was a pilot study without a characterisation of diet among participants and without data on soy composition (isoflavone or antioxidant contents). On the other hand, many perplexities have been raised about possible negative mechanisms leading to endocrine disruptor effects(Reference Bar-El and Reifen20). These alterations easily lead to hyperandrogenism and irregular menstrual cycles. No significant differences were found in the spontaneous abortion rate, the number and quality of embryos transferred or oocytes fertilised. 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(Reference Unfer, Casini and Costabile31,Reference Unfer, Casini and Gerli32) . No investigation into the individual's ability to absorb and use isoflavones from soy milk was performed. 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). For these reasons, studies that evaluated the ovarian hormones secretion were aimed at exploring the potential beneficial effect of soy on breast cancer prevention, but they were not designed for the evaluation of endocrine consequences, including fertility. The intervention period was extended only to one menstrual cycle. Follicular development, the number of preovulatory follicles and the pulsatility index values were not different between groups after intervention. 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. However, there were also limitations: the duration of the study which was limited to two menstrual cycles and an evaluation of equol-producers among individuals was lacking. 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). A weak, not clinically relevant effect has been highlighted on cycle length and hormonal status. Soy is a very popular food and its consumption is part of the traditional cuisine of South-East Asian countries. Furthermore, there was no characterisation of dietary regimen, although it was a standard hospital diet. Furthermore, the type of dietary survey carried out in the proposed environmental questionnaire was not clear. No changes in progesterone and SHBG concentrations from baseline were observed. 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. The disease etiology is still debated but it seems to involve inflammatory mechanisms and oxidative stress(Reference Escobar-Morreale, Luque-Ramrez and Gonzlez65,Reference Showell, Mackenzie-Proctor and Jordan66) . However, the evaluation of ability to absorb and metabolise isoflavones was lacking in the present study. 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. However, the terms are often interchangeably, being closely associated with the possibility of giving birth to children. Soy isoflavones can help induce ovulation in such women. 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). In another prospective study, 471 healthy American women were followed for 12 months or until delivery without showing significant correlations between urinary isoflavones, quantified by HPLC-MS analysis, and fertility, defined with adjusted Cox Model using time-to-pregnancy assessment(Reference Mumford, Sundaram and Schisterman39), while lignan concentrations in urine were significantly associated with shorter time to pregnancy. Moreover, significant improvement of oxidative markers such as total glutathione and malondialdehyde levels was observed. Phytoestrogens and breast cancer promoters or protectors? PMID: 35320928. Finally, the authors made a detailed assessment of confounders (diet, ethnicity, age and BMI). Independent Researcher, Via Venezuela 66, 98121Messina, Italy, Laboratory of Cardiovascular Endocrinology, IRCCS San Raffaele Roma, 00166Rome, Italy, Department of Human Sciences and Promotion of the Quality of Life, San Raffaele Roma Open University, 00166Rome, Italy, Center for Complementary Medicine, Department of Internal Medicine II, Faculty of Medicine, University of Freiburg, Freiburg, Germany, Reference Mosallanezhad, Mahmoodi and Ranjbar, Reference Setchell, Brown and Lydeking-Olsen, Reference Hamilton-Reeves, Vazquez and Duval, Reference Reed, Camargo and Hamilton-Reeves, Reference Oyawoye, Abdel Gadir and Garner, Reference Mumford, Sundaram and Schisterman, Reference Jacobsen, Jaceldo-Siegl and Knutsen, Reference Crawford, Pritchard and Herring, Reference Andrews, Schliep and Wactawski-Wende, Reference Sdergrd, Bckstrm and Shanbhag, Reference Escobar-Morreale, Luque-Ramrez and Gonzlez, Reference Showell, Mackenzie-Proctor and Jordan, Reference Romualdi, Costantini and Campagna, Reference Chavarro, Mnguez-Alarcn and Chiu, Reference Sinai, Ben-Avraham and Guelmann-Mizrahi, Reference Ropero, Alonso-Magdalena and Ripoll, Reference Valles, Dolz-Gaiton and Gambini, Reference Gunnarsson, Ahnstrm and Kirschner, 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, Cumulative meta-analysis of the soy effect over time, Soy, soy isoflavones, and protein intake in relation to mortality from all causes, cancers, and cardiovascular diseases: a systematic review and dose-response meta-analysis of prospective cohort studies, Consensus: soy isoflavones as a first-line approach to the treatment of menopausal vasomotor complaints, Soy isoflavones for osteoporosis: an evidence-based approach, Soy and isoflavone consumption and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational studies and randomized trials in humans, Soy intake is associated with lowering blood pressure in adults: a systematic review and meta-analysis of randomized double-blind placebo-controlled trials, The antioxidant role of soy and soy foods in human health, Non-isoflavone phytochemicals in soy and their health effects. 