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Peer-reviewedCC BY-NC 4.0Reproduction & Fertility

Paternal metabolic dysfunction and pregnancy loss following assisted reproduction: a cross-sectional study

  • Andrew Peel1,2,3
  • Rashmi Baid2,3,4
  • Andrew D Vincent1
  • David Jesudason5
  • Lachlan M Moldenhauer2,6
  • Leanne Pacella-Ince7
  • Nicole O McPherson1,2,3
  • Gary Wittert1,2
  • M Louise Hull2,4
7 affiliations
  1. 1Freemasons Centre for Male Health and Wellbeing, Adelaide University, Adelaide, South Australia, Australia
  2. 2Robinson Research Institute, Adelaide University, Adelaide, South Australia, Australia
  3. 3Adelaide Health and Medical School, College of Health, Discipline of Reproduction and Development, Adelaide University, Adelaide, South Australia, Australia
  4. 4Embrace Fertility, 1 The Parade, Norwood, South Australia, Australia
  5. 5The Queen Elizabeth Hospital, Woodville, South Australia, Australia
  6. 6School of Pharmacy and Biomedical Science, College of Health, Adelaide University, Adelaide, South Australia, Australia
  7. 7Repromed, Dulwich, South Australia, Australia
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Abstract

There is substantial heterogeneity in the relationship between paternal obesity and pregnancy outcomes following assisted reproduction, possibly related to the presence of obesity-related metabolic complications (e.g. insulin resistance, dyslipidaemia). A retrospective study of heterosexual couples aged over 18 years who underwent metabolic function testing (fasting total cholesterol, triglycerides, high-density lipoproteins, low-density lipoproteins, insulin, or glucose) within 1 year of embryo transfer was performed. Couples utilising donor sperm or oocytes or assisted reproduction in the context of malignancy were excluded. Binomial logistic regression was utilised to examine the relationship between pregnancy outcomes (conception/pregnancy loss) and both paternal ‘metabolic dysfunction’ (any metabolic test exceeding the laboratory reference range) and individual metabolic parameters. A total of 363 couples met the inclusion criteria, of whom 229 underwent fresh embryo transfers (63.1%) and 134 underwent frozen embryo transfers (36.9%). The overall pregnancy rate was 40.8%. Metabolic dysfunction was present in 58.4% of men and 39.4% of women. Neither paternal BMI nor metabolic dysfunction was associated with the likelihood of conception. Metabolic dysfunction was associated with pregnancy loss (odds ratio (OR) = 2.57, 95% confidence interval (CI) = 1.10, 6.04). Specifically, serum triglyceride concentration was associated with pregnancy loss both numerically (OR = 1.84, 95% CI = 1.09, 3.13) and categorically (>1.7 mmol/L: OR = 2.88, 95% CI = 1.17, 7.10), as was a Homeostatic Model Assessment of insulin resistance score > 2 (OR = 2.70, 95% CI = 1.10, 6.61). These data support an association between paternal peri-conception metabolic state and pregnancy loss. Further prospective studies are necessary to validate this association and determine whether paternal therapeutic interventions can reduce pregnancy loss.

Lay summary: We studied whether a man’s metabolic health around the time of undergoing assisted reproduction was linked to pregnancy outcomes (conception and pregnancy loss). Men’s weight and metabolic blood tests, including cholesterol, triglycerides, insulin and glucose, were assessed in 363 couples, of whom 41% became pregnant. More than half of all men had at least one abnormal metabolic result. We found that male body mass index and overall metabolic problems were not associated with the likelihood of conceiving; however, among couples who conceived, abnormalities in male metabolic blood tests were linked to more than twice the risk of pregnancy loss. High triglyceride levels and insulin resistance were most closely associated with pregnancy loss. Overall, the study suggests that the father’s metabolic health may affect the risk of losing a pregnancy; however, further research is needed to confirm this.

