Poster Presentation ESA-SRB-ANZOS 2025 in conjunction with ENSA

Male metabolic dysfunction is associated with a higher likelihood of miscarriage (128346)

Andrew Peel 1 2 3 , Rashmi Baid 2 4 , Andrew Vincent 3 , David Jesudason 5 , Leanne Pancella-Ince 6 , Nicole McPherson 1 2 3 , Gary Wittert 1 3 , Louise Hull 1 6
  1. Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia
  2. Adelaide Health and Medical School, School of Biomedicine, University of Adelaide, Adelaide, South Australia, Australia
  3. Freemason Centre for Male Health and Wellbeing, The University of Adelaide and South Australian Health and Medical Research Institute, Adelaide, South Australia, Australia
  4. Embrace Fertility, Adelaide, South Australia, Australia
  5. The Queen Elizabeth Hospital, Adelaide, South Australia, Australia
  6. Repromed, Adelaide, South Australia, Australia

Obesity is estimated to affect 23-30% of reproductive-aged Australians(1). The negative effects of obesity on fertility and pregnancy loss are well documented(2-4), additionally, female metabolic dysfunction (insulin resistance, dyslipidaemia) is independently associated with poorer pregnancy outcomes(5, 6). The data examining paternal metabolic dysfunction is less robust, although epidemiological data suggests a link with miscarriage(3, 7, 8). We aimed to examine the relationship between male metabolic function and fertility outcomes in a cohort of Australian couples attending a fertility clinic.

 

A retrospective review of couples undergoing assisted reproduction (ART) at an Adelaide-based fertility clinic was performed. Inclusion criteria: Heterosexual couples >18 years seeking assisted reproduction who undertook measurement of metabolic function (fasting cholesterol, triglycerides, HDL, LDL, insulin, glucose) within 1.5 years of ART. Exclusion criteria: couples requiring donor sperm/oocytes or receiving malignancy related ART. Statistics: A baseline regression model was established via bidirectional stepwise logistical regression incorporating couples’ age, BMI, reproductive comorbidities and number of abnormal female metabolic biomarkers. Subsequent addition of individual male biochemical parameters allowed interrogation of the relationship between paternal biochemical derangements and both pregnancy and miscarriage (conditional on pregnancy).

 

Between 2020-2025, 388 couples underwent ART, with a  mean female age of 37.3 and male age of 38.6 years. Of these, 237 undertook a fresh transfer in an in-vitro fertilisation cycle, and 151 had a frozen embryo transfer (FET). Male BMI and metabolic parameters were not associated with conception, however after adjusting for couples’ BMI, ART intervention and female metabolic state, paternal hypertriglyceridemia (>1.7 mmol/L, OR 2.38, p=0.04) and reduced HDL concentration (<0.9 mmol/L, OR 2.39, p=0.02) were both associated with higher miscarriage risk.

 

Our findings are consistent with previous epidemiological data suggesting male metabolic function impacts miscarriage risk(8). Further prospective studies and examination of embryo quality are necessary to validate this finding.

  1. Australian Institute of Health And Welfare. Overweight and Obesity 2018 1 July 2025]. Available from: https://www.aihw.gov.au/reports/overweight-obesity/overweight-and-obesity/contents/overweight-and-obesity.
  2. Cavalcante MB, Sarno M, Peixoto AB, Araujo Júnior E, Barini R. Obesity and recurrent miscarriage: A systematic review and meta-analysis. J Obstet Gynaecol Res. 2019;45(1):30-8.
  3. Service CA, Puri D, Al Azzawi S, Hsieh TC, Patel DP. The impact of obesity and metabolic health on male fertility: a systematic review. FERTILITY AND STERILITY. 2023;120(6):1098-111.
  4. Ribeiro LM, Sasaki LMP, Silva AA, Souza ES, Oliveira Lyrio A, A CMGF, Gottems LBD. Overweight, obesity and assisted reproduction: A systematic review and meta-analysis. Eur J Obstet Gynecol Reprod Biol. 2022;271:117-27.
  5. He Y, Lu Y, Zhu Q, Wang Y, Lindheim SR, Qi J, et al. Influence of metabolic syndrome on female fertility and in vitro fertilization outcomes in PCOS women. Am J Obstet Gynecol. 2019;221(2):138.e1-.e12.
  6. Thong EP, Codner E, Laven JSE, Teede H. Diabetes: a metabolic and reproductive disorder in women. Lancet Diabetes Endocrinol. 2020;8(2):134-49.
  7. Cohen DJ, Giaccagli MM, Herzfeld JD, González LN, Cuasnicú PS, Da Ros VG. Metabolic syndrome and male fertility disorders: Is there a causal link? Rev Endocr Metab Disord. 2021;22(4):1057-71.
  8. Kasman AM, Zhang CA, Li S, Lu Y, Lathi RB, Stevenson DK, et al. Association between preconception paternal health and pregnancy loss in the USA: an analysis of US claims data. Hum Reprod. 2021;36(3):785-93.