Studies Supporting Ingredients in FertileCM

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Key studies supporting the FertileCM formula include:

• Morlin B, Hammarstrom M., 2005. Nitric oxide increases cervical secretion at the ovulatory phase in the female.
Acta Obstet Gynecol Scand. Sep; 84 (9): 883-6

Abstract: Uterine cervical mucus is crucial for reproduction, facilitating sperm transport and survival in certain mammals. Cholinergic autonomic nervous secretory innervation has been established, and modulation of secretion by prostaglandins and non-steroidal anti-inflammatory drugs has been postulated. It has been suggested that glandular nitric oxide (NO) production is a prerequisite for the autonomic cholinergic nervous modulation of cervical, endometrial, and the seminal vesicle secretion. Most secretory genital tract cells, female as well as male, seem to display NO synthase activity.

METHODS: Cervical secretion at ovulation time was studied in 10 women with regular menstruation. In an in vivo model with repeated collection of mucus samples during four 60-min periods, the amount of mucus was estimated in a control experimental series and in an experimental series following sublingual administration of the NO donor nitroglycerin.

RESULTS: This administration markedly increased cervical secretion, while no changes in cervical secretion were seen in the control experimental series.

CONCLUSIONS: The results suggest that NO production increases cervical secretion. Thus, cervical secretion may, apart from hormonal regulation, be influenced by the autonomic nervous system, and in addition, NO may be a prerequisite for this influence. This in turn may have implications on fertilization and fertility regulation.

• Gorodeski GI., 2000. NO increases permeability of cultured human cervical epithelia by cGMP-mediated increase in G-actin. Am J Physiol Cell Physiol., May; 278(5):C942-52

Human cervical epithelial cells express mRNA for the nitric oxide (NO) synthase (NOS) isoforms ecNOS, bNOS, and iNOS and release NO into the extracellular medium. N(G)-nitro-L-arginine methyl ester (L-NAME), an NOS inhibitor, and Hb, an NO scavenger, decreased paracellular permeability; in contrast, the NO donors sodium nitroprusside (SNP) and N-(ethoxycarbonyl)-3-(4-morpholinyl)sydnonimine increased paracellular permeability across cultured human cervical epithelia on filters, suggesting that NO increases cervical paracellular permeability. The objective of the study was to understand the mechanisms of NO action on cervical paracellular permeability.... On the basis of these results, it is suggested that NO acts on guanylate cyclase and stimulates an increase in cGMP; cGMP, acting via cGMP-dependent protein kinase, shifts actin steady-state toward G-actin; this fragments the cytoskeleton and renders cells more sensitive to decreases in cell size and resistance of the lateral intercellular space and, hence, to increases in permeability. These results may be important for understanding NO regulation of transcervical paracellular permeability and secretion of cervical mucus in the woman.

• Morlin B, Andersson E, Bystrom B, Hammarstrom M. Nitric oxide induces endometrial secretion at implantation time. Acta Obstet Gynecol Scand. Nov; 84(11): 1029-34.

Abstract: Uterine cervical secretory cells receive a sympathetic cholinergic secretomotor innervation. Glandular nitric oxide (NO) production has been proposed to be a prerequisite for muscarine-induced carbohydrate secretion from endometrial glands and cervical glands at ovulation time and from the seminal vesicle glands. Nitric oxide has also been suggested to have a significant role in the process of implantation and early pregnancy, a process, which has also been compared with an inflammatory response.

CONCLUSIONS: The results of this study suggest that glandular NO production is a prerequisite for the autonomic nervous modulation of endometrial secretion in the guinea pig and that NO may play a role in the implantation time.

Other Clinical Data and Background Research for FertileCM

The Nobel Prize in Physiology or Medicine 1998: The Nobel Assembly at the Karolinska Institute in Stockholm, Sweden, awarded the Nobel Prize in Physiology or Medicine for 1998 to Robert F Furchgott, Louis J Ignarro and Ferid Murad for their discoveries concerning "the nitric oxide as a signalling molecule in the cardiovascular system". Aitken RJ., 2006. Sperm function tests and fertility. International Journal of Andrology Feb;29(1):69-75.

Lerman, A. et al. 1998. Long-term L-arginine supplementation improves small-vessel coronary endothelial function in humans. Circulation. 97:2123-2128. Creager M. et al. 1992. L-arginine improves endothelium-dependent vasodilation in hypercholesterolemic humans. J Clin Invest. 90:1248-1253. Moncada S., Higgs A. 1993. The LArginine –Nitric Oxide Pathway. The New England Journal of Medicine. 329 (27):2002-2012.

Bigelow JL, Dunson DB, Stanford JB, Ecochard R, Gnoth C, Colombo B., 2004. Mucus observations in the fertile window: a better predictor of conception than timing of intercourse. Hum Reprod. Apr; 19(4):889-92.

