These conclusions cover several physiological aspects, including those concerning women's fertility, consistently with the conclusions of this review that highlighted nine additional articles compared with Messina's selection about the topic. Hamilton-Reeves JM, Vazquez G, Duval SJ, et al. However, urinary phytoestrogen levels were only detected at baseline and this increased the correlation uncertainty. The intervention period was extended only to one menstrual cycle. This was a short pilot study with a small sample size in subgroups. However, the mechanisms underlying isoflavones effects on human health are manifold. Nevertheless, these studies often suffer difficulties in evaluating individual effectiveness as well as in identifying possible confounding factors and population characteristics (ethnicity, health conditions, equol-competence, etc.). On the other hand, many perplexities have been raised about possible negative mechanisms leading to endocrine disruptor effects(20). The same amount of genistein was used in a parallel clinical trial on 137 Iranian women with PCOS with a 3-month follow-up(35). While isoflavones and their metabolites were undetectable in the pre-soy phase, during intervention the 24h output of urinary excretion was 312mg for genistein (74% of the ingestion). Miso intake was inversely associated with SHBG levels. The study did not evaluate circulating or urinary levels of isoflavones to verify the ability to metabolise isoflavones. From the analysis of urinary excretion of isoflavones normalised for creatinine during the intervention with soy, Asian women had significantly greater excretion of isoflavones than non-Asian women. However, results are questionable due to the lack of hormone level measurements or reproductive functions. This could be done by empirically monitoring ovulation to get a real information of menstrual phase, such as quantifying the urinary LH peak as a marker of ovulation, as done by Wu et al.(28). However, the sampling during the various days of the cycle allowed a detailed characterisation of serum LH surge day. In the only clinical trial available, even if it is considered a pilot study, it emerges that a significant role could be played not only by isoflavones, but also by phytochemicals present in soy, particularly in black soy. FOIA 1. Regarding observational studies, in 2015 Andrews and colleagues conducted a prospective cohort study on 246 American women with normal menstrual cycle, aged 1844 and with 13% of participants of Asian ethnicity, for a follow-up of 12 whole menstrual cycles(41). Furthermore, even at high concentrations, they did not show a clear influence on fertility. Isoflavones concentrations did not show significant differences between participants at baseline. Products containing isolated soy isoflavones may be especially problematic. Infertility is a condition that prevents pregnancy despite having regular sexual intercourse with your partner for at least a year. This aspect was different from the results of the clinical trials with high intakes listed above, perhaps due to very different intakes (mean isoflavone consumption of 34mg/d in this cohort). The concentration of isoflavones in the amniotic fluid was related to soy intake, but there was no significant association between soy intake or phytoestrogens in the amniotic fluid and complications of pregnancy or previous infertility. Instead, in the cohort study by Filiberto and colleagues, 259 American women were followed for at least 2 menstrual cycles. The .gov means its official. This could be due to the scarcity of studies on the topic and the presence of few clinical trials, adequately designed to evaluate soy effect on fertility with consistent timing, with an adequate number of participants, blinding, and randomisation for physiological conditions and the presence of equol-producer individuals. Using food frequency questionnaires, researchers found that women with high isoflavone intake ( 40 mg/day) had a 3% lower lifetime probability of giving birth to a live child compared to women with a low intake (< 10mg/day). Based on this cross-sectional study, high consumption of soy isoflavones was identified (94% of participants). The lack of variation in gonadotropins can explain the absence of variation in menstrual cycle. To our knowledge, this is the first comprehensive review on soy effect on women's fertility. Eating a few servings of soy each week could improve fertility and metabolic aspects of PCOS. The authors declare that they have no conflicts of interest. It affects one out of every six couples and affects the majority women aged between 15 to 44 years. Soy is a very popular food and its consumption is part of the traditional cuisine of South-East Asian countries. Find technical definitions and synonyms by letter for drugs/agents used to treat patients with cancer or conditions related to cancer. Soy and soy-derived products contain isoflavones that mimic the actions of oestrogens and may exert adverse effects on male fertility. (2009), Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement, Petrakis NL, Barnes S, King EB, et al. (2000), Effects of soy foods on ovarian function in premenopausal women, Lu LJ, Anderson KE, Grady JJ, et al. Sampling involved synchronisation on the third day of menstrual cycle follicular phase, spontaneous or pharmacologically