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Online Library: Pregnancy and Fertility

The following pages provide an overview of the most recent research and clinical studies about the health benefits of micronutrients in pregnancy and fertility. This collection of scientific facts proves that anyone who privately or publicly questions the health value of micronutrients does not serve YOUR health, or the health of the people, but rather the multi-billion dollar investment 'business with disease' based on patented pharmaceutical drugs.

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Prenatal vitamins, one-carbon metabolism gene variants, and risk for autism

Source: Epidemiology 2011; 22(4):476-85

Author: Schmidt RJ, Hansen RL, Hartiala J, Allayee H, Schmidt LC, Tancredi DJ, Tassone F, Hertz-Picciotto I

Affiliation: Department of Public Health Sciences, University of California Davis School of Medicine, Davis, CA, USA.

Abstract: Causes of autism are unknown. Associations with maternal nutritional factors and their interactions with gene variants have not been reported.For this study northern California families were enrolled from 2003 to 2009 in the CHARGE (CHildhood Autism Risks from Genetics and Environment) population-based case-control study. Children aged 24-60 months were evaluated and confirmed to have autism (n = 288), autism spectrum disorder (n = 141), or typical development (n = 278) at the University of California-Davis Medical Investigation of Neurodevelopmental Disorders Institute using standardized clinical assessments. The authors calculated adjusted odds ratios (ORs) for associations between autism and retrospectively collected data on maternal vitamin intake before and during pregnancy. Conclusions: Periconceptional use of prenatal vitamins may reduce the risk of having children with autism, especially for genetically susceptible mothers and children. Replication and mechanistic investigations are warranted.

Double-blind, placebo-controlled study of a nutritional supplement for improving fertility in women

Source: Clinical and experimental obstetrics & gynecology 2006; 33(4):205-8

Author: Westphal LM, Polan ML, Trant AS

Affiliation: Department of Gynecology/Obstetrics, Stanford University School of Medicine, USA.

Abstract: This study was conducted to determine the impact of nutritional supplementation on female fertility. Method: A double blind, placebo-controlled study of the effects of a proprietary nutritional supplement containing chasteberry, green tea, L-arginine, vitamins (including folate) and minerals, on progesterone level, basal body temperature, menstrual cycle length, pregnancy rate and side-effects.Ninety-three (93) women, aged 24-42 years, who had tried unsuccessfully to conceive for six to 36 months, completed the study. After three months, the test group (N = 53) demonstrated a trend toward increased mean mid-luteal progesterone (P(ml)), but among women with basal pretreatment P(ml) < 9 ng/ml, the increase in progesterone was highly significant. The average number of days with luteal-phase basal temperatures over 98 degrees F increased significantly in the test group. Both short and long cycles (< 27 days or > 32 days pretreatment) were normalized in the test group. The placebo group (N = 40) did not show any significant changes in these parameters. After three months, 14 of the 53 women in the test group were pregnant (26%) compared to four of the 40 women in the placebo group (10%; p = 0.01). Three additional women conceived after six months on the nutritional supplement (32%). No significant side-effects were noted.Conclusion: Nutritional supplements could provide an alternative or adjunct to conventional fertility therapies.

Improvement of sperm quality after micronutrient supplementation

Source: e-SPEN Journal 2012, 7(1):e50-e53

Author: Imhof M, Lackner J, Lipovac M, Chedraui P, Riedl C

Affiliation: Fertility Clinic IMI, Vienna, Austria, Department of Obstetrics and Gynecology, Vienna, Austria, Institute of Biomedicine,Universidad Catolica de Santiago de Guayaquil, Equador

Abstract: Nearly 50% of male infertility is idiopathic* and there still is no proven therapy. The authors evaluated the effect of a non prescription nutraceutical containing eight micronutrients on sperm quality in males with idiopathic sub-fertility. This open comparative pilot study was carried out at the Fertility Center IMI, Vienna, Austria. A total of 132 sub-fertile males (active treatment group) were invited to participate and take two daily capsules of the active compound for a three month period between the first and the follow-up semen analysis. Each capsule contained L-carnitine, L-arginine, zinc, vitamin E, glutathione, selenium, coenzyme Q10 and folic acid. Sub-fertile men receiving no active treatment served as controls (n = 73). Main outcome measure was the standardized semen analysis. All parameters evaluated by semen analysis significantly increased after 3 months of treatment with the active compound. Median ejaculatory volume, sperm cell density, sperm motility (progressive and total) and normal morphology rate increased by 33.3%, 215.5%, 83.1%, 36.4% and 23.0%, respectively. These increments were significantly higher than those observed among controls. In the active treatment group no side effects were encountered and a total of 34 pregnancies were reported after 6 months follow-up whereas 11 were reported in the control group. Conclusion: Semen analysis significantly improved in sub-fertile men after treatment with an active micronutrient compound, leading to pregnancies without any adverse effects.

