L26/P-705 Serum omega-3 and omega-6 polyunsaturated fatty acids and ovarian stimulation outcomes in assisted reproductive technologies: A prospective cohort study

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Abstract Study question Are serum polyunsaturated fatty acids (PUFAs) levels, a biomarker of intake, associated with ovarian stimulation outcomes in assisted reproductive technology (ART) treatment cycles? Summary answer: Summary answer Serum ω-6 PUFAs levels were positively associated with peak estradiol levels, and this association depended on serum ω-3 PUFAs levels. What is known already ω-3 and ω-6 PUFAs are considered essential fatty acids as they cannot be synthesized de novo by humans and must be obtained from diet. PUFAs are involved in important biological processes in the female reproductive system, acting as energy substrates during oocyte maturation and early embryo development, and serving as precursors of prostaglandin and steroid hormones. Epidemiological evidence suggests higher intakes of ω-3 PUFAs and their food sources are associated with favorable fertility-related outcomes, including lower risk of anovulation and higher live birth rates in ART. However, literature on their relationship with ovarian stimulation outcomes during infertility treatment remains limited. Study design, size, duration We analyzed ovarian stimulation outcomes of 456 fresh cycles from 353 women aged 18 to 45 years old, who participated in the Environment and Reproductive Health (EARTH) Study, a prospective cohort study that enrolled couples seeking infertility treatment at the Massachusetts General Hospital Fertility Center (Boston, MA, USA) (2004-2019). Examined exposures were serum fatty acids and fatty acid ratios. Outcomes were peak estradiol levels, total and metaphase II (MII) oocytes counts, and fertilization rate. Participants/materials, setting, methods Fatty acid levels were quantified by capillary gas chromatography in non-fasting blood samples collected during or shortly before their first in-study ART cycle. Generalized estimating equations (GEE) were used to account for repeated treatment cycles, with adjustments for age, body mass index, smoking status, education level and physical activity hours. When testing the associations of ω-3:ω-6 ratios, the models were additionally adjusted for both of the ω-3 and ω-6 PUFAs. Main results and the role of chance The participants had a median age of 35 years and BMI of 23.1 kg/m2. Most participants were white, highly educated, and had never smoked. Participants had a median (interquartile range, IQR) serum total ω3 and ω6-PUFAs of 4.31 (3.63, 5.87) % and 39.54 (36.70, 42.45) % of total fatty acids, respectively. Serum ω3-PUFAs were not associated with any outcomes examined. Instead, serum linoleic acid (LA) and total ω6-PUFAs exhibited significant positive associations with peak estradiol, but not with oocyte counts or fertilization rate. An IQR increase in serum LA and total ω6-PUFAs was associated with an increase in peak estradiol of 105.35 (0.90, 209.81) and 134.92 (37.92, 231.92) pmol/L, respectively. The ω6:ω3-PUFA and LA: a-linoleic acid (ALA) ratios were significantly related to peak estradiol and total/MII oocyte counts. Stratified analyses showed that the positive association between ω6-PUFAs and peak estradiol was more pronounced in participants with total ω3-PUFA levels above the median (4.31%), while a suggestive positive association between LA and peak estradiol was identified among women with ALA levels above the median (0.68%). No serum fatty acid or fatty acid ratio was associated with fertilization rates. Limitations, reasons for caution First, the findings might not be generalizable to couples seeking to conceive naturally. Second, a single pre-conception measurement of serum fatty acids may not be representative of serum PUFAs levels throughout the study period. Third, despite comprehensive adjustment in this study, unmeasured and residual confounding may still exist. Wider implications of the findings More observational studies are warranted to better understand the interaction between ω3-PUFA, ω6-PUFA and ART outcomes, followed by randomized controlled trials to test for the possible causal effect, whether in the form of dietary supplements or food-based interventions, on ovarian stimulation outcomes to translate it into clinically actionable recommendations. Trial registration number No

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