induced. The standard guidelines for Clomid are to take it either on cycle days 3-7 or 5-9. However, this omission does not necessarily imply that the assessment has not been carried out. Bethesda, MD 20894, Web Policies However, after removing data from studies with elevated bias risk, three studies were included in the sensitivity analysis with consequent loss of statistical significance. Besides, the lack of a placebo group warrants caution. Adapted from SMART: Servier Medical Art(89). Notably, these latter compounds are present in several foods such as legumes, cereals and seeds, whereas soy is almost the only source of isoflavones in human diet. Soy has been used to treat certain symptoms of menopause (such as hot flashes) and to help prevent bone loss ( osteoporosis ).Some supplement products have been found to contain possibly . Moreover, two recent observational cohort studies by Chavarro and colleagues evaluated the association between soy consumption and in vitro fertilisation outcomes(40,42). This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (, Assisted, Fecundability, Fertility, Infertility, Isoflavones, Phytoestrogens, Reproductive techniques, Soy, Soybeans, Soy foods, {"type":"clinical-trial","attrs":{"text":"NCT00616395","term_id":"NCT00616395"}}, Soy, soy foods and their role in vegetarian diets, Consumption of soy foods and isoflavones and risk of type 2 diabetes: a pooled analysis of three US cohorts, Jenkins DJA, Blanco Mejia S, Chiavaroli L, et al. Soy Isoflavones experiment November 22, 2022 | by happyone18 I'm going to document my experience taking soy isoflavones (SI) this cycle. (2001), Isolation and determination of anthocyanins in seed coats of black soybean (, Oyawoye O, Abdel Gadir A, Garner A, et al. These function as phytoestrogens, meaning that they can attach to and activate estrogen receptors in. No significant differences were appreciated for free testosterone and DHEAS. Moreover, isoflavones act as selective estrogen receptor modulators (SERMs) showing both agonist and antagonist effects on ER, with subsequent estrogenic, anti-estrogenic or even neutral effects(14). (2018), Bacterial metabolite S-equol modulates glucagon-like peptide-1 secretion from enteroendocrine L cell line GLUTag cells via actin polymerization. official website and that any information you provide is encrypted This could favour the bioavailability of sex hormones(60). The dietary intake of isoflavones did not appear to be associated with fertility in the two cohorts but some marginal evidence of amelioration of fertility was related to a higher intake of isoflavones among 30 years old individuals after age stratification (Fecundability Ratios: 112, 95% CI 994, 134 and 119, 95% CI 092, 155 in the two cohorts comparing 90th with <24th percentile). The fertility concept differs from the fecundity one, which refers to reproductive potential and depends on reproductive physiology, from the production of gametes phase to the ability to carry a pregnancy to term. In particular, information about the adequate choice of updated nutritional tables as well as specific nutritional choices, such as increased soy consumption due to pre-existing socio-cultural and physiological aspects should be collected. (2020), Soy isoflavones accelerate glial cell migration via GPER-mediated signal transduction pathway, Patel RP, Boersma BJ, Crawford JH, et al. In the mid-1990s he was accused of transferring ova harvested from women . soy isoflavones fertility twins tastylia. [cited 2021 Jul 26]. (2020), Gaskins AJ, Nassan FL, Chiu Y-H, et al. However, the work had several strengths: the real evaluation of luteal and follicular phase through the dosage of urinary LH:creatinine ratio, the characterisation of sampling according to the cycle; the evaluation of isoflavone content in foods used for the intervention and quantification of urinary isoflavones to check compliance; the use of soy foods and not supplements or extracts to approach a real-life pattern; the characterisation of diet at various steps of clinical trial to avoid confounding mechanisms; the stratification by ethnicity which indirectly showed the effect on equol-producer individuals. The disease etiology is still debated but it seems to involve inflammatory mechanisms and oxidative stress(65,66). In the ten women who participated in the second study(29), there were no significant changes in the levels of luteinizing and follicle-stimulating hormones. Live birth odds in the multivariable-adjusted analysis was higher among women in the second tertile of soy intake, consuming 264755mg/d of soy isoflavones (OR: 187; 95% CI 112, 314) and among women in the third tertile of soy intake, consuming 7562789mg/d of isoflavones (OR: 177; 95% CI 103, 303) compared with no consumption, but without a significant linear trend. The use of urinary phytoestrogens and their metabolites is a more reliable system compared to the evaluation of dietary intake. Four papers were found about assisted reproduction technology, two of which were interventional studies by Unifer and colleagues, using high intakes of soy phytoestrogens as adjuvant(31,32). The power analysis concerning variation in isoflavone urinary excretion accounted for a sample size of 25 for >90% detection power. SMART [Internet]. (2019), Consumption of soy-based infant formula is not associated