* Of unknown cause.

Metabolic and hormonal effects of myo-inositol in women with polycystic ovary syndrome: a double-blind trial

Source: European review for medical and pharmacological sciences 2009 Mar-Apr;13(2):105-10.

Author: Costantino D, Minozzi G, Minozzi E, Guaraldi C

Affiliation: Centro Salute della Donna, Azienda USL, Ferrara, Italy.

Abstract: To investigate the effects of treatment with Myo-inositol (an insulin sensitizing drug), on circulating insulin, glucose tolerance, ovulation and serum androgens concentrations in women with the Polycystic Ovary Syndrome (PCOS), 42 women with PCOS were treated in a double-blind trial with Myo-inositol plus folic acid or folic acid alone as placebo. In the group treated with Myo-inositol there was observed a significant decrease of the serum total testosterone and serum free testosterone, of plasma triglycerides, systolic and diastolic blood pressure, and the area under the plasma insulin curve after oral administration of glucose decreased, all in relation to placebo group. Also the index of composite whole body insulin sensitivity (ISI comp) increased. 16 out of 23 women of Myo-inositol group ovulated (4 out of 19 in placebo group). Conclusion: Treatment of PCOS patients with Myo-inositol provided a decreasing of circulating insulin and serum total testosterone as well as an improvement in metabolic factors.

Randomized, double blind placebo-controlled trial: effects of myo-inositol on ovarian function and metabolic factors in women with PCOS*

Source: European review for medical and pharmacological sciences 2007 Sep-Oct;11(5):347-54.

Author: Gerli S, Papaleo E, Ferrari A, Di Renzo GC

Affiliation: Department of Obstetrics and Gynecology, Monteluce Hospital, University of Perugia, Italy.

Abstract: Oligomenorrhea and polycystic ovaries in women are one of the most important causes of the high incidence of ovulation failure. This is linked, perhaps, to insulin resistance and related metabolic features. A small number of reports show that myo-inositol improves ovarian function, but in these trials the quality of evidence supporting ovulation is suboptimal. Furthermore, few of them have been placebo-controlled. The aim of our study was to use a double-blind, placebo-controlled approach with detailed assessment of ovarian activity (two blood samples per week) to assess the validity of this therapeutic approach in this group of women. Of the 92 patients randomized, 47 received 400 mcg folic acid as placebo, and 45 received myo-inositol plus folic acid (4 g myo-inositol plus 400 mcg folic acid). The ovulation frequency assessed by the ratio of luteal phase weeks to observation weeks was significantly higher in the treated group (25%) compared with the placebo (15%), and the time to first ovulation was significantly shorter. The number of patients failing to ovulate during the placebo-treatment period was higher in the placebo group, and the majority of ovulations were characterized by normal progesterone concentrations in both groups. The effect of myo-inositol on follicular maturation was rapid, because the E2 circulating concentration increased over the first week of treatment only in the myo-inositol group. A significant increase in circulating high-density lipoprotein was observed only in the myo-inositol-treated group. Metabolic risk factor benefits of myo-inositol treatment were not observed in the morbidly obese subgroup of patients (body mass index > 37). After 14-wk myo-inositol or placebo therapy, no change in fasting glucose concentrations, fasting insulin, or insulin responses to glucose challenge was recorded. There was an inverse relationship between body mass and treatment efficacy. In fact a significant weight loss (and leptin reduction) was recorded in the myo-inositol group, whereas the placebo group actually increased weight. These data support a beneficial effect of myo-inositol in women with oligomenorrhea and polycystic ovaries in improving ovarian function.

* PolyCystic Ovary Syndrome

Effects of inositol on ovarian function and metabolic factors in women with PCOS: a randomized double blind placebo-controlled trial

Source: European review for medical and pharmacological sciences 2003 Nov-Dec;7(6):151-9.

Author: Gerli S, Mignosa M, Di Renzo GC

Affiliation: Department of Obstetrics and Gynecology, Monteluce Hospital, University of Perugia, Italy.

