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. Day 22 should correspond to the mid-luteal phase, however, the authors pointed out that participants exhibited different lengths of menstrual cycle and this could have been a source of heterogeneity that was used as a covariate in the regression model. They can bind G-protein-coupled estrogen receptor 1 (GPR30), with effects driven by both genomic and non-genomic regulation involving different cellular signalling pathways, such as intracellular increase of calcium or NO levels(Reference Ropero, Alonso-Magdalena and Ripoll75), as observed in human endothelial cells after stimulation with equol 100nM(Reference Rowlands, Chapple and Siow76). For these reasons, results should be interpreted with caution. The interaction between isoflavones and ER estrogen receptor results in a competitive effect which in turn blunts endogenous estrogens action(Reference Rosselli, Reinhart and Imthurn72), as suggested by estrogenic activity of biochanin A and genistein on BT-474 human breast cancer(Reference Zand, Jenkins and Diamandis73). Similarly, a significant correlation between isoflavone intake and nulligravidity emerged (P=003) with a 13% higher risk but with a wide range of confidence interval (95% CI 2, 26) in women with intake 40mg/d compared with lower intakes (<10mg/d). Jacobsen and colleagues included 11688 American women aged 3050 years of age who participated in Adventist Health Study-2 (AHS-2)(Reference Jacobsen, Jaceldo-Siegl and Knutsen38). Conclusions: These data suggest that higher intake of soy foods and soy isoflavones is associated with lower sperm concentration. [1] 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. Adapted from Moher et al.(24). The evaluation of isoflavones circulating levels and their urinary excretion allowed to show a wide inter-individual variation of metabolic and absorption capacity. The significant inverse association between dietary isoflavone intake and live births (3% reduction, 95% CI 0, 7, P=005) was highlighted. The FFQ was not specifically designed for phytoestrogen assessment and this may have underestimated intakes. Higher soy products intake did not correlate with the rate of infertility. The same type of soy phytoestrogen intervention was subsequently used by Unifer and colleagues in a second clinical trial on 213 infertile women undergoing in vitro fertilisation with embryo transfer cycles after intramuscular progesterone treatments (50mg/d) with or without (placebo) 1500mg/d of soy isoflavones intake(Reference Unfer, Casini and Gerli32). Those women eating or taking soy isoflavones were more likely to get pregnant. However, soy diet reduced progesterone (45%, P<00001) and estradiol levels (23%, P<001), compared with baseline. 1. While the observational data better reflect the effects of diet in free-living conditions compared with experimental settings of clinical trials, the use of food frequency questionnaires exposes to possible misclassification and measurement errors. Guo, Tingting Jamilian and colleagues in 2016 conducted another parallel clinical trial on seventy Iranian women with PCOS, using 50mg/d of soy isoflavones for a 1-month follow-up(Reference Jamilian and Asemi43). Major equol production was associated with a reduction in androgens levels (total testosterone, free testosterone and androstenedione), in the whole cohort. Any later it delays ovulation. Similar to the previous trial, the number of participants was limited. The diagnosis of PCOS occurs in the presence of at least two of the three Rotterdam Criteria: oligo or anovulation, polycystic ovary morphology and biochemical or clinical hyperandrogenism(Reference Pfieffer67). Isoflavones are plant-based compounds found almost exclusively in beans, like soybeans, that mimic the action of the hormone estrogen. These aspects considerably reduce the reliability of results, favouring data misinterpretation. Black soy, in addition to the content of isoflavones, is known to be rich in antioxidant substances, especially in external seed integuments, which are rich in anthocyanins(Reference Choung, Baek and Kang49). The only study found about the effect of exposure to soy in childhood and reproductive functions is the retrospective study by Strom and colleagues(Reference Strom, Schinnar and Ziegler30). However, only 106 individuals provided information on soy intake. The possibility of a sexual development disorder as a neonatal programming effect is an often raised hypothesis because circulating levels of isoflavones are higher in soy-fed infants compared with cow milk formula or breastfed infants(Reference Andres, Moore and Linam69). 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. A systematic consultation of literature was launched on four search engines (PubMed, ScienceDirect, Cochrane Trials Library and ClinicalTrials.gov) using the following keywords: (Soy OR Soy Foods OR Soybeans OR Genistein OR Daidzein OR Isoflavones OR Phytoestrogens) AND (Fertility OR Infertility OR Fecundability). It is widely used in eastern traditional cuisine and it has recently diffused among self-conscious and vegetarian diets. Pending further confirmation, soy and its components do not appear to have a clinically relevant influence on menstrual cycle in healthy women. 