Written by Taylor Woosley, Science Writer. Multivariable logistic regression findings show that for two women with the same BMI, the odds of becoming pregnant in the omega-3 group was 65-fold higher than the placebo group (p=0.022).
Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting women of reproductive age, with a complex etiology of reproductive, metabolic, and physiological features1. It is characterized by a combination of anovulation and hyperandrogenism, excessive androgen and luteinizing hormone concentrations, and polycystic ovaries, and is often associated with obesity and the impairment of reproductive health2. The presence of insulin resistance and subsequent hyperinsulinemia in PCOS can affect ovarian hormone production and promote decreased ovulation3.
Lifestyle changes and nutritional interventions along with weight loss are successful treatments for patients with PCOS, with an emphasis on improving dietary factors like anti-inflammatory foods that may have a significant role in improving metabolic disorders of the syndrome4. Early studies have shown that an intake of an appropriate amount of unsaturated fatty acids, such as omega-3s, in the diet can remarkably improve dyslipidemia, impaired vascular endothelial function, and insulin resistance in PCOS patients5. Previous research on omega-3 treatment resulted in a significant reduction in inflammatory hs-CRP, luteinizing hormone, total testosterone, and sex hormone binding globulin levels in women with PCOS6.
Trop-Stienberg et al. conducted a prospective, randomized, double-blind, placebo-controlled trial to investigate the effect of omega-3 supplementation on infertile women with PCOS, including overweight and obese women, during ovulation induction using clomiphene citrate, a medication used to treat infertility. Subject inclusion consisted of women aged 25 to 38, who were unable to conceive for 12-30 months, who were undergoing ovulation induction with 50 mg of clomiphene citrate for 5 days. All participants were measured for weight, height, body mass index (BMI), luteinizing hormone (LH), follicle-stimulating hormone (FSH), total testosterone, free androgen index (FAI), and androstenedione levels before beginning the intervention.
Subjects were randomized to either the omega-3 fatty acid group or to a placebo, with both groups receiving 50 mg of clomiphene citrate for 5 days starting on day 12 of their cycle. Those in the intervention group also received 3 x 600 mg capsules of Omega Max-3 per day. Each capsule contained 360 mg EPA and 240 mg DHA for a total of 1800 mg fish oil daily. Subjects in the placebo group received three placebo capsules of sunflower oil daily. Both groups followed the treatment protocol until the women either conceived or completed two clomiphene cycles. Subjects were followed monthly and data regarding size and quantity of follicles, estradiol (E2) (pMol) and progesterone (P) level (nMol) in the blood, and thickness of the endometrium at ovulation were collected via serial transvaginal ultrasonography.
Chi-squared or Fisher’s exact test were utilized to compare categorical variables between groups. 34 subjects who completed 60 ovulatory cycles were included in the final analysis. The mean BMI in the study group (30.67 ± 2.09) was significantly higher than the mean BMI of the placebo group (27.26 ± 1.96) (p=0.02). Furthermore, the basal estradiol level in the placebo group (178.4 ± 13.9 pmol/L) was significantly higher than that of the intervention group (120.1 ± 11.6 pmol/L) (p=0.03). Significant findings of the study are as follows:
- Of the 30 total cycles completed by the women in both groups, there were eight pregnancies (26.7%) in the omega-3 group versus four pregnancies (13.3%) in the placebo group (p<0.3). Within two cycles, there were eight pregnancies in the omega-3 group (53.5%) versus four (28.6%) in the placebo (p<0.17).
- Among overweight and obese women in the two groups, there was a significantly higher pregnancy rate in the omega-3 group, with clinical pregnancies in 8/27 cycles (29.6%) versus 1/19 cycles (5.3%) in the placebo group (p<0.04).
- Multivariate logistic regression findings including pregnancy as the dependent variable and group (omega-3/placebo) and BMI as independent variables show that the model was highly significant (p=0.006), with P-values of 0.003 and 0.016 for group and BMI effects.
Results of the study show that a total of 1800 mg fish oil daily (360 mg EPA and 240 mg DHA) significantly improved the rate of clinical pregnancy compared to placebo. Further research on the potential benefits of omega-3 supplementation on PCOS using larger sample studies and varying dosages of omega-3s is necessary to better comprehend findings.
Source: Trop-Steinberg, Shivtia, Eliyahu M. Heifetz, Yehudit Azar, Irit Kafka, Amir Weintraub, and Michael Gal. “Omega-3 Intake Improves Clinical Pregnancy Rate in Polycystic Ovary Syndrome Patients: A Double-Blind, Randomized Study.” The Israel Medical Association Journal: IMAJ 25, no. 2 (2023): 131-136.
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Posted March 13, 2024.
Taylor Woosley studied biology at Purdue University before becoming a 2016 graduate of Columbia College Chicago with a major in Writing. She currently resides in Glen Ellyn, IL.
References:
- Teede HJ, Tay CT, Laven JJE, et al. Recommendations From the 2023 International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome. The Journal of clinical endocrinology and metabolism. Sep 18 2023;108(10):2447-2469. doi:10.1210/clinem/dgad463
- Calcaterra V, Verduci E, Cena H, et al. Polycystic Ovary Syndrome in Insulin-Resistant Adolescents with Obesity: The Role of Nutrition Therapy and Food Supplements as a Strategy to Protect Fertility. Nutrients. May 28 2021;13(6)doi:10.3390/nu13061848
- Papaetis GS, Kyriacou A. GLP-1 receptor agonists, polycystic ovary syndrome and reproductive dysfunction: Current research and future horizons. Adv Clin Exp Med. Nov 2022;31(11):1265-1274. doi:10.17219/acem/151695
- Heidari H, Hajhashemy Z, Saneei P. A meta-analysis of effects of vitamin E supplementation alone and in combination with omega-3 or magnesium on polycystic ovary syndrome. Sci Rep. Nov 19 2022;12(1):19927. doi:10.1038/s41598-022-24467-0
- Huang Y, Zhang X. Meta-analysis of the efficacy of ω-3 polyunsaturated fatty acids when treating patients with polycystic ovary syndrome. Medicine (Baltimore). Sep 29 2023;102(39):e35403. doi:10.1097/md.0000000000035403
- Yuan J, Wen X, Jia M. Efficacy of omega-3 polyunsaturated fatty acids on hormones, oxidative stress, and inflammatory parameters among polycystic ovary syndrome: a systematic review and meta-analysis. Ann Palliat Med. Aug 2021;10(8):8991-9001. doi:10.21037/apm-21-2018