Does the father matter? The association between the periconceptional paternal folate status and embryonic growth

In spontaneously conceived pregnancies, both low and high periconceptional paternal folate status are associated with reduced embryonic growth.


Volume 111, Issue 2, Pages 270–279


Jeffrey Hoek, M.D., Maria P.H. Koster, M.D., Ph.D., Sam Schoenmakers, M.D., Ph.D., Sten P. Willemsen, Ph.D., Anton H.J. Koning, Ph.D., Eric A.P. Steegers, M.D., Ph.D., Régine P.M. Steegers-Theunissen, M.D., Ph.D.



To study the association between periconceptional paternal folate status and embryonic growth trajectories in early pregnancy.


Prospective periconceptional cohort study.


Single tertiary hospital.


A total of 511 singleton pregnancies, with 303 conceived spontaneously and 208 after in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment.



Main Outcome Measure(s)

Crown–rump length (CRL) and embryonic volume (EV) at 7, 9, and 11 weeks of gestation measured offline using three-dimensional ultrasound data and a virtual reality system.


Using the third quartile of paternal red blood cell (RBC) folate levels as reference values, we found statistically significantly negative associations between RBC folate and longitudinal CRL measurements in the second quartile (beta: −0.14 √mm [95% confidence interval (CI), −0.28 to −0.006]) and fourth quartile (beta: −0.19 √mm [95% CI, −0.33 to −0.04]) in spontaneously conceived pregnancies. Comparable results were found for longitudinal EV measurements in the fourth quartile (beta: −0.12 ∛cm3 [95% CI, −0.20 to −0.05]). No statistically significant associations were observed between RBC folate levels and embryonic growth trajectories in IVF-ICSI pregnancies.


These data demonstrate for the first time that low and high periconceptional paternal RBC folate levels are associated with reduced embryonic growth trajectories in spontaneously conceived pregnancies. These data underline the importance of paternal folate status during the periconception period.

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Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders. The journal publishes juried original scientific articles in clinical and laboratory research relevant to reproductive endocrinology, urology, andrology, physiology, immunology, genetics, contraception, and menopause. Fertility and Sterility® encourages and supports meaningful basic and clinical research, and facilitates and promotes excellence in professional education, in the field of reproductive medicine.

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