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 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). Many of its components show an antioxidant activity that can at least partially explain its effectiveness(Reference Rizzo9). Put simply, most of the evidence indicates that isoflavones do not adversely affect men's fertility. The phytoestrogen actions of soy isoflavones may increase estrogen levels in the body and induce ovulation in women, thus, may speed up the process of pregnancy. 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. In addition, equol acts on incretins levels in endocrine L cell line GLUTag cells at concentration ranging from 50 to 300M, with long-term metabolic consequences(Reference Harada, Sada and Sakaguchi79). The FFQ was not specifically designed for phytoestrogen assessment and this may have underestimated intakes. 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. Isoflavones are non-steroidal compounds with a chemical structure similar to endogenous estrogens and for this reason, they are defined as phytoestrogens: a functional classification that also includes lignans, coumestans and stilbenes(Reference Basu and Maier12). Fig. Women who also have the problem of irregular periods can consume these isoflavones to get much-needed relief. Finally, they show antioxidant activity: a shared property among polyphenols(Reference Patel, Boersma and Crawford19). Pettitt, Claire In response, your body starts a cascade of events to boost estrogen production. 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. [cited 2021 Jul 26]. Smaoui, Slim There are clues about the association between soy intake and the increase in SHBG levels. Furthermore, the use of spot urine samples could generate an underestimation of urinary isoflavones quantification. The two observational studies also show different limitations, in particular, one of these studies uses a follow-up of only 2 months. However, after removing data from studies with elevated bias risk, two studies were included in the sensitivity analysis with a consequent loss of statistical significance for LH levels. The reduction of estradiol concentrations observed became statistical marginal (89%, P=006) when analysis was restricted to the clean dataset: data after exclusion of thirteen specimens collected too soon or too late after ovulation. The study must be considered exploratory, because of the limited number of luteal phase deficiency cycles and a small number of fertility-related outcomes. 3 Department of Human Sciences and Promotion of the Quality of Life, San Raffaele Roma Open University, 00166 Rome, Italy. The chemical structure similarity between soy isoflavones and endogenous estrogens has always stimulated the attention for this class of compounds. The study included the evaluation of patients microbiota composition as the primary endpoint, but androgen levels were also evaluated with AMH as markers of fertility as a secondary endpoint. Adapted from SMART: Servier Medical Art(89). 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 . These aspects were poorly characterised by self-reporting of the participants. Flowchart for studies selection. In 2015, a longitudinal study found no differences in sexual organ development at 5 years of age between cow milk formula, breast milk and soy formula feeding(Reference Andres, Moore and Linam69). 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. Table 2 summarises main limitations about the studies discussed. The urinary or serum levels of isoflavones did not affected progesterone levels in the multiple regression analysis. conducted a 7-month interventional study on twenty healthy American women aged 2144, half of them of Asian origin, using various types of soy foods (soy milk, edamame, tofu) for an overall daily intake of about 32mg of isoflavones(Reference Wu, Stanczyk and Hendrich28). 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. Introduction. Similar to the previous observational study, Chavarro et al. Render date: 2023-03-02T11:20:28.481Z SHBG levels were not associated with the intake of soy foods, except in the case of miso intake on the 22nd day of cycle (r: 036, P=002). Found in the present study summarises main limitations about the association between soy isoflavones can help induce ovulation such. Effectiveness ( Reference Rizzo9 ) body starts a cascade of events to boost estrogen production levels isoflavones... 'S ability to absorb and use isoflavones from soy milk was performed characterised by self-reporting of traditional... Spot urine samples could generate an underestimation of urinary isoflavones quantification the intervention period was extended only to menstrual!: a shared property among polyphenols ( Reference Patel, Boersma and Crawford19.... Underestimation of urinary isoflavones quantification, the evaluation of ability to absorb and metabolise isoflavones was lacking the. 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