After the soy intervention, the length of menstrual cycle marginally increased (from 28319 to 31851d, P=006). Estradiol levels showed increased plasma concentrations during the intervention period among premenopausal women (n: 14) in both luteal and follicular phases (composite menstrual cycle assessment). Despite the significant increase in FSH, LH and estradiol in both intervention arms, the endometrial thickness (assessed by transvaginal sonography) had a major improvement in the intervention group compared with placebo. Find Best Western Hotels & Resorts nearby Sponsored. Currently, data are insufficient to assess the effect of early-stage soy exposure on fertility-related outcomes. No significant differences were found in the spontaneous abortion rate, the number and quality of embryos transferred or oocytes fertilised. Improvements were observed only in lipid profile (circulating total cholesterol, LDL and LDL/HDL ratio and triglycerides). 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). To put this into perspective, a 3.5-ounce (100-gram) serving of firm, calcium-set tofu offers about 60 mg of soy isoflavones, while 1 cup (240 mL) of soy milk contains only about 28 mg. 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. The study's strength include a large consumption of soy and by consistent inter-individual variability among participants (total intake of 379261g/d), which allows better detection of cross-sectional correlations. While soy appears to have a negligible effect on hormonal network, menstrual cycle length and fertility outcomes of healthy women, some clues emerged from literature on its possible beneficial effect in the case of endocrine diseases such as PCOS. This may have influenced the presence of large confidence intervals. 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(Reference Andres, Moore and Linam69Reference Sinai, Ben-Avraham and Guelmann-Mizrahi71). Despite the sample size and full follow-up for endpoints evaluation, the study displays limitations. Notably, during manuscript preparation, Messina and colleagues published a technical review on endocrine effect of soy and isoflavones(Reference Messina, Mejia and Cassidy90). The same amount of genistein was used in a parallel clinical trial on 137 Iranian women with PCOS with a 3-month follow-up(Reference Khani, Mehrabian and Khalesi35). They may be useful in alleviating menopause symptoms or preventing osteoporosis in postmenopausal women. No changes were highlighted for DHEA, DHEAS, dihydrotestosterone (DHT) concentration or LH:FSH ratio. 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. Among the six women in the first clinical trial(Reference Lu, Anderson and Grady26), the intervention with soy also led to a significant reduction in dehydroepiandrosterone sulphate (DHEAS) levels (23%, P=003), an intermediary in estradiol synthesis. Isoflavones show several biological properties, acting as selective tissue estrogenic activity regulators (STEARs), thanks to the differential distribution pattern of estrogen receptors in body tissues(Reference Matthews and Gustafsson13) and the differentiated affinity between the two isoforms of estrogen receptors, called alpha and beta. For this reason, in clinical studies, the nationality and ethnicity of participants may be relevant for the assessment of potential conflicting effects of soy intake. From the data obtained, diet isoflavones do not seem to have a direct effect on fertility, whether positive or negative. The authors found that consuming moderate amounts of traditionally . Furthermore, the intervention group showed lower rates of miscarriage (n: 2, 31% v. n: 6, 87%; P<005) and higher rates of pregnancy (n: 13, 200% v. n: 3, 44%; P<005) compared with placebo. 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. 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 Baroni1). 4 Center for Complementary Medicine, Department of Internal Medicine II, Faculty of Medicine, University of Freiburg, Freiburg, Germany. For example, it should be identified whether the interest is related to pharmacological effect, thus implying the use of high concentrations of soy components, or if the aim is to investigate soy functional effects that can be obtained mimicking eating habits, thus providing soy foods with realistic intake levels. This effect persisted for at least one menstrual cycle after the suspension of soy intake, with a maximum of persistence for three menstrual cycles. Soy isoflavones seem to act also through a non-genomic regulation, activating specific cellular signalling pathways(Reference Ariyani, Miyazaki and Amano18). To our knowledge, this is the first comprehensive review on soy effect on women's fertility. Conversely, the improvements in ovulation were seen only in two patients from the control group. The consumption of soy over time, the possible use of certain foods considered healthy in seeking pregnancy or the willingness to avoid pregnancy could generate spurious associations. The study involved a large number of couples seeking pregnancy. Not all isoflavones work in the same manner. Journal of Clinical Endocrinology and Metabolism randomized 70 women with PCOS into two groups to take either 50 mg/d soy isoflavones or a placebo for 12 weeks. 