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Cite

BibTeXRIS
BibTeX
@article{peel2026paternal,
  title = {{Paternal metabolic dysfunction and pregnancy loss following assisted reproduction: a cross-sectional study}},
  author = {Andrew Peel and Rashmi Baid and Andrew D Vincent and David Jesudason and Lachlan M Moldenhauer and Leanne Pacella-Ince and Nicole O McPherson and Gary Wittert and M Louise Hull},
  journal = {Reproduction \& Fertility},
  year = {2026},
  month = oct,
  doi = {10.1530/raf-26-0089},
  url = {https://doi.org/10.1530/raf-26-0089},
  note = {CC BY-NC 4.0},
}
RIS
TY  - JOUR
TI  - Paternal metabolic dysfunction and pregnancy loss following assisted reproduction: a cross-sectional study
AU  - Andrew Peel
AU  - Rashmi Baid
AU  - Andrew D Vincent
AU  - David Jesudason
AU  - Lachlan M Moldenhauer
AU  - Leanne Pacella-Ince
AU  - Nicole O McPherson
AU  - Gary Wittert
AU  - M Louise Hull
PY  - 2026
DA  - 2026/10/27
JO  - Reproduction & Fertility
DO  - 10.1530/raf-26-0089
UR  - https://doi.org/10.1530/raf-26-0089
AB  - There is substantial heterogeneity in the relationship between paternal obesity and pregnancy outcomes following assisted reproduction, possibly related to the presence of obesity-related metabolic complications (e.g. insulin resistance, dyslipidaemia). A retrospective study of heterosexual couples aged over 18 years who underwent metabolic function testing (fasting total cholesterol, triglycerides, high-density lipoproteins, low-density lipoproteins, insulin, or glucose) within 1 year of embryo transfer was performed. Couples utilising donor sperm or oocytes or assisted reproduction in the context of malignancy were excluded. Binomial logistic regression was utilised to examine the relationship between pregnancy outcomes (conception/pregnancy loss) and both paternal ‘metabolic dysfunction’ (any metabolic test exceeding the laboratory reference range) and individual metabolic parameters. A total of 363 couples met the inclusion criteria, of whom 229 underwent fresh embryo transfers (63.1%) and 134 underwent frozen embryo transfers (36.9%). The overall pregnancy rate was 40.8%. Metabolic dysfunction was present in 58.4% of men and 39.4% of women. Neither paternal BMI nor metabolic dysfunction was associated with the likelihood of conception. Metabolic dysfunction was associated with pregnancy loss (odds ratio (OR) = 2.57, 95% confidence interval (CI) = 1.10, 6.04). Specifically, serum triglyceride concentration was associated with pregnancy loss both numerically (OR = 1.84, 95% CI = 1.09, 3.13) and categorically (>1.7 mmol/L: OR = 2.88, 95% CI = 1.17, 7.10), as was a Homeostatic Model Assessment of insulin resistance score > 2 (OR = 2.70, 95% CI = 1.10, 6.61). These data support an association between paternal peri-conception metabolic state and pregnancy loss. Further prospective studies are necessary to validate this association and determine whether paternal therapeutic interventions can reduce pregnancy loss.  Lay summary: We studied whether a man’s metabolic health around the time of undergoing assisted reproduction was linked to pregnancy outcomes (conception and pregnancy loss). Men’s weight and metabolic blood tests, including cholesterol, triglycerides, insulin and glucose, were assessed in 363 couples, of whom 41% became pregnant. More than half of all men had at least one abnormal metabolic result. We found that male body mass index and overall metabolic problems were not associated with the likelihood of conceiving; however, among couples who conceived, abnormalities in male metabolic blood tests were linked to more than twice the risk of pregnancy loss. High triglyceride levels and insulin resistance were most closely associated with pregnancy loss. Overall, the study suggests that the father’s metabolic health may affect the risk of losing a pregnancy; however, further research is needed to confirm this.
SN  - 2633-8386
ER  -