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Clinical Study for Sex Lubricants
Fertil Steril. 2008 Feb;89(2):375-9. Epub 2007 May 16.
Effect of vaginal lubricants on sperm motility and chromatin integrity: a prospective comparative study.
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 44195, USA. agarwaa@ccf.org
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.
PMID: 17509584 [PubMed - indexed for MEDLINE]
Clinical Study for Chemicals
As stated by Moline et al [Moline JM, et al.,(2000). Environ Health Perspect. 108:803-13.] paternal exposure to solvents, pesticides, and metals has been associated in animals and humans with the occurrence of spontaneous abortion, low birth weight, birth defects, childhood leukemia, brain cancer, change in the male-female sex ratio of offspring, and other end points related to growth and development. Certain paternal occupations - rubber, petroleum, and agricultural- chemical workers, painter, welder and janitor have been particularly implicated as detrimental to the reproductive health of men.
What makes the male particularly susceptible to toxin-induced damage is that, in contrast to the female ovary, the testis is characterized by a very high rate of cell proliferation with millions of sperm produced daily. Furthermore, the precursor stem cells undergo highly complex cell differentiation with specific steps known to be highly susceptible to certain types of chemical exposures.
Among the most well known toxicants to produce negative effects on sperm DNA are DDT and PCB (Hauser R. (2006) The environment and male infertility: recent research on emerging chemicals and semen quality. Semin Reprod Med vol 24 156-157].pesticide (Swan SH, Kruse RL, Liu F, Barr DB, Drobnis EZ, Redmon JB, Wang C, Brazil C, Overstreet JW; Study for Future Families Research Group. (2003) Semen quality in relation to biomarkers of pesticide exposure. Environ Health Perspect. Sep;111:1478-84] and herbicide (2, 4-D, alachlor and atrizine). Other chemicals, including styrene (used to make plastics, rubber and resins, chemical additives, self-care products and prescription medications, are suspect in causing sperm DNA damage.
Another potential source of environmental toxicants is phthalates which are used to improve flexibility in a variety of plastic like products. They are also found in nail polish, flooring, and adhesives and in an assortment of personal care products. Hauser et al. (Hauser R, Meeker JD, Singh NP, Silva MJ, Ryan L, Duty S, Calafat AM. (2007) DNA damage in human sperm is related to urinary levels of phthalate monoester and oxidative metabolites. Hum Reprod. 22(3):688-95) found a positive association for sperm DNA damage from exposure to monoethyl phthalate (MEP) in 379 men attending an infertility clinic. In pioneering studies, the SCSA test showed a very high correlation between dose of many toxicants and mouse sperm DNA fragmentation.
A recent study by Dr. Peter Schlegel's research group raised a major concern on sperm DNA fragmentation for men being prescribed anti-depressant SSRI's, in this case Paxil. Men who had an average %DFI (by Tunel assay) of 12% experienced a raise to 30% after two months on standard dosage medication. Given that data from Tunel and SCSA are close, but not necessarily the same, this 30% DFI is the threshold for clinical concerns. Thus, men on SSRI's should have an SCSA test to determine what their status is prior to attempting conception. With physician directives, men may go off of this medication while attempting natural conception, or, for freezing a number of semen samples to be used later. The %DFI should return to its level prior to the medication within a month or two.
Steroids. Steroids can interfere with proper development of healthy sperm. For example, cortisone shots (1) for e.g., back pain, can cause a major increase in sperm DNA fragmentation, well above the clinical threshold of 30%. Fortunately, this effect will come back to normal within a month or so; thus, wait at least this long prior to conception attempts, especially the costly IVF/ICSI procedures.
Radiation. Radiation that exposes the testis is negative for production of healthy sperm. In mouse model systems, doses as low as 25 rads caused a significant rise in SCSA defined % DFI.
Clinical Study for Mutagens
Mutagenic agents (agents that cause DNA mutations) have been shown to increase DNA fragmentation. These agents may be industrial chemicals, but also they are used to treat cancer patients with the hope that the mutagens will kill the cancer cells and cause as little damage to other body cells as possible. An example of an industrial chemical is methyl methanesulfonate. Sperm DNA fragmenation occured in all epidiymal mouse sperm by three days after exposure. Embryo death occurs from matings with males exposed to MMS; thus, the sperm with fragmented DNA fertilized the eggs and the embryo implanted. But the extensive DNA damage did not allow survival of the embryo.
Clinical Study for Pesticides
Exposure to certain pesticides may cause increased sperm DNA fragmentation. In Villa Juarez, State of Durango, Mexico nearly three-fourths of the agricultural men exposed to organophosphorus pesticides had DFI values greater than 30% (Sanchez-Pena et al. 2004).
Clinical Study for Pollution
In the mountain valley village of Teplice, Czech Republic, there was a high rate of infertility and miscarriages. The US EPA and Czech Republic Health Ministry sponsored a study (Rubes et al 2005) to determine the effects of valley smog during the winter inversion times as compared to the summer time cleaner air. The smog was produced by industrial and home burning of soft brown coal. 18-year-old army recruits in Teplice were compared to the recruits from Prachatic, a clean air mountain town.
The above chart shows that 90% of the young men had elevated %DFI values. 25% of these young men had values at the level (30%DFI) of being a risk for infertility - in spite of the fact of a normal semen evaluation! 18-20 yr old men normally have an approximate 5% DFI.
In a two year longitudinal study, the only semen sample measure that responded to the seasonal variation level of smog was the SCSA derived % DFI - the routine semen measures did not vary in response to the level of smog.