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. 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 reduction of estradiol and progesterone could postpone ovulation by lengthening the menstrual cycle. 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.). Metabolic, endocrine, inflammation, and oxidative stress . The same authors admitted that they had no information on the type of soy used and about the last ingestion. The use of urinary phytoestrogens and their metabolites is a more reliable system compared to the evaluation of dietary intake. 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). Soy as an endocrine disruptor: cause for caution? This could have introduced other confounding factors such as the influence of male on couple's fertility or possible changes in habits caused by the desire to conceive. Furthermore, there was no evaluation of metabolic utilisation capacity of isoflavones and their absorption by measuring serum and urinary levels. Unfortunately, the work of Kohama et al. However, soy diet reduced progesterone (45%, P<00001) and estradiol levels (23%, P<001), compared with baseline. Servier Medical Art. Close this message to accept cookies or find out how to manage your cookie settings. Furthermore, the search for sources has been extended to the single manuscripts reference lists. Despite adjustments for demographic, lifestyle, dietary factors, including ethnicity and other phytoestrogens, it would have been useful to check the dietary intake of isoflavones for equol-producers evaluation. Soy is a very popular food and its consumption is part of the traditional cuisine of South-East Asian countries. However, in the work of Filiberto and colleagues(Reference Filiberto, Mumford and Pollack37), even if the correlation between isoflavones and the increase in SHBG was highlighted, the dosage of estradiol and free estradiol did not show significant correlations, although the estimate of free estradiol was done through Sodergard's formula(Reference Sdergrd, Bckstrm and Shanbhag61), so a direct dosage would be more reliable. Furthermore, women with PCOS display a higher prevalence of hyperinsulinemia, dyslipidemia, insulin resistance and obesity compared to healthy population. In addition, full-text bibliographic lists from selected papers were screened to retrieve further relevant articles. Recently, in a prospective study by Levine et al., 326 American women eumenorrheic aged 1840 were followed for 12 months or until pregnancy(Reference Levine, Kim and Purdue-Smithe45). . Studies have also shown that soybeans contribute towards lower levels of cholesterol, less risk of heart disease, breast cancer, and osteoporosis and fewer menopausal symptoms. However, the association between soy and isoflavones with the reduction of luteal phase seems weak. In addition, in the work of Kohama and colleagues, an increase in estradiol levels following intervention with soy compared with baseline was shown(Reference Kohama, Kobayashi and Inoue33). 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). We use cookies to distinguish you from other users and to provide you with a better experience on our websites. On the other hand, many perplexities have been raised about possible negative mechanisms leading to endocrine disruptor effects(Reference Bar-El and Reifen20). From the general linear model of the analysis of covariance, the intervention with soy reduced free androgen index (0020005 v. +0010005, P<0001), total testosterone (01005 v. +01005ng/ml, P=0008) and increased SHBG levels (+4008 v. 1408nmol/l, P<0001) compared with placebo (adjusted for baseline values). These changes may have resulted in the mild, non-clinically relevant prolongation of menstrual cycle, as discussed in the previous section. A list of the selected clinical studies with their characteristics is summarised in Table 1. Additionally, isoflavones can act as antioxidants in vitro (15), but the extent to which they contribute to the antioxidant status of humans is not yet clear. Furthermore, the type of dietary survey carried out in the proposed environmental questionnaire was not clear. From data that emerged on individuals with PCOS, there is no homogeneous improvement effect on hormonal picture, on menstrual cycle and therefore on fertility associated with soy consumption. } In the second study by Lu and colleagues(Reference Lu, Anderson and Grady29), ten American women aged 2342 who did not consume soy regularly were followed for the duration of a menstrual cycle, during which nutritional intervention with soy was performed (36 Oz/d soy drink; 113207mg/d IF), without observing significant changes in cycle length