Clinical Studies

Publications

Quantitative perceptual differences among over-the-counter vaginal products using a standardized methodology - Contraception 2011;84:184-193 (The Pennsylvania State University)

An quantitative approach was used evaluate perceptual differences in vaginal products. The authors found that Pre-Seed was very slippery and smooth with less stickiness or rubberiness as compared to KY or Replens. Astroglide was more “ropey” (stringing between fingers) than Pre-Seed.

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Sperm Toxicity of ‘Nonspermicidal’ Lubricant and Ultrasound Gels Used in Reproductive Medicine - Fertility & Sterility. 2011;95:835-836 (Foundation for Andrology, Biology and Endocrinology of Reproduction, Switzerland)

Josefina Vargas, M.Sc.; Michel Crausaz, M.Sc.; Alfred Senn, Ph.D.; Marc Germond, M.D. Fondation F.A.B.E.R., Rue de la Vigie 5, 1003 Lausanne, Switzerland

Objective: To compare sperm toxicity of four commercial “non-spermicidal” gels used in Reproductive Medicine including: Aquasonic Ultrasound Gel, Felis Lubricant, Pre-Seed Lubricant and Replens Moisturizer, in a range of concentrations (0.083% - 8.3%) believed to be physiologically relevant. Results: Sperm toxicity was observed as shown by significant declines in motility over the 24-hr assay following incubation with Aquasonic, Felis and Replens at higher gel concentrations. Although Replens, even at only 0.83% v/v resulted in sperm toxicity. Pre-Seed alone was not toxic to sperm at any concentration, including the highest (8.3%). Conclusions: Three of the “nonspermicidal” gels were toxic to sperm, including Aquasonic Gel which is widely used for transvaginal ultrasound during ovulation. Pre-Seed alone did not cause sperm toxicity at any time or concentration. It is appropriate for use by patients trying to conceive or clinicians during fertility procedures, including facilitating vaginal insertion of ultrasound probes.

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Safety and Anti-HIV Activity of Over-the-Counter Lubricant Gels - International Microbicides Conference 2010 Abstract #347 (Magee-Womens Research Institute, University of Pittsburgh)

This study confirmed that the Pre-Seed formula is isotonic with a neutral pH. Pre-Seed’s formula was found to not cause harm to uterine or rectal cells in culture, whereas other water-based lubricants such as KY and Astroglide “disrupted” these cells.

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Mucosal Irritation Potential of Personal Lubricants Relates to Product Osmolality as Detected by the Slug Mucosal Irritation Assay - Sexually Transmitted Diseases. 2008 May;35:512-516 (Ghent University, Belgium)

Els Adriaens, PhD; Jean Paul Remon, PharmD. Laboratory of Pharmaceutical Technology, Ghent University, Harelbekestraat 72, 9000 Ghent, Belgium

BACKGROUND: The slug mucosal irritation assay has recently been used as a sensitive measure of mucus membrane tolerance for vaginal microbicide products and carriers. In the current study, it was determined whether mucosal irritation potency of personal lubricants is related to varying product osmolalities.
METHODS: Five commercial lubricants with an osmolality range were evaluated using the previously validated slug mucosal irritation assay. Specifically, Arion lusitanicus were treated with lubricants over 5 days to quantify mucus production and tissue damage, allowing assignment of each product into an irritation potency category (none, mild, moderate, or severe). RESULTS: The irritation potency (assessed by the mucus production) of the lubricants showed a significant, quadratic relationship with the product osmolality (P = 0.001; R (2) = 0.99). Femglide, a hypo-osmotic lubricant (32 mOsm/kg), caused a negative mucus production. Pré, an iso-osmotic lubricant (316 mOsm/kg), caused no changes. Two moderately hyperosmotic lubricants, Replens and K-Y jelly (2143 and 2463 mOsm/kg), induced mild and moderate irritation, respectively. The highly hyperosmotic lubricant Astroglide (5848 mOsm/kg) resulted in severe irritation and tissue damage. CONCLUSIONS: Commonly used personal lubricants show a full range of mucosal irritation potential, which is related to product osmolality.

