Pilot Study of FertilityBlend™

by Lynn Westphal, MD*, Mary Lake Polan, MD, PhD, MPH, Aileen Sontag Trant, PhD, Stephen B. Mooney, MD

Abstract

Objective: To determine the impact of nutritional supplementation on the optimization of reproductive health in women.

Design: A double-blind, placebo-controlled clinical pilot study was initiated to determine the effects of FertilityBlend™, a proprietary, natural nutritional supplement containing chasteberry and green tea extracts, the amino acid L-arginine, vitamins E, B6, B12 and folate, iron, magnesium, zinc and selenium. Changes in mid-luteal phase progesterone level and basal body temperature, as well as length of menstrual cycle, pregnancy rate and incidence of side effects were monitored.

Results: Twenty-nine (29) women, age 24-46 years, who have tried unsuccessfully to conceive for 6 to 36 months were enrolled in the study. None of the participants received any pharmacological treatments for infertility during the course of the study. Of the 29, 15 received placebo and 14 received FertilityBlend™. After 3 months, an increase in mean mid-luteal phase progesterone levels was noted in the supplement group (from 8.2 to 13.1 ng/ml, p=0.08). The supplement group also demonstrated an increase in the average number of days in cycle with basal temperatures over 98F during luteal phase (6.8 to 9.7 days, p=0.04). The placebo group did not show any notable changes, before or after treatment, in any of the parameters studied. By the end of the 3-month study, 4 of the 14 women in the supplement group were pregnant (29%), and none of the 15 women in the placebo group were pregnant (p=0.02). No significant side effects were noted.

Conclusion: Nutritional supplementation may provide an alternative or complement to conventional fertility therapies. This supplement is a potentially attractive option for use in the management and optimization of reproductive health. The pilot study is being expanded to a multi-center study, with the goal of evaluating at least 100 women. Similarly, evaluation of a FertilityBlend™ formulated for men is in progress to determine its effect on sperm concentration and motility.

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Introduction

One out of every six couples in the U.S., and one out of every three couples in their late 30's, have difficulty conceiving a child. In about one third of these cases, it is the man that is infertile or subfertile; in another third, the female has fertility issues. The remaining third is attributable to both men and women, or is of unknown causes. In many of these cases, the causes of infertility are treatable. If low fertility is due to hormonal imbalance or nutritional deficiencies, nutritional supplementation may play an important role and should be considered as a reasonable alternative in the optimization of one's overall reproductive health.

It is well established in the literature that a healthy lifestyle is important in optimizing one''s reproductive health. Vitamins, minerals, and specific co-factors play a major role in fertility function. Good nutrition is a pre-requisite for fertility and childbearing. William Keye, Jr., M.D., (Wong, 2002), President of the American Society for Reproductive Medicine commented that "…The more we discover about the effects of nutrition on fertility, the better advice we can give our patients."

Hormonal imbalance can be determined by blood tests of reproductive hormone levels. Measuring follicle stimulating hormone (FSH), luteinizing hormone (LH), estrogen on day 3 and progesterone on day 21 can indicate whether the hormonal state is compatible with pregnancy. Abnormal LH or progesterone production may result in an abnormal monthly basal body temperature chart. If progesterone is low, there is less of an expected increase in temperature during the second half of the cycle after ovulation. Without sufficient progesterone, the endometrium cannot be prepared adequately for implantation of the embryo.

Vitex agnus-castus is an herb used to optimize luteal phase function. Vitex increases LH production and mildly inhibits the release of FSH. This appears to result in better corpus luteum development, with improved progesterone levels in the luteal phase. Clinical studies in Europe (Propping, 1988 as cited in Brown, 1995) used Vitex tincture successfully (40 drops daily) to restore progesterone balance, and induce fertility (39 of 45 women increased progesterone levels and 7 became pregnant within 3 months). Loch, et al. (2000) noted an increase in the pregnancy rate of women taking Vitex in a study of its effects on PMS symptoms. No serious side effects were noted in this study of 1634 patients in Germany. One advantage of using Vitex rather than the commonly prescribed drug, clomiphene citrate, is the decreased risk of multiple gestation. Vitex functions in a more natural and gentle fashion with the body to harmonize hormonal balance. Vitex has also been shown to reduce PMS symptoms and menstrual cycle irregularities (Dittmar, et al. 1992; Loch, et al.2000; Peteres-Welter & Albrecht, 1994).

Vitamin B6 (pyridoxine) has been shown to improve conception rates, as well as treat PMS symptoms, but whether this is due to a primary insufficiency is unclear (Abraham & Hargrove, 1979). Vitamin B12 (Bennett, 2001), folic acid (Dawson & Sawers, 1982), vitamin E (Bayer, 1960), multivitamins (Czeizel, 1996), magnesium and selenium (Howard, 1994), iron (Rushton, 1991) and zinc (Bedwal, 1994) have been shown to improve female fertility (McLeod, 1996, review).

Antioxidants have proven to be helpful in reducing free radical damage to ova, sperm and reproductive organs. Vitamins C and E are usually used for this purpose, but green tea looks promising as well. In studying the effects of caffeine on conception (usually considered a negative effect), Caan et al. (1998) found that drinking tea (as opposed to other caffeinated beverages) approximately doubled the odds of conception per cycle.