Industrial Pollution. Numerous industrial chemicals are of serious concern for general health including reproductive health. In contrast to years ago, the EPA and NIOSH more carefully monitor and regulate the level of exposure considered to be of no danger to health. For example, the figure below shows the data from a married man with couple idiopathic infertility. For the first 10 years he worked in an industrial firm with coded chemicals but without proper human shielding from exposure. The second ten years he wore adequate protection. During this time with natural intercourse this couple experienced 16 miscarriages and no live births. As seen in the figure the man had a very high SCSA defined %DFI, highly likely to be incompatible with normal embryo growth and development.
Clinical Study for Ambient Air Pollution
Clinical Study for Lifestyle
To mimic elevated testis temperatures caused by clothing and other insulating items, a wool sock was placed over bull testes for 48 hours. This elevated scrotal temperature adversely affected both epididymal and testicular sperm seen by an increased doubling of the %DFI (4% to 8%) within three days and a 5 fold increase by 12 days after the sock removal. Of interest, sperm at 12 days post stress had significant presence of sperm nuclear vacuoles. (Karabinus et al (1997) J Androl 18:549-555.
Mouse body temperature is about 37C. Placing mice into a heated water bath so just the testes are exposed showed that after 1 hr at 38C had minor effects on sperm DNA fragmentation 3 days after the increased temperature had very little effect on increased sperm DNA fragmentation. However, raising the temperature only 2C to 40C caused a more than doubling of %DFI and a more than tripling of %DFI by day 14. Testicular weights of mice under such exposure did not decrease after 35 days; thus, the damage from what may seem as a minor exposure to heat caused very significant sperm DNA fragmentation.
These results from animals and that seen from humans clearly shows the highly negative effect that excess heat to testis/epididymis can have on DNA fragmentation, and likely negative pregnancy outcomes from the damaged sperm.
Sailer et al (1997) J. Andrology 18:294-301
Clinical Study for Age
While maternal age over 35 years is a well-known risk factor for decreased fertility, it has clearly been demonstrated that sperm DNA fragmentation increases with age (Wyrobek et al, Evenson and Wixon, 2006). In a clinical study of 17,000 IUI cycles (Belloc et al, 2008) (Belloc et al (2008) RBM Online 17:392-397) the overall pregnancy rate was 12.7% per cycle but decreased from 14.4% before 30 years of age to 8.9% after 42 years. Of great importance, the miscarriage rate increased more than 4 X from 11.1% before 30 yrs to 45.6% after 42 years of age. This is in agreement from the data showing that men of couples that had two or more miscarriages had 4 times greater amount of sperm DNA fragmentation. (see above) (D Carroll) Remember, men's sperm DNA integrity varies with individuals, check to see if your man is on the better or not better side.
ACTION POINT: If the man of a TTC couple is over 40 yrs and/or has experienced infertility and/or miscarriages, do an SCSA test to determine if this is the cause.)
Clinical Study for Varicocele
Varicocele is found in 19 to 41% of infertile men and considered as the most common cause of male infertility. The exact mechanism(s) by which varicocele affects male fertility is still unknown. Recent data indicate a strong negative impact of increased DNA damage on the fertility potential of men.
Zini showed decreases in %DFI after varicocele repair. Hum Reprod. 2005. 20:1018-21
Clinical Study for Fever
Many environmental conditions also affect DNA fragmentation such as: prescription drugs, chemotherapy, radiation, air pollution, heat, smoking, pesticides, household and industrial chemicals and semen preparation protocols for IVF (due to oxygen exposure).
Clinical Study for Cancer
Cancer often causes temporary to permanent male infertility, most likely from both the disease and the drug therapies used to treat the disease, which have been found to damage sperm DNA and elevate DFI levels. However, the disease itself often damages sperm DNA. Thus, the general practice of collecting semen sample for freezing upon diagnosis of cancer is a good policy; however, the semen quality is often compromised prior to therapy. Therefore, at a time when the cancer patient is recovering from treatment it is often a question of whether the sperm DNA is a higher quality in the pre-treatment sample or the sample following recovery.
Distribution of individual %DFI values. Cross-hatched bars,18 samples from healthy semen donors; solid bars, 39 semen samples from patients with testicular cancer after unilateral orchiectomy before further treatment. From Fossa et al 1997.
In general, men with good DNA integrity prior to chemotherapy have better DNA integrity recovery after chemotherapy than those with poor DNA integrity prior to chemotherapy. Patients with testicular, Hodgkin's disease, non-Hodgkin's disease and other neoplasm's (abnormal growth, i.e. tumor) were evaluated with SCSA analysis. The results showed the cancer patients as a group had significantly higher DNA damage when compared to proven fertile donors (Kobayashi et al. 2001).
In another study, semen from six men with acute lymphocytic leukemia was analyzed for DNA fragmentation 10 to 52 months after completion of therapy. All men had DNA fragmentation consistent with a normal fertile reproductive status. After treatment one patient fathered a normal child and a second fathered a child with multiple congenital malformations followed by a second normal child (Evenson et al. 1984).
Patients with testicular cancer were evaluated by SCSA after unilateral orchiectomy (removal of one testis) but before treatment. Twenty-three of the thirty-nine patients displayed abnormal DNA fragmentation during pre-treatment. After treatment with radiotherapy or chemotherapy in 19 returning patients, recovery of spermatogenesis was seen in 4 out of 5 patients and was observed more in patients with normal DNA fragmentation during pre-treatment (Fossa et al. 1997).