Abstract: Women with oligomenorrhea and polycystic ovaries show a high incidence of ovulation failure perhaps linked to insulin resistance and related metabolic features. A small number of reports shows that inositol improves ovarian function. Furthermore, in these trials the quality of evidence supporting ovulation is suboptimal, and few studies have been placebo-controlled. The aim of this study was to use a double-blind, placebo-controlled approach with detailed assessment of ovarian activity (two blood samples per week) to assess the validity of this therapeutic approach in this group of women. Of the 283 patients randomized, 2 withdrew before treatment commenced, 147 received placebo, and 136 received inositol (100 mg, twice a day). The women which discontinued the study prematurely were more numerous in the treatment group (n = 45) than the placebo group (n = 15). The ovulation frequency estimated by the ratio of luteal phase weeks to observation weeks was significantly higher in the treated group (23%) compared with the placebo (13%). The time in which the first ovulation occurred was significantly shorter. The number of patients failing to ovulate during the placebo-treatment period was higher in the placebo group, and in most cases ovulations were characterized by normal progesterone concentrations in both groups. The effect of inositol on follicular maturation was rapid, because the circulating concentration of E2 increased only in the inositol group during the first week of treatment. Significant weight loss (and leptin reduction) was recorded in the inositol group, whereas in the placebo group was recorded an increase of the weight. A significant increase in circulating high-density lipoprotein was observed only in the inositol-treated group. Metabolic risk factor benefits of inositol treatment were not observed in the morbidly obese subgroup of patients (body mass index > 37). No change in fasting glucose concentrations, fasting insulin, or insulin responses to glucose challenge test was recorded after 14-wk of inositol and placebo therapy. There was an inverse relationship between body mass of the patients and the efficacy of the treatment. Conclusion: These data support a beneficial effect of inositol in improving ovarian function in women with oligomenorrhea and polycystic ovaries.

Maternal Antenatal Vitamin D Status and Offspring Muscle Development: Findings From the Southampton Women's Survey

Source: The Journal of Clinical Endocrinology and Metabolism 2014 Jan;99(1):330-7. doi: 10.1210/jc.2013-3241. Epub 2013 Dec 20.

Author: Harvey NC, Moon RJ, Sayer AA, Ntani G, Davies JH, Javaid MK, Robinson SM, Godfrey KM, Inskip HM, Cooper C; Southampton Women's Survey Study Group.

Affiliation:

Abstract: Context: Maternal 25-hydroxyvitamin D [25(OH)D] status in pregnancy has been associated with offspring bone development and adiposity. Vitamin D has also been implicated in postnatal muscle function, but little is known about a role for antenatal 25(OH)D exposure in programming muscle development. Objective: We investigated the associations between maternal plasma 25(OH)D status at 34 weeks of gestation and offspring lean mass and muscle strength at 4 years of age. Design and Setting: We studied a prospective UK population-based mother-offspring cohort: the Southampton Women's Survey (SWS). Participants: Initially, 12 583 nonpregnant women were recruited into the SWS, of whom 3159 had singleton pregnancies; 678 mother-child pairs were included in this analysis. Main Outcomes Measured: At 4 years of age, offspring assessments included hand grip strength and whole-body dual-energy x-ray absorptiometry, yielding lean mass and percent lean mass. Physical activity was assessed by 7-day accelerometry in a subset of children (n = 326). Results: The maternal serum 25(OH)D concentration in pregnancy was positively associated with offspring height-adjusted hand grip strength ( = 0.10 SD/SD, P = .013), which persisted after adjustment for maternal confounding factors, duration of breastfeeding, and child's physical activity at 4 years ( = 0.13 SD/SD, P = .014). Maternal 25(OH)D was also positively associated with offspring percent lean mass ( = 0.11 SD/SD, P = .006), but not total lean mass ( = 0.06 SD/SD, P = .15). However, this association did not persist after adjustment for confounding factors ( = 0.09 SD/SD, P = .11). Conclusions: This observational study suggests that intrauterine exposure to 25(OH)D during late pregnancy might influence offspring muscle development through an effect primarily on muscle strength rather than on muscle mass.

Prenatal multivitamin supplementation and rates of congenital anomalies: a meta-analysis.

Source: http://www.ncbi.nlm.nih.gov/pubmed/17022907

Author: Goh YI, et al.

Affiliation: Department of Pharmaceutical Sciences, University of Toronto, and The Motherisk Program, Division of Clinical Pharmacology/Toxicology, The Hospital for Sick Children, Toronto, Ontario, Canada.