L-arginine, an amino acid, helps improve circulation to the reproductive organs which may enhance oocyte devevelopment and implantation of the embryo. Battaglia, et al. (1999) monitored uterine and follicular doppler flow in response to L-arginine treatment during in-vitro fertilization treatment of poor responder patients. The L-arginine treated group demonstrated improved Doppler flow rates, a lower cancellation rate, and an increased number of oocytes collected and embryos transferred. Of the 17 in the L-arginine supplementation group, 3 became pregnant, compared to none of the 17 in the non-supplemented group.

As a result of the proposed and elicited mechanisms of various natural products in the scientific literature, it was postulated that a combination regimen (FertilityBlend™) as a systematically designed blend of natural products could provide a synergistic impact in support of human reproductive health.

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Materials and Methods

Twenty-nine (29) women, age 24-46 years, who had tried unsuccessfully to conceive for 6 to 36 months were enrolled in the study, and completed the 3-month trial. None of the participants received any pharmacological treatments for infertility during the course of the study, and at least one month prior to enrolling. Of the 29, 15 received placebos and 14 received FertilityBlend™; administered in a randomized, double blind, placebo-controlled fashion. Supplements were taken daily, 3 capsules per day, for 3 menstrual cycles after initial baseline measurements. FertilityBlend™ is a proprietary, natural nutritional supplement containing chasteberry and green tea extracts, the amino acid L-arginine, vitamins E, B6, B12 and folate, iron, magnesium, zinc and selenium. Changes in mid-luteal phase progesterone level and basal body temperature, as well as length of menstrual cycle, pregnancy rate and incidence of side effects were monitored. Progesterone levels were evaluated via immunoassay, specifically using the Immulite 2000 Hormone Analyzer. Measurements were made at baseline and after 3 months of nutritional supplementation.

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Results

Mean age, weight and months of attempting to become pregnant were similar (p>0.10) for the supplement and placebo groups (Table 1). Mean ages for the supplement and the placebo groups were 34 and 35 years of age, average weights were 143 and 142 pounds, and months of attempting to conceive were 17.6 and 14.2, respectively.

After 3 months, an increase in mean mid-luteal phase progesterone levels was noted in the supplement group (from 8.2 to 13.1 ng/ml, p=0.08), whereas the placebo group remained relatively constant (from 11.4 to 12.3 ng/ml, p=0.38; Figure 1). The supplement group also demonstrated an increase in the average number of days in cycle with basal temperatures over 98F during luteal phase (6.8 to 9.7 days, p=0.04; Figure 2). The placebo group remained relatively constant in temperature at an average of 6.7 days over 98F at month 1, to 6.5 at month 3 (p=0.44). Neither group exhibited any consistent patterns in cycle lengths (Table 2).

By the end of the 3-month study, 4 of the 14 women in the FertilityBlend™ supplement group were pregnant (29%; p=0.02), and none of the 15 women in the placebo group were pregnant (0%; Table 1). The four women who became pregnant ranged in age from 24 to 38 years (mean age of 32.3 years), and had been attempting to conceive from 12 to 30 months (mean of 18 months). Two had abnormally low progesterone levels initially. All four demonstrated an increase in the number of days over 98F on their basal temperature charts. Two noted distinct signs of ovulation on their temperature charts that they hadn't seen before. Ovulation was confirmed by home ovulation kit.

No significant side effects were noted in this study. Two women in the active group (none in the placebo group) complained of nausea if the supplement was taken on an empty stomach. One woman in the supplement group noted that menstrual cycles were more regular, two noted shortened cycles, and one noted more irregular cycles. Of the 14 on the supplement, one noted less spotting and improved PMS symptoms. Two women on placebo noted increased PMS symptoms, and four noted irregular cycles. Since this was the first time many of these women had charted their basal body temperature, they may have become more aware of irregularities in their cycles.

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Discussion

Nutritional supplementation may play an important role in optimizing fertility health, which may lead to improved conception rates, and provide an alternative or complement to conventional fertility therapies. Without significant side effects, FertilityBlend™ is an attractive option for use in the management and optimization of reproductive health in women. Good nutrition is a pre-requisite for fertility and childbearing, and is particularly important for those deciding to become pregnant at a more advanced age. In the current pilot study, nutritional supplementation increased mean mid-luteal phase progesterone levels, increased the average number of days in cycle with basal temperatures over 98F during luteal phase, and resulted in a pregnancy rate of 29% compared to 0% in the placebo group.

The role of nutritional supplementation in fertility health is an extremely important area of research. This pilot study is being expanded to a larger multi-center study, with a goal of evaluating at least 100 women, including those with low luteal phase progesterone or menstrual irregularities. Similarly, evaluation of a FertilityBlend™ formulated for men is in progress, to determine its effect on sperm concentration and motility in men initially low in these levels.

Acknowledgements: Many thanks to the REI lab at Stanford Hospital that performed the progesterone analyses.

