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Cited by 379Reproductive System and PregnancyPregnancy and preeclampsia studiesReproductive Health and Technologies

Infertility and reproductive disorders: impact of hormonal and inflammatory mechanisms on pregnancy outcome

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Vannuccini, Silvia, Clifton, Vicki L., Fraser, Ian S., Taylor, Hugh S., Critchley, Hilary, Giudice, Linda C., Petraglia, Felice·2016·Human Reproduction Update
DOI 10.1093/humupd/dmv044PMC PMC7289323
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Abstract

BACKGROUND: Reproductive disorders and infertility are associated with the risk of obstetric complications and have a negative impact on pregnancy outcome. Affected patients often require assisted reproductive technologies (ART) to conceive, and advanced maternal age is a further confounding factor. The challenge is to dissect causation, correlation and confounders in determining how infertility and reproductive disorders individually or together predispose women to poor pregnancy outcomes. METHODS: The published literature, to June 2015, was searched using PubMed, summarizing all evidences concerning the perinatal outcome of women with infertility and reproductive disorders and the potential mechanisms that may influence poor pregnancy outcome. RESULTS: Reproductive disorders (endometriosis, adenomyosis, polycystic ovary syndrome and uterine fibroids) and unexplained infertility share inflammatory pathways, hormonal aberrations, decidual senescence and vascular abnormalities that may impair pregnancy success through common mechanisms. Either in combination or alone, these disorders results in an increased risk of preterm birth, fetal growth restriction, placental pathologies and hypertensive disorders. Systemic hormonal aberrations, and inflammatory and metabolic factors acting on endometrium, myometrium, cervix and placenta are all associated with an aberrant milieu during implantation and pregnancy, thus contributing to the genesis of obstetric complications. Some of these features have been also described in placentas from ART. CONCLUSIONS: Reproductive disorders are common in women of childbearing age and rarely occur in isolation. Inflammatory, endocrine and metabolic mechanisms associated with these disorders are responsible for an increased incidence of obstetric complications. These patients should be recognized as ‘high risk’ for poor pregnancy outcomes and monitored with specialized follow-up. There is a real need for development of evidence-based recommendations about clinical management and specific obstetric care pathways for the introduction of prompt preventative care measures.

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  • Inflammatory cytokines released by visceral fat may negatively impact fertility by impairing endometrial receptivity.

    “Moreover, the inflammatory cytokines released by visceral fat may negatively impact fertility by impairing the endometrial receptivity necessary for successful implantation20,38.”

    From The nonlinear association between body roundness index and infertility in married women (2025) · cites this paper as [38]

    The Endometrium section says inflammatory processes in women with endometriosis can reduce endometrial receptivity and affect pregnancy outcomes. It also discusses fat-tissue hormones in obesity and PCOS, but does not identify inflammatory cytokines released by visceral fat as the cause of impaired receptivity. (LLM, conf=0.87)

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Cited by

Sorted by citations

Authors
Vannuccini, S., Clifton, V. L., Fraser, I. S., Taylor, H. S., Critchley, H., Giudice, L. C., & Petraglia, F.
Affiliations
  • University of Siena (IT)
  • The University of Adelaide (AU)
  • UNSW Sydney (AU)
  • Yale University (US)
  • MRC Centre for Reproductive Health (GB)
  • University of California, San Francisco (US)
Corresponding author
Giudice, Linda C.
ORCID
Venue
Human Reproduction Update
Publisher
Oxford University Press (OUP)
Published
2015-09-22
Volume
22
Issue
1
Pages
104-115
ISSN
  • 1355-4786 (ISSN-L)
  • 1460-2369
DOI
10.1093/humupd/dmv044
PMC
PMC7289323
OpenAlex
W1947692703
Cited by
379
References
15
Citations by year
2026: 32 · 2025: 40 · 2024: 55 · 2023: 45 · 2022: 48 · 2021: 38 · 2020: 36 · 2019: 29 · 2018: 21 · 2017: 18 · 2016: 17
FWCI
1.73
Type
journal article
Language
en
Open access
Licence
Locations
  • Human Reproduction Update (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • Florence Research (University of Florence) (submittedVersion)
  • HighWire Press Open Archive (submittedVersion)
  • Use Siena air (University of Siena) (submittedVersion)
  • NOVA (University of Newcastle Australia) (submittedVersion)
Funders
NIH
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
  • Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
  • Health Sciences › Medicine › Reproductive Medicine › Reproductive Health and Technologies
Keywords
infertility, reproductive disorders, pregnancy outcomes, endometriosis, adenomyosis, polycystic ovary syndrome, uterine fibroids, unexplained infertility, inflammation, preterm birth, fetal growth restriction, placental pathology, hypertensive disorders of pregnancy, assisted reproduction, advanced maternal age, pregnancy complications
MeSH terms
Cervix Uteri, Female, Humans, Infertility, Female, Inflammation, Leiomyoma, Maternal Age, Placenta, Polycystic Ovary Syndrome, Pregnancy, Pregnancy Complications, Pregnancy Outcome, Gonadal Steroid Hormones, Signal Transduction, Reproductive Techniques, Assisted, Premature Birth, Female Urogenital Diseases

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