Table 1.
Summary of the Potential Mechanistic Links Between PCOS and NVP
| Biological Domain | Pre-Existing Features Associated with PCOS | Associated Changes in NVP | Proposed Overlapping Mechanisms | References |
|---|---|---|---|---|
| Neuroendocrine regulation | Infertile women with PCOS exhibit reduced serum levels of 5-HT and 5-HIAA, which are associated with altered LH secretion. | Women with HG exhibit elevated plasma 5-HT levels that correlate with PUQE scores. 5-HT may exert emetic effects through 5-HT3 receptors, vagal afferent fibres, and brainstem emetic pathways. | Pre-existing alterations in 5-HT regulation associated with PCOS may lower the response threshold for pregnancy-related emetic signals, resulting in a theoretical process of 5-HT sensitisation. | PCOS:28 NVP:30–32 |
| Placental-derived factors |
GDF15: Women with PCOS may exhibit altered GDF15 homeostasis. IGFBP7: Increased IGFBP7 expression is associated with insulin resistance, inflammation, and ovarian dysfunction. |
GDF15: Circulating fetoplacental GDF15 levels are elevated in women with NVP, and its effects may be mediated through the brainstem GFRAL–RET signalling pathway. IGFBP7: In early pregnancy, women with HG exhibit elevated IGFBP7 levels associated with symptom severity; additionally, the 4q12 locus harbouring IGFBP7 has been linked to genetic susceptibility to HG. |
Pre-existing metabolic abnormalities in PCOS may influence maternal sensitivity to gestational changes in GDF15 and IGFBP7, thereby altering the threshold for emetic responses. | PCOS:35–39,43–45 NVP:40–42,46,47 |
| Appetite and energy balance | Ghrelin: Women with PCOS commonly exhibit reduced circulating ghrelin levels and blunted postprandial ghrelin suppression; these abnormalities are associated with insulin resistance and hyperandrogenism. Leptin: Women with PCOS often exhibit elevated leptin levels, which are associated with obesity, insulin resistance, and altered androgen-related indices. |
Ghrelin: Women with HG may exhibit reduced ghrelin levels and elevated PYY and PP levels. Leptin: In women with NVP, the increase in leptin levels from early to mid-pregnancy is attenuated. |
Abnormalities in appetite-regulating hormones and energy homeostasis in both conditions may impair metabolic adaptation during early pregnancy and influence appetite, gastrointestinal motility, and susceptibility to NVP. | PCOS:49–55,57–60 NVP:24,25,61 |
| Gut microbiota–endocrine interactions | Women with PCOS may exhibit reduced gut microbial α-diversity and altered β-diversity, accompanied by an increased abundance of Gram-negative bacteria, a reduction in SCFA-producing bacteria, and LPS–TLR4-related chronic low-grade inflammation. | Alterations in gut microbial diversity and composition have been observed in women with NVP, and specific microbial taxa are associated with the risk of HG. However, severe vomiting and nutritional deprivation may also induce secondary alterations in the gut microbiota. | Shared gut microbial dysbiosis may influence NVP through the LPS–TLR4 inflammatory pathway and the SCFA–gut hormone–gut–brain axis; however, the causal direction remains unclear. | PCOS:63–67 NVP:68–71 |
| Androgen signalling | Hyperandrogenism is a major feature of PCOS and is accompanied by an insulin–androgen feedback loop and possible alterations in monoamine neurotransmitters. | Gestational levels of A4, DHEAS, T, and the FAI are associated with NVP symptoms or vomiting scores. Women with HG may also exhibit elevated androstanediol glucuronide levels and reduced A4 levels. | Pre-existing hyperandrogenism and metabolic abnormalities in PCOS may affect neuroendocrine and metabolic adaptation during pregnancy, thereby increasing susceptibility to NVP. | PCOS:73,74 NVP:75,76 |
Abbreviations: PCOS, polycystic ovary syndrome; NVP, nausea and vomiting of pregnancy; HG, hyperemesis gravidarum; 5-HT, 5-hydroxytryptamine; 5-HIAA, 5-hydroxyindoleacetic acid; LH, luteinising hormone; PUQE, Pregnancy-Unique Quantification of Emesis; GDF15, growth differentiation factor 15; IGFBP7, insulin-like growth factor-binding protein 7; GFRAL, glial cell line-derived neurotrophic factor family receptor alpha-like; RET, rearranged during transfection receptor tyrosine kinase; PYY, peptide YY; PP, pancreatic polypeptide; SCFA, short-chain fatty acids; LPS, lipopolysaccharide; TLR4, Toll-like receptor 4; A4, androstenedione; DHEAS, dehydroepiandrosterone sulfate; T, testosterone; FAI, free androgen index.