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Can GnRH analogs cause autoimmunity postinfertility treatment?

1 Division of Rheumatology, P. D. Hinduja Hospital and Medical Research Centre, Mumbai, Maharashtra, India
2 Department of In Vitro Fertilization, P. D. Hinduja Hospital and Medical Research Centre, Mumbai, Maharashtra, India

Date of Submission09-Dec-2021
Date of Acceptance10-Feb-2022
Date of Web Publication21-Apr-2022

Correspondence Address:
Rohini Samant,
Division of Rheumatology, P. D. Hinduja Hospital and Medical Research Centre, Mahim-West, Mumbai - 400 016, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/injr.injr_271_21

How to cite this URL:
Dubey S, Hinduja I, Samant R. Can GnRH analogs cause autoimmunity postinfertility treatment?. Indian J Rheumatol [Epub ahead of print] [cited 2022 Nov 30]. Available from:

Dear Editor,

Hormonal changes during puberty, pregnancy, and menopause are associated with manifestations of autoimmune diseases. GnRH is the first key hormone of reproduction. This immune-stimulatory peptide exerts effects on the expression and gender differences in autoimmune disorders.[1] Estrogens enhance the humoral response with an activating role in autoimmune disorders, and testosterone is incriminated to enhance suppressor T-cell activity. Few studies demonstrate that GnRH and sex steroids exert hormonal effects along with playing an important role in immune system modulation.[2]

The influence of GnRH analogs on the development of autoimmune disorders as well as worsening of preexisting autoimmunity has been described by several authors. However, most of the published literature in this area consists of case reports detailing findings in one or a few cases.[3] There is also some data which suggest that infertility may be caused by autoimmune ovarian failure. A high rate of premature ovarian failure has been seen to be associated with polyendocrine autoimmune disease.[4] No such association has been looked for with other systemic or limited autoimmune diseases and we therefore would like to study any possible association between the two.

Our study aimed to look at the possible causal association of the use of infertility treatment including GnRH analogs with the onset of autoimmune disorders. We studied a total of 305 infertility patients visiting the in vitro fertilization clinic at P. D. Hinduja Hospital and MRC. At the time of enrollment, a preplanned questionnaire (attached below) was filled out by the patients. The questionnaire involved the presence of common rheumatic symptoms. We followed up the patients for a year after the treatment. Patients were requested to inform the research fellow in case of the appearance of any of the symptoms during this period. Out of 305, six patients visited the clinic for gynecologist consultation only. Remaining 299 patients received treatment for infertility. All these patients were administered GnRH analog. Among 299 patients, 203 patients had primary infertility, whereas 96 patients had secondary infertility.

All patients were followed up for a year for the development of any rheumatic disease after institution of infertility treatment. Seventy-two patients were not available for follow-up despite repeated attempts to contact them. Contact numbers of such patients were tried the maximum of ten times within a time span of 1 month. Remaining 227 patients were available for the follow-up. However, only seven patients considered the pain and discomfort to be very severe and agreed to come for consultation with the rheumatologist. The following table shows the symptoms of the patients who agreed to the consultation with the rheumatologist [Table 1].
Table 1: Patients who developed symptoms

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Only one patient showed clear symptoms of knee synovitis and oligoarticular arthritis within a year of institution of infertility treatment which was confirmed by a rheumatologist. Brouwer et al. reported although subfertility is common in subfertile rheumatoid arthritis patients due to periconceptional nonsteroidal anti-inflammatory drug use, the fertility treatments are favorable among these women.[5]

Patient had a reported paternal history of rheumatic arthritis. A causal relationship of infertility treatment with the development of rheumatic diseases was not observed in this study. Conclusively, we would like to comment that by far GnRH analogs appear to be safe for use in females of childbearing age.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Ngo ST, Steyn FJ, McCombe PA. Gender differences in autoimmune disease. Front Neuroendocrinol 2014;35:347-69.  Back to cited text no. 1
Haller-Kikkatalo K, Salumets A, Uibo R. Review on autoimmune reactions in female infertility: Antibodies to follicle stimulating hormone. Clin Dev Immunol 2012;2012:762541.  Back to cited text no. 2
Desai M, Brinton R. Autoimmune Disease in Women: Endocrine Transition and Risk Across the Lifespan. Frontiers in Endocrinology. 2019;10:1-19.  Back to cited text no. 3
Ebrahimi M, Akbari Asbagh F. The role of autoimmunity in premature ovarian failure. Iran J Reprod Med 2015;13:461-72.  Back to cited text no. 4
Brouwer J, Fleurbaaij R, Hazes JM, Dolhain RJ, Laven JS. Subfertility in women with rheumatoid arthritis and the outcome of fertility assessments. Arthritis Care Res (Hoboken) 2017;69:1142-9.  Back to cited text no. 5


  [Table 1]


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