Background An increased body mass index (BMI) can lead to subfertility; however, current literature fails to exclude the effect of other confounding medical conditions, raising questions regarding the direct link between increased BMI and fertility outcomes. Objectives To conduct a systematic review and meta-analysis to elucidate the effects of increased BMI on fertility outcomes in females with no other comorbidities. Search strategy A comprehensive search was conducted using EMBASE, MEDLINE and the Cochrane library from January 2000 until July 2023. Data collection and analysis Two authors independently conducted data extraction and assessed study quality. Odds ratio (OR) (dichotomous data), standardised mean difference (SMD) (continuous data) and 95% CIs were calculated. Main results Nine eligible studies were identified: one natural conception and eight assisted reproductive technology (ART). Aggregated data revealed women with BMI ≥25 were less likely to attain clinical pregnancy (OR 0.76, 95% CIs 0.62 to 0.93, p=0.007), with BMI ≥30 associated with a further decreased likelihood of clinical pregnancy (OR 0.61, 95% CIs 0.39 to 0.98, p=0.04). Women with raised BMI required longer duration of stimulation (SMD=0.08, 95% CIs 0.00 to 0.16, p=0.04) and obtained reduced oocytes (SMD=−0.11, 95% CIs −0.18 to −0.04, p=0.002). Conclusions These data demonstrate an adverse impact of being overweight/obese on ART outcomes in women with no other diagnosed medical comorbidities and highlight the distinct lack of data concerning the effects of isolated obesity on natural conception. Infertility represents an enormous burden for couples and society; it is essential to identify and tackle modifiable risk factors to improve chances of conception. PROSPERO registration number CRD42022293631.

Recurrent implantation failure (RIF) and recurrent pregnancy loss (RPL), collectively referred to as recurrent reproductive failure (RRF), are both challenging conditions with many unanswered questions relating to causes and management options. Both conditions are proposed to be related to an aberrant endometrial microenvironment, with different proposed aetiologies related to a restrictive or permissive endometrium for an invading embryo. The impressive regenerative capacity of the human endometrium has been well-established and has led to the isolation and characterisation of several subtypes of endometrial stem/progenitor cells (eSPCs). eSPCs are known to be involved in the pathogenesis of endometrium-related disorders (such as endometriosis) and have been proposed to be implicated in the pathogenesis of RRF. This review appraises the current knowledge of eSPCs, and their involvement in RRF, highlighting the considerable unknown aspects in this field, and providing avenues for future research to facilitate much-needed advances in the diagnosis and management of millions of women suffering with RRF.

Endometrial cancer (EC) is the most common gynaecological malignancy. Nucleolin (NCL) is involved in rDNA transcription, cell proliferation, and apoptosis, with high expression associated with worse overall survival (OS) in other adenocarcinomas. Our aims were to assess NCL gene and protein expression and explore the differential expression of NCL-associated genes (NAGs) in endometrial carcinogenesis. Endometrial samples were obtained from 157 women to include healthy, hyperplastic (EH), EC, and metastatic groups. RT-qPCR and immunohistochemistry were employed to assess NCL gene and protein levels. In silico analysis of NAGs in TCGA and GEO datasets was performed, with the prognostic value determined via Human Protein Atlas. NCL mRNA level of EC was lower than in healthy post-menopausal endometrium (p < 0.01). EH samples had lower NCL immuno-expression scores than healthy pre-menopausal (p < 0.001), benign post-menopausal (p < 0.01), and EC (p < 0.0001) samples. Metastatic lesions demonstrated higher NCL quick scores than primary tissue (p = 0.04). Higher NCL Immuno quick scores carried a worse OS in high-grade EC (p = 0.01). Interrogating Uterine Corpus Endometrial Carcinoma (TCGA-UCEC) and Uterine Carcinosarcoma (TCGA-UCS) cohorts revealed NCL to be the most highly upregulated gene in carcinosarcoma, with S100A11, LMNB2, RERG, E2F1 and CCNA2 representing key dysregulated NAGs in EC. Since NCL is implicated in transforming hyperplastic glands into cancer, with further involvement in metastasis, it is suggested to be a promising target for better-informed diagnosis, risk stratification, and management of EC.