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References
  1. *Department of Gynecology/Obstetrics, Stanford University School of Medicine, Stanford, CA
    **The Daily Wellness Company, Sunnyvale, CA
  2. Abraham GE, Hargrove JT. 1979. Reported in Medical World News, March 19.
  3. Battaglia C, et al. 1999. Adjuvant L-arginine treatment for in-vitro fertilization in poor responder patients. Human Reproduction 14(7):1690-97.
  4. Bayer R. 1960. Treatment of infertility with vitamin E. Int J Fertil 5:70-8.
  5. Bedwal RS, Bahuguna A. 1994. Zinc, copper and selenium in reproduction. Experientia 50(7):626-40.
  6. Bennett M. 2001. Vitamin B12 deficiency, infertility and recurrent fetal loss. J Reprod Med 46(3):209-12.
  7. Brittenden, J. et al. 1994. Nutritional pharmacology: effects of L-Arginine on host defences, response to trauma and tumour growth. Clin. Sci. 86:123-132.
  8. Brown DJ. 1995. Vitex agnus-castus Clinical Monograph. Townsend Letter for Doctors & Patients, October.
  9. Caan B, Quesenberry CP, Coates AO. 1998. Differences in fertility associated with caffeinated beverages. Am J Public Health 88(2):270-4.
  10. Czeizel AE, Metneki J, Dudas I. 1996. The effect of preconceptual multivitamin supplementation on fertility. Internat J Vit Nutr Res 66:55-8.
  11. Dawson DW, Sawers AH. 1982. Infertility and folate deficiency. Case reports. Br J Obstet Gynaecol 89:678-80.
  12. Dittmar F, et al. 1992. Premenstrual syndrome: treatment with a phytopharmaceutical. Therapiewoche Gynakol 5(1):60-68.
  13. Howard JM, Davies S, Hunnisett A. 1994. Red cell magnesium and glutathine peroxidase in infertile women- effects of oral spplementation with magnesium and selenium. Magnesium Research 7(1):49-57.
  14. Khalsa KP. 1999. Spotlight on green tea extract. Nutraceuticals World July/Aug.
  15. Lerman A, Burnett Jr. J, Higano S, McKinley L, Holmes Jr. D. 1998. Long-term L-arginine supplementation improves small-vessel coronary endothelial function in humans. Circulation 97:2123-28.
  16. Loch E, Selle H, Boblitz N. 2000. Treatment of premenstrual syndrome with a phytopharmaceutical formulation containing Vitex agnus castus. J Women's Health and Gender-Based Med 9(3):315-20.
  17. McLeod D. 1996. Female infertility: a holistic approach. Aust J Med Herbalism 8(3):68-77.
  18. Peteres-Welter C, Albrecht M. 1994. Menstrual abnormalities and PMS. Vitex agnus-castus in a study of application. Therapiewoche Gynakol 7:49-52.
  19. Propping D, et al. 1988. Diagnosis and therapy of corpus luteum deficiency in general practice. Therapiewoche 38:2992-3001.
  20. Rushton DH, Ramsay ID, Gilkes JJH, Norris MJ. 1991. Ferritin and fertility. Lancet 337:1554 [letter].
  21. Wong WY, et al. 2002. Effects of folic acid and zinc sulfate on male factor subfertility: a double-blind, randomized, placebo-controlled trial. Fertility and Sterility 77(3):491-8.

Reprints and correspondence to:
Lynn Westphal, MD
Department of Gynecology/Obstetrics
Stanford University School of Medicine
300 Pasteur Drive
Stanford, California 94305
phone: 650-498-7317
fax: 650-723-7737
email: lynnw@stanford.edu

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Table 1

Comparison of Age, Weight, Months Attempting to Conceive, and % Becoming Pregnant
Between Supplement and Placebo Groups

 
Supplement
Mean (N=15)
Placebo
Mean (N=14)
Mean age (years) 34.4 35.3
Weight 143.4 141.9
Months trying* 17.6 14.2
% becoming pregnant 29%a 0%

* Months of actively trying to conceive.
a Significantly higher number than placebo group at p= 0.02; Bayesian binomial analysis.

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Table 2

Comparison of Progesterone Levels, Days Over 98F on Basal Temperature Chart (Luteal Phase),
and Menstrual Cycle Length Between Supplement and Placebo Groups

  Supplement
Mean (N=15)
Placebo
Mean (N=14)
Initial progesterone (ng/ml) 8.2 11.4
End progesterone (ng/ml) 13.1a 12.3
 
Days over 98F** month 1 6.8 6.4
Days over 98F** month 2 8.5 5.9
Days over 98F** month 3 9.7b 6.4
 
Cycle length - month 1 30.5 29.3
Cycle length - month 2 28.8 30.4
Cycle length - month 3 29.7 29.9

**Number of days in cycle with basal temperature readings over 98F during luteal phase.
a Significantly higher than initial time value at p=0.08, one-tailed t-test.
b Significantly higher than initial time value at p=0.04, and higher than placebo group value at p=0.06, one-tailed t-test.

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Figure 1

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Figure 2

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Copyright © Lynn Westphal. Permission to republish granted to Pregnancy.org, LLC.