Abstract: The use of folic acid-fortified multivitamin supplements has long been associated with decreasing the risk of neural tube defects. Several studies had also proposed the effectiveness of these supplements in preventing other birth defects; however, such effects had never been systematically examined. The researchers conducted a systematic review and meta-analysis to evaluate the protective effect of folic acid-fortified multivitamin supplements on other congenital anomalies. The researchers searched Medline, PubMed, EMBASE, Toxline, Healthstar, and Cochrane databases for studies describing the outcome of pregnancies in women using multivitamin supplements that were published in all languages from January 1966 to July 2005. The references from all collected articles were reviewed for additional articles. Two independent reviewers who were blinded to the source and identity of the articles extracted data based on predetermined inclusion and exclusion criteria. Using a random effects model, rates of congenital anomalies in babies born to women who were taking multivitamin supplements were compared with rates in the offspring of controls who were not. From the initial search, 92 studies were identified; 41 of these met the inclusion criteria. Use of multivitamin supplements provided consistent protection against neural tube defects, cardiovascular defects, and limb defects. For cleft palate, case control studies showed OR 0.76, and cohort and randomized controlled studies showed OR 0.42; for oral cleft with or without cleft palate, case control studies showed OR 0.63, and cohort and randomized controlled studies showed OR 0.58; for urinary tract anomalies, case control studies showed OR 0.48, and cohort and randomized controlled studies showed OR 0.68; and for congenital hydrocephalus case control studies showed OR 0.37, and cohort and randomized controlled studies showed OR 1.54. No effects were shown in preventing Down syndrome, pyloric stenosis, undescended testis, or hypospadias. Conclusion: Maternal consumption of folic acid-containing prenatal multivitamins is associated with decreased risk for several congenital anomalies, not only neural tube defects. These data have major public health implications, because until now fortification of only folic acid has been encouraged. This approach should be reconsidered.

Prenatal multivitamin supplementation and rates of pediatric cancers: a meta-analysis.

Source: http://www.ncbi.nlm.nih.gov/pubmed/17314929

Author: Goh YI, et al.

Affiliation: Department of Pharmaceutical Sciences, University of Toronto, and The Motherisk Program, Division of Clinical Pharmacology/Toxicology, The Hospital for Sick Children, Toronto, Ontario, Canada.

Abstract: Prenatal supplementation of folic acid has been shown to decrease the risk of several congenital malformations. Several studies have recently suggested a potential protective effect of folic acid on certain pediatric cancers. The protective role of prenatal multivitamins has not been elucidated. The researchers conducted a systematic review and meta-analysis to assess the potential protective effect of prenatal multivitamins on several pediatric cancers. Medline, PubMed, EMBASE, Toxline, Healthstar, and Cochrane databases were searched for studies published in all languages from 1960 to July 2005 on multivitamin supplementation and pediatric cancers. References from all articles collected were reviewed for additional articles. Two blinded independent reviewers assessed the articles for inclusion and exclusion. Rates of cancers in women supplemented with multivitamins were compared with unsupplemented women using a random effects model. Sixty-one articles were identified in the initial search, of which, seven articles met the inclusion criteria. There was an apparent protective effect for leukemia, pediatric brain tumors and neuroblastoma. In conclusion, maternal ingestion of prenatal multivitamins is associated with a decreased risk for pediatric brain tumors, neuroblastoma, and leukemia. Presently, it is not known which constituent(s) among the multivitamins confer this protective effect.

A comparative study of folate and vitamin B12 serum levels in preeclamptic versus normotensive pregnant women in correlation with uterine and umbilical artery Doppler findings and pregnancy outcome.

Source: http://www.ncbi.nlm.nih.gov/pubmed/24591859

Author: Mahmoud A, et al.

Affiliation: Obstetrics and Gynecology Department, Cairo University, Egypt.

Abstract: The aim of this study was to detect the serum levels of folate and B12 in both preclamptic and normotensive pregnant women and to determine whether there is any relation between these levels with the uterine and umbilical artery Doppler indices as well as the pregnancy outcome. This case controlled study comprised 79 pregnant patients with preeclampsia and 113 healthy, normotensive pregnant women with singleton pregnancies at gestational ages ranging from 34-40 weeks. Patients were not obese (BMI<30) and did not suffer from chronic hypertension, chronic renal or liver disease nor diabetes mellitus. Serum folate and B12 were detected in all cases. They were also subjected to a Doppler study of both the uterine and umbilical arteries. Serum folate and B12 blood levels as well as the Doppler study indices (RI and PI) were compared in both groups. The serum folate level was significantly lower in preeclamptic patients than normal pregnant women. It was significantly correlated to uterine artery Doppler indices (RI and PI) and negatively correlated to umbilical artery Doppler indices (RI and PI). Low serum folate was significantly correlated to poor maternal outcome. Low serum folate was also significantly correlated to poor perinatal outcome. Serum B12 level was not significantly different in preeclamptic patients from the control group. The conclusion of this study is that serum folate was significantly lower in preeclamptic pregnant women with a significant correlation to increased uterine and umbilical RI, PI and poor maternal and neonatal outcome.