with early onset of puberty, Rosselli M, Reinhart K, Imthurn B, et al. These changes may have resulted in the mild, non-clinically relevant prolongation of menstrual cycle, as discussed in the previous section. Jacobsen and colleagues included 11688 American women aged 3050 years of age who participated in Adventist Health Study-2 (AHS-2)(38). Compliance with the intervention was suggested by urinary excretion of isoflavones. Among the studies already cited, however, we must consider the work of Kohoama and colleagues(33), which showed fertility improvements following intervention with black soy extract in individuals with secondary amenorrhea, including patients with PCOS. The interaction between isoflavones and ER estrogen receptor results in a competitive effect which in turn blunts endogenous estrogens action(72), as suggested by estrogenic activity of biochanin A and genistein on BT-474 human breast cancer(73). One of the first research papers to look directly at soy and fertility outcomes was from the Adventist Health Study-2. The present study used a community-based approach with recruitment of couples seeking pregnancy. After the soy intervention, the length of menstrual cycle marginally increased (from 28319 to 31851d, P=006). However, the intakes of isoflavones in the studied cohorts were limited (range: 0331mg/d). (2003), Antioxidants and reactive oxygen species in follicular fluid of women undergoing IVF: relationship to outcome, Kent LM, Morton DP, Ward EJ, et al. Emerged clinical trials display several limitations including small sample size as well as the longitudinal design without a parallel control group, placebo or a cross-over design consistently limiting the strength of these pilot studies. Steroid hormones (estradiol, progesterone and DHEAS) play a role in epithelial cell proliferation in mammals. (2004), Phytoestrogens may improve the pregnancy rate in in vitro fertilizationembryo transfer cycles: a prospective, controlled, randomized trial, The effect of soybeans on the anovulatory cycle, Romualdi D, Costantini B, Campagna G, et al. Although some works investigate the relationship between consumption of soy formulations in infancy and age at menarche, as well as the onset of puberty or pre-puberty reproductive organ size, these outcomes are not strictly related to fertility in reproductive age(6971). I've heard soy increases chances of having twins. Individuals who are not equol-producers have likely limited response to isoflavone intake(16). M. L. contributed to drafting and revising the manuscript. Thus, consumption of soy containing 32-200 mg/d of isoflavones seems to increase menstrual cycle length and the ratios of 2- to 16- (OH) and 2- to 4- (OH) estrogens and to decrease plasma concentrations of estradiol, progesterone, midcycle gonadotropins and SHBG as well as urinary estrogens. Furthermore, the use of spot urine samples for BPA quantification may have underestimated its exposure. (2021), Health beliefs, behavior, spiritual growth, and salvation in a global population of seventh-day adventists, A brief historical overview of the past two decades of soy and isoflavone research, Mumford SL, Steiner AZ, Pollack AZ, et al. These substances could play a role in the ovaries circulatory functions(50). Based on our literature search, we also identified two observational studies: a cross-sectional study published in 1997 by Nagata et al. (27) and a longitudinal study published in 2013 by Filiberto et al.(37). Furthermore, women with PCOS display a higher prevalence of hyperinsulinemia, dyslipidemia, insulin resistance and obesity compared to healthy population. Progesterone and sex hormone-binding globulin (SHGB) levels were not significantly changed by soy intake. SOY ISOFLAVONES (soi iso FLA vons) may relieve the symptoms of menopause. (2010), Non-isoflavone phytochemicals in soy and their health effects, Aulisa G, Binda C, Padua E, et al. I usually. sharing sensitive information, make sure youre on a federal Although not strictly related to the aspect of fertility, the study is still ongoing (Clinicaltrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT00616395","term_id":"NCT00616395"}}NCT00616395) intending to follow the participants to evaluate effects on reproductive functions, later in life. (2012), Early-life soy exposure and age at menarche, Sinai T, Ben-Avraham S, Guelmann-Mizrahi I, et al. If you look around that sight you will see several posts about just using Soy Isoflavones if Clomid isn't in your work up. (As part of this process, a group of eggs matures so that one will be ready for release during ovulation .) I started taking 60mg every 12 hours (120mg daily) beginning the evening of CD2 and will finish the morning of CD8. This latter aspect suggests a differential capacity for metabolising isoflavones even if these differences were no longer significant when corrected for the intake of isoflavones and estradiol levels were not significantly associated with urinary excretion of isoflavones. Anni and Ashot Manukyan had spent several months unsuccessfully trying to get pregnant through IVF when they received a bewildering message this April . The present paper aims to conduct a review of available data on the effect of soy, soy foods and soy components on women's fertility and related outcomes. However, the association between soy and isoflavones with