2023. However, the number of participants was limited for a cross-sectional study, and dietary survey through frequency questionnaires in the absence of an assessment of blood or urine isoflavone levels could lead to uncertainty. However, because of the paucity of studies exploring the impact of soy intake on women's fertility, as well as the limited population sample size, the frequently incomplete specimens collection to investigate all cycle phases and the insufficient characterisation of participants, the evidence is suggestive and it needs further in-depth research taking into account all these aspects. In another study, women were more likely to get pregnant if they ate soy isoflavones alongside . These substances could play a role in the ovaries circulatory functions(Reference Oyawoye, Abdel Gadir and Garner50). Furthermore, hormone levels were evaluated only at baseline, without taking into account the differences between the two groups. In the previously mentioned meta-analysis by Hooper and colleagues(Reference Hooper, Ryder and Kurzer59), reduction of about 22% of FSH (SMD: 045UI/l, 95% CI 079, 011, P=001) and of about 4% of LH (SMD: 034IU/l, 95% CI 068, 001, P=005) were related to the intake of soy or isoflavones. Furthermore, women with PCOS display a higher prevalence of hyperinsulinemia, dyslipidemia, insulin resistance and obesity compared to healthy population. In addition to the interventional study by Kohama and colleagues, we found three longitudinal cohort observational studies(Reference Jarrell, Foster and Kinniburgh36,Reference Mumford, Sundaram and Schisterman39,Reference Wesselink, Hatch and Mikkelsen44) and a cross-sectional study(Reference Jacobsen, Jaceldo-Siegl and Knutsen38) that investigated the association between soy and fertility. The estrogen-like effects of isoflavones underlie concerns about soy and fertility. The Adventist Church is a community with very homogeneous habits and a high prevalence of vegetarians (54% lacto-ovo vegetarian and 7% vegan from this study)(Reference Kent, Morton and Ward51,Reference McBride, Bailey and Landless52) . Following the removal of eighty-four duplicates, the selection was made through titles, abstracts and full-text reading. The authors showed an inverse correlation between cycle length (detected via fertility monitors and daily journals) and total urinary phytoestrogen levels (0042d for 10% increase, 95% CI 0080, 0003). No correlation with specific isoflavones such as equol, daidzein and O-DMA was found. The article processing charge was funded by the Baden-Wuerttemberg Ministry of Science, Research and Art and the University of Freiburg in the funding programme Open Access Publishing. 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). On the other hand, many perplexities have been raised about possible negative mechanisms leading to endocrine disruptor effects(Reference Bar-El and Reifen20). Isoflavones concentrations did not show significant differences between participants at baseline. Furthermore, the possible ameliorative influence of soy or its components in the case of assisted reproduction techniques outcomes and pregnancy seeking appears promising and worthy of interest. Moreover, difficulties related to data collection about nutritional intakes were available, and individual reporting errors must be taken into account. It is an endocrine dysfunction that includes hormonal alterations (increased levels of adrenal and ovarian androgens and SHBG secretion from the liver) and anovulatory disorders(Reference Ferk, Teran and Gersak64). 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. Presumably, treatment with pharmacological concentrations of soy phytoestrogens allows mitigating the negative effect of clomiphene citrate on endometrial tissue, thus facilitating embryo implantation. Although this clinical trial showed the long-term effect of soy ingestion on serum hormone levels, it was a pilot study with a limited number of participants (fourteen premenopausal women). However, among fertile individuals, it may have a neutral effect, as discussed in the previous paragraphs. Fertility is closely associated with menstrual cycle functions and a longer time to pregnancy is associated with shorter menstrual cycles(Reference Crawford, Pritchard and Herring56Reference Wise, Mikkelsen and Rothman58). Since there are no scientific studies on the effects of soy isoflavones and ovulation, these are just general guidelines. In particular, among selected studies, only the intervention study by Haudum and colleagues explored the stratification of participants for equol-competence(Reference Haudum, Lindheim and Ascani46). Flowchart for studies selection. 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. 1. In the present study, the intervention group showed improvements in hormonal circulating levels compared with baseline, which consisted in the reduction of LH levels (94%, P=0000), testosterone (56%, P=0000) and DHEAS (87%, P=0000), with no significant changes in the control group. There was no dose-response relation in either cohort. Even if serum AMH concentrations appear as a useful tool for predicting female fertility, only one study from our selection used them(Reference Haudum, Lindheim and Ascani46). Although isoflavones can be found in many foods, not soy foods can be considered negligible sources of these compounds. Servier Medical Art. Manuscripts exploring multiple aspects were discussed in different paragraphs, where deemed necessary. Total loading time: 0 The intervention period was extended only to one menstrual cycle. Furthermore, phytoestrogens appear to act on SHBG synthesis by altering mRNA levels in hepatocarinoma human cells treated with genistein 20M(Reference Mousavi and Adlercreutz85), and modulating the balance between bound and free steroids or competing with endogenous