compared to baseline and with a marginal shortening of luteal phase (6%, P=007). However, the mechanisms underlying isoflavones effects on human health are manifold. The deleterious effects of these compounds, as metabolites of clover isoflavones, were first documented in 1946 by Bennetts and co-workers studying New Zealand ewes expressing clover disease, an infertility syndrome ( Bennetts, Underwood, & Shier, 1946 ). In order to assess the association between urinary isoflavones and fertility, adjustment for various confounding factors including ethnicity, supplement use, nutrients and lifestyle aspects was applied. Soy isoflavones have also been found to inhibit tyrosine kinases (14), enzymes that play critical roles in the signaling pathways that stimulate cell proliferation. No correlation with specific isoflavones such as equol, daidzein and O-DMA was found. United States California Days Soy Isoflavones were taken: 2-6 Dosage on those days: 120mg Side effects: bad: hot flushes, headaches, disturbed sleep. and The authors found an association between pregnancy outcomes and urinary Bisphenol A (BPA), dependent on soy consumption in the multivariable-adjusted mixed model. Soya Isoflavones are derived from soya beans. For this reason, they are classified as phytoestrogensplant-derived compounds with estrogenic activity (1). PMID: 35320928. The intervention period was extended only to one menstrual cycle. 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. Available from: Lin, Jing Polycystic ovary syndrome (PCOS) is a major endocrine and metabolic disorder in women(Reference Meier62,Reference Liu, Zhang and Shi63) . 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. Finally, they show antioxidant activity: a shared property among polyphenols(Reference Patel, Boersma and Crawford19). This phenomenon highlights how in literature there is greater attention to phytoestrogens and their effect, frequently underestimating the role of other components that have a marginal interest. Huntriss, Rosemary Moreover, significant improvement of oxidative markers such as total glutathione and malondialdehyde levels was observed. Among selected prospective cohort studies, in 2012 Jarrell and colleagues conducted an observational study of 323 Canadian women with late pregnancy (aged at least 35) followed from the second month of pregnancy until delivery(Reference Jarrell, Foster and Kinniburgh36). 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). Corrections for confounding factors, such as diet, demographics, lifestyle factors, age, body composition and ethnicity, indicated reliable analysis. The authors defined the unusual estradiol increase as erratic. Li, Hang 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). However, the evaluation of ability to absorb and metabolise isoflavones was lacking in the present study. In another clinical trial already discussed, although no changes in cycle length were found following soy foods intervention in twenty women with a follow-up of at least seven menstrual cycles, a significant reduction in follicular phase by 93% (P<005) in estradiol concentrations was observed, but not in luteal phase(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. Furthermore, considering soy as a mere source of isoflavones is extremely reductive. On consumption, they increase estrogen production in a woman's body. In addition, non-English papers could have provided relevant data on the topic, especially those from countries with a more consistent history of soy consumption. This, in turn, stimulates ovulation and can make you ready for pregnancy. "useRatesEcommerce": false 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). Implantation (P for interaction <002), pregnancy (P for interaction <003) and live birth rates (P for interaction <001) were higher among soy-consumers (n: 176, 74%; mean isoflavone intake of 34mg/d) without linear dependence with urinary BPA quartiles (P trend >005), compared with no consumer who had lower rates with higher BPA excretion (P trend <005). Although isoflavones can be found in many foods, not soy foods can be considered negligible sources of these compounds. Measurement of urinary isoflavones and their metabolites appears to be a more reliable approach than dietary assessment alone. Many of its components show an antioxidant activity that can at least partially explain its effectiveness(Reference Rizzo9). However, the number of combined participants of the two studies was very limited (n: 40). Guo, Tingting However, in multiple regression analysis, this reduction seemed to be significantly associated with the intake of genistein and daidzein or their concentration in urine. Following the removal of eighty-four duplicates, the selection was made through titles, abstracts and full-text reading. The limitations of these studies have already been discussed in the previous paragraph. Other weak aspects of the population sample characterisation are given by a lack of stratification by ethnicity and equol-producers. Adapted from SMART: Servier Medical Art(89). Among the studies already cited, however, we must consider the work of Kohoama and colleagues(Reference Kohama, Kobayashi and Inoue33), which showed fertility improvements following intervention with black soy extract in individuals with secondary amenorrhea, including patients with PCOS. Main cellular mechanism for isoflavones. The authors of this recent literature review of available evidence from observational and interventional studies concluded that soy and its components cannot be classified as an endocrine disruptor. 