the reduction of luteal phase seems weak. The same authors admitted that they had no information on the type of soy used and about the last ingestion. A. F. contributed to drafting and revising the manuscript. National Library of Medicine In 2000, Wu et al. I started taking soy in December on CD4-8 and I got digital bfp on at 9dpo. Four clinical trials were found among search engines results: two longitudinal pilot studies(34,46) and two interventional studies with a parallel design, both conducted in Iranian populations(35,43). Women who try soy isoflavones to conceive should understand the following: Do not take soy isoflavones and vitex (chaste berry) at the same time. Luteal phase deficiency can represent a relevant aspect for pregnancy outcomes and fertility disorders. After 6 months, estradiol levels of patients in the intervention group were higher compared with basal (P<005), whereas luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were unchanged. (1997), Decreased serum estradiol concentration associated with high dietary intake of soy products in premenopausal Japanese women, Wu AH, Stanczyk FZ, Hendrich S, et al. Table 2 summarises main limitations about the studies discussed. There was a significant correlation between dietary soy consumption and fertilisation rate (77% v. 71%, P=0004), age-adjusted pregnancy (52% v. 41%, P=003) or age-adjusted live birth rate (44% v. 31%, P=0007) among soy consumers compared with non-consumers. 1 High Risk Pregnancy These types of products contain phytoestrogens in much higher concentrations than traditional whole-food sources. Although this was a randomised, placebo-controlled and double-blinded trial with a sample size appropriate to the power of detection, there was no evaluation of serum and urinary levels of isoflavones and/or metabolites. Even if the clinical trial did not include a placebo group or randomisation, the presence of a control group and the evaluation of equol-producer individuals mitigated these issues. Soy can contain numerous other phytochemicals such as saponins, phytosterols, phytic acid, non-isoflavone flavonoids, peptides, protease inhibitors and other bioactive substances. (2013), Usual dietary isoflavone intake and reproductive function across the menstrual cycle, Jacobsen BK, Jaceldo-Siegl K, Knutsen SF, et al. Recent research suggests that consumption of soy may have a more . However, the terms are often interchangeably, being closely associated with the possibility of giving birth to children. Reduced E2 levels in follicular phase but not in the luteal phase. Researchers did not observe any clinical improvement, alteration of menstrual cycle or hormonal alteration (estradiol, SHBG, DHEAS, androstenedione, testosterone, FSH, LH) compared with baseline levels. (2004), High dose of phytoestrogens can reverse the antiestrogenic effects of clomiphene citrate on the endometrium in patients undergoing intrauterine insemination: a randomized trial, Unfer V, Casini ML, Gerli S, et al. (2011), A prospective cohort study of menstrual characteristics and time to pregnancy, Hooper L, Ryder JJ, Kurzer MS, et al. The concomitant treatment with soybean phytoestrogens significantly increased the implantation rate (254% v. 202%; P<005), the pregnancy rate (393% v. 209%; P<005) and the pregnancy-to-delivery rate (303% v. 162%; P<005) compared with placebo. Additional considerations regarding hormonal influences will be discussed in the next paragraph. Previously, Petrakis and colleagues proposed an interventional study with a soy isolate (374g of soy protein containing 374mg of genistein) on twenty-four women (pre- and post-menopause) followed for 6 months plus 3 months pre-intervention and 3 months post-washout(25). Recently, in a prospective study by Levine et al., 326 American women eumenorrheic aged 1840 were followed for 12 months or until pregnancy(45). The effects obtained from selected studies do not seem to show a clear significance regarding fertility and menstrual cycle length, as discussed in the previous paragraph. This suggests a protective effect of soy against fertility disturbance by BPA. (2016), Menstrual cycle characteristics and fecundability in a North American preconception cohort, Wise LA, Mikkelsen EM, Rothman KJ, et al. Many of its components show an antioxidant activity that can at least partially explain its effectiveness(9). (2014), Soy isoflavone intake and the likelihood of ever becoming a mother: the adventist health study-2, Mumford SL, Sundaram R, Schisterman EF, et al. However, a clear effect on reproductive system has never been highlighted, especially due to the absence of observational studies designed for this purpose. If we eat soy, do we keep the beneficial effects of the Mediterranean diet? The advantages of observational cohort studies include longer times and wider population samples. For these reasons, results should be interpreted with caution. In the first of the two papers by Lu and colleagues(26), the intake of 36 Oz/d of soy milk (~200mg/d IF) for 1 month caused a reduction in mean estradiol levels of 31% at days 57, P=009; 81% at days 1214, P=003; 49% at days 2022, P=002, compared with the baseline. This may have influenced the presence of large confidence intervals. M. A. S. contributed to drafting and revising the manuscript. 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