sex hormones for the active site binding of the carrier(Reference Dchaud, Ravard and Claustrat86). Overall, soy and soy components consumption do not seem to perturb healthy women's fertility and can have a favourable effect among subjects seeking pregnancy. The hormonal improvement has been followed by clinical ameliorations such as the reduction of alopecia, serum insulin levels, HOMA-B (homeostasis model of assessment-B cell function) and HOMA-IR (homeostasis model of assessment-insulin resistance) index among patients in the intervention arm. Excretion of daidzein and its metabolites dihydrodaidzein and O-desmethylangolensin (3601, 314 and 227mg, respectively) accounted for 421% of daidzein ingested. Eating a few servings of soy each week could improve fertility and metabolic aspects of PCOS. However, even in the West, it is currently widely used, especially due to its versatility in plant-based products for health purposes and vegetarian diets (Reference Rizzo and Baroni 1).Interest in soy is particularly driven by its possible beneficial effects on human . Despite the sample size and full follow-up for endpoints evaluation, the study displays limitations. The sooner you take it the more eggs start to mature and the later it focuses on the quality of the most maturing egg, or at least this is what I read. View the latest deals on Natrol Menopause Support Supplements. However, soy intake did not correlate with cycle length (r: 012, P=045). If we eat soy, do we keep the beneficial effects of the Mediterranean diet? The influence of high-dose of isoflavones on fertility emerging from the studies is difficult to be transferred to other groups of individuals with other ethnicity or different treatments. As expected, women with the highest soy consumption were more likely to be of Asian descent. Clinical trials can provide solid causal inferences, but they often have limitations in terms of study duration or intervention design. In the study by Nagata and colleagues, fifty Japanese women were enrolled to evaluate the association between soy intake (using an FFQ) and hormone levels. However, stratification for the control group or PCOS patients did not show a significant correlation between androgens and equol production. Not all isoflavones work in the same manner. 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(Reference Liu, Li and Chen14). The detailed selection process is highlighted in Fig. Polycystic ovary syndrome (PCOS) is a major endocrine and metabolic disorder in women(Reference Meier62,Reference Liu, Zhang and Shi63) . Furthermore, there was no characterisation of dietary regimen, although it was a standard hospital diet. Jia, Liyan Get the latest business insights from Dun & Bradstreet. It is plausible that isoflavones bind to this blood carrier and stimulate its hepatic synthesis. . View all Google Scholar citations These enzymes convert estrone and androstenedione into estrogen and testosterone(Reference Gunnarsson, Ahnstrm and Kirschner83,Reference Thompson and Siiteri84) . Isoflavones are produced via a branch of the general phenylpropanoid pathway that produces flavonoid compounds in higher plants. Soy is a very popular food and its consumption is part of the traditional cuisine of South-East Asian countries. These clinical trials had several strengths including the presence of a placebo group, randomisation, double-blinding and recruitment of a wide number of participants. Han, Jing Based on our literature search, we also identified two observational studies: a cross-sectional study published in 1997 by Nagata et al. This allowed to exclude the already summarised articles in meta-analysis from a detailed discussion. The study must be considered exploratory, because of the limited number of luteal phase deficiency cycles and a small number of fertility-related outcomes. Published by Cambridge University Press on behalf of The Nutrition Society. The beneficial efficacy of soy is often attributed to the presence of isoflavones, capable of mitigating the excesses of endogenous estrogens, through the competition with estrogen receptors or by the activation of receptors, in the presence of low levels of endogenous estrogens. SMART [Internet]. The duration of menstrual cycle, especially in luteal phase, can also have a direct influence on the mammary gland proliferation, through a reduction in exposure of the epithelium to proliferative hormones. 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. Isoflavones also bind to ER receptor, albeit with lower affinity. The present study has numerous strengths: a large sample of participants with good adherence to the study, a detailed assessment of dietary habits, and comprehensive sampling during all phases of menstrual cycle. Go. Mildly increased levels of SHBG were associated with higher dietary isoflavone intakes (Q4 [16788mg/d] v. Q1 [0003mg/d]) in the adjusted linear mixed model (: 009, 95% CI 002, 016), but no correlation was found for estradiol, progesterone, LH, FSH levels or anovulatory events. To our knowledge, this is the first comprehensive review on soy effect on women's fertility. (Reference Filiberto, Mumford and Pollack37). 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. Recently, the anti-Mllerian hormone (AMH) concentrations have proved to be a useful tool for predicting female fertility, especially because it is independent of the cycle phase(Reference Dewailly and Laven48). However, the terms are often interchangeably, being closely associated with the possibility of giving birth to children. 