Cameron, IT and Campbell, S., 1998. Nitric oxide in the endometrium Human Reproduction Update / European Society of Human Reproduction and Embryology, Vol.4, No.5 pp.565-569

Ceric F, Silva D, Vigil P. 2005. Ultrastructure of the human periovulatory cervical mucus. J Electron Microsc (Tokyo) Oct; 54 (5): 479-84.

Dolgushin II, Telesheva LF, Savochkina AIu, Markina OV. 2004. Anti-inflammatory cytokines of cervical secretions and the blood serum in women with genital infections. Zh Mikrobiol Epidemiol Immunobiol Jul-Aug;(4):43-6.

Dunson DB, Bigelow JL, Colombo B., 2005. Reduced fertilization rates in older men when cervical mucus is suboptimal. Obstet Gynecol Apr;105(4):788-93

Fordney-Settlage D., 1981. A review of cervical mucus and sperm interactions in humans., Int J Fertil. ;26(3):161-9.

Geva E, et al. 1996. The effect of antioxidant treatment on human spermatazoa and fertilization rate in an in vitro fertilization program. Fertil & Steril 66(3):430-4.

Gianotten WL, te Velde ER., 2005. The influence of sexual function on the chance of pregnancy. Ned Tijdschr Geneeskd. May 28;149(22):1207-10.

Gorodeski GI., 2000. NO increases permeability of cultured human cervical epithelia by cGMP-mediated increase in G-actin. Am J Physiol Cell Physiol., May; 278(5):C942-52

Gruberova J, Bikova S, Ulcova-Gallova Z, Reischig J, Rokyta Z., 2006. Ovulatory mucus and its pH, arborization and spermagglutination antibodies in women with fertility disorders.,Ceska Gynekol Jan;71(1):36-40.

Fetic S, Yeung CH, Sonntag B, Nieschlag E, Cooper TG., 2006 Relationship of cytoplasmic droplets to motility, migration in mucus and volume regulation of human spermatozoa. Journal of Andrology Feb 10 2006

Frank-Herrmann P, Gnoth C, Baur S, Strowitzki T, Freundl G., 2005. Determination of the fertile window: reproductive competence of women--European cycle databases. Gynecol Endocrinol Jun; 20(6):305-12.

Kaczmarek A, Robak-Cholubek D, Sowa I, Jakiel G., 2004. Comparison of the levels of copper, zinc and iron in cervical mucus and in blood serum of women of childbearing age. Ann Univ Mariae Curie Sklodowska 59(1):72-5.

Kataranovski M, Radojcic L, Prokic V, Vojvodic D., 2004. Presence of interleukin-8 and the IL-1 receptor antagonist in the cervical mucus of fertile and infertile women. Vojnosanit Pregl Jul-Aug;61(4):359-64.

Marsden JS, Strickland CD, Clements TL. 2004. Guaifenesin as a treatment for primary dysmenorrhea. J Am Board Fam Pract. Jul-Aug;17(4):240-6.

Maul, H.; Longo, M.; Saade, G.R.; Garfield, R.E. 2003 Nitric Oxide and its Role During Pregnancy: From Ovulation to Delivery Current Pharmaceutical Design, Volume 9, Number 5, February 2003, pp. 359-380(22)

Morlin B, Hammarstrom M., 2005. Nitric oxide increases endocervical secretion at the ovulatory phase in the female. Acta Obstet Gynecol Scand. Sep; 84 (9):883-6.

Morlin B, Andersson E, Bystrom B, Hammarstrom M. Nitric oxide induces endometrial secretion at implantation time. Acta Obstet Gynecol Scand. Nov; 84(11): 1029-34

Nasir-ud-Din, Hoessli DC, Rungger-Brandle E, Hussain SA, Walker-Nasir E. 2003. Role of sialic acid and sulfate groups in cervical mucus physiological functions. Biochim Biophys Acta Oct 13;1623(2-3):53-61

Sakai M, Ishiyama A, Tabata M, Sasaki Y, Yoneda S, Shiozaki A, Saito S. 2004. Relationship between cervical mucus interleukin-8 concentrations and vaginal bacteria in pregnancy. Am J Reprod Immunol Aug; 52(2):106-12.

Scarpa B, Dunson DB, Colombo B., 2006. Cervical mucus secretions on the day of intercourse: An accurate marker of highly fertile days. European Journal Obstet Gynecol Reproductive Biololgy Mar 1;125(1):72-8

Stanford JB, Smith KR, Dunson DB. 2003. Vulvar mucus observations and the probability of pregnancy. Obstet Gynecol. Jun;101(6):1285-93.

Telesheva LF, Dolgushin II, Korobeinikova EN. 2004. Neutrophils and antioxidant activity of cervical secretion in women with the acute inflammation in the upper section of the reproductive tract. Zh Mikrobiol Epidemiol Immunobiol May-Jun;(3):90-2.