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A Systematic Review of Autoimmune Oophoritis Therapies

  • Reproductive Endocrinology: Review
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Abstract

Autoimmune primary ovarian insufficiency (POI) is a devastating disease with limited clinical guidance. The objective of this systematic review was to identify treatments for autoimmune POI and analyze their efficacy. A comprehensive search of CINAHL, Cochrane, Embase, PubMed, Scopus, and Web of Science was performed from inception to April 2022. English language publications that evaluated women with autoimmune POI after a documented intervention were included. Animal models of autoimmune POI were also included. Risk of bias was assessed with the SYRCLE’s risk of bias tool for animal studies or the NIH Quality Assessment Tool for Case Series as appropriate. Twenty-eight studies were included in this review, with 11 RCTs, 15 case reports, and 2 case series. Seventeen studies were in humans, and 11 were in animal models. No completed RCTs, cohort studies, or case-control studies were identified in humans. In observational human studies, corticosteroids were effective in select patients. In many case reports, adequate treatment of comorbid autoimmune conditions resulted in return of menses, hormonal normalization, or spontaneous pregnancy. In terms of assisted reproductive technologies, there was case report evidence for both in vitro fertilization (IVF) and in vitro maturation (IVM) in women wishing to conceive with their own oocytes. Ovulation induction, IVF, and IVM resulted in a total of 15 pregnancies and 14 live births. In animal models, there was additional evidence for stem cell therapies and treatments used in traditional Chinese medicine, although this research may not be generalizable to humans. Furthermore, litter size was not evaluated in any of the animal studies. Additional research is needed to establish the efficacy of current treatments for autoimmune POI with a controlled experimental design and larger sample size. Additionally, there is a critical need to develop novel therapies for this condition, as understanding of its pathophysiology and  available tools to modulate the immune response have progressed.

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Data Availability

The data that support the findings of this study were derived from the following resources available in the public domain: CINAHL, Cochrane, Embase, PubMed, Scopus, and Web of Science databases.

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Funding

This research was supported in part by the Howard and Georgeanna Seegar Jones Endowment to JHS.

Author information

Authors and Affiliations

  1. University of Virginia School of Medicine, Charlottesville, VA, USA

    Elizabeth Levit

  2. Division of Reproductive Sciences & Women’s Health Research, Department of Gynecology & Obstetrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Bhuchitra Singh

  3. Informationist Services, Welch Medical Library, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Elisabeth Nylander

  4. Division of Reproductive Sciences & Women’s Health Research, Department of Gynecology & Obstetrics, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross Research Building, Room 624, Baltimore, MD, 21205, USA

    James H. Segars

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Contributions

JS conceived of the idea and supervised the findings of this work and edited the manuscript. EN searched databases for relevant publications. EL interpreted the data and wrote the manuscript with help from BS. All authors discussed the results and contributed to the final manuscript.

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Correspondence to James H. Segars.

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Appendices

Appendix 1 Search terms

Database

Search statements

CINAHL Plus with Full Text (EBSCOhost)

TI ( (autoantibody OR autoimmune OR autoimmunity) AND ("ovarian insufficiency" OR "ovarian failure") ) OR AB ( (autoantibody OR autoimmune OR autoimmunity) AND ("ovarian insufficiency" OR "ovarian failure") ) OR SU ( (autoantibody OR autoimmune OR autoimmunity) AND ("ovarian insufficiency" OR "ovarian failure") ) OR TI ( "inflammatio ovarica" OR "inflammation of the ovary" OR "inflammation of the ovaries" OR "gonadotropin resistant ovary*" OR "gonadotropin-resistant ovary*" OR "gonadotropin resistant ovaries*" OR "gonadotropin-resistant ovaries*" OR "oophoritides" OR "oophroritis" OR "ovarial inflammation*" OR "ovarian autoimmune disease" OR "ovaritis" OR "ovary inflammation*" OR "resistance ovary syndrome*" OR "resistant ovary*" OR "resistant ovaries*" ) OR AB ( "inflammatio ovarica" OR "inflammation of the ovary" OR "inflammation of the ovaries" OR "gonadotropin resistant ovary*" OR "gonadotropin-resistant ovary*" OR "gonadotropin resistant ovaries*" OR "gonadotropin-resistant ovaries*" OR "oophoritides" OR "oophroritis" OR "ovarial inflammation*" OR "ovarian autoimmune disease" OR "ovaritis" OR "ovary inflammation*" OR "resistance ovary syndrome*" OR "resistant ovary*" OR "resistant ovaries*" ) OR SU ( "inflammatio ovarica" OR "inflammation of the ovary" OR "inflammation of the ovaries" OR "gonadotropin resistant ovary*" OR "gonadotropin-resistant ovary*" OR "gonadotropin resistant ovaries*" OR "gonadotropin-resistant ovaries*" OR "oophoritides" OR "oophroritis" OR "ovarial inflammation*" OR "ovarian autoimmune disease" OR "ovaritis" OR "ovary inflammation*" OR "resistance ovary syndrome*" OR "resistant ovary*" OR "resistant ovaries*" )

Cochrane Library (Wiley)