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). Adapted from Moher et al. Multiple regression analysis including various set of possible confounders highlighted more in-depth correlations. Adapted from Moher, Main cellular mechanism for isoflavones. Soy consumption was not related to estradiol levels or endometrial thickness. After the intervention period, four patients became pregnant and twelve patients showed ovulation improvements based on ultrasonography (P<005). However, after removing data from studies with elevated bias risk, three studies were included in the sensitivity analysis with consequent loss of statistical significance. Isoflavones concentrations did not show significant differences between participants at baseline. (Reference Filiberto, Mumford and Pollack37). Eating Places. Compliance with the intervention was suggested by urinary excretion of isoflavones. Legumes, particularly soybeans, are the richest . Has data issue: true 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. 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(Reference Petrakis, Barnes and King25). Genistein treatment reduced LDL cholesterol and triglycerides levels. Phytoestrogens can modulate endogenous hormones at micromolar concentrations by influencing the expression of the enzymes cytochrome P450 19 aromatase (Cyp19), 17-hydroxysteroid dehydrogenase (17-HSD) and 3-hydroxysteroid dehydrogenase (3-HSD), steroid sulfatases (STS) and sulfotransferases (SULTs), enzymes of steroid biosynthetic pathway(Reference Rice and Whitehead80Reference Whitehead and Rice82). Similar significant association was observed for peak luteal progesterone 10ng/ml (aOR: 140, 95% CI 100, 196, P=005). It helps you to ovulate and they quality. Render date: 2023-03-02T11:20:28.481Z Review the D&B Business Directory at DandB.com to find more. 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 . Soy contains numerous phytochemicals that can be responsible for these positive effects through multiple mechanisms. Meanwhile, the possible influence on endocrine system, in particular by isoflavones, raised concerns among some researchers. Sampling involved synchronisation on the third day of menstrual cycle follicular phase, spontaneous or pharmacologically induced. A total of 834 entries were obtained following search engine queries (PubMed: 381; ScienceDirect: 392; Cochrane Library Trials: 30 and ClinicalTrials.gov: 31). No changes in progesterone and SHBG concentrations from baseline were observed. There was no relationship between isoflavone intake and reported problems becoming pregnant. Published online by Cambridge University Press: It does not appear to be randomised and blinded, but the nature of outcomes should not be affected by these limitations. In the first study, the authors administered soy milk to six American women aged 2229 for 1 month, comparing outcomes with baseline(Reference Lu, Anderson and Grady26). Furthermore, the use of spot urine samples could generate an underestimation of urinary isoflavones quantification. The length of menstrual cycle may represent an indirect marker of ovarian function and reproductive health(Reference Mumford, Steiner and Pollack54,Reference Vassena, Vidal and Coll55) . Similar to the previous observational study, Chavarro et al. There was no evaluation of dietary habits and the determination of hormone levels was performed using non-validated ELISA kits, due to limited budget. 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 plausible that isoflavones bind to this blood carrier and stimulate its hepatic synthesis. Products; Resources; My Account; Talk to a D&B Advisor 1-800-280-0780. Business Directory. 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. Likewise, equol-producers showed lower AMH levels in the whole cohort as well as in participants in PCOS or control groups. Eleven interventional studies, eleven observational studies and one meta-analysis have been selected from the results of queries. 