The Role of the Immune System in Fertility
One of the main functions of our immune system (IS) is to differentiate between self and foreign structures. During pregnancy, the IS must tolerate the presence of an organism that is immunologically different from maternal tissue: the embryo. Additionally, the IS plays an active role in the development of essential organs such as the placenta.
Alterations in immune system function can lead to diseases and complications during pregnancy.
What Immune-Related Issues Can Affect Fertility?
Antiphospholipid Syndrome
This disorder occurs when the IS produces antibodies against the body’s own proteins associated with phospholipids in vascular membranes. It is associated with:
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Increased risk of arterial or venous thrombosis
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Recurrent miscarriages
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Preterm birth
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Fetal growth restriction
The accepted treatment includes:
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Low molecular weight heparin
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Acetylsalicylic acid
Alloimmune Response
In this reaction, the body recognizes the embryo’s cells—which carry paternal genetic material—as foreign. Investigations typically assess:
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Maternal KIR genotype
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Maternal and paternal/donor HLA-C
NK cells make up 70–90% of uterine lymphocytes. Their functions include:
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Controlling blood vessel formation
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Facilitating embryo implantation
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Developing a tolerant immune response
KIR receptors can be:
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KIR A: inhibitory
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KIR B: activating
Maternal genotypes may be AA, AB, or BB. These receptors interact with HLA-C, which is inherited from both parents. The combination of KIR AA + HLA-C2 has been linked to:
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Miscarriage
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Implantation failure
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Preeclampsia
Recommended approaches include:
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Single embryo transfer
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Selection of compatible gametes in recipient patients
Undiagnosed Celiac Disease or Gluten Sensitivity
This may be associated with:
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Infertility
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Recurrent miscarriages
Treatment involves a strict gluten-free diet following proper diagnosis.
Autoimmune Diseases
These are conditions in which the IS attacks the body’s own tissues, such as:
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Rheumatoid arthritis
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Multiple sclerosis
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Autoimmune hypothyroidism
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Crohn’s disease
If well-controlled and in the absence of active flare-ups, patients can plan for pregnancy with:
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Multidisciplinary medical supervision
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Prevention of inflammatory episodes
Conclusion
An imbalance in the immune system can cause implantation failure and recurrent miscarriages. Key to prevention are:
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Early diagnosis
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Personalized treatment
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Lifestyle changes
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Emotional support and stress management
At Clínica Fertia, we approach each case individually, optimizing the chances of achieving a successful pregnancy even in the presence of immune-related issues.
- Knight JS, Branch DW, Ortel TL. Antiphospholipid syndrome: advances in diagnosis, pathogenesis, and management. BMJ. 2023 Feb 27;380:e069717. doi: 10.1136/bmj-2021-069.
- Cuadrado-Torroglosa I, García-Velasco JA, Alecsandru D. Maternal-Fetal Compatibility in Recurrent Pregnancy Loss. J Clin Med. 2024 Apr 19;13(8):2379. doi: 10.3390/jcm13082379. PMID: 38673652; PMCID: PMC11051463.717. PMID: 36849186.
- Casella G, Orfanotti G, Giacomantonio L, Bella CD, Crisafulli V, Villanacci V, Baldini V, Bassotti G. Celiac disease and obstetrical-gynecological contribution. Gastroenterol Hepatol Bed Bench. 2016 Fall;9(4):241-249. PMID: 27895849; PMCID: PMC5118848.
- Tańska K, Gietka-Czernel M, Glinicki P, Kozakowski J. Thyroid autoimmunity and its negative impact on female fertility and maternal pregnancy outcomes. Front Endocrinol (Lausanne). 2023 Jan 11;13:1049665. doi: 10.3389/fendo.2022.1049665. PMID: 36714589; PMCID: PMC9874701.
