studies to increased risk of infertility and sterility of autoimmune origin.

Women with autoimmune diseases have an increased risk of premature ovarian failure, which may decrease their chances of having children, especially in those patients who, for medical or social reasons, must delay motherhood. In addition, the antibodies these women develop may play an important role in fertilisation and embryo implantation rates as well as placental development. This increases the risk of embryo implantation failure, repeated miscarriage, as well as increased risks during pregnancy such as pre-eclampsia and preterm birth.

Immune system alteration has also been found in some diseases to increase the risk of infertility, such as endometriosis.

The autoimmune diseases with the greatest impact on fertility and pregnancy are systemic lupus erythematosus, antiphospholipid syndrome, multiple sclerosis, rheumatoid arthritis, type 1 diabetes mellitus and Hashimoto’s thyroiditis.

Autimmune diseases affecting fertility and pregnancy

1. Systemic lupus erythematosus (SLE)

SLE is a chronic inflammatory autoimmune disease with high prevalence in women of childbearing age. It affects multiple organs such as the kidneys, heart, lungs, skin… Although currently most of these patients have good gestational outcomes, they are at increased risk of complications during pregnancy such as pre-eclampsia, preterm birth, intrauterine growth retardation (IUGR), repeated miscarriage or stillbirth. It also increases the caesarean section rate. Similarly, some antibodies generated by these patients can cross the placenta and cause cardiac abnormalities in the newborn or neonatal lupus.

Therefore, pregnancy in these patients is considered as a high-risk pregnancy, and may increase the number of disease outbreaks. For this reason, it is important for these patients to maintain their follow-up and treatment compatible with pregnancy.

Some of the treatments used in these patients, such as cyclophosphamide, increase the risk of low ovarian reserve and premature ovarian failure, and consequently infertility risk.

2. Antiphospholipid syndrome (APS)

APS is an autoimmune disease in which clinical symptoms such as repeated miscarriages and increased risk of thrombotic complications during pregnancy are associated with the presence of antiphospholipid antibodies in blood. It increases the risk of pathologies such as pre-eclampsia, RIC and preterm birth.

These patients should be followed up both preconceptionally and during pregnancy and puerperium by gynaecologists and obstetricians, and have a treatment of low-dose acetylsalicylic acid and low-molecular-weight heparin.

3. Multiple sclerosis (MS)

Multiple sclerosis is a neurological disease where antibodies against the nerves myelin sheaths are generated. It affects mostly women, and the symptoms onset age is usually around 35 years old, so it affects women of childbearing age. This can increase the risk of delayed childbearing as well as female infertility.

The most common symptoms are muscle weakness, mobility loss, sensory disturbances such as paraesthesia (tingling) and loss of visual acuity.

Genetic and environmental factors, low vitamin D levels, smoking and infection by some viruses have been described as being involved in the disease development.

There is much controversy about whether fertility may be affected in women with MS. Some studies have seen a lower ovarian reserve in women with uncontrolled MS. No increased risk of miscarriage, caesarean section or ectopic pregnancy has been seen in these patients.

Pregnancy seems to decrease the number of disease recurrences, which increase in the postpartum period.

Assisted reproductive techniques are not contraindicated in patients with MS, but it is recommended to undergo treatment in a stable phase of the disease, and also to keep the patients’ medication.

4. Rheumatoid arthritis (RA)

RA is chronic inflammatory autoimmune disease that affects multiple joints. It affects young people of reproductive age. Impaired fertility has been observed in these patients, which could be due to the evolution of the disease, treatments used (NSAIDs, corticosteroids, etc.) or the reduced frequency of sexual intercourse.

In men with RA, lower testosterone concentrations and seminal alterations have been reported, which may be a cause of autoimmune male infertility.

Disease symptoms usually improve during pregnancy. However, this is not observed in all patients in whom active disease persists during pregnancy. These patients are at increased risk of complications during pregnancy such as pre-eclampsia, preterm delivery and an increased rate of caesarean section.

5. Type 1 diabetes mellitus (T1DM)

T1DM is characterised by the destruction of insulin-producing cells in the pancreas. This leads to increased blood glucose levels, which is what causes the disease’s systemic complications. The disease is treated with insulin and strict glycaemic control.

In men, it can decrease seminal quality and increase the risk of retrograde ejaculation, leading to male infertility. In women, it can cause infertility by provoking ovulatory alterations and early menopause, as well as increasing risk of complications during pregnancy such as pre-eclampsia, congenital malformations, foetal macrosomia and increased perinatal mortality. For this reason, these patients should have their pregnancies monitored in high-risk obstetrics unit.

6. Hashimoto’s thyroiditis

Patients with Hashimoto’s thyroiditis have decreased thyroid function due to the presence of antibodies against the thyroid gland. It is much more common in women than in men.

Adequate thyroid hormone levels are essential for the reproductive system proper functioning. Thyroid dysfunction can alter ovarian function.

Thyroid autoimmunity does not seem to affect embryo implantation, but may increase the risk of repeated miscarriages, as well as increase the risks during pregnancy of premature birth, foetal distress during delivery or alterations in the foetal nervous system development.

Thyroid hormone treatment improves the patient’s reproductive outcomes.

Treatment

Patients with systematic autoimmune diseases should plan their pregnancy and delay childbearing until the disease is stable for 6 months to reduce the pregnancy associated risks.

Depending on the patient’s disease, usually prescribed treatments are:

1. Immunosuppressive treatments: corticoids or other drugs to control the immune system activity.
2. Nonsteroidal anti-inflammatory drugs (NSAIDs) to control pain.
3. Low-dose acetylsalicylic acid and low-molecular-weight heparin at prophylactic doses in patients with APS.
4. Insulin in patients with type 1 DM.
5. Thyroid hormone in patients with Hashimoto’s Thyroiditis.

Patients who must delay childbearing for medical or social reasons, should be offered oocyte vitrification techniques.

In case of infertility or sterility, assisted reproductive treatments are safe in these patients, but strategies to minimise the risk of ovarian hyperstimulation syndrome and multiple pregnancy should be considered as these complications may pose a higher risk in patients with autoimmune diseases.

Dr Cristina Ajofrín – (MD Associated number 28286434), gynecologist at Instituto Bernabeu