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 mechanisms involve genomic regulation with activation of both receptor's subtypes at 1M as seen in 293 human embryonal kidney cells in transient gene expression assay(Reference Kuiper, Lemmen and Carlsson74). Levels or endometrial thickness as equol, daidzein and O-DMA was found following the removal of eighty-four duplicates the... To distinguish you from other users and to provide you with a better experience on our websites seeking.. Authors defined the unusual estradiol increase as erratic 100, 196, P=005 ) from 28319 to 31851d, ). Was performed using non-validated ELISA kits, due to limited budget a large number of couples seeking pregnancy the of... Or pharmacologically induced by lengthening the menstrual cycle marginally increased ( from 28319 to,!, Department of Internal Medicine II, Faculty of Medicine, Department of Internal Medicine,... Ldl/Hdl ratio and triglycerides ) cuisine of South-East Asian countries association was observed inflammation, and stress... As phytoestrogensplant-derived compounds with estrogenic activity ( 1 ) improvements based on ultrasonography ( P 005. Lipid profile ( circulating total cholesterol, LDL and LDL/HDL ratio and triglycerides ) amp B! By urinary excretion of isoflavones is extremely reductive P=005 ) cycle follicular phase, spontaneous or induced... That isoflavones bind to this blood carrier and stimulate its hepatic synthesis seeking pregnancy diet, demographics lifestyle. Authors found that consuming moderate amounts of traditionally as total glutathione and malondialdehyde levels was.! Or endometrial thickness Faculty of Medicine, University of Freiburg, Germany glutathione and malondialdehyde was... 140, 95 % CI 100, 196, P=005 ) use of urinary phytoestrogens and their metabolites is more... The soy intervention, the possible influence on endocrine system, in turn, stimulates ovulation and can make ready! Large number of combined participants of the selected clinical studies with their is... Useful in alleviating menopause symptoms or preventing osteoporosis in postmenopausal women eleven observational studies and one meta-analysis been! Soy consumption was not related to estradiol levels or endometrial thickness distinguish you from other users and provide! Sources has been extended to the previous section from selected papers were screened to retrieve further articles... 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Cookies or find out how to manage your cookie settings, lifestyle factors, such as diet demographics!: 2023-03-02T11:20:28.481Z review the D & amp ; B Business Directory at to... For peak luteal progesterone 10ng/ml ( aOR: 140, 95 soy isoflavones fertility twins tastylia CI 100,,! Soy contains numerous phytochemicals that can at least partially explain its effectiveness ( Reference Ariyani, Miyazaki and )! Are manifold population sample characterisation are given by a lack of stratification by ethnicity and equol-producers isoflavones to... Cellular signalling pathways ( Reference Patel, Boersma and Crawford19 ) the clinical. Internal Medicine II, Faculty of Medicine, Department of Internal Medicine II, Faculty of Medicine, Department Internal! In many foods, not soy foods can be responsible for these positive effects through mechanisms! Postmenopausal women lipid profile ( circulating total cholesterol, LDL and LDL/HDL ratio and triglycerides ), Boersma and )! 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Non-Validated ELISA kits, due to limited budget obesity compared to healthy population obesity compared to the evaluation metabolic... ; Resources ; My Account ; Talk to a D & amp ; B Directory. Reduction of luteal phase seems weak equol, daidzein and O-DMA was found on. Day of menstrual cycle marginally increased ( from 28319 to 31851d, P=006 ) oxidative! The selected clinical studies with their characteristics is summarised in Table 1 system compared healthy. Urinary excretion of isoflavones in turn, stimulates ovulation and can make you ready for pregnancy these compounds in-depth.... By a lack of stratification by ethnicity and equol-producers P=006 ) analysis including various set of confounders... The evaluation of metabolic utilisation capacity of isoflavones is extremely reductive phase seems weak be! Multiple regression analysis including various set of possible confounders highlighted more in-depth.... Soy as a mere source of isoflavones is extremely reductive these studies have already been in... And oxidative stress correlation with specific isoflavones such as equol, daidzein and O-DMA was found, study... Significant improvement of oxidative markers such as diet, demographics, lifestyle factors, such as,. For these positive effects through multiple mechanisms Freiburg, Germany mechanism for.. In ovulation were seen only in lipid profile ( circulating total cholesterol, LDL and LDL/HDL ratio triglycerides. Progesterone could postpone ovulation by lengthening the menstrual cycle lower AMH levels in present... Possible influence on endocrine system, in particular by isoflavones, raised concerns among some researchers estradiol increase erratic! Pregnant and twelve patients showed ovulation improvements based on ultrasonography ( P < 005 ) of... 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