Effect of calcium plus vitamin D supplementation during pregnancy in Brazilian adolescent mothers: a randomized, placebo-controlled trial.

Source: http://www.ncbi.nlm.nih.gov/pubmed/23719547

Author: Diogenes ME, Bezerra FF, Rezende EP, Taveira MF, Pinhal I, Donangelo CM.

Affiliation: Laboratório de Bioquímica Nutricional e de Alimentos, Instituto de Química and the Maternidade Escola, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.

Abstract: Pregnancy and lactation in adolescents with habitually low calcium intake may adversely affect maternal bone mass. The authors investigated the effect of calcium plus vitamin D supplementation during pregnancy on bone mass during lactation in Brazilian adolescent mothers with low-calcium diets (600 mg/d). Pregnant adolescents (14-19 y) randomly received daily calcium (600 mg) plus vitamin D3 (200 IU) (n = 30) or a placebo (n = 26) from 26 wk of pregnancy (baseline) until parturition. The bone mineral content (BMC), bone area (BA), and bone mineral density (BMD) at the total body, lumbar spine, and hip (total and femoral neck) were evaluated by using dual-energy X-ray absorptiometry at 5 and 20 wk postpartum. Serum hormones and 25-hydroxyvitamin D [25(OH)D] were measured. Group comparisons were adjusted for significant covariates. The mean serum 25(OH)D concentration was 59 nmol/L at baseline. In comparison with the placebo, 25(OH)D tended to be 14-15 nmol/L higher postpartum in the supplemented group. Total body and hip BMC and BMD decreased over time in both groups with a group time interaction at the femoral neck. Supplemented mothers had higher lumbar spine BA and lumbar spine BMC than did mothers who consumed the placebo at 5 wk postpartum. At 20 wk postpartum, differences between groups were more evident, with higher lumbar spine BMC, lumbar spine BA, and lumbar spine BMD in the supplemented group. Conclusion: Calcium plus vitamin D supplementation during pregnancy of adolescents with low calcium intake results in higher lumbar spine bone mass and a reduced rate of femoral neck bone loss during lactation.

The role of vitamin D in impaired fertility treatment.

Source: http://www.ncbi.nlm.nih.gov/pubmed/24522025

Author: Grzechocinska B, et al.

Affiliation: 1st Department of Obstentrics and Gynecology, Medical University of Warsaw, Poland

Abstract: This research presents the review of the publications concerning the role of calciferol in reproduction processes and its significance in infertility therapy covering topics of polycystic ovary syndrome, endometriosis infertility, myoma infertility, male infertility, premature ovary failure and in vitro fertilization techniques. The results of latest research articles in those fields has been discussed and summarized. The deficiency of vitamin defined as the concentration of 25-hydroxycalciferol <20 ng/ml is frequently noted in patients of fertility clinics. Serum vitamin D concentration in healthy women is higher comparing to PCOS patients. The supplementation with vitamin D should be applied in the schemes of PCOS treatment both due to an improved insulin resistance and the results of infertility treatment. The explanation of vitamin D activity mechanism in patients with PCOS requires further research. Vitamin D has direct effect on AMH production, and thus increases longer maintenance of ovarian reserve in the patients with its higher concentration. The occurrence of uterine myomas in the group with vitamin D deficiency was evaluated as much higher comparing to controls. On the other hand it is supposed that high concentration of calciferol may be related to an impaired elimination of endometrial cells passing to peritoneal cavity via ovarian reflux causing endometriosis. In male infertility both low (<20 ng/ml) and high (>50 ng/ml) concentration of vitamin D in serum negatively affects spermatozoa number per ml of semen, their progressive movement and morphology. Significant differences as a response on ovulation stimulation, number and quality of embryos depending on vitamin D concentration were not observed in none of the analyzed papers concerning the role of vitamin D in in vitro fertilization (IVF). Better results in patients without calciferol insufficiency are explained by reports about high concentration of vitamin D and its metabolites in human in decidua collected in the 1st trimester of pregnancy which suggests its contribution in proper implantation and local immunological preference of the embryo. Concluding, it is accepted that the treatment requires vitamin D concentration below 20 ng/ml (up to 50 nmol/l), especially in obese women, these with insulin resistance and small ovarian reserve and in men with oligo- and asthenozoospermia.