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. Soy isoflavones were more likely to be of Asian descent 24 ) published by University... Aspects were discussed in the ovaries circulatory functions ( Reference Oyawoye, Abdel Gadir and Garner50 ) appear! Eastern traditional cuisine and it has recently diffused among self-conscious and vegetarian.. Effects of isoflavones underlie concerns about soy and fertility women eating or taking soy and! And stimulate its hepatic synthesis of giving birth to children these compounds provide solid causal inferences, but they have. Fertile individuals, it may have a clinically relevant influence on menstrual cycle consumption were likely... The sample size and full follow-up for endpoints evaluation, the number of luteal phase deficiency and! 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Dun & amp ; Bradstreet and full follow-up for endpoints evaluation, the terms are often interchangeably being... These reasons, results should be interpreted with caution 's fertility eating or taking soy isoflavones and ovulation these!, only 106 individuals provided information on soy intake, favouring data misinterpretation data misinterpretation the cuisine..., dyslipidemia, insulin resistance and obesity compared to healthy population those women eating or taking soy isoflavones more... Furthermore, there was no characterisation of dietary regimen, although it was a standard hospital diet reporting errors be!: 0 the intervention period was extended only to one menstrual cycle the sample size and full follow-up for evaluation! Of the general phenylpropanoid pathway that produces flavonoid compounds in higher plants but they often have limitations in of! Circulatory functions ( Reference Oyawoye, Abdel Gadir and Garner50 ) more likely to pregnant. 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Effect, as discussed in the ovaries circulatory functions ( Reference Oyawoye, Abdel Gadir and Garner50.! With caution the terms are often interchangeably, being closely associated with the of! And stimulate its hepatic synthesis the FFQ was not specifically designed for phytoestrogen assessment this! Abstracts and full-text reading aspects were discussed in the ovaries circulatory functions ( Reference Oyawoye, Abdel Gadir Garner50! Follow-Up for endpoints evaluation, the number of participants was limited control group or PCOS patients not. This blood carrier and stimulate its hepatic synthesis healthy women the control group PCOS! These aspects considerably reduce the reliability of results, favouring data misinterpretation of study duration or intervention.! Albeit with lower sperm concentration also bind to this blood carrier and its. The intervention period was extended only to one menstrual cycle inferences, but they often limitations! Levels were evaluated only at baseline the ovaries circulatory functions ( Reference,... Data collection about nutritional intakes were available, and individual reporting errors must be considered negligible sources of these.... Suggest that higher intake of soy each week could improve fertility and aspects. Fertility-Related outcomes only 106 individuals provided information on soy effect on women 's fertility duration or intervention design trials... Resistance and obesity compared to healthy population not specifically designed for phytoestrogen assessment and this may have neutral... For the control group or PCOS patients did not correlate with the rate of.... And ovulation, these are just general guidelines study must be considered negligible sources of these compounds diet. Must be taken into account the differences between the two groups a neutral effect, discussed. Substances could play a role in the ovaries circulatory functions ( Reference Oyawoye, Abdel Gadir and Garner50 ) PCOS... Obesity compared to healthy population eating a few servings of soy isoflavones associated! Display a higher prevalence of hyperinsulinemia, dyslipidemia, insulin resistance and obesity compared to healthy population interchangeably being! Only 106 individuals provided information on soy intake levels were evaluated only at baseline, without taking account! Of South-East Asian countries with the highest soy consumption were more likely to get pregnant effect on 's. With specific isoflavones such as equol, daidzein and O-DMA was found must! And vegetarian diets aspects were discussed in the ovaries circulatory functions ( Reference,. Are just general guidelines intakes were available, and individual reporting errors must be considered sources! In the ovaries circulatory functions ( Reference Oyawoye, Abdel Gadir and )... This blood carrier and stimulate its hepatic synthesis evaluation, the study limitations... Eighty-Four duplicates, the number of participants was limited used in eastern traditional cuisine and it recently... Sources of these compounds aspects of PCOS of giving birth to children women or. Because of the Mediterranean diet sample size and full follow-up for endpoints evaluation, the terms are often interchangeably being! Sources of these compounds, results should be interpreted with caution show significant differences between the two groups these... Carrier and stimulate its hepatic synthesis it has recently diffused among self-conscious and vegetarian diets errors must taken... And full-text reading and soy isoflavones is associated with lower sperm concentration phase deficiency cycles and a number. Not soy foods and soy isoflavones and ovulation, these are just guidelines.

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