RASH AND RUSH? Linking between allergies, inflammation, and fertility
Elizabeth Choong, iBSc, is a Research Intern, while Sonia Gayete-Lafuente, MD, PhD, is a Clinical Research Fellow at the FRM and the CHR. Both can be reached through the editorial office at the VOICE.
When we think about fertility and pregnancy outcomes, our minds often go straight to age, hormones, egg and sperm quality, or genetics. However, there is increasing evidence of the central role of another factor at play: the immune system. For many women, especially those with allergies or chronic inflammation, this hidden factor—so often overlooked—could be shaping pregnancy success. In this article, we are reviewing how immune disbalances affect fertility.
Pregnancy as a balancing act of immune function
Conceiving and carrying a baby requires a high level of biological coordination. A baby inherits DNA from both parents, making it partly “foreign” to the mother’s immune system. To avoid rejection, the maternal immune response shifts in pregnancy towards tolerance, dampening certain aggressive immune pathways while allowing others to remain active. At first glance, this seems to align with atopic conditions such as asthma, eczema, or hay fever, which are characterized by a predominant response of type 2 helper T cells (Th2, are specifically antibody-producing lymphocytes) and elevated immunoglobulin E (IgE). However, exaggerated allergic inflammation often also brings a heightened state of mast cell activation, histamine release, and eosinophil recruitment, all of which can disturb the delicate interactions between the embryo and endometrium during and beyond implantation.
Allergic inflammation, implantation failure and early pregnancy loss
Here at the CHR we recently published data demonstrating a link between elevated IgE levels and early -euploid- miscarriage (see Barad et al., in reading list). Although the specific underlying molecular mechanisms remain unclear, this finding points towards a maternal cause, possibly involving allergic inflammation in the uterine lining that could disrupt early placental development or vascular adaptation. In fact, it is known that mast cell activation and histamine release in allergic reactions can impair uterine vascular adaptation and early placental development, hence logically jeopardizing implantation and/or leading to early miscarriage.
The allergy-mediated connection between the gut and fertility
Amongst the many ways allergy can impair fertility, recent studies have focused on gut microbiome disruptions, as they lead to inflammation susceptibility. In allergic individuals, gut bacteria often show reduced diversity and a skewed balance towards pro-inflammatory species. A disrupted microbiome can make the gut lining more permeable, allowing bacterial components to leak into the bloodstream and trigger systemic inflammation, which feeds back the loop (this is often called a “leaky gut”). The main marker of generalized inflammation, C-reactive protein (CRP), we here at CHR have linked to reduced implantation rates and higher miscarriage risk in IVF patients. While pregnancy particularly in later trimesters naturally changes the microbiome, women who start with an imbalanced gut ecosystem may be more vulnerable to harmful inflammatory signaling at critical early stages leading to infertility.
Asthma, atopy, and obstetric complications
Asthma offers perhaps the clearest example of how allergic disease can affect pregnancy. Poorly controlled asthma increases the risk of pre-eclampsia, preterm birth, and low birth weight. This may result from hypoxia during flare-ups, but chronic airway inflammation and systemic immune activation have also been reported to play major roles. Even seemingly mild allergic conditions, such as seasonal hay fever, can remarkably raise systemic inflammatory mediators. For women conceiving during high-pollen months, this could theoretically influence implantation and early pregnancy development, an area which has high potential for further research.
Therapeutic and preventive strategies
If allergic and gut-driven inflammations do influence reproductive outcomes, the logical step is to identify and manage them early. For women with known conditions such as asthma or severe eczema, pre-conception optimization of disease control is already recommended with gold-standard treatment such as antihistamines.
Newer biologic therapies, such as dupilumab, target specific immune pathways. Early reports on their use increasingly suggest that they may be safe in pregnancy, though more data are needed. Additionally, in women with history of infertility or recurrent pregnancy loss, immune markers should be investigated, as we, here at the CHR, do routinely during initial fertility evaluations.
Targeted immune-inflammatory modulation, with low-dose corticosteroids, intravenous immunoglobulin (IVIg) and/or hydroxychloroquine should be carefully considered in cases of reproductive failure with suspected immune involvement. Whether these strategies specifically benefit allergy-associated inflammation is still uncertain, and antihistamines should be definitely trialed in this setting.
Additional anti-inflammatory dietary changes such as probiotics and prebiotics are low-risk measures that could also be trialed before conception. While evidence in reproductive outcomes is still limited, studies suggest that applying these measures could reduce systemic inflammation and may promote a more favorable immune profile for pregnancy.
Why this matters
While particularly in high-income countries rates of allergic disease have significantly increased in recent decades, fertility challenges and use of assisted reproductive technologies are rising. If allergic inflammation and gut dysbiosis are quietly reducing reproductive success, they deserve a far more prominent place in both research and clinical settings. Bringing immunologists and reproductive specialists together could open new possibilities for prevention and treatment. Expanding fertility investigations to include immune and inflammatory profiling—not just autoimmune markers—may help identify women who would benefit from individualized interventions and, hopefully, improve pregnancy outcomes.
Reading List
Barad DH, Darmon SK, Albertini DF, Molinari E, Gleicher N. Is Immunoglobulin IgE Relevant for Pregnancy Loss? Fertil Steril. 2020;114(3)e356.
Murphy VE, Namazy JA, Powell H, et al. Asthma in pregnancy: A review. BMJ. 2021;372:n530. doi:10.1136/bmj.n530.
Nuriel-Ohayon M, Neuman H, Koren O. Microbiome and pregnancy—Where do we stand? Birth Defects Res. 2019;111(17):1132-1148. doi:10.1002/bdr2.1530.
Robison JG, Kumar R, Bakos O, Hoang A, Christodoulou J, Nanan R. Allergic diseases and reproductive outcomes: A systematic review. Am J Reprod Immunol. 2021;85(6):e13382. doi:10.1111/aji.13382.
Weghofer A, Barad DH, Darmon SK, Kushnir VA, Albertini DF, Gleicher N. Euploid miscarriage is associated with elevated serum C-reactive protein levels in infertile women: a pilot study. Arch Gynecol Obstet. 2020;301(3):831-836. doi:10.1007/s00404-020-05461-1.