Preconception maternal lipoprotein levels in relation to fecundability.
Are maternal preconception lipid levels associated with fecundability?



Fecundability was reduced for all abnormal female lipid levels including total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and total triglyceride levels.



Subfecundity affects 7-15% of the population and lipid disorders are hypothesized to play a role since cholesterol acts as a substrate for the synthesis of steroid hormones. Evidence illustrating this relationship at the mechanistic level is mounting but few studies in humans have explored the role of preconception lipids in fecundity.



A secondary analysis of the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial (2007-2011), a block-randomized, double-blind, placebo-controlled trial.



A total of 1228 women, with 1-2 prior pregnancy losses and without a diagnosis of infertility, attempting pregnancy for up to six menstrual cycles were recruited from clinical sites in Utah, New York, PA and Colorado. Time to pregnancy was the number of menstrual cycles to pregnancy as determined by positive hCG test or ultrasound. Individual preconception lipoproteins were measured at baseline, prior to treatment randomization and dichotomized based on clinically accepted cut-points as total cholesterol ≥200 mg/dl, LDL-C ≥130 mg/dl, HDL-C <50 mg/dl and triglycerides ≥150 mg/dl.



There were 148 (12.3%) women with elevated total cholesterol, 94 (7.9%) with elevated LDL-C, 280 (23.2%) with elevated triglycerides and 606 (50.7%) with low HDL-C. The fecundability odds ratio (FOR) was reduced for all abnormal lipids before and after confounder adjustment, indicating reduced fecundability. Total cholesterol ≥200 mg/dl was associated with 24% (FOR: 0.76, 95% CI: 0.59, 0.97) and 29% (FOR: 0.71, 95% CI: 0.55, 0.93) reduced fecundability for hCG-detected and ultrasound-confirmed pregnancy, respectively, compared with total cholesterol <200 mg/dl. There was a 19-36% decrease in the probability of conception per cycle for women with abnormal lipoprotein levels, though additional adjustment for central adiposity and BMI attenuated observed associations.



Although the FOR is a measure of couple fecundability, we had only measures of female lipid levels and can therefore not confirm the findings from a previous study indicating the independent role of male lipids in fecundity. The attenuated estimates and decreased precision after adjustment for central adiposity and obesity indicate the complexity of potential causal lipid pathways, suggesting other factors related to obesity besides dyslipidemia likely contribute to reduced fecundability.



Our results are consistent with one other study relating preconception lipid concentrations to fecundity and expand these findings by adding critically important information about individual lipoproteins. As lipid levels are modifiable they may offer an inexpensive target to improve female fecundability.



This study was funded by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The authors have declared that no conflicts of interest exist.



#NCT00467363.
Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Rockville, MD, USA.
Sarah J
SJ
Pugh
Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Rockville, MD, USA.
Enrique F
EF
Schisterman
Department of Biotechnical and Clinical Laboratory Sciences, University at Buffalo, Buffalo, NY, USA.
Richard W
RW
Browne
Department of Obstetrics and Gynecology, University of Colorado, Denver, CO, USA.
Anne M
AM
Lynch
Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Rockville, MD, USA.
Sunni L
SL
Mumford
Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Rockville, MD, USA.
Neil J
NJ
Perkins
Department of Obstetrics and Gynecology, University of Utah, Salt Lake City, UT, USA.|Intermountain Healthcare, Salt Lake City, UT, USA.
Robert
R
Silver
Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Rockville, MD, USA.
Lindsey
L
Sjaarda
Department of Family and Preventive Medicine, University of Utah, Salt Lake City, UT, USA.
Joseph B
JB
Stanford
Department of Epidemiology and Environmental Health, University at Buffalo, Buffalo, NY, USA.
Jean
J
Wactawski-Wende
Department of Clinical Sciences, Geisinger Commonwealth School of Medicine, Scranton, PA, USA.
Brian
B
Wilcox
Epidemiology Branch, Division of Intramural Population Health Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Rockville, MD, USA.
Katherine L
KL
Grantz
D000293:Adolescent; D000328:Adult; D004311:Double-Blind Method; D005260:Female; D005298:Fertility / Q000502:physiology*; D005306:Fertilization / Q000502:physiology*; D006801:Humans; D008074:Lipoproteins / Q000097:blood*; D011247:Pregnancy; D055815:Young Adult
D008074:Lipoproteins
cholesterol; fecundity; lipids; lipoprotein; preconception; pregnancy; triglycerides