[mh Oophoritis] OR ((autoantibody OR autoimmune OR autoimmunity) AND ("ovarian insufficiency" OR "ovarian failure")):ti,ab,kw OR ("inflammatio ovarica" OR "inflammation of the ovary" OR "inflammation of the ovaries" OR "gonadotropin resistant ovary*" OR "gonadotropin-resistant ovary*" OR "gonadotropin resistant ovaries*" OR "gonadotropin-resistant ovaries*" OR "oophoritides" OR "oophroritis" OR "ovarial inflammation*" OR "ovarian autoimmune disease" OR "ovaritis" OR "ovary inflammation*" OR "resistance ovary syndrome*" OR "resistant ovary*" OR "resistant ovaries*"):ti,ab,kw

Embase (Elsevier)

'ovary inflammation'/de OR ((autoantibody:ti,ab,kw OR autoimmune:ti,ab,kw OR autoimmunity:ti,ab,kw) AND ('ovarian insufficiency':ti,ab,kw OR 'ovarian failure':ti,ab,kw)) OR 'inflammatio ovarica':ti,ab,kw OR 'inflammation of the ovary':ti,ab,kw OR 'inflammation of the ovaries':ti,ab,kw OR 'gonadotropin resistant ovary*':ti,ab,kw OR 'gonadotropin-resistant ovary*':ti,ab,kw OR 'gonadotropin resistant ovaries*':ti,ab,kw OR 'gonadotropin-resistant ovaries*':ti,ab,kw OR 'oophoritides':ti,ab,kw OR 'oophroritis':ti,ab,kw OR 'ovarial inflammation*':ti,ab,kw OR 'ovarian autoimmune disease':ti,ab,kw OR 'ovaritis':ti,ab,kw OR 'ovary inflammation*':ti,ab,kw OR 'resistance ovary syndrome*':ti,ab,kw OR 'resistant ovary*':ti,ab,kw OR 'resistant ovaries*':ti,ab,kw

PubMed

"Autoimmune oophoritis" [Supplementary Concept] OR "Oophoritis"[Mesh] OR ((autoantibody[Text Word] OR autoimmune[Text Word] OR autoimmunity[Text Word]) AND ("ovarian insufficiency"[Text Word] OR "ovarian failure"[Text Word])) OR "inflammatio ovarica"[Text Word] OR "inflammation of the ovary"[Text Word] OR "inflammation of the ovaries"[Text Word] OR "gonadotropin resistant ovary*"[Text Word] OR "gonadotropin-resistant ovary*"[Text Word] OR "gonadotropin resistant ovaries*"[Text Word] OR "gonadotropin-resistant ovaries*"[Text Word] OR "oophoritides"[Text Word] OR "oophroritis"[Text Word] OR "ovarial inflammation*"[Text Word] OR "ovarian autoimmune disease"[Text Word] OR "ovaritis"[Text Word] OR "ovary inflammation*"[Text Word] OR "resistance ovary syndrome*"[Text Word] OR "resistant ovary*"[Text Word] OR "resistant ovaries*"[Text Word]

Scopus (Elsevier)

TITLE-ABS-KEY ( ( autoantibody OR autoimmune OR autoimmunity ) AND ( "ovarian insufficiency" OR "ovarian failure" ) ) OR TITLE-ABS-KEY ( "inflammatio ovarica" OR "inflammation of the ovary" OR "inflammation of the ovaries" OR "gonadotropin resistant ovary*" OR "gonadotropin-resistant ovary*" OR "gonadotropin resistant ovaries*" OR "gonadotropin-resistant ovaries*" OR "oophoritides" OR "oophroritis" OR "ovarial inflammation*" OR "ovarian autoimmune disease" OR "ovaritis" OR "ovary inflammation*" OR "resistance ovary syndrome*" OR "resistant ovary*" OR "resistant ovaries*" )

Web of Science Core Collection (Clarivate)

ts=(((autoantibody or autoimmune or autoimmunity) and ("ovarian insufficiency" or "ovarian failure")) or "inflammatio ovarica" or "inflammation of the ovary" or "inflammation of the ovaries" or "gonadotropin resistant ovary*" or "gonadotropin-resistant ovary*" or "gonadotropin resistant ovaries*" or "gonadotropin-resistant ovaries*" or "oophoritides" or "oophroritis" or "ovarial inflammation*" or "ovarian autoimmune disease" or "ovaritis" or "ovary inflammation*" or "resistance ovary syndrome*" or "resistant ovary*" or "resistant ovaries*")

Appendix 2 Criteria for inclusion and exclusion of studies

 

Inclusion criteria

Exclusion criteria

Population

Women with diagnosis of autoimmune oophoritis or autoimmune primary ovarian insufficiency (POI). Animal models of autoimmune oophoritis.

Non-autoimmune etiologies of POI. Cellular/in vitro studies.

Diagnosis specificity

Patients have clinical diagnosis of autoimmune oophoritis or autoimmune POI

Study includes patients with other causes of POI

Treatment

Documented treatment intervention

No documented treatment intervention

Results

Documented clinical or experimental outcome after treatment intervention

No documented clinical or experimental outcome after treatment intervention

Study design

Randomized controlled trials, observational studies

Literature reviews, conference proceedings, unpublished data

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Levit, E., Singh, B., Nylander, E. et al. A Systematic Review of Autoimmune Oophoritis Therapies. Reprod. Sci. 31, 1–16 (2024). https://doi.org/10.1007/s43032-023-01299-5

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