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Effect of Vaginal Lubricants on Sperm Motility and Chromatin Integrity: A Prospective Comparative Study - Fertility & Sterility. 2008 Feb;89:375-379 (Cleveland Clinic)

Agarwal A, Deepinder F, Cocuzza M, Short RA, Evenson DP. Reproductive Research Center, Glickman Urological Institute and Department of Obstetrics-Gynecology, Cleveland Clinic, Cleveland, Ohio

Objective: To evaluate the effect of vaginal lubricants Pre-Seed®, FemGlide®, Astroglide®, and Replens® on human sperm motility and chromatin integrity. Design: Prospective, comparative, in vitro study. Setting: Andrology laboratory at tertiary care hospital. Patient(s): Thirteen normozoospermic donors.Intervention(s): Semen samples from 13 subjects were incubated in human tubal fluid media (HTF) controls and 10% (vol/vol) of Pre-Seed®, FemGlide®, Astroglide®, and Replens® lubricants. After 30 minutes, progressive sperm motility was assessed by light microscopy. Semen samples of 12 patients were placed in positive control (HTF), negative control (10% K-Y Jelly® lubricant), and 10% vol/vol Pre-Seed® and FemGlide® lubricants. After 4 hours culture, spermatozoa were analyzed for percent DNA fragmentation index with use of the acridine orange-based sperm chromatin structure assay. Main Outcome Measure(s): Sperm motility and percent DNA fragmentation index. Results: Percent motility did not differ significantly between HTF controls and Pre-Seed®, whereas FemGlide®, Replens®, and Astroglide® lubricants demonstrated a significant decrease in motility. There was no significant difference in percent DNA fragmentation index between the HTF controls and Pre-Seed®, but a significant decline in sperm chromatin quality occurred with FemGlide® and K-Y Jelly®. Conclusion: Pre-Seed® does not cause a significant decrease in progressive sperm motility or chromatin integrity in contrast to other lubricants used by couples.

Medical Review Articles

Products for Sexual Lubrication: Understanding and Addressing Options With Your Patients - Nursing for Women’s Health. 2011 Jun/Jul;15:253-257

Megan Andelloux, BS, AASECT, ACS

The author writes that “for patients who wish to maintain optimal fertility, there is only one lubricant currently on the market (Pre-Seed) that has been shown not to interfere with conception. ‘Even the water-soluble lubricants containing no spermicide, …have negative effects on sperm motility’ and thus may adversely affect conception.”

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Optimizing Natural Fertility - Fertility & Sterility. 2008 Nov;90(Suppl 3):S1-S6 (Practice Committee of the American Society for Reproductive Medicine)

Practice Committee of the American Society for Reproductive Medicine in collaboration with the Society for Reproductive Endocrinolgy and Infertility

Synopsis: Some vaginal lubricants may decrease fertility, based on their observed effects on sperm survival in vitro. Whereas commercially available water-based lubricants (e.g., Astroglide®, KY Jelly®, and Touch®) inhibit sperm motility in vitro by 60% to 100% within 60 minutes of incubation, canola oil has no similar detrimental effect (32). KY Jelly, olive oil, and saliva diluted to concentrations even as low as 6.25% adversely affect sperm motility and velocity.... Hydroxyethylcellulose-based lubricants such as Pre-Seed® (INGfertility, Valleyford, WA) also have no demonstrable adverse impact on semen parameters (35). Although there is no evidence to indicate that use of any vaginal lubricant decreases fertility, it seems prudent to recommend... hydroxyethylcellulose-based lubricants when they are needed.

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Dyspareunia and Vaginal Dryness after Breast Cancer Treatment - SRM Sexuality, Reproduction & Menopause. 2008 Aug;6:18-22 (Center for Sexuality, Intimacy & Fertility, Women and Infants Hospital of Rhode Island)

Doreen Leyden Wiggins, MD1 & Don S. Dizon, MD2. 1Clinical Assistant Professor, Program in Women's Oncology and 2Assistant Professor, Obstetrics and Gynecology and Medicine. Co-Directors, Center for Sexuality, Intimacy & Fertility, Women and Infants Hospital of Rhode Island, Providence, RI

An animal model using slugs has been validated to test mucosal irritation in human mucosal membranes. A recent study using the slug mucosal irritation assay determined that product osmolality was an important component to mucosal tolerability. The iso-osmotic lubricant (Pre-Seed) caused no changes and, therefore, was the best tolerated. The hypoosmotic lubricant (Femglide) caused negative mllCllS production, thereby decreasing natural response. Two moderately hyperosmotic lubricants (Replens, K-Y jelly) induced mild and moderate irritation, respectively. The highly hyperosmotic lubricant (Astroglide) resulted in severe irritation and tissue damage.Pre-Seed has been marketed to couples who need lubrication that does not inhibit fertility.

Clinical Textbook Mentions

CANCER AND SEXUAL HEALTH
John P. Mulhall, editor © 2011
In this reference book for cancer care providers, Pre~Seed is listed as a water-soluble lubricant that does not decrease sperm motility.

AN INTRODUCTION TO MALE REPRODUCTIVE MEDICINE
Craig Niederberger MD, editor © 2011
In this medical text written by well-renowned experts, Dr. Craig Niederberger writes: "Virtually all lubricants impair sperm, including saliva. However, some couples need lubricants for intercourse. A recent survey of the effects of various lubricants on sperm motility and DNA quality suggested that Pre-Seed appears to have the least negative effect on sperm [7].”

MALE INFERTILITY: PROBLEMS AND SOLUTIONS
Edmund S. Sabanegh MD, editor © 2011
Dr. Wayne Kuang states in his chapter on the initial consultation for male infertility: "In 2008, in vitro studies suggest that a newer commercially available hydroxyethylcellulose-based lubricant, such as Pre-Seed, has minimal deleterious effects on mobility and sperm chromatin integrity (Agarwal et al. 2008).”

HACKER & MOORE’S ESSENTIALS OF OBSTETRICS AND GYNECOLOGY
Neville Hacker MD, Joseph Gambone DO, MPH, Calvin Hobel MD © 2010
In this classic textbook for medical students, the authors write: "Lubricants may be toxic to sperm. A nontoxic lubricant, Preseed, has been developed for infertile couples."

A PRACTICAL GUIDE TO BASIC LABORATORY ANDROLOGY
Lars Bjorndahl, David Mortimer, et al. © 2010
In this laboratory guide, the authors state: "If a lubricant must be used then it must not show any toxicity to spermatozoa. Currently, the only suitable commercial product for this particular purpose is Pre’, an external use version of the Pre~Seed vaginal lubricant…"

MATERNITY AND PEDIATRIC NURSING
Susan Scott Ricci & Terri Kyle © 2009
In this book for nursing professionals, Pre~Seed is listed as a water-soluble lubricant that can reduce discomfort during intercourse.

Related Background References

Personal Lubricants and Sperm Function

Anderson L, Lewis SE, McClure N. The effects of coital lubricants on sperm motility in vitro. Hum Reprod 1998; 13: 3351- 3356.

Frishman GN, Luciano AA, Maier DB. Evaluation of Astroglide, a new vaginal lubricant: effects of length of exposure and concentration on sperm motility. Fertil Steril 1992; 58: 630-632.

Kutteh WH, Choe CH, Ritter JO, et al. Vaginal lubricants for the infertile couple: effect on sperm activity. Int J Fertil Meno Stud 1996; 41: 400-404.

Miller B, Klein TA, Opsahl MS. The effect of surgical lubricant on in vivo sperm penetration of cervical mucus. Fertil Steril 1994; 6: 1171-1173.

Ozgur K, Franken DR, Kaskar K, Gabriel LK, Kruger TF. The influence of a mineral oil overlay on the zona pellucida binding potential of human spermatozoa. Andrologia 1995; 27: 155-159.

Tagatz GE, Okagake T, Sciarra JJ. The effect of vaginal lubricants on sperm motility and viability in vitro. Am J Obstet Gynecol 1972; 113: 88-90.

Tulandi T, Plouffe L Jr, McInnes RA. Effect of saliva on sperm motility and activity. Fertil and Steril 1982; 38: 721-723.

Tulandi T, McInnes RA. Vaginal lubricants: effect of glycerin and egg white on sperm motility and progression in vitro. Fertil